Afifi, Adel K. - Bergman, Ronald Arly - Functional Neuroanatomy Text and Atlas-McGraw Hill Professional (2011)

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FUNCTIONAL
NEUROANATOMY
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Notice
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FUNCTIONAL
NEUROANATOMY
text and atlas
second edition
Adel K. Afifi, M.D., M.S.

Professor of Pediatrics, Neurology, and Anatomy and Cell Biology
University of Iowa, College of Medicine
Iowa City, Iowa
Ronald A. Bergman, Ph.D.

Professor Emeritus of Anatomy and Cell Biology
University of Iowa, College of Medicine
Iowa City, Iowa
Lange Medical Books/McGraw-Hill

Medical Publishing Division
New York Chicago San Francisco Lisbon London
Madrid Mexico City Milan New Delhi San Juan Seoul
Singapore Sydney Toronto
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FUNCTIONAL NEUROANATOMY: Text and Atlas, Second Edition
Copyright © 2005, 1998, by The McGraw-Hill Companies, Inc. All rights reserved. Printed in the United States of America. Except as per-
mitted under the United States Copyright Act of 1976, no part of this publication may be reproduced or distributed in any form or by any
means, or stored in a data base or retrieval system, without prior written permission of the publisher.
1234567890 QPD QPD 098765
ISBN: 0-07-140812-6
This book was set in Adobe Garamond by MidAtlantic Books and Journals.
The editors were Isabel Nogueira, Janet Foltin, Jason Malley, and Lester A. Sheinis.
The production supervisor was Richard C. Ruzycka.
The text designer was Eve Siegel.
The illustration manager was Charissa Baker.
The illustration coordinator was Maria T. Magtoto.
The cover designer was Janice Bielawa.
The indexer was Alexandra Nickerson.
Quebecor Dubuque was printer and binder.
This book is printed on acid-free paper.
Library of Congress Cataloging-in-Publication Data are on file for this title at the Library of Congress.
FM_6082_Afifi_MGH 12/10/04 10:22 AM Page v
To our families
and
to the memories of our parents
and
Mohammed A. Soweid, Samih Y. Alami, and
Ramez and Nabih K. Afifi
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Contents
Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .ix
PART I TEXT
Chapter 1 Neurohistology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .3
Chapter 2 Gross Topography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .24
Chapter 3 Spinal Cord . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .45
Chapter 4 Clinical Correlates of Spinal Cord Anatomy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .70
Chapter 5 Medulla Oblongata . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .78
Chapter 6 Medulla Oblongata: Clinical Correlates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .98
Chapter 7 Pons . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .103
Chapter 8 Pons: Clinical Correlates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .123
Chapter 9 Mesencephalon (Midbrain) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .129
Chapter 10 Mesencephalon (Midbrain): Clinical Correlates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .150
Chapter 11 Diencephalon . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .155
Chapter 12 Diencephalon: Clinical Correlates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .172
Chapter 13 The Basal Ganglia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .180
Chapter 14 Basal Ganglia: Clinical Correlates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .195
Chapter 15 Cerebellum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .200
Chapter 16 Cerebellum: Clinical Correlates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .223
Chapter 17 Cerebral Cortex . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .228
Chapter 18 Cerebral Cortex: Clinical Correlates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .258
Chapter 19 Hypothalamus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .268
Chapter 20 Hypothalamus: Clinical Correlates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .276
Chapter 21 Limbic System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .280
Chapter 22 Limbic System: Clinical Correlates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .297
Chapter 23 Special Senses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .304
Chapter 24 Special Senses: Clinical Correlates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .323
Chapter 25 Central Nervous System Development . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .326
Chapter 26 Central Nervous System Development: Clinical Correlates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .337
Chapter 27 Cerebral Circulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .348
Chapter 28 Cerebral Vascular Syndromes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .359
Chapter 29 Cerebrospinal Fluid and the Barrier System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .368
Chapter 30 Cerebrospinal Fluid and the Barrier System: Clinical Correlates . . . . . . . . . . . . . . . . . . . . . . . . . . .379
Chapter 31 Major Sensory and Motor Pathways . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .389
Chapter 32 Reticular Formation, Wakefulness, and Sleep . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .398
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viii / CONTENTS
Chapter 33 Reticular Formation, Wakefulness, and Sleep: Clinical Correlates . . . . . . . . . . . . . . . . . . . . . . . . . . .407

Chapter 34 Control of Posture and Movement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .411
Chapter 35 Approach to a Patient with a Neurologic Disorder . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .421
PART II ATLAS
Section 1 Sectional Anatomy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .431
Section 2 Sagittal Yakovlev . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .435
Section 3 Axial Yakovlev . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .440
Section 4 Coronal Yakovlev . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .447
Section 5 Brain Stem . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .453
Section 6 Spinal Cord . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .463
Section 7 Sagittal MRI . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .467
Section 8 Axial MRI . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .470
Section 9 Coronal MRI . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .474
Bibliography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .479
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .481
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Preface
The attractive features of the second edition are the same as We are grateful to the many colleagues and students who
those of the first edition, namely: limited authorship, consistent wrote reviews and/or made comments or suggestions about the
and easy-to-read style, complete and balanced but nonexhaustive first edition. Their comments and suggestions were helpful in de-
coverage of neuroanatomy, emphasis on human neuroanatomy, veloping the second edition. We want in particular to acknowl-
simplified schematics to illustrate neural pathways, clinical corre- edge the following colleagues and students: Steven Anderson,
lation chapters, key concepts for easy pre-exam review, derivation Nadia Bahuth, Antoine Becharea, Daniel Bonthius, Deema
of terms and historical perspective of common eponyms, and an Fattal, Aleyamma Fenn, Tiny Jaentsch, Jean Jew, Kokoro Ozaki,
extensive atlas of spinal cord and brain sections as well as mag- Paul Reimann, Ergun Uc, and Gary Van Hoesen.
netic resonance images (MRI) in three planes. We want to thank Karen Boatman who was instrumental in
In this edition, all chapters have been updated to reflect the typing additions to the chapters and the new chapters. Her in-
current state of knowledge. Four new chapters are added: two are quisitive interest in the subject made it a pleasure to work with
related to the Reticular Formation, Wakefulness and Sleep; one her. Karolyn Leary assisted us in typing some of the text and re-
on the Control of Posture and Movement, and one on The lieved Karen from many other office tasks to allow her to devote
Approach to the Patient with Neurologic Disorder. The illustra- time to the book.
tions have been improved and several new illustrations have also Special thanks to the staff of McGraw-Hill and in particular
been added. The Key Concepts have been placed at the beginning to Isabel Nogueira who initiated the proposal for the second edi-
of each chapter and can easily be identified by this icon . tion and provided valuable advice and guidance during the early
New references have been added to the Suggested Readings at the phase of its preparation; Janet Foltin, Jason Malley, and Lester A.
end of each chapter. The text in the margins of the pages has been Sheinis who most ably oversaw the tedious editorial task of its
expanded and relocated for more efficient use of space. Boldface production; Richard C. Ruzycka, production supervisor; Eve
emphasis of some terms in the text has been removed to allow Siegel, text designer; Charissa Baker, illustration manager; Maria
easier flow of text. These terms are now listed in the Terminology T. Magtoto, illustration coordinator; Janice Bielawa, cover de-
section at the end of each chapter and are highlighted in blue signer; Alexandra Nickerson, indexer; and Keith Donnellan, of
color in the text. Leaders in the Atlas have been improved to Dovetail Content Solutions, who directed the copyediting of the
make it easier for the reader to identify the intended structures. manuscript.
Adel K. Afifi, M.D., M.S.

Ronald A. Bergman, Ph.D.
ix
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ch01_6082_Afifi_MGH_new 12/10/04 10:27 AM Page 1
PART I
text
Neurohistology 1
The Cells and Their Unique Characteristics Synapse

Overview of Neurons Neuromuscular Junction
Perikaryon Receptor Organs of Sensory Neurons
Axon (Axis cylinder, Remak’s band) Free (Nonencapsulated) Nerve Endings
Dendrites Encapsulated Nerve Endings
Neuroglia Reaction of Neurons to Injury
Ganglia Cell Body and Dendrites
Craniospinal Ganglia Axon
Autonomic Ganglia Nerve Growth Factors
Nerve Fibers Clinical Correlation
Myelinated Nerve Fibers Neuronal Plasticity
Unmyelinated Nerve Fibers
Conduction of Nerve Impulses
Axonal Transport
KEY CONCEPTS
A neuron consists of a perikaryon (cell body) and its pro- Microglia play a role in repair of the central nervous
cesses (axon and dendrites). Neurons vary in size and system.
shape,and each neuron has one axon and many dendrites.
Craniospinal ganglia include the dorsal root ganglia and
Perikaryal organelles that are found in axons include mito- the ganglia of cranial nerves V, VII, VIII, IX, and X.
chondria, microtubules, microfilaments, neurofilaments,
Peripheral nerves are surrounded by three connective
neurotubules, smooth endoplasmic reticulum, lysosomes,
tissue sheaths. Endoneurium invests individual axons,
and vesicles.
perineurium invests groups of axons in fascicles, and
Dendrites contain all the perikaryal organelles except the epineurium invests the whole nerve.
Golgi complex.
Two types of axonal transport occur in axons: antero-
Neuroglia are the supporting elements of the central ner- grade and retrograde.
vous system. They include macroglia (astrocytes and
On the basis of their function, synapses are classified into
oligodendroglia), microglia, and ependymal cells.
excitatory and inhibitory.
Astrocytes are metabolic intermediaries for nerve cells.
Sensory receptor organs are classified according to their
Fibrous astrocytes also serve a repair function after neural
location (skin or joints), structure (encapsulated or free),
injury.
function (nociceptor or mechanoreceptor), adaptive prop-
Oligodendroglia elaborate central nervous system myelin. erties (slowly or quickly adapting), or a combination of
these categories.
(continued on next page)
3
4 / CHAPTER 1
(continued from previous page) Clinically, nerve injury is classified according to the degree
of severity into conduction block (neurapraxia), loss of
Neurons react to injury by undergoing characteristic axonal continuity (axonotmesis), and loss of nerve trunk
changes that occur proximal (chromatolysis) and distal continuity (neurotmesis).
(wallerian degeneration) to the site of the injury.
The cells of the nervous system can be divided into two groups:
nerve cells (neurons) and supporting cells (glia). Nerve cells are
all associated with each other as a functional syncytium, a com-
plex network somewhat like that found in a telephone company
switch board. Neurons communicate with each other through
specialized areas of neuronal contact called synapses. The com-
plexity of the synaptic relationships among billions of neurons cb
forms the basis for the behavioral complexity of humans.
cb
THE CELLS AND THEIR UNIQUE B Ax

CHARACTERISTICS
Overview of Neurons
A neuron, or nerve cell (the terms may be used inter- cb
Ax
changeably), has a cell body, or perikaryon (the part Ax
containing the nucleus), and all its processes (axon and
dendrites). The names given to neurons were suggested by their
size, shape, appearance, functional role, or presumed discoverer A C
[e.g., Purkinje cell (neuron) of the cerebellum]. The size and
shape of neuronal cell bodies are remarkably variable. The di-
ameter of the cell body may be as small as 4 m (granule cell of
the cerebellum) or as large as 125 m (motor neuron of the
spinal cord). Nerve cells may have a pyramidal, flask, stellate, or Ax
granular shape (Figure 1–1). An additional feature of these
perikarya is the number and organization of their processes. cb
Some neurons have few dendrites, while others have numerous D
dendritic projections. With two known exceptions (the axonless
amacrine cell of the retina and the granule cells of the olfactory
bulb), all neurons have at least one axon and one or more
dendrites. cb
In general, three basic types of neurons are recognized:
1. Unipolar or pseudounipolar neurons (e.g., sensory [or dorsal Ax
root] ganglion cells) have a spherical cell body with single E

process that bifurcates (Figure 1–1H ).
2. Bipolar neurons (e.g., cochlear and vestibular peripheral gan-
glia and olfactory and retinal receptor cells) are spindle- F
Ax
cb
shaped, with one process at each end of the cell (Figure 1–1I ).
3. Multipolar neurons (e.g., autonomic ganglia and the enor- cb
mous population of cells in the central nervous system) have G
cb
Ax
one axon and many dendritic processes (Figure 1–1 A–G ).

H I
The most interesting feature of the neurons is their processes.
In humans, the axon of a neuron, the effector part of the cell, Figure 1–1. Schematic diagram illustrating variations in neu-
may be a meter or more in length, extending from the spinal ronal size, shape, and processes. A. Pyramidal neuron. B. Flask-
cord to the fingers or toes or from the neurons of the cerebral shaped Purkinje neuron. C. Stellate neuron. D. Granular neuron.
cortex to the distal extent of the spinal cord. The dendrites, the E. Multipolar anterior horn neuron. F. Multipolar sympathetic
primary receptor area of the cell, are variable in number and in ganglion neuron. G. Multipolar parasympathetic ganglion neu-
branching pattern, which in some cases enormously increases a ron. H. Pseudounipolar dorsal root ganglion neuron. I. Bipolar
neuron’s surface area. neuron. cb, cell body; Ax, axon.
NEUROHISTOLOGY / 5
Axon
Dendrites
Nucleus
Axon hillock
Golgi
Nissl apparatus
Nucleolus substance
A Nucleus B
Neurofibrils
Nucleus
Nucleus
Lipochrome
pigment Melanin
Perikaryon
Dendrite
C D E
Figure 1–2. Schematic diagram of motor neuron and its organelles. A. Neuronal cell body and its processes. B. Golgi apparatus.
C. Neurofilaments. D. Lipochrome pigment. E. Melanin pigment.
Perikaryon this case, the term nuclei refers to a cluster of cell bodies in the cen-
tral nervous system rather than the nuclei of neurons). Nissl bodies,
The perikaryon, or cell body, contains the nucleus and a number which are distinctive in shape and abundant, are composed of
of organelles (Figure 1–2). membrane-bound ribonucleoproteins (also known as granular en-
The nucleus is usually round and centrally located. The nu- doplasmic reticulum). The role of the nucleus, nucleolus, and cyto-
cleoplasm is typically homogeneous and stains poorly with basic plasmic RNA in protein synthesis is well established. Thus, the cell
dyes (nuclear stains). This indicates that the deoxyribonucleic body synthesizes cytoplasmic proteins and other essential con-
acid (DNA) is dispersed and is in its functionally active form. stituents, which are distributed throughout the neuron for mainte-
The nucleoplasm is said to be in its euchromatic form. In stark nance and the functional activities that will be discussed below.
contrast, each nucleus contains one deeply stainable (with basic Nissl bodies are found not only in the cell body but also in
dyes) nucleolus, composed in part of ribonucleic acid (RNA), dendrites. Hence, they too are involved in synthetic activity. The
which normally is present within the nucleus. The nuclear con- presence of Nissl bodies in dendrites confirms their identity as
tents are enclosed in a distinct nuclear membrane. dendrites, something that otherwise would be impossible in the
The cytoplasm surrounding the nucleus is filled with a variety study of the dense mix of dendrites and axons in the neuropil.
of organelles and inclusions. Nissl bodies are absent from the axon hillock (part of the
The most dramatic organelle is the so-called chromophil sub- perikaryon from which the axon arises). Nissl bodies undergo
stance (because of its affinity for basic dyes), or Nissl bodies (after characteristic changes (chromatolysis) in response to axonal in-
its discoverer). Nissl bodies (Figure 1–2A) are particularly promi- jury (see below).
nent in somatic motor neurons, such as those found in the anterior Numerous mitochondria dispersed throughout the cytoplasm
horn of the spinal cord or in some motor cranial nerve nuclei (in play a vital role in the metabolic activity of the neuron.
6 / CHAPTER 1
The Golgi apparatus (Figure 1–2B), which originally was dis- Perikaryon Vesicle Neuropil
covered in neurons, is a highly developed system of flattened Golgi complex Neuro ilament
f
vesicles and small oval and/or round agranular vesicles. The Nucleolus
Golgi apparatus is thought to be the region of the cell that re-
ceives the synthetic products of the Nissl substance to allow ad-
ditional synthetic activity. It is thought that the Golgi area is the
site where carbohydrates are linked to protein in the synthesis of
glycoproteins. The small vesicles arising from this organelle may Axon
be the source of synaptic vesicles and their contents, which are
found in axon terminals.
Neurofibrils (Figure 1–2C ) are found in all neurons and are Neurotubule
continuous throughout all their processes. They are composed of
subunits (neurofilaments) that are 7.5 to 10 nm in diameter and
thus are below the limit of resolution of the light microscope. Smooth
Nucleus Rough Axon hillock endoplasmic
Aggregates of abnormal neurofibrils (neurofibrillary tangles)
endoplasmic reticulum
accumulate in neurons in Alzheimer’s disease. In addition to
neurofilaments, there are neurotubules with an external diameter reticulum
of about 25 nm; these structures are similar to those found in Mitochondrion Ribosomes
cells that are not neuronal. Neurotubules are concerned with the Figure 1–3. Schematic diagram showing part of neuronal
rapid transport of protein molecules synthesized in the cell body, perikaryon, its axon hillock, and axon.
which are carried through the dendrites and axon. Neuronal
perikarya also contain 5- to 8-nm neurofilaments or actin fila-
ments, which form a network under the plasma membrane.
Most large nerve cells contain lipochrome pigment granules
(Figure 1–2D). These granules apparently accumulate with age
and are more evident during the advancing age of the organism. out the axoplasm, but not in a recognizable pattern. Neuro-
In addition, certain nerve cells found in specific locations of the filaments are composed of three proteins with a molecular mass
brain contain black (melanin pigment) granules (Figure 1–2E ). of 68 to 200 kDa, subunits of the protein tubulin. They are read-
All these organelles and inclusions are features of the peri- ily disassembled by intrinsic proteases and disappear rapidly in
karyon, marking it as the neuron’s trophic center. The separation damaged axons. Microtubules are axially arranged hollow cylin-
of a process (axon or dendrite) from the perikaryon results in the ders that measure 23 to 25 nm in diameter and are of indefinite
disintegration of the process. length. The number of microtubules within an axon varies in di-
rect relation to axonal mass and the type of nerve; they are more
Axon (Axis Cylinder, Remak’s Band) numerous in unmyelinated axons.
Mitochondria vary in number in an inverse ratio to axonal
A single axon arises from the cell body. The point of departure of cross-sectional area. They are often topographically related to
the axon is known as the axon hillock. The axon may be very one or more microtubules.
long (120 cm or more) and is uniformly cylindrical. The diame- Smooth endoplasmic reticulum (SER) provides secretory vesi-
ter of axons is also variable and is related to their function. cles along the axon. SER is functionally concerned with axonal
The origin of the axon is the axon hillock, a small part of the transport. Secretory vesicles range in size from 40 to 100 m.
cell body that is devoid of Nissl substance. Beneath the neu- Concentrations of vesicles are found in association with nodes of
ronal membrane at the axon hillock is a dense layer of granular Ranvier (see below) and within nerve terminals.
material about 200 Å thick. In addition, there is a confluence of Lysosomes usually are found near nodes of Ranvier and accu-
microtubules that exhibit clustering and cross-linkage. The area mulate rapidly during the degeneration of nerves after an injury.
between the perikaryon (and axon hillock) and the axon is Axons retain a uniform diameter throughout their length.
called the initial segment. This segment is short, narrow, and Axons may have collateral branches proximally and usually
devoid of myelin. It is at this segment that the nerve impulse or branch extensively at their distal ends (telodendria) before termi-
action potential is initiated. Just beyond the initial segment, nating by synaptic contact with dendrites and cell bodies of
many axons become myelinated; this increases their diameter in other neurons or on effector organs (muscles and glands).
a uniform manner until an axon terminates at its end Axons may be myelinated or unmyelinated (Figure 1–4). In
organ. The axoplasm contains many organelles, such as both cases, however, the axons are ensheathed by supporting
mitochondria, microtubules, microfilaments, neurofila- cells: Schwann cells in the peripheral nervous system and oligo-
ments, neurotubules, smooth endoplasmic reticulum, lyso- dendroglia cells in the central nervous system.
somes, and vesicles of various sizes (Figure 1–3). The axon, un- Myelinated axons are formed when they become wrapped
like the cell body, does not have any structures associated with (Figure 1–5) in multiple layers of Schwann or oligodendroglia
protein synthesis or assembly (ribosomes, rough endoplasmic plasmalemma (cell membrane). The process of myelination is
reticulum [Nissl substance], and the Golgi complex). The discussed later in this chapter.
smallest axoplasmic components are the microfilaments, which The myelin sheath is discontinuous at the distal ends of each
are paired helical chains of actin. The microfilaments usually are cell (Schwann or oligodendroglia) involved in the ensheathing
located in the cortical zone near the axolemma; their protein, process. The area of discontinuity between cells is known as a
actin (associated with the contractile process), may play a role in node of Ranvier (Figure 1–6) and is the site of voltage-gated
intraaxonal transport. sodium channels and other ionic displacements involved in im-
Neurofilaments (7.5 to 10 nm in diameter) are larger than pulse conduction (action potentials). The electric impulse flows
microfilaments and more prevalent. They are scattered through- across a myelinated axon by jumping from node to node. This
NEUROHISTOLOGY / 7
Small Nucleus Schwann cell Axon

myyelinated
f iber
Connective
tissue
M yelin sheath
Axon space c midt-

S h Myeli s e t
n h a h Node of
Lanterman R vier
an
cle ts
A f
Figure 1–6. Schematic diagram of the structure of a myelin-

ated peripheral nerve.
Axon
M yelin space sues are continuous with each other throughout the nerve, but
they are named differently according to their locations. The tis-
sue covering individual axons is known as endoneurium, that
surrounding a grouping of axons is known as perineurium, and
Nonmyelinated that covering the entire nerve (a recognizable multibundle of
fiber axons) is known as the epineurium. The perineurium constitutes
a barrier preventing certain substances from entry to the axons.
B Myelinated axons vary in diameter from 1 to 20 m,
whereas unmyelinated axons are not larger than 2 m. The size
Figure 1–4. Schematic diagram of cross sections of a peripheral of the nerve fiber (the axon plus its myelin) has a direct rela-
nerve stained to show myelin sheaths (A) and axons (B). tionship to the rate of impulse conduction; large myelinated
fibers conduct nerve impulses at a faster rate than do small un-
myelinated axons.
type of impulse conduction is known as saltatory conduction; it

tends to increase the conduction speed of the action potential. Dendrites
The nodes of Ranvier are not lined up with those of adjacent Neurons possess a single axon but usually have more than one
axons, and the myelin sheaths serve as electric insulation; hence, dendrite, although there are exceptions (see below). Dendrites
there is little if any spurious activation of axons. may increase the receptive surface area of the cell body enor-
Myelin, which is composed of a variable number of tight wrap- mously. Another method of increasing the receptive surface area
pings of cell membrane around axons, is a lipid-protein complex. of dendrites involves numerous projections from the dendrites
When it is prepared for light microscopy, lipid is extracted or lost known as spines or gemmules, which represent sites of synaptic
during tissue preparation, leaving behind in the sectioned tissue a contact by axon terminals from other neurons.
resistant proteolipid artifact known as neurokeratin. Dendrites contain all the organelles found in the
In addition to myelin sheaths, peripheral nerve fibers are sur- neuroplasm of the perikaryon except the Golgi appara-
rounded by connective tissue, the endoneurium. Connective tis- tus. Neurons that receive axon terminal or synaptic con-
tacts from a variety of central nervous system sources may have
an extremely complex dendritic organization. An outstanding
example of this complexity is found in Purkinje cells in the cere-
bellum. Cells of the central nervous system and autonomic gan-
SC Ax glia have dendrites extending from their perikarya. Cells with
multiple dendrites are called multipolar; those which possess
only axonlike processes extending from each end of the cell are
named bipolar neurons. Bipolar neurons are found only in the
retina of the eye, olfactory receptors, and the peripheral ganglia
of the vestibulocochlear nerve (cranial nerve VIII). Sensory neu-
rons in the dorsal root ganglia of spinal neurons are referred to as
A B C D pseudounipolar because only a single process leaves the cell body
before bifurcating to form proximal and distal segments.
Figure 1–5. Schematic diagram of the process of formation of The processes of bipolar and pseudounipolar neurons are
myelin sheaths. A and B show formation of myelin sheath by axonlike in structure; they have a limited or specific receptive ca-
concentric double layers of Schwann cell (SC) membranes wrap- pacity. These neurons of the peripheral nervous system usually
ping themselves around the axon (Ax). C shows how protoplas- retain the diversified terminal axonal branching when they enter
mic surfaces of the membrane become fused together to form the central nervous system (brain and spinal cord).
the major dense lines. D shows how several unmyelinated axons A unique and unusual cell found in the retina, the amacrine
are contained within the infoldings of a single Schwann cell. cell, is regarded as an axonless neuron.
8 / CHAPTER 1
Neuroglia
The supporting cells between the neurons of the central
nervous system are referred to as neuroglia (Figure 1–7).
There are several varieties, which may be organized as Nuclear
follows: region
1. Astrocytes Microglia
a. Fibrous cell
b. Protoplasmic
2. Oligodendroglia
3. Ependymal cells
4. Microglia Protoplasmic
A astrocytes 20 mm
Astrocytes and oligodendroglia are also known as the macroglia.
A. ASTROCYTES (ASTROGLIA)
Astrocytes are the largest of the neuroglia. They are branched Protoplasmic
astrocyte
stellate cells. The nuclei of these cells are ovoid, are centrally lo-
cated, and stain poorly because they lack significant amounts of
heterochromatin and have no nucleoli. The nuclei do contain
euchromatin, which does not stain with typical nuclear stains and
is characteristic of active nuclear activity in its cellular function.
The cytoplasm of astrocytes may contain small round gran- Neuron
ules and glial filaments composed of glial fibrillary acidic protein
(GFAP).
The processes of astroglia attach to and completely cover the
outer surface of capillaries (perivascular end feet or footplates) as
well as the pia mater (glia limitans).
During development, astrocytes (radial glia) provide a frame-
work which guides neuronal migration.
B
1. Fibrous astrocytes. Fibrous astrocytes (Figure 1–7C ) have
thin, spindly processes that radiate from the cell body and termi-
nate with distal expansions or footplates, which are also in con- Neuron
tact with the external walls of blood vessels within the central
nervous system. The foot processes form a continuous glial Fibrous
sheath, the so-called perivascular limiting membrane, surround- astrocyte
ing blood vessels.
The cytoplasm of fibrous astrocytes contains filaments that
extend throughout the cell as well as the usual (the generic group
of ) cytoplasmic organelles.
Fibrous astrocytes, which are found primarily within Blood
the white matter, are believed to be concerned with vessel
metabolite transference and the repair of damaged tissue Oligodendroglia
(scarring).
C D
2. Protoplasmic astrocytes. Protoplasmic astrocytes (Figure
1–7A, B) have thicker and more numerous branches. They are in
close association with neurons and may partially envelop them;
thus, they are known as satellite cells. Since they have a close re-
lationship to neurons, they are located primarily in the gray mat- Ependymal
cells
ter, where the cell bodies are found. Their function is not entirely
clear, but they serve as a metabolic intermediary for nerve cells.
B. OLIGODENDROGLIA
Central
Oligodendroglia (Figure 1–7D) have fewer and shorter branches E canal
than do astrocytes. Their nuclei are round and have condensed,
stainable (heterochromatin) nucleoplasm. The cytoplasm is Figure 1–7. Schematic diagram of types of neuroglia showing
densely filled with mitochondria, microtubules, and ribosomes the thick and numerous processes of protoplasmic astrocytes
but is devoid of neurofilaments. Oligodendroglia cells are found and the slender and few processes of microglia (A), protoplasmic
in both gray and white matter. They usually are seen astrocytes in close proximity to neurons (B), fibrous astrocyte
lying in rows among axons in the white matter. Electron with processes in contact with a blood vessel (C), oligoden-
microscopic studies have implicated the oligodendroglia droglia in close proximity to a neuron (D), and ependymal cells
in myelination within the central nervous system in a lining central canal of the spinal cord (E).
NEUROHISTOLOGY / 9
manner similar to that of Schwann cells in the peripheral nervous Craniospinal ganglion cells vary in size from 15 to 100 m.
system. Within the gray matter, these cells are closely associated In general, these cells fall into two size groups. The smaller neu-
with neurons (perineuronal satellite cells), as are the protoplas- rons have unmyelinated axons, whereas the larger cells have
mic astrocytes. myelinated axons. Each ganglion cell is surrounded by connec-
tive tissue and supporting cells (the perineuronal satellite cells or
C. EPENDYMAL CELLS capsule cells). From each cell, a single process arises to bifurcate
Ependymal cells (Figure 1–7E) line the central canal of the and by doing so forms an inverted T or Y shape (Figure 1–1H ).
spinal cord and the ventricles of the brain. They vary from This axonlike structure extends to appropriate proximal and dis-
cuboidal to columnar in shape and may possess cilia. Their cyto- tal locations. The intracapsular process may be coiled (so-called
plasm contains mitochondria, a Golgi complex, and small gran- glomerulus) or relatively straight. The bipolar ganglion cells
ules. These cells are involved in the formation of cerebrospinal of the vestibular and cochlear cranial nerves are not, however,
fluid. A specialized form of ependymal cell is seen in some areas encapsulated by satellite cells.
of the nervous system, such as the subcommissural organ.
Autonomic Ganglia
D. MICROGLIA
The microglia (Figure 1–7A), unlike other nerve and glial cells, Autonomic ganglia are clusters of neurons found from the base of
are of mesodermal origin and enter the central nervous system the skull to the pelvis, in close association with and bilaterally
early in its development. Their cell bodies are small, usually with arranged adjacent to vertebral bodies (sympathetic ganglia), or lo-
little cytoplasm, but are densely staining and have somewhat cated within the organ they innervate (parasympathetic ganglia).
flattened and elongated nuclei. These cells have few processes, In contrast to cranial-spinal ganglia, the ganglion cells of the
occasionally two, at either end. The processes are spindly and autonomic nervous system (sympathetic and parasympathetic)
bear small thorny spines. Normally, the function of the are multipolar (Figure 1–1F, G) and receive synaptic input from
microglia is uncertain, but when destructive lesions occur various areas of the nervous system. Autonomic ganglion cells
in the central nervous system, these cells enlarge and be- are surrounded by connective tissue and small perineuronal
come mobile and phagocytic. Thus, they become the satellite cells that are located between the dendrites and are in
macrophages, or scavenger cells, of the central nervous system. close association with the cell body.
Glial cells have been described as the electrically passive ele- Autonomic cells range in diameter from 20 to 60 m and
ments of the central nervous system. However, it has been shown have clear (euchromatic) spherical or oval nuclei, with some cells
that glial cells in culture can express a variety of ligand- and voltage- being binucleate. The cytoplasm contains neurofibrils and small
gated ion channels that previously were believed to be properties aggregates of RNA, a Golgi apparatus, small vesicles, and the
of neurons. Although numerous ion channels have been de- ubiquitous mitochondria.
scribed—sodium, calcium, chloride, and potassium—their full The dendritic processes of two or more adjacent cells often
functional significance is uncertain. Oligodendrocytes have been appear tangled and may form dendritic glomeruli; such cells usu-
shown to quickly change the potassium gradient across their cell ally are enclosed in a single capsule. The terminal arborizations
membranes, giving rise to a potential change; thus, they serve as of the ganglionic axons synapse on these dendritic glomeruli as
highly efficient potassium buffers. well as on the dendrites of individual ganglion cells. In general,
Receptors for numerous neurotransmitters and neuromodula- the preganglionic arborization of a single axon brings that axon
tors, such as gamma-aminobutyric acid (GABA), glutamate, nor- into synaptic contact with numerous ganglion cells. The axons
adrenaline, and substance P, have been demonstrated on glia cells, of these ganglion cells are small in diameter (0.3 to 1.3 m).
particularly astrocytes. Patch clamp studies have revealed that these Autonomic ganglion cells within the viscera (intramural, para-
glial receptors are similar in many respects to those on neurons. sympathetic ganglia) may be few in number and widely distrib-
uted. They are not encapsulated but are contained within con-
nective tissue septa in the organ that is innervated. The cells of
the autonomic ganglia innervate visceral effectors such as smooth
GANGLIA muscle, cardiac muscle, and glandular epithelium.
Ganglia are defined as collections of nerve cell bodies located
outside the central nervous system. There are two types of gan-
glia: craniospinal and autonomic. NERVE FIBERS
A peripheral nerve is composed of nerve fibers (axons) that vary
Craniospinal Ganglia in size, are myelinated or unmyelinated, and transmit nerve im-
pulses either to or from the central nervous system. Peripheral
The craniospinal ganglia (Figure 1–1H ) are located in the nerves are often mixed nerves because they usually are composed
dorsal roots of the 31 pairs of spinal nerves and in the of both motor and sensory fibers. Nerves containing only sen-
sensory roots of the trigeminal (cranial nerve V), facial sory fibers are called sensory nerves; those which contain only
(cranial nerve VII), vestibulocochlear (cranial nerve VIII), glos- motor fibers are called motor nerves. The structural organization
sopharyngeal (cranial nerve IX), and vagus (cranial nerve X) changes along the length of the nerve because of the repeated di-
nerves. The dorsal root ganglia and the cranial nerve ganglia are vision and union of different nerve fascicles, resulting in com-
concerned with sensory reception and distribution. They receive plex fascicular formations.
stimulation from the external and internal environments at their The nerve fibers that make up a peripheral nerve have been clas-
distal ends and transmit nerve impulses to the central nervous sified according to size and other functional characteristics (Table
system. The ganglion cells of the spinal group are classified as 1–1). Axons designated as A alpha axons range in size from 12 to
pseudounipolar neurons, whereas the ganglion cells of the vestibu- 22 m; A beta, from 5 to 12 m; A gamma, from 2 to 8 m; and
lar and cochlear nerves are bipolar neurons (Figure 1–1I ). A delta, from 1 to 5 m. Preganglionic sympathetic fibers that are
10 / CHAPTER 1
Table 1–1. Some Properties of Mammalian Peripheral Nerve Fibers.
Nerve fiber Number Function and/or source Fiber size Myelination Conduction
type designation (m) velocity (ms)
A alpha () Ia Proprioception, stretch (muscle, spindle, 12–22 70–120

annulospiral receptor), and motor
to skeletal muscle fibers (extrafusal)
Ib Contractile force (Golgi tendon organ) 12–22 70–120
A beta () II Pressure, stretch (muscle spindle, 5–12 30–70
flower spray receptor), touch, and
vibratory sense
A gamma () II Motor to muscle spindle (intrafusal 2–8 15–30
muscle fibers)
A delta () III Some nerve endings serving pain, 1–5 5–30
temperature, and touch
B — Sympathetic preganglionic axons 3 3–15
C IV Other pain, temperature, and 0.1–1.3 0.6–2.0
mechanical receptors; sympathetic,
postganglionic axons (motor to smooth
muscle and glands)
NOTE: ++, thickly myelinated; +, thinly myelinated; –, nonmyelinated.
less than 3 m in diameter are designated as B fibers. All these cells from and into the nerve fascicles. It also acts as a diffusion
structures are myelinated nerve fibers. The smallest axons (0.1 to (blood-nerve) barrier similar to the pia-arachnoid, with which it
3 m in diameter) are designated C fibers and are unmyelinated. is continuous.
A peripheral nerve may be composed of thousands of axons, The innermost sheath of connective tissue, the endoneurium,
but the number of axons in each peripheral nerve is variable. invests each individual axon and is continuous with the connec-
Some axons supply many end structures; others, a few.
Examination of nerve cross sections reveals that the amount
Endoneurium Perineurium Endoneurium
of connective tissue varies from 25 to 85 percent. This value also
varies from place to place and from nerve to nerve. For example, Nerve fiber
connective tissue is increased at points where nerves cross joints Epineurium fascicles
or where there are relatively greater numbers of smaller nerve fas-
cicles or bundles within the peripheral nerve. The connective
tissue elements provide the great tensile strength of peripheral
nerves; because connective tissue ensheaths the axons, it prevents
injury or damage caused by stretching.
Three parts of the connective tissue sheath are recognized
(Figure 1–8). The outer sheath, the epineurium, is rela-
tively thick and is partially composed of loose (areolar)
connective tissue. It contains blood and lymphatic ves-
sels. It is also contiguous with the dura mater where a peripheral
nerve leaves the central nervous system. The epineurium gives
the nerve its cordlike appearance and consistency and separates it
from the surrounding tissues. The epineurium acts as a “shock
absorber” that dissipates stresses set up in a nerve when that
nerve is subjected to pressure or trauma. Nerves composed of
closely packed fasciculi with little supporting epineurial tissue
are more vulnerable to mechanical injury than are nerves in
which fasciculi are more widely separated by a greater amount of
epineurial tissue. Epineurial collagenous fibers are continuous
with the dense perineurium, which separates and encompasses
groups of axons into fascicles of different sizes. The perineurium
also partitions the fascicles and follows nerve branches to the pe-
riphery, where they terminate on each individual axon (so-called
sheath of Henle). These partitions, or septa, may be traversed by
small blood vessels, and the perineurium is continuous with Artery Vein
the pia-arachnoid membrane. The perineurium also gives tensile
strength and some elasticity to the nerve. Figure 1–8. Schematic diagram of a cross section of a periph-
The perineurium is also considered a specialized structure that eral nerve showing the formation of three connective tissue sep-
provides active transport of selected materials across the perineural tae: endoneurium, epineurium, and perineurium.
NEUROHISTOLOGY / 11
tive tissue that forms the perineurium and epineurium. This con- lysosomelike granules are also more numerous at this site. There
nective tissue provides a tough, protective tubular sheath for the is also a relative swelling of the axon at the node.
delicate axons. Within the endoneurium and surrounding each The remarkable ultrastructural organization of the node of
myelinated or unmyelinated axon are Schwann cells. Schwann Ranvier suggests that the entire paranodal region, the adjacent
cells produce the myelin sheath (Figure 1–6). This nucleated Schwann cell membranes, and the nodal region of the axon may
sheath of peripheral nerve fibers is also known as the neuro- constitute or be thought of as a single functional unit.
lemma or the sheath of Schwann. Occasionally, myelin shows localized incomplete fusion of
In general, large axons are myelinated and small axons are Schwann cell membrane, and small amounts of Schwann cell pro-
unmyelinated. It is not known which factors determine the se- toplasm may be found trapped between the membranes. These ar-
lection of fibers for myelination, but axon caliber and trophic in- eas of incomplete fusion are called Schmidt-Lanterman clefts
fluences on Schwann cells by the axon have been implicated. The (Figure 1–6). Their significance is not understood, but they may
conduction velocity of axons is directly related to axon diameter be an artifact or represent a shearing deficit in the formation of
and the thickness of the myelin sheath. Conduction velocity rises myelin or may merely represent a distension of areas of the myelin
with increasing axon diameter and increasing thickness of the sheath in which Schwann cell cytoplasm was inadvertently left be-
myelin sheath. hind as the cell wound around the axon in the process of forming
Nerves are well supplied by a longitudinally arranged anasto- the myelin sheath. Once trapped, it is probably irremovable but
mosing system of blood vessels that originate from larger arteries produces no demonstrable change in function.
and veins, perforating muscular vessels, and periosteal vessels. Axonal myelin ends near the terminal arborization of the axon.
These vessels ramify within the epineurium and extend to reach Research has established the fact that the axon provides the
the perineurium and endoneurium. “signal” for myelination to take place. This signal probably is car-
Anastomoses between arterioles, between venules, and be- ried by molecules on the axonal membrane.
tween arterioles and venules are common. There are numerous Myelination within the central nervous system is accom-
anastomoses between epineurial and perineurial arterioles and plished by oligodendroglia cells in a manner similar to that
endoneurial capillaries. described above for the peripheral nervous system. The major
Electron microscopy has revealed structural differences be- difference in the central nervous system myelin is that the in-
tween epineurial and endoneurial vessels. The endothelial cells ternodal distance and the gap of the node of Ranvier are smaller.
that make up epineurial vessels have cell junctions of the “open” In addition, in the peripheral nervous system one Schwann cell
variety, which allow extravasation of protein macromolecules. produces myelin for a part of a single axon, whereas in the cen-
Small amounts of serum proteins can diffuse into the epineurium tral nervous system one oligodendroglia cell produces the myelin
but cannot pass through the perineurium. Endoneurial vessels, sheath segment for an entire group of axons in its vicinity, with
in contrast, have endothelial cells with tight junctions, which the number ranging from 3 to 200 axons.
prevent the extravasation of proteins within the endoneurial space.
These vessels, along with the perineurium, constitute the blood- Unmyelinated Nerve Fibers
nerve barrier.
Unlike their larger counterparts, several (8 to 15) small axons
may be contained within the infolding of a single Schwann cell
Myelinated Nerve Fibers (Figure 1–5D), from which they are separated by a constant peri-
axonal space. The invested axon appears in cross section to be
Electron microscopic studies have demonstrated that most axons suspended in the cytoplasm by a short segment of the invagi-
greater than 1 m in diameter are myelinated. The myelin sheath, nated outer membrane, which, after surrounding the axon, is di-
a proteophospholipid complex, is formed by many concentric rected back to the surface in close approximation to the incom-
double layers of Schwann cell membrane. The double layer of cell ing membrane. The similarity in appearance of this arrangement
membrane is tightly wound, expressing the neuroplasm between to a cross-sectional intestine with its supporting mesentery has
the layers, and the inner or protoplasmic surfaces of the cell mem- prompted the use of the term mesaxon for nonmyelinated axons
brane become fused, forming the dense, thicker lamellae of the suspended by the cell membrane and located below the cell’s
myelin sheath (so-called major dense lines) seen on electron mi- outer surface (and surrounded by neuroplasm). Unmyelinated
croscopy. The inner, less dense lamellae (so-called intraperiod axons do not have nodes of Ranvier. Within the central nervous
lines) are formed by the outer surfaces of the cell membrane. system, glia cells have the same function as Schwann cells in that
The myelin sheath is not continuous over the entire length of they ensheathe the nonmyelinated axons.
the axon but is interrupted at either end because Schwann cells are
much shorter than axons. Therefore, a gap always exists between Conduction of Nerve Impulses
adjacent Schwann cells; this gap is referred to as a node of Ranvier.
Many Schwann cells are needed to myelinate a single axon. The cell membrane plays a key role in nerve transmission. In un-
Sodium channels are known to be clustered at nodes of Ranvier, myelinated fibers the electric impulse is conducted via ion move-
but they are also present in lower numbers in the internodal ax- ment across an ionic destabilized cell membrane. The change in
onal membrane. The electron microscope has revealed that inter- permeability of the membrane allows the influx of sodium ions
digitating processes of Schwann cells partially cover the node. and the efflux of potassium ions, resulting in a localized reversal
The internodal distance is inconstant because of variations in of charge of the cell membrane; this is followed by a destabiliza-
the size of Schwann cells, differences in fiber diameter, and differ- tion of adjacent membrane segments, resulting in a propagated
ences between animal species; it ranges between 400 and 1500 m. action potential. This is followed by the restoration of the resting
The axon at the node of Ranvier also shows variations unique to potential difference between the inside and the outside of the
this region. For example, the number of mitochondria at the axon of the previously freely permeable membrane. Sodium and
node is fivefold that found in other areas. Lamellated autophagic potassium levels inside and outside the axon are restored to their
vesicles, smooth endoplasmic profiles, glycogen granules, and resting values.
12 / CHAPTER 1
In myelinated fibers, permeability changes occur only at the Substances that are moved are carried in the mitochondria or
nodes of Ranvier. The insulating effect of the myelin between small vesicles of SER. The substances that are transported in-
the nodes prevents propagation of the action potential along the clude enzymes of neurotransmitter metabolism and peptide
axon; instead, the impulse jumps from node to node. This type neurotransmitters and neuromodulators. Fast axonal transport
of conduction is known as saltatory conduction and is consider- requires energy in the form of high-energy phosphate com-
ably faster than the process of continuous conduction found in pounds (adenosine triphosphate [ATP]); therefore, it is necessary
nonmyelinated nerve fibers. Loss of the myelin sheath, known as for the neuron to be oxygenated adequately. Any interruption of
demyelination, can disrupt conduction. Diseases in which this is mitochondrial oxidative phosphorylation causes the cessation of
known to occur (e.g., multiple sclerosis) produce profound neu- axoplasmic flow and transport.
rologic deficits. Substances transported by the slow component include struc-
tural proteins such as tubulin, actin, and neurofilamentous pro-
Axonal Transport teins. The underlying mechanism of motility for slow transport
is unclear.
Proteins synthesized in the perikaryon are transported through- Based on the concept of anterograde and retrograde axonal
out the cell and through the axon to its terminal. Axonal transport, neuroanatomic tracing methods have been developed
transport flows in two directions: anterograde, or toward to study neural connectivity. A radioactively labeled amino acid
the axon terminal, and retrograde, or from the axon ter- injected into a region of neuronal perikarya is incorporated into
minal to the cell body (Figure 1–9). Anterograde transport flows proteins and is transported anterogradely to the axon terminal.
primarily at two rates: a fast rate (100 to 400 mm/day) and a Alternatively, a histochemically demonstrable enzyme such as
slow rate (0.25 to 3 mm/day). horseradish peroxidase travels retrogradely from the axonal termi-
The retrograde transport system is very important for re- nals to the soma, or cell body. Different fluorescent dyes injected
cycling intraaxonal proteins and neurotransmitters and for the at different sites travel retrogradely to the neuron or neurons that
movement of extraneural substances from nerve endings to the project on those sites. Cell bodies sending axons to the two in-
neuron, providing a mechanism that allows trophic influences jected sites fluoresce in different colors. A neuron whose axon
from end organs to have an effect on neurons. Retrograde axo- branches end in both injected areas will be labeled in two colors.
plasmic transport is fast and occurs at about half the velocity The existence of a transport system in axons was surmised by
(50–250 mm/day) of the fast anterograde component. There Descartes and rediscovered in the 1940s by Paul Weiss and his
is no slow retrograde transport component. There is also no co-workers who coined the term axonal flow.
rate difference of material transport between sensory and motor
axons.
Microtubules are involved in fast anterograde and retrograde SYNAPSE
transport; thus, microtubule-disrupting drugs such as colchicine
and vinblastine prevent fast axonal transport. In fast anterograde The simplest unit of segmental nerve function requires two neu-
transport, a characteristic protein called kinesin is known to pro- rons: a sensory or receptor neuron and a motor or effector neuron.
vide the motive force to drive organelles along microtubules. A This arrangement is found in the simplest reflexes, for example,
different protein, dynein, is involved in fast retrograde transport. the patellar tendon reflex (knee jerk). The structural-functional
coupling of these two neurons occurs through what is termed a
synapse. The terminal arborizations of the sensory neuron (axons)
are dilated into small knobs or boutons (so-called boutons ter-
minaux, a term coined by a French investigator), which lie in con-
Perikaryon tact with the dendrites, cell bodies, and axons of effector neurons
(Figure 1–10). These small bulbs contain synaptic vesicles that
range in size from 300 to 600 nm and may be round or flattened
on two sides. The vesicles appear empty but actually contain the
neurotransmitter acetylcholine. In other kinds of synapses, the
vesicles may contain an electron-dense dark particle termed a core
or a dark core vesicle that is presumed to be catecholamine.
Acetylcholine and catecholamine are only two of several chemical
Retrograde transmitter substances that facilitate the transfer of nerve impulses
transport
Axonal transport from one neuron to another, at and across the synapse, or to a
nonneuronal effector organ such as a gland or muscle.
Fas Electron microscopy has revealed the specialized structure of
lo t
S
w t
Fas the synapse, which consists of thickened pre- and/or postsynap-
tic membranes separated by a synaptic gap (or cleft) of about
20 nm. Although not all synapses are structurally identical, they
are recognizably related. The membrane thickenings of the pre-
Anterograde Anterograde
slow transport fast transport
and postsynaptic membranes represent accumulations of cyto-
plasmic proteins beneath the plasmalemma (cell membrane). In
Axon
addition to synaptic vesicles, the synaptic terminal contains a
collection of mitochondria and some neurofilaments.
Axon terminal When an action potential arrives at an axon terminal (end
bulb or bouton terminaux), the membrane of the terminal is de-
Figure 1–9. Schematic diagram of anterograde and retrograde polarized and Ca2+ ions enter the permeable terminal and pro-
axonal transport. mote the fusion of synaptic vesicles with the presynaptic mem-
NEUROHISTOLOGY / 13
Dendrite
Axosomatic
Axon
synapses
Dense core Round clear Mitochondrion Flat clear
vesicles vesicles vesicles
Presynaptic bulb
Axoaxonic
synapses
A Axodendritic B Postsynaptic membrane Synaptic cleft

synapses
Figure 1–10. Schematic diagram showing axosomatic, axodendritic, and axoaxonic synapses (A), and ultrastructural compo-
nents of the synapse (B).
brane (membrane of the terminal bulb). The neurotransmitter, Synapses have been classified by their structural associations
for example, acetylcholine, contained within the synaptic vesicles as follows:
is released by exocytosis into the synaptic gap, or cleft (a space of
20 nm), where it diffuses out and binds to receptors on the post- 1. Axoaxonic: axon to axon
synaptic membrane and promotes increased permeability of the 2. Axodendritic: axon to dendrite
postsynaptic membrane. The ionic permeability of the post- 3. Axosomatic: axon to cell body
synaptic membrane is increased, leading to the membrane’s 4. Dendrodendritic: dendrite to dendrite
depolarization and the generation of an action potential in the 5. Neuromuscular: axon to muscle fiber
target postsynaptic cell (gland, muscle, or nerve) membrane.
Increasing evidence indicates the importance of protein phos- In chemical synapses, the following substances have been
phorylation in the regulation of the function of a presynaptic identified as transmitters:
nerve terminal. Major synaptic vesicle–associated proteins in-
clude the synapsins (Ia and Ib, IIa and IIb), synaptophysin, and 1. Acetylcholine
synaptobrevin. The precise physiologic functions of these phos- 2. Monoamines (noradrenaline, adrenaline, dopamine, serotonin)
phoproteins are unknown, but that of synapsin I is becoming in- 3. Glycine
creasingly apparent. Phosphorylation of synapsin I occurs in re- 4. GABA
sponse to nerve impulses and to a variety of neurotransmitters 5. Glutamic acid
acting at presynaptic receptors. Dephosphosynapsin I binds to
vesicles and inhibits their availability for release. Two natural brain peptide neurotransmitters—endorphins
Phosphorylation of synapsin I decreases its affinity for synap- and enkephalins—have been shown to be potent inhibitors of
tic vesicles, which then become available for release. In addition pain receptors. They exhibit a morphinelike analgesic effect.
to their role in neurotransmitter release, proteins of the synapsin Other peptide hormones, such as substance P, cholecysto-
family may regulate the formation of presynaptic nerve termi- kinin, vasopressin, oxytocin, vasoactive intestinal peptides (VIP),
nals. Synapsin expression has been shown to correlate temporally and bombesin, have been described in different regions of the
with synapse formation during development and to play a causal brain, where they act as modulators of transmitter action.
role in synaptogenesis. The available data assign a role for peptides in chemical trans-
Functionally, synapses may be excitatory or inhib- mission that is auxiliary to that of classical neurotransmitters,
itory; transmission usually is unidirectional and not but in some neuronal systems peptides play the main role. This is
obligatory, except at the neuromuscular junction. Elec- especially apparent in hypothalamic neurosecretory cells that
tron microscopy, however, has shown a wide variety of structural produce and release the posterior pituitary hormones vasopressin
arrangements in synapses; this suggests that transmission may in and oxytocin.
some cases be bidirectional. Besides their role in transmission, peptides seem to have a
Some synapses, termed electric, have no synaptic vesicles, and trophic function. Tachykinins have been shown to stimulate the
the adjacent cell membranes (pre- and postsynaptic) are fused. growth of fibroblasts and smooth muscle fibers; VIPs affect bone
The fused membranes of electric synapses are called tight junc- mineralization and stimulate the growth of human keratinocytes.
tions or gap junctions. The transmission at these junctions oc- Increasing evidence has suggested a messenger role for pep-
curs by electrotonic depolarization; it may be bidirectional, and tides in the nervous system. Peptides have their own receptors in
this type of synapse is considered obligatory. These synapses are the nervous system, and receptors for tachykinins, substance P,
not common in the mammalian nervous system. neurokinin A (substance K), and neurotensin have been cloned.
14 / CHAPTER 1
Neuromuscular Junction nerve and muscle is about 50 m. The postsynaptic membrane of
the muscle has numerous infoldings called junctional folds. When
The neuromuscular junction (also called the myoneural junction a motor neuron is activated (fired), the nerve impulse reaches the
or motor end plate) is a synapse between a motor nerve terminal axon terminal and the contents of the synaptic vesicle (acetyl-
and the subjacent part of the muscle fiber. Motor neurons branch choline) in the terminal are discharged into the gap or cleft be-
variably and extensively near their termination at the muscle tween the pre- and postsynaptic membranes. Once the acetyl-
fiber. One neuron may innervate as few as 10 (eye muscles) or as choline is released into the cleft, it diffuses very quickly to combine
many as 500 (leg muscles) or more skeletal muscle fibers. A mo- with acetylcholine receptors in the muscle membrane. The binding
tor neuron and the muscle fibers that it innervates constitute a of acetylcholine to the receptor makes the muscle membrane more
motor unit. The motor unit, not the individual muscle fiber, is the permeable to sodium. This in turn depolarizes the muscle cell
basic unit of function. membrane, leading to the appearance of a propagated muscle ac-
As a nerve fiber approaches a muscle fiber, it loses its myelin tion potential and muscular contraction. This synaptic activity is
sheath and forms a bulbous expansion that occupies a trough on always excitatory and is normally obligatory, that is, all or none.
the muscle fiber surface (Figure 1–11). The trough is variable in The subneural sarcolemma or postsynaptic membrane con-
its complexity, and no two subneural troughs appear exactly tains the enzyme acetylcholinesterase, which breaks down the
alike. There is no evidence that this variability has functional sig- depolarizing transmitter. This allows the muscle membrane to
nificance. The terminal expansion of the nerve fiber is covered by reestablish its resting condition.
a cytoplasmic layer of Schwann cells, the neurilemmal sheath. The most common disorder of the neuromuscular junction is
The endoneurial sheath of connective tissue that surrounds the a disease known as myasthenia gravis, which is characterized by
nerve fiber outside the neurilemmal sheath is, however, continu- the onset of muscular weakness after muscle use and the im-
ous with the connective tissue sheath of the muscle fiber. provement of muscular strength with rest. In this disease, anti-
The motor end plate (or end plate) is 40 to 60 m in diame- bodies bind to acetylcholine receptors and render them less ac-
ter. They are typically located near the midpoint of the muscle cessible to released acetylcholine. Receptor blockade also occurs
fiber or are somewhat more proximal. with curare (South American arrow poison) and with a family of
The axonal terminal contains synaptic vesicles (filled with small protein toxins that are found in the venoms of various poi-
acetylcholine) and mitochondria. The synaptic gap between the sonous snakes. Commercial pesticides and nerve gases interfere
Muscle
fiber
Axon
Motor
end plate
Muscle
striations
20 mm
Axon terminal
Mitochondrion
Synaptic Axon
vesicles
Myelin sheath
Sarcolemma
Sarcoplasm Junctional
folds Axon terminal branches
Muscle
nucleus Figure 1–11. Schematic diagram of
Myofibrils the motor end plate. A. Light micro-
scopic appearance. B. Ultrastructural
B appearance.
NEUROHISTOLOGY / 15
with neuromuscular transmission by inhibiting the hydrolysis (de- that gradually decrease in strength in response to constant and
struction) of acetylcholine, thus prolonging its effect on the mus- unvarying stimuli. Slowly adapting receptors (tonic receptors)
cle and thereby inactivating the muscle. Botulinum toxin, some continue their response level throughout their activation and the
snake toxins, and a toxin in the venom of black widow spider, duration of stimulation. Fast adapting receptors thus detect tran-
however, interferes with neuromuscular transmission by blocking sient and rapidly changing stimuli, whereas slow adapting recep-
the release of acetylcholine from the presynaptic membrane. tors detect a sustained stimulus.
Slowly adapting receptors are of two types. Type I receptors
RECEPTOR ORGANS OF SENSORY NEURONS have no spontaneous discharge at rest and are more sensitive to
vertical displacement. Type II receptors maintain a slow regular
Sensory receptors may be classified by function, for ex- discharge at rest and are more sensitive to stretch. A more detailed
ample, nociceptor (pain) or mechanoreceptor; by struc- discussion of specific receptor types appears in Chapter 23.
ture, for example, encapsulated or nonencapsulated (so-
called free); by a combination of both structure and function; or Free (Nonencapsulated) Nerve Endings
by anatomic location, for example exteroceptors (skin receptors),
proprioceptors (muscle, tendon, joint receptors), and viscerocep- The receptors known as free nerve endings are the axonal end-
tors (receptors in internal body organs). ings designed for sensory reception. Their name arose not in a
Sensory receptors provide information about the location, in- functional sense but rather in a structural one.
tensity, and duration of a peripheral stimulus. They are designed This type of receptor has the widest distribution throughout
to change (transduce) one kind of energy to another (i.e., touch to the body and is most numerous in the skin. Additional locations
electrochemical nerve impulse). include the mucous membranes, deep fascia, muscles, and vis-
Each receptor possesses a different sensitivity and different ceral organs; these receptors are ubiquitous. The distal arboriza-
adaptive properties based on its response to continuous monotonic tions are located in the epithelium between the cells, the epithe-
stimulation. Receptors may adapt quickly or slowly. Quickly lium of the skin (Figure 1–12A), the cornea, and the mucous
(fast) adapting receptors (phasic receptors) produce impulses membranes lining the digestive and urinary tracts, as well as in
Figure 1–12. Schematic diagram of receptor organs. A. Free nerve endings. B. Taste bud. C. Meissner’s corpuscle. D. Pacinian cor-
puscle. E. Krause’s corpuscle. F. Ruffini’s corpuscle.
16 / CHAPTER 1
all the visceral organs and blood vessels. In addition, they are as- posed of concentric lamellae of flattened cells (fibroblasts) sup-
sociated with hair follicles and respond to the movement of hair. ported by collagenous tissue that invests the unmyelinated distal
Certain specialized epithelial cells (neuroepithelium), such as segment of a large myelinated (A beta) axon. The interlamellar
those found in taste buds (Figure 1–12B), olfactory epithelium, spaces are filled with fluid. Because of their size, these corpuscles
and the cochlear and vestibular organs (hair cells), receive free are provided with their own blood supply, which also makes
(receptor) endings. Tendons, joint capsules, periosteum, and them unique. Histologically, when cut or sectioned, they look
deep fascia also may have this type of ending. Endings of this like a divided onion, to which they have been likened.
kind probably respond directly to a wide variety of stimuli, in- Vater-Pacini corpuscles are mechanoreceptors that are sensi-
cluding pain, touch, pressure, and tension, and respond indi- tive to vibration. They are maximally responsive at 250 to 300 Hz.
rectly through so-called neuroepithelia to sound, smell, taste, These corpuscles are rapidly adapting receptors that respond
and position sense. The axons of these sensory receptors may be only transiently to on vibration and off vibration or at the end
myelinated or unmyelinated. of a step-wise change in stimulus position. The recovery cycle of
Merkel’s corpuscles are slowly adapting type I mechanorecep- this receptor is very short (5 to 6 ms). The rapid adaptation of
tors that are distributed in the germinal layer (stratum basale) of pacinian corpuscles is a function of the connective tissue capsule
the epidermis. Groups of 5 or 10 of these corpuscles are inter- that surrounds the central neural elements. The removal of the
spersed among the basal layer cells. Unmyelinated free nerve connective tissue capsule transforms a pacinian corpuscle from a
endings form an axonal expansion (e.g., Merkel’s disk) that is rapidly adapting receptor to a slowly adapting one.
closely applied to a modified epidermal cell (Merkel’s cell). These ubiquitous receptors are distributed profusely in the
Merkel’s cells are found in glabrous skin and in the outer sheaths subcutaneous connective tissue of the hands and feet. They are
of hairs in hairy skin. These endings are also found in areas of also found in the external genitalia, nipples, mammary glands,
transition between hairy skin and mucous membrane. Synapselike pancreas and other viscera, mesenteries, linings of the pleural
junctions have been observed between Merkel’s disks and and abdominal cavities, walls of blood vessels, periosteum, liga-
Merkel’s cells; their functional significance is uncertain. This re- ments, joint capsules, and muscles. Of the estimated 2 109
ceptor subserves the sensory modality of constant touch or pres- pacinian corpuscles in the human skin, more than one-third are
sure and is responsible for the tactile gnosis of static objects. in the digits of the hand and more than 1000 can be found in a
They are thus important for Braille reading. The discharge single finger.
frequency of Merkel’s corpuscles is temperature-dependent.
Cooling the skin increases the discharge frequency, and warming C. GOLGI-MAZZONI CORPUSCLES
inhibits the discharge rate. Golgi-Mazzoni corpuscles are quickly adapting receptor organs
that are lamellated (like the pacinian corpuscles); however, in-
Encapsulated Nerve Endings stead of a single receptor terminal, the unmyelinated receptor is
arborized with varicosities and terminal expansions. These cor-
This group of receptors includes the corpuscles of Meissner, Vater- puscles are distributed in the subcutaneous tissue of the hands,
Pacini, Golgi-Mazzoni, and Ruffini; the so-called end bulbs; the on the surface of tendons, in the periosteum adjacent to joints,
neuromuscular spindles; and the tendon organ of Golgi. and elsewhere. Their function is uncertain but probably is re-
lated to the detection of vibration with a maximal response under
A. MEISSNER’S TACTILE CORPUSCLES 200 Hz.
Meissner’s corpuscles are elongated, rounded bodies of spirals of
receptor endings (Figure 1–12C ) that are fitted into dermal D. RUFFINI’S CORPUSCLES
papillae beneath the epidermis; they are about 100 m in diam- Elongated and complex, Ruffini’s corpuscles (Figure 1–12F ) are
eter. A Meissner’s corpuscle possesses a connective tissue sheath found in the dermis of the skin, especially the fingertips, but are
that encloses the spiral stacks of horizontally arranged epithelioid widely distributed, especially in joint capsules. The receptor end-
cells. The endoneurium is continuous with the capsule. When ings within the capsule ramify extensively among the supporting
the myelin sheath terminates, the axon (A beta fiber) arborizes connective tissue bundles. These type II slowly adapting mech-
among the epithelial cells. From one to four myelinated axons, as anoreceptors have been associated with sensations of pressure
well as unmyelinated axons, enter the capsule. Meissner’s corpus- and touch as a velocity and position detector. The discharge of
cles are distributed widely in the skin but are found in the great- Ruffini’s corpuscles is temperature-dependent, increasing with
est numbers in the hairless (glabrous) skin of the finger, palm skin cooling and decreasing with skin warming. Three types of
of the hand, plantar surface of the foot, toes, nipples, and lips. Ruffini’s corpuscles have been identified in joint capsules, based on
These corpuscles are rapidly adapting mechanoreceptors. their position-related discharge. All three maintain constant base-
Sensory modality subserved by Meissner’s corpuscles is low- line output, but each type responds differently. One type responds
frequency (30 to 40 Hz) flutter-vibration and moving touch. maximally at extreme flexion, another type at extreme extension,
Under sustained pressure, an impulse is produced at the onset, and a third midway between flexion and extension of the joint.
removal, or change of magnitude of the stimulus. Meissner’s cor-
puscles are thus best suited to signal direction and velocity of E. END BULBS
moving objects on the skin. The end bulbs resemble the corpuscles of Golgi-Mazzoni. They
have a connective tissue capsule enclosing a gelatinous core in
B. VATER-PACINI CORPUSCLES which the terminal, unmyelinated endings arborize extensively.
Vater-Pacini, more commonly known as pacinian, corpuscles The end bulbs of Krause (Figure 1–12E ) have been associated
(Figure 1–12D) are the largest and most widely distributed en- with sensations of temperature (cold) and are located strategi-
capsulated receptor organs. They range up to 4 mm in length cally and distributed widely. The structural complexity of these
but usually are smaller; they are the only macroscopic receptor end bulbs varies remarkably, as does their size. It is likely that
organ in the body. The capsule is elliptical in shape and is com- they serve a wide variety of different functions; their size and dis-
NEUROHISTOLOGY / 17
tribution, however, preclude easy analysis. Much confusion has The receptor endings of intrafusal muscle fibers respond to
arisen regarding the end bulbs of Krause, since Krause identified the stretching of extrafusal muscle fibers or their tendons. The
and named two morphologically different structures of end bulbs. activity of the spindle ceases with the relaxation of tension in the
spindle, when the skeletal muscle contracts. The receptor end-
F. NEUROMUSCULAR SPINDLES ings also may be stimulated by the stretching of intrafusal muscle
Neuromuscular spindles are found in skeletal muscle and are fibers secondary to gamma motor nerve activity, which contracts
highly organized. Muscle spindles are distributed in both flexor the polar ends of intrafusal muscle fibers, thus stretching the re-
and extensor muscles but are more abundant in muscles that ceptor portions of the fibers.
control fine movements (extraocular muscles, intrinsic hand A static stimulus such as that which occurs in sustained mus-
muscles). Each muscle spindle is less than 1 cm long and con- cle stretching stimulates both the annulospiral and the flower
tains 2 to 12 specialized striated fibers (intrafusal fibers) in a spray endings. By contrast, only the annulospiral (primary) end-
capsule parallel with the surrounding skeletal muscle fibers ings respond to brief (dynamic) stretching of the muscle or to
(extrafusal muscle fibers). Histologically, the muscle spindle vibration.
is composed of two types of intrafusal muscle fibers (Figure The afferent nerves emanating from the receptor endings
1–13A). The nuclear chain fiber is smaller in diameter and shorter (type Ia fibers from primary endings, and type II fibers from sec-
in length and contains a single row of centrally located nuclei. ondary endings) project on alpha motor neurons in the spinal
The nuclear bag fiber, which is larger and longer, contains a clus- cord, which in turn supply the extrafusal fibers. Thus, when a
ter of many nuclei in a baglike dilatation in the central part of muscle is stretched by tapping its tendon, as is done clinically,
the fiber. In contrast to extrafusal skeletal muscle fibers, cross- the stimulated receptor endings initiate an impulse in the affer-
striations in intrafusal fibers are limited to the ends of the muscle ent nerves which stimulates the alpha motor neurons and results
fibers. Thus, intrafusal muscle fibers contract their end parts but in a reflex muscle contraction. As soon as the skeletal muscle
not their middle. contracts, the tension in the intrafusal muscle fibers decreases,
Each intrafusal muscle fiber is supplied with both efferent the receptor response diminishes or ceases, and the muscle re-
and afferent nerve fibers. The efferent fibers (gamma efferents), laxes. This is the basis of all monosynaptic stretch reflexes (e.g.,
axons of gamma motor neurons in the anterior horn of the knee jerk, biceps jerk). Gamma efferent activity plays a role in
spinal cord, terminate on the polar ends of both the nuclear sensitizing the receptor endings to a stretch stimulus and helping
chain fibers and the nuclear bag fibers. The afferent nerve fibers maintain muscle tone.
originate from two types of receptor endings on the intrafusal
fibers: the annulospiral (primary) endings and the flower spray G. TENDON ORGANS OF GOLGI
(secondary) endings. The annulospiral endings are reticulated Tendon organs of Golgi are slowly adapting receptors (Figure
branching endings that are situated around the central portion of 1–13B) located in tendons close to their junction with skeletal
both nuclear chain fibers and nuclear bag fibers; they are better muscle fibers and are in series with extrafusal muscle fibers. The
developed, however, on the nuclear bag fibers. The so-called organ consists of fascicles of tendon ensheathed by a connective
flower spray endings are scattered diffusely along the length of the tissue capsule. The capsule encloses the distal end of a large
intrafusal fibers but are found especially on each side of the cen- (12 m) myelinated fiber, which divides repeatedly before it
tral portion adjacent to the annulospiral endings. Both nuclear splits into unmyelinated (receptor) segments. These branchlets
chain fibers and nuclear bag fibers contain this type of ending. terminate in ovoid expansions that intermingle with and encircle
Flower spray endings
Annulospiral
γ-Efferent endings
Muscle Axon
fibers
Tendon
Afferents
A B
Nuclear Nuclear
bag chain
INTRAFUSAL FIBERS
Figure 1–13. Schematic diagram of the neuromuscular spindle (A) and the Golgi tendon organ (B).
18 / CHAPTER 1
the fascicles of collagenous tissue that constitute the tendon. 2. The Nissl bodies (tigroid substance) undergo chromatolysis
Tendon organs respond to tension in skeletal muscle fibers that is (i.e., they become dispersed, and the sharp staining pattern
developed by stretching the muscle or actively contracting the disappears). This process is most marked in the central por-
muscle. The tension thus developed deforms the receptor end- tion of the cell (former perinuclear location) but may extend
ings and “sets off ” a nerve impulse that is transmitted to the peripherally to involve Nissl bodies in the dendrites. The pro-
spinal cord. Afferent nerves (type Ib fibers) emanating from cess of chromatolysis reflects a change in the metabolic pri-
Golgi tendon organs project on inhibitory interneurons in the ority from that geared to the production of neurotransmit-
spinal cord. Thus, when a muscle (along with its tendon) is ters needed for synaptic activity to that involving the
stretched excessively, the muscle relaxes. In contrast to muscle production of materials needed for axonal repair and
spindles, Golgi tendon organs do not receive efferent innerva- growth. The central cell body must synthesize new messen-
tion from the spinal cord, and thus are not influenced by the ger RNA, lipids, and cytoskeletal proteins. The components
central nervous system. of the cytoskeleton most important for axonal regeneration
are actin, tubulin, and neurofilament protein. These proteins
are carried by slow anterograde axonal transport at a rate of 5
REACTION OF NEURONS TO INJURY to 6 mm/day, which correlates with the maximal rate of ax-
The reaction of neurons to injury has been studied extensively in onal elongation during regeneration. Another group of pro-
experimental animals, with the findings confirmed in humans; teins whose synthesis is increased during regeneration of
in fact, this has become one of the methods employed in the nerve cells consists of growth-associated proteins (GAPs),
study of cell group (nuclei) and fiber tracts. Responses which travel by fast axonal transport at a rate of up to 420
can be divided into those which occur proximal to the mm/day. Although GAPs do not initiate, terminate, or regu-
site of the injury and those which occur distal to it late growth, they are essential for regeneration. Neurono-
(Figure 1–14). If death of the nerve cell does not occur, regenera- tropic factors (NTFs) from the periphery signal to the cell
tive activity in the form of nerve sprouts emanating from the body that an injury has occurred and travel by retrograde
proximal stump may begin as early as 24 hours after an injury. axonal transport.
3. The other organelles, including the Golgi apparatus and mito-
Cell Body and Dendrites chondria, proliferate and swell.
The speed at which these changes occur, as well as their de-
If an axon is severed or crushed, the following reactions can be gree, depends on several factors, including the location of the in-
found in the cell body (Figure 1–14C ) and dendrites proximal jury, the type of injury, and the type of neuron involved. The
to the site of injury. closer the injury is to the cell body and the more complete the in-
1. The entire cell, including the nucleus and nucleolus, swells; terruption of the axon is, the more severe the reaction is and the
the nucleus shifts from its usual central position to a periph- poorer are the chances of full recovery. In general, this reaction is
eral part of the cell. seen more often in motor neurons than in sensory neurons.
Dendrites
Nucleus Synapse
Nucleolus Myelin Axon

Perikaryon
A Normal neuron
Site of transection
B Injury
Eccentric Synaptic degeneration

nucleus Myelin breakdown
C Reaction to injury
Chromatolysis Proximal and distal

axon fragmentation
Figure 1–14. Schematic diagram of a normal neuron (A), site of injury (B),
and reaction to injury (C).
NEUROHISTOLOGY / 19
The reactions of the cell body and dendrites to axonal injury generate. This may occur within 2 or 3 weeks, since regenerative
are termed retrograde cell changes. After about 3 weeks, if the growth normally takes place at a rate of 1.5 to 4 mm/day. Failure to
cell survives the injury, the cell body and its processes begin to establish a pathway for regrowth of the axonal sprouts may result
regenerate. Full recovery takes 3 to 6 months. The nucleus rein the formation of a neuroma, which is often a source of pain.
turns to its central location and is normal in size and configura- It must be pointed out that chance plays a major role in this
tion. The staining characteristics and structure of the organelles regenerative activity. If a sensory axon enters a sheath formerly
also return to normal. If regeneration fails, the cell atrophies and occupied by a motor axon or vice versa, the growing axon will be
is replaced by glia. nonfunctional and the neuron will atrophy. Accurate growth and
innervation of the appropriate distal target are thus of critical
importance to the success of nerve regeneration. In this context,
Axon the target of innervation can exert a guiding “neurotropic” influ-
After an injury, the axon undergoes both retrograde (proximal) ence on a regenerating axon. Forrsman in 1898 and Ramon y
and anterograde (distal) degeneration. Retrograde degeneration Cajal subsequently showed that the advancing tip of a regenerat-
usually involves only a short segment of the axon (a few inter- ing axon is chemotropically attracted to its appropriate distal
nodes). If the injury to the neuron is reversible, regenerative nerve target. Recent experimental studies have confirmed this. In
processes begin with the growth of an axon sprout as soon as new addition, although the process of degeneration is similar in the
cytoplasm is synthesized and transported from the cell body. The central and peripheral nervous systems, there is a marked differ-
regenerative sprouting of the proximal axon stump requires elon- ence in the success of the regenerative process in the two systems.
gation of the axon. This process is mediated by a growth cone at What has been described above applies primarily to regeneration
the tip of the regenerating fiber. Growth cones were first de- in the peripheral nervous system. Degeneration of a neuron usu-
scribed by Ramon y Cajal, who compared their advance through ally is limited to its perikaryon and processes. In certain areas of
solid tissue to that of a battering ram. Growth cones release a the nervous system, however, degeneration of a neuron is trans-
protease that dissolves the matrix, permitting their advance mitted to the neuron, with which it makes a connection. This
through the tissues. Growth cones have mobile filopodia (ex- type of degeneration is known as transneuronal degeneration.
truding from a flattened sheet of lamellipodia), enabling them to
move actively and explore the microenvironment of a regenerat-
ing axon. Growth cones play an essential role in axon guidance Nerve Growth Factors
and can respond to contact guidance clues provided by laminin Successful nerve regeneration requires neuronal growth. Four
and fibronectin, two major glycoprotein components of the classes of nerve growth factors are essential for optimal nerve
basal laminae of Schwann cells. growth: (1) NTFs, or survival factors, (2) neurite-promoting fac-
Shortly after a nerve injury and before the onset of wallerian tors (NPFs), which control axonal advance and influence the rate,
degeneration, severe degeneration of the tips of the proximal and incidence, and direction of neurite growth, (3) matrix-forming
distal stumps occurs. This injury is secondary to an influx of precursors (MFPs), possibly fibrinogen and fibronectin, which
sodium and calcium and a massive loss of potassium and pro- contribute fibrin products to the nerve gap and provide a scaffold-
tein. The axonal debris and normal tissue scarring may prevent ing for the ingrowth of cells, and (4) metabolic and other factors.
the growth cone of the proximal stump from reaching a healthy NTFs are macromolecular proteins that promote the survival
distal stump. and growth of neuronal populations. They are present in the tar-
Distal to the site of the injury (Figure 1–14C ), the severed get of innervation, where they are taken up by the nerve termi-
axon and its myelin sheath undergo what is known as secondary, nals and transported by retrograde axonal transport back to the
or wallerian, degeneration, named in recognition of its descrip- cell body. These factors exert a supportive or survival-promoting
tion by Augustus Waller in 1852. The axon, deprived of its con- effect. The best known NTF is nerve growth factor (NGF).
tinuity with the supporting and nutritive materials from the cell NPFs are substrate-bound glycoproteins that strongly pro-
body, begins to degenerate within 12 hours. The axon degener- mote the initiation and extension of neurites. Laminin and fibro-
ates before its Schwann cell sheath does and appears beaded and nectin, two components of the basal lamina, have been shown to
irregularly swollen within 1 week. The axonal reaction extends promote neurite growth. Although NPFs were presumed to exert
distally to involve the synapse. The fragmented portions of the their neurite-promoting activity by increasing the adhesion of
axon are phagocytized by invading macrophages. This process the growth cones to the surface of the basal lamina, recent stud-
may take considerably longer within the central nervous system. ies have shown that NPFs promote neurite growth independent
Along with degeneration of the axon, the myelin sheath be- of growth cone adhesion.
gins to fragment and undergo dissolution within the Schwann After a nerve injury, a polymerized fibrin matrix is formed
cell. Macrophages also play an important role in the removal of from the fibrinogen and fibronectin found in exudates from the
myelin breakdown products. The degenerative process occurs cut nerve ends. This matrix is important for the migration of
within the endoneurium and is soon followed by mitotic activity Schwann cells and other cells into the gap between the cut ends.
in the Schwann cells, which form a tubelike sleeve within the en- Metabolic and other factors that promote nerve regeneration
doneurium along the entire length of the degenerated axon. include sex hormones, thyroid hormone, adrenal hormones, in-
Endoneurial tubes persist after the myelin and the axonal debris sulin, and protease inhibitors.
have been cleared. The proliferating Schwann cells align longitu-
dinally within the endoneurial tube, creating a continuous col-
umn of cells named Büngner’s bands. The growth of axons from Clinical Correlation
the proximal stump begins within 10 hours and may traverse the
gap between the proximal and distal ends of the axon and enter There are at present two classifications of nerve injury that are
the Schwann cell tubes (neurolemma). Although many small based on the nature of the lesion in the nerve. The first
axonal sprouts may enter a single tube, only one will develop its classification, proposed by Seddon, recognizes three de-
normal diameter and appropriate sheath; the others will degrees of severity of nerve injury: (1) conduction block
20 / CHAPTER 1
Table 1–2. Nerve Injury.
Degree of Wallerian Endoneurium Perineurium Epineurium Nerve Nerve

severity degeneration continuity continuity continuity fiber trunk
continuity continuity
I
II
III
IV
V
NOTE: , present; , absent.
I Axon IV Axon
(conduction block) Perineurium (intact) (wallerian
degeneration) Perineurium (discontinuous)
Epineurium
(intact) Epineurium
Endoneurium (intact) (intact)
Endoneurium (discontinuous)
Perikaryon
Perikaryon
II Axon
Perineurium (intact)
(wallerian V Axon
degeneration) (discontinuous) Perineurium (discontinuous)
Epineurium
(intact)
Endoneurium (intact) Epineurium
(discontinuous)
Perikaryon
Perikaryon
III Axon
(wallerian
degeneration) Perineurium (intact)
Epineurium
(intact)
Perikaryon
Figure 1–15. Schematic diagram of the five types of nerve injury.

NEUROHISTOLOGY / 21
(neurapraxia), (2) loss of axonal continuity (axonotmesis), and physiologically, and biochemically, the behavior of humans differs
(3) loss of nerve trunk continuity (neurotmesis). The second from individual to individual. This difference in behavior reflects
classification, proposed by Sunderland, includes five degrees of the plasticity of the brain in adapting to its environment.
nerve injury (Table 1–2, Figure 1–15).
I. The first and least severe degree consists of a temporary physi-
ologic conduction block in which axonal continuity is not TERMINOLOGY
interrupted. The conduction across the injured segment of
nerve is blocked. Conduction proximal and distal to the block Astrocyte (Greek astron, “star”; kytos, “hollow vessel”). A
is normal. The three connective tissue sheaths are intact. starlike cell. The processes of astrocytes give them a starlike
II. In the second degree wallerian degeneration is present distal shape.
to the nerve lesion. Continuity of the endoneurial sheath Axon (Greek axon, “axis”). The process of a neuron by which
is preserved and permits regeneration of the distal segment impulses are conducted. The axon, passing through its tubular
of the nerve. The peri- and epineurial sheaths are also pre- sheaths, forms the axis of the nerve. The axis cylinder, of un-
served. myelinated nerve fibers, was described by Robert Remak in
III. The third degree is characterized by the loss of continuity of 1838.
nerve fibers. The internal fascicular structure is disorga- Axon hillock. The part of a neuron perikaryon that gives rise to
nized, the endoneurial sheath becomes discontinuous, and the axon.
wallerian degeneration is present. Peri- and epineurial sheaths Axonotmesis. A lesion of a peripheral nerve that produces dis-
are, however, preserved. Axon regeneration in this type of continuity of axons with preservation of the supporting connec-
injury is negligible because of the development of intrafascic- tive tissue sheaths.
ular fibrosis and the loss of continuity of the endoneurial Boutons terminaux. A French term for what Cajal in 1903 called
sheath. terminal buttons to describe axon terminations in a synapse.
IV. In the fourth degree fascicular nerve structure is destroyed. Büngner’s bands. Chains of multiplying Schwann cells that facil-
Endo- and perineurial sheaths are discontinuous. The epi- itate the regeneration of axons after an axonal injury. Described
neurial sheath is intact. Regenerating axon growth is blocked by Otto von Büngner (1858–1905), a German surgeon.
by fibrous tissue scarring. This type of injury requires excision Chromatolysis (Greek chromatos, “color”; lysis, “dissolu-
of the injured nerve segment and nerve repair. tion”). Dissolution of the Nissl bodies of a neuron as a result of
V. The fifth degree represents the complete loss of continuity injury to its axon. The term was introduced by Georges Marinesco,
of the nerve trunk. There is discontinuity of the axon and a Romanian neurologist, in 1909.
the endo-, peri-, and epineurial sheaths. Dendrite (Greek dendron, “tree”). Processes of neurons may
Table 1–2 gives a summary of Sunderland’s classification; branch in a treelike fashion. This term was introduced by
Figure 1–15 shows a diagrammatic representation of the differ- Camillo Golgi, an Italian anatomist, in about 1870.
ent stages of nerve injury. End bulbs of Krause. Encapsulated end organs which are
widely distributed and are associated with temperature sensation.
Neuronal Plasticity Named after Wilhelm Johann Friedrich Krause (1833–1910),
who described them in 1860.
It was thought at one time that the mature central nervous sys- Ependyma (Greek, upper “garment”). The lining cells of the
tem is incapable of recovering its function after an injury. brain ventricles and the central canal of the spinal cord. The term
However, recent studies have demonstrated that the central ner- was introduced by Rudolph Ludwig Karl Virchow, a German
vous system may not be so static or rigid. It has been shown that pathologist.
after an injury the neuronal circuitry may reorganize itself by Golgi apparatus. A perinuclear accumulation of smooth mem-
forming new synapses to compensate for those lost to injury. brane vesicles and cisternae that are well developed in cells en-
This property of forming new channels of communication after gaged in protein synthesis and secretion. Described by Camillo
an injury is known as neuronal plasticity. Golgi, an Italian anatomist, in 1896.
Neuronal plasticity is most dramatic after partial denervation.
In such a situation, the remaining unaffected axons projecting Golgi, Camillo (1844–1926). Italian anatomist who, in his
on the partially denervated region develop axonal sprouts that kitchen, developed, in 1873, the Golgi stain (silver chromate
grow and form new synaptic contacts to replace those lost by or nitrate, and osmic tetroxide) to demonstrate neurons and
denervation. myelin sheath respectively. He shared the Nobel Prize, in
The ability of the mature central nervous system to form 1906, with Ramon y Cajal. He is credited with description of
these sprouts and functional synapses varies from one region to the Golgi apparatus, the Golgi tendon organ, and Golgi-type
another and from one species to another. The factor or factors neurons.
that promote sprout formation and synaptogenesis in some but Golgi-Mazzoni corpuscles. Described by Camillo Golgi (1844–
not all regions or species are not fully known and are the subject 1926), an Italian anatomist, and Vittorio Mazzoni, an Italian
of intensive research. The identification of factors that promote physician.
neuronal plasticity in the injured mature central nervous system Henle, Friedrich Gustav Jacob (1809–1885). German
may have a great impact on the recovery of function in para- anatomist and pathologist. Made many important contributions
plegic patients and stroke victims. in microscopic anatomy and especially in the study of epithelium
This discussion of plasticity has focused on the regenerative and endothelium. He led a life filled with politics, romance, and
ability of the central nervous system after an injury. It must be em- intrigue. His importance to the development of histology is
phasized, however, that plasticity in its broader sense is an ongoing comparable to that of Andreas Vesalius in gross anatomy. Among
phenomenon. Although brains are grossly similar anatomically, his friends was the composer Felix Mendelsohn.
22 / CHAPTER 1
Meissner’s corpuscles. Encapsulated nerve endings. They were Vater-Pacini corpuscles. Encapsulated nerve endings with a wide
described by George Meissner, a German anatomist, in 1853. distribution. Rapidly adapting mechanoreceptors. Named after
Merkel’s corpuscles. Free nerve endings distributed in the germi- Abraham Vater (1684–1751), a German anatomist, and Filippo
nal layer of the epidermis. They convey touch sensation. Described Pacini (1812–1883), an Italian anatomist who rediscovered them
by Friedrich Sigmund Merkel, a German anatomist, in 1880. about a century after Vater. The corpuscles were first depicted by
Merkel (1845–1919) also introduced into anatomic illustrations Lehman in 1741 from a preparation made by Vater, who called
the colors red for arteries, blue for veins, and yellow for nerves. them papillae nervae. Shekleton (1820–1824) dissected the same
Microglia (Greek mikros, “small”; glia, “glue”). Small intersti- nerves and receptors 10 years before they were seen by Pacini. He
tial, nonneural supporting cells in the central nervous system. placed a beautiful specimen in the Museum of the Royal College
Also known as Hortega cells after del Rio Hortega, who described of Surgeons in Dublin. Pacini then “rediscovered” them in 1835.
them in 1921. The name pacinian corpuscles was used by Friedrich Henle, a
German anatomist, and Rudolph Kolliker, a Swiss anatomist, in
Neurapraxia (Latin neuralis, “nerve”; Greek apraxia, “ab- 1844. Shekleton’s contribution has almost been forgotten.
sence of action”). Failure of nerve conduction in the absence of
structural damage. Wallerian degeneration. Changes in an axon and its myelin
sheath distal to the site of severance of the axon. Named after
Neurotmesis (Latin neuralis, “nerve”; Greek tmesis, “cut- Augustus Waller (1816–1870), an English physiologist who de-
ting”). Partial or complete severance of a nerve with disruption scribed the phenomenon between 1850 and 1852.
of the axon and myelin sheath and connective tissue elements.
Nissl, Franz (1860–1919). German neurologist. Described the
chromophil substance named after him (Nissl substance) in 1884. SUGGESTED READINGS
He was known by his students as the “punctator maximus” be-
cause of his enthusiasm to perform lumbar punctures. Afifi AK, Bergman RA: Basic Neuroscience: A Structural and Functional
Approach, 2nd ed. Baltimore, Urban & Schwarzenberg, 1986.
Nissl bodies. Granular endoplasmic reticulum of neurons. Altman J: Microglia emerge from the fog. Trends Neurosci 1994; 17:47–49.
Named after Franz Nissl, a German neurologist, who described Barr ML, Kiernan JA: The Human Nervous System: An Anatomical Viewpoint,
it in 1884. 6th ed. Philadelphia, Lippincott, 1993.
Nodes of Ranvier. Interruptions in a myelin sheath along the Bergman RA et al: Atlas of Microscopic Anatomy. Philadelphia, Saunders, 1989.
axon at which Schwann cell cytoplasm comes in contact with the Bergman RA et al: Histology. Philadelphia, Saunders, 1996.
axon. Described by Louis Antoine Ranvier, a French histologist, Edelman G: Cell adhesion molecules in the regulation of animal form and
in 1871. Prior to that time, interruptions of the myelin sheaths tissue pattern. Annu Rev Cell Biol 1986; 2:81–116.
at regular intervals were considered artifactual. Using silver im- Fawcett D et al: A Textbook of Histology, 12th ed. New York, Chapman & Hall,
pregnation staining method, Ranvier described “small black, 1994.
transverse lines of remarkable clarity like rungs of a ladder” Gluhbegovic N, Williams TH: The Human Brain: A Photographic Guide.
which he called “the constriction ring of the nerve tube”. Ranvier Philadelphia, Harper & Row, 1980.
also concluded that each internodal segment was a cellular unit Hall ZW: An Introduction to Molecular Neurobiology. Sunderland, MA, Sinauer,
joined to its neighbor at the constriction. 1992.
Oligodendroglia (Greek oligos, “little, few”; dendron, “den- Hillman H, Darman J: Atlas of the Cellular Structure of the Human Nervous
System. London, Academic Press, 1991.
drite”; glia, “glue”). Neuroglial cells with few branches.
Hogan MJ et al: Histology of the Human Eye. Philadelphia, Saunders, 1971.
Described by Rio del Hortega, Spanish neuroanatomist, in 1921.
Hudspeth AJ: The hair cells of the inner ear. Sci Am 1983; 248:54–64.
Purkinje cells. Flask-shaped large cells in the cerebellum. Jones E: The nervous tissue. In Weiss L (ed): Cell and Tissue Biology: A
Described by Johannes Purkinje, a Bohemian physiologist, in Textbook of Histology, 6th ed. Baltimore, Urban & Schwarzenberg,
1837. 1988:277–352.
Remak, Robert (1815–1865). German physiologist and neu- Junge D: Nerve and Muscle Excitation, 3rd ed. Sunderland, MA, Sinauer
rologist who described the axon (named it axis cylinder) and the Associates, 1992.
origin of axons from nerve cells. Kimelberg H, Norenberg M: Astrocytes. Sci Am 1989; 260:66–76.
Ruffini’s corpuscles. Encapsulated nerve endings described by Laws ER Jr; Udvarhelyi GB: The Peripheral Nerves. In Walker EA (ed): The
Angelo Ruffini (1874–1929), an Italian anatomist, in 1898. Genesis of Neuroscience. Park Ridge, Illinois, The American Association
of Neurological Surgeons, 1998:145–155.
Schmidt-Lanterman clefts. Areas of incomplete fusion of Levi-Montalcini R: The nerve growth factor 35 years later. Science 1987;
Schwann cell membranes around the axon. Named after Henry D. 237:1154–1162.
Schmidt, an American pathologist who described them in 1874, 3 Levitan I, Kaczmarek L: The Neuron: Cell and Molecular Biology. New York,
years before A. J. Lanterman, a German anatomist, described them. Oxford University Press, 1991.
Schwann cell. A myelin-forming cell in the peripheral nervous Lim DJ: Functional structure of the organ of corti: A review. Hear Res 1986;
system. Named after Theodor Schwann, a German anatomist, 22:117–146.
who described them in 1838. Matthews GG: Cellular Physiology of Nerve and Muscle, 2d ed. Boston,
Blackwell, 1991.
Synapse (Greek synapsis, “a conjunction, connection, clasp”).
Meredith GE, Arbuthnott GW: Morphological Investigations of Single Neurons
A term introduced by Sherrington in 1897 to describe the junc- in Vitro. New York, Wiley, 1993.
tion between two neurons and between neurons and muscles.
McDevitt D: Cell Biology of the Eye. New York, Academic Press, 1982.
Sherrington had considered the term syndesm but changed to
Murphy S: Astrocytes: Pharmacology and Function. New York, Academic Press,
synapse at the suggestion of the Greek scholar Verrall. 1993.
Tendon organs of Golgi. Stretch receptors in tendons close to Nicholls JG, Martin AR: From Neuron to Brain: A Cellular Approach to the
their junction with the muscle fiber. Named after Camillo Golgi, Function of the Nervous System, 3rd ed. Sunderland, MA, Sinauer
an Italian anatomist. Associates, 1992.
NEUROHISTOLOGY / 23
Pappas G, Purpura D: Structure and Function of Synapses. New York, Raven Smith CUM: Elements of Molecular Neurobiology. New York, Wiley, 1989.
Press, 1972. Steward O: Principles of Cellular, Molecular and Developmental Neuroscience.
Peters A et al: The Fine Structure of the Nervous System: The Neurons and Their New York, Springer, 1989.
Supporting Cells, 3rd ed. New York, Oxford University Press, 1990. Terzis JK, Smith KL: The Peripheral Nerve: Structure, Function, and Recon-
Robinson P et al: Phosphorylation of dynamin I and synaptic vesicle recycling. struction. New York, Raven Press, 1990.
Trends Neurosci 1994; 17:348–353. Thoenen H, Kreutzberg G: The role of fast transport in the nervous system.
Schwartz J: The transport of substances in nerve cells. Sci Am 1980; Neurosci Res Prog Bull 1982; 20:1–138.
242:152–171. Vallee RB, Bloom GS: Mechanism of fast and slow transport. Annu Rev
Shepherd G: The Synaptic Organization of the Brain, 3rd ed. New York, Neurosci 1991; 14:59–92.
Oxford University Press, 1990. Walz W: Role of glial cells in the regulation of the brain ion microenviron-
Siegel G et al: Basic Neurochemistry. New York, Raven Press, 1989. ment. Prog Neurobiol 1989; 33:309–333.
ch02_6082_Afifi_MGH 12/10/04 10:31 AM Page 24
Gross Topography 2
Central Nervous System Internal Topography of the Brain

Brain Coronal Sections
Cerebral Dural Venous Sinuses Axial Sections
External Topography of the Brain
Lateral Surface
Medial Surface
Ventral Surface
Cerebellum and Brain Stem
KEY CONCEPTS
The nervous system can be divided into three parts: cen- On the lateral surface of the cerebral hemisphere three
tral, peripheral, and autonomic. landmarks—the central (rolandic) sulcus, the lateral
(sylvian) fissure, and a line connecting the tip of the pari-
The brain is composed of the two cerebral hemispheres,
eto-occipital sulcus and the preoccipital notch—delin-
the brain stem, and the cerebellum.
eate four lobes: frontal, parietal, temporal, and occipital.
There are three layers of meninges: dura mater, arachnoid
The medial surface of the hemisphere shows the corpus
mater, and pia mater.
callosum, septum pellucidum, fornix, and diencephalon,
The epidural space, a potential space between the skull along with the medial surfaces of the frontal, parietal,
and the dura mater, is the site of epidural arterial hemor- occipital, and temporal lobes.
rhage, a life-threatening condition that usually is due to a
Components of the limbic lobe, the subcallosal gyrus, the
traumatic rupture of the middle meningeal artery.
cingulate gyrus, the parahippocampal gyrus, and the un-
The subdural space,between the dura mater and the arach- cus are seen to advantage on the medial surface of the
noid mater,is the site of subdural venous hemorrhage. cerebral hemisphere.
The subarachnoid space, between the arachnoid mater Cranial nerves and related structures commonly seen on
and the pia mater, contains cerebrospinal fluid. It is also the ventral surface of the brain include the olfactory tract
the site of subarachnoid hemorrhage resulting from rup- and bulb, the optic chiasm, and the oculomotor, trigemi-
ture of cerebral blood vessels on the pia mater. nal, abducens, facial, and cochleovestibular nerves.
For didactic purposes, the nervous system is conven- effort has been expended to elucidate the structure, connectiv-
tionally divided into three major parts: the central ner- ity, and function of the nervous system. The methodologic cre-
vous system (CNS), peripheral nervous system, and au- ativity and observational acumen of anatomists, physiologists,
tonomic nervous system. Although this division simplifies the psychologists, and physicians have been impressive and reward-
study of a complex system, the three component parts act in ing, but their work is far from finished.
concert in the overall control and integration of the motor, sen- The term central nervous system refers to the brain and the
sory, and behavioral activities of the organism. A great deal of spinal cord. The term peripheral nervous system refers to cranial
24
GROSS TOPOGRAPHY / 25
nerves, the spinal nerves, the ganglia associated with the cranial Table 2-1. Brain Weights of Some Notable Persons.
and spinal nerves, and the peripheral receptor organs. The term
autonomic nervous system refers to the part of the nervous system Person Weight
involved mainly in the regulation of visceral function; its com-
ponent parts are located partly within the CNS and partly Anatole France (French writer and Nobel laureate) 1040 g
within the peripheral nervous system. Franz Gall (father of cerebral localization) 1198 g
This chapter is concerned mainly with the gross features of Baron George Eugene Housmann (French city planner) 1225 g
the CNS. Its purposes are to acquaint the student with the ter- Friedrich Tiedemann (German physician) 1253 g
minologic jargon used in the neurologic sciences and provide an Louis Agassiz (Swiss American zoologist) 1495 g
orientation to the major components of this system. Daniel Webster (American statesman and lawyer) 1518 g
Immanuel Kant (German metaphysician) 1600 g
William Makepeace Thackeray (English novelist) 1658 g
George Leopold Chretien Cuvier (French zoologist) 1830 g
CENTRAL NERVOUS SYSTEM Ivan Turgenieff (Russian novelist) 2010 g
The CNS usually is considered to have two major divisions: the
brain and the spinal cord. The brain is subdivided into the fol-
lowing structures:
1. The two cerebral hemispheres The bony skull is the major barrier against physical trauma to
2. The brain stem, consisting of the diencephalon, mes- the brain.
encephalon (midbrain), pons, and medulla oblongata The meninges are organized into three layers named
3. The cerebellum in order of their proximity to the skull:
The cerebral hemispheres and diencephalon are discussed in 1. Dura mater
this chapter. The gross topography of the rest of the brain stem, 2. Arachnoid mater
the cerebellum, and the spinal cord are presented in other chap- 3. Pia mater
ters in this book.
The dura mater (Latin, “hard mother”) is a tough, fibrous
connective tissue (Figure 2–1) arranged in two layers. An outer
parietal (periosteal) layer adheres to the skull and forms its peri-
BRAIN osteum, and an inner meningeal layer is in contact with the
The word brain derives from the Anglo-Saxon word Braegen, arachnoid mater. These two layers of dura are adherent to each
which may have common root with the Greek word Bregma (the other except at the sites of formation of dural venous sinuses
upper part of the head). The first mention of the brain specifi- such as the superior sagittal (Figure 2–2).
cally as an organ occurs in the papyri of ancient Egypt. The an- The meningeal dura mater has three major reflections which
cient Egyptians (3,000–2,500 BC) did not consider the brain of separate components of the brain. The falx cerebri (Figure 2–2) is
importance. They promoted the cardiocentric concept in which a vertical reflection between the two cerebral hemispheres. The
the heart was the seat of the soul. Among the ancient Greeks, tentorium cerebelli (Figure 2–2) is a horizontal reflection between
Plato promoted the cephalocentric theory and coined the term the posterior (occipital) parts of the cerebral hemispheres and the
“enkephalon”. According to Plato, the brain gyri and sulci were cerebellum. The falx cerebelli is a vertical reflection which incom-
analogous to ridges and furrows of a plowed field for planting of pletely separates the two cerebellar hemispheres at the inferior
a divine seed to produce consciousness. In contrast, Aristotle surface. The meningeal layer of the dura mater of the brain is
promoted the Egyptian cardiocentric theory. He considered the continuous with the dura mater that covers the spinal cord.
heart to be the center of the body. The brain was analogous to The arachnoid mater (Greek arachne, “spider”) (Figure 2–3)
clouds of steam where the blood pumped by the heart is cooled. is a nonvascular membrane of an external mesothelium that is
Gyri and sulci were believed to be ripples on the clouds. For cen- joined with weblike trabeculae to the underlying pia mater.
turies, arguments persisted as to the function of the brain, The pia mater is a thin translucent membrane that is inti-
whether it was the seat of emotions or the abode of the soul. It is mately adherent to brain substance. Blood vessels of the brain are
only within the last two hundred years that any real conception located on the pia mater (Figure 2–3). The arachnoid mater and
of the function of the brain began to be obtained. the pia mater are collectively referred to as the pia-arachnoid
The brain is semisolid in consistency and conforms to the membrane because of their close structural and functional
shape of its container. It weighs approximately 1400 g in an relationships.
adult. The male brain is on average slightly heavier than the fe- The meninges are subject to the infection known as meningi-
male brain, although this has no relationship to intelligence. The tis. This is a serious, life-threatening condition that requires im-
largest human brain on record weighed 2850 g and came from a mediate medical treatment. The three layers of meninges are sep-
mentally defective individual with epilepsy. In contrast, Einstein’s arated from each other and from the bony skull by the following
brain weighed 1230 g. The brain weights of other notable per- spaces.
sons are listed in Table 2–1. 1. The epidural space is located between the dura mater
The brain is protected from the external environment by three and the bony skull. Trauma to the skull with rupture of
barriers: the middle meningeal artery (Figure 2–1) leads to
epidural hemorrhage, or the accumulation of arterial blood in the
1. Skull epidural space. Because of the pressure produced by a hemor-
2. Meninges rhage in a closed container such as the skull, an epidural hemor-
3. Cerebrospinal fluid rhage is handled as an acute, life-threatening emergency calling
Dura Mater
Middle Meningeal
Artery
Globe
Figure 2–1. Lateral view of the brain showing the dura mater meningeal layer and the middle meningeal artery. (From
N. Gluhbegovic and T. H. Williams: The Human Brain: A Photographic Guide. Harper & Row, 1980, courtesy of the
authors.)
Superior
Sagittal
Sinus
Arachnoid
Falx Cerebri Granulations
Tentorium
Cerebelli
Figure 2–2. Midsagittal section of the cranium showing the falx cerebri and tentorium cerebelli. (From N. Gluhbegovic and
T. H. Williams: The Human Brain: A Photographic Guide. Harper & Row, 1980, courtesy of the authors.)
26
Cerebral Vessels in
Arachnoid Granulations
Subarachnoid Space
Arachnoid Mater
Figure 2–3. Dorsal view of the brain showing the arachnoid meningeal layer and arachnoid granulations. (From
N. Gluhbegovic and T. H. Williams: The Human Brain: A Photographic Guide. Harper & Row, 1980, courtesy of the
authors.)
for surgical intervention to evacuate the accumulated arterial ingeal layers of dura mater. The superior and inferior sagittal
blood in the epidural space and control the bleeding. sinuses lie in the superior and inferior margins of the falx cerebri,
2. The subdural space lies between the dura mater and respectively. Caudally, the inferior sagittal sinus is joined by the
the arachnoid mater. Trauma to the skull may rupture great cerebral vein of Galen to form the straight sinus (sinus rec-
the bridging veins, leading to subdural hemorrhage, or tus) located at the junction of the falx cerebri and tentorium
the accumulation of blood in the subdural space. This cerebelli. The straight sinus drains into the confluence of sinuses
condition also calls for surgical intervention to evacuate the ac- (torcular Herophili). The two transverse sinuses arise from the
cumulated venous blood and control the bleeding. confluence of sinuses and pass laterally and forward in a groove
3. The subarachnoid space is located between the arach- in the occipital bone. At the occipitopetrosal junction, the two
noid mater and the pia mater. This space contains cere- transverse sinuses curve downward and backward to form the
brospinal fluid (CSF) and cerebral blood vessels (Figure sigmoid sinuses, which drain into the internal jugular veins. The
2–3). Rupture of such vessels leads to subarachnoid occipital sinus connects the confluence of sinuses to the marginal
hemorrhage, or the accumulation of blood in the subarachnoid sinus at the foramen magnum. The superior petrosal sinus lies in
space. This condition may result from trauma to the head, con- the dura at the anterior border of the tentorium cerebelli. The in-
genital abnormalities in vessel structure (aneurysms), or high ferior petrosal sinus extends between the clivus and the petrous
blood pressure. The subarachnoid space underlying the superior bone. The cavernous sinus lies on each side of the sphenoid sinus,
sagittal sinus contains arachnoid granulations (Figures 2–2 and the sella turcica, and the pituitary gland. Dural venous sinuses
2–3), sites of CSF absorption into the superior sagittal sinus. serve as low-pressure channels for venous blood flow back to the
systemic circulation. Obstruction of one or more of these sinuses
The third barrier that protects the brain, the CSF, is the sub- as a result of trauma, infection, or hypercoagulable states results
ject of Chapter 29. in major neurologic signs including stroke, increased intracranial
pressure, loss of consciousness, and intracranial bleed.
CEREBRAL DURAL VENOUS SINUSES EXTERNAL TOPOGRAPHY OF THE BRAIN

(Figure 2–4)
For convenience, the topography of the brain will be discussed as
Cerebral dural venous sinuses are endothelial-lined venous chan- it is viewed on the lateral, the medial, and the ventral surfaces of
nels, devoid of valves, located between the periosteal and men- the brain.
28 / CHAPTER 2
Superior Sagittal Sinus Transverse Sinus
Confluence of
Sinuses
(A) Occipital Sinus
Sigmoid Sinus
Superior Petrosal Sinus Inferior Petrosal Sinus
Superior Sagittal Inferior Sagittal

Sinus Sinus
Straight Sinus
Confluence of Internal
Sinuses Cerebral Vein
(B)
Vein of Galen
Figure 2–4. Lateral (A) and medial (B) surfaces of brain showing sites of dural venous sinuses.
Lateral Surface cally represented in the primary motor area. The representation of
the face is lower than the upper extremity representation, fol-
The lateral surface of the brain is marked by two princi- lowed in ascending order by the trunk and the lower extremity.
pal landmarks that divide the cerebral hemispheres into The leg and foot are represented on the medial surface of the
lobes (Figure 2–5). The lateral fissure (sylvian fissure) and precentral gyrus. In the face area of the precentral gyrus, the lip
the central sulcus (rolandic sulcus) divide the cerebral hemi- representation is disproportionately large compared with its ac-
sphere into the frontal lobe (dorsal to the lateral fissure and ros- tual size on the face; the same applies to the thumb representa-
tral to the central sulcus), temporal lobe (ventral to the lateral fis- tion in the hand area. This disproportionate representation of
sure), and parietal lobe (dorsal to the lateral fissure and caudal to body parts in the primary motor cortex is known as the motor
the central sulcus). If a line were drawn from the parieto-occipital homunculus.
sulcus (best seen on the medial aspect of the hemisphere) onto Stimulation of specific areas of the precentral gyrus results in
the lateral aspect of the hemisphere down to the preoccipital notch, the movement of a single muscle or a group of muscles in the
it would delineate the boundaries of the parietal and temporal contralateral part of the body. Lesions of the precentral gyrus re-
lobes rostrally from that of the occipital lobe caudally. The sult in contralateral paralysis (loss of movement). This is most
frontal, temporal, parietal, and occipital lobes are named after marked in muscles used for fine motor performance, such as but-
the skull bones that overlie them. Lying deep within the lateral toning a shirt or writing.
fissure and seen only when the banks of the fissure are separated Rostral to the precentral sulcus is the premotor area, another
is the insula, or island of Reil (Figure 2–6), which is involved important area for movement. Blood flow studies have shown
primarily with autonomic function. that this area plays a role in initiating new programs for move-
ment and introducing changes in programs that are in progress.
A. FRONTAL LOBE Rostral to the premotor area, the frontal lobe is divided by
Rostral to the central sulcus, between it and the precentral sul- two sulci—the superior and inferior frontal sulci—into three
cus, is the precentral gyrus (primary motor area), which is one gyri: the superior, middle, and inferior frontal gyri. The middle
of the most important cortical areas involved with movement frontal gyrus contains Brodmann’s area, which is important for
(Figure 2–7). Although movement can be elicited by stimulation conjugate eye movements. This area is known as the area of frontal
of a number of cortical areas, movement developed by stimulation eye fields. The inferior frontal gyrus is subdivided by two sulci
of the precentral gyrus is achieved at a relatively low threshold of extending from the lateral (sylvian) fissure: the anterior horizontal
stimulation. Body parts are disproportionately and somatotopi- and anterior ascending rami. Rostral to the anterior horizontal
Central (Rolandic)
Sulcus
Parieto-Occipital
Sulcus
L
TA
N A L
R
O
R I E T
F P A
L
I P I TA
OCC
A L
P O R
M
T E
Pre-Occipital
M Notch
LU
B EL
RE
CE
Lateral (Sylvian)
Fissure
Figure 2–5. Lateral view of the brain showing the four lobes (frontal, parietal, temporal, occipital) and the cerebellum.
(From N. Gluhbegovic and T. H. Williams: The Human Brain: A Photographic Guide. Harper & Row, 1980, courtesy of the authors.)
30 / CHAPTER 2
Lesions in this area result in an inability to express oneself in spo-

Frontal Parietal ken language (aphasia).
lobe lobe
B. PARIETAL LOBE
Caudal to the central sulcus, between it and the postcentral sul-
cus, is the postcentral gyrus, a primary sensory (somesthetic) area
involved in general body sensation (Figure 2–8). Body represen-
tation in the primary sensory area is similar to that described
Lateral above for the primary motor area. The disproportionate and so-
fissure matotopic representation of body parts in this area is known as
the sensory homunculus. Stimulation of this area in humans and
other primates elicits sensations of tingling and numbness in the
part of the body that corresponds to (and is contralateral to) the
Insula Temporal area stimulated. A lesion in this area results in the loss of sensa-
lobe tion contralateral to the site of the lesion.
Figure 2–6. Schematic diagram of the brain showing the insula Caudal to the postcentral gyrus, the intraparietal sulcus ex-
in the depth of the lateral fissure.
tends horizontally across the parietal lobe, dividing it into supe-
rior and inferior parietal lobules. The superior parietal lobule is
involved with the behavioral interaction of an individual with the
surrounding space. A lesion in this lobule, especially in the right
ramus is the orbital gyrus; between the two rami is the triangular (nondominant) hemisphere, results in neglect of body parts con-
gyrus, and caudal to the anterior ascending ramus is the opercu- tralateral to the lesion. Such individuals may neglect to shave the
lar gyrus. The triangular gyrus and the immediately adjacent face or dress body parts contralateral to the lesion. The inferior
part of the opercular gyrus constitute Broca’s area, which in the parietal lobule contains two important gyri: the supramarginal
dominant (left) hemisphere represents the motor area for speech. and angular gyri. The supramarginal gyrus caps the end of the
Precentral Central
Sulcus Sulcus
G
S F
MA
CG
Superior Frontal G
F
Sulcus M
Pre
G
Pre
F
I
Inferior Frontal
P
O
Sulcus R
T
Anterior
Ascending Ramus ORB
Anterior
Horizontal
Ramus
Lateral (Sylvian)
Fissure
Figure 2–7. Lateral view of the brain showing the major sulci and gyri in the frontal lobe. SFG, superior frontal
gyrus; MFG, middle frontal gyrus; IFG, inferior frontal gyrus; ORB, orbital gyrus; TR, triangular gyrus; OP, opercular
gyrus, Pre CG, precentral gyrus; Pre MA, premotor area. (From N. Gluhbegovic and T. H. Williams: The Human
Brain: A Photographic Guide. Harper & Row, 1980, courtesy of the authors.)
Central Postcentral
Sulcus Sulcus
Intraparietal
S
Sulcus
P L
G
C
st
Po
S M
G
G
A
Lateral
(Sylvian)
Fissure
Superior
Temporal
Sulcus
Figure 2–8. Lateral view of the brain showing the major sulci and gyri in the parietal lobe. Post CG, postcentral gyrus; SPL, superior
parietal lobule; SMG, supramarginal gyrus; AG, angular gyrus. (From N. Gluhbegovic and T. H. Williams: The Human Brain:
A Photographic Guide. Harper & Row, 1980, courtesy of the authors.)
sylvian fissure, whereas the angular gyrus caps the end of the supe- Medial Surface
rior temporal sulcus. The two gyri are involved in the integration
of diverse sensory information for speech and perception. Lesions The corpus callosum, in a midsagittal section of the brain, stands
in these two gyri in the dominant hemisphere result in distur- out prominently as a C-shaped massive bundle of fibers
bances in language comprehension and object recognition. (Figure 2–11). The corpus callosum generally is sub-
divided into a head (rostrum) at the rostral extremity, a
C. TEMPORAL LOBE large body extending across the frontal and parietal lobes, a genu
Three gyri constitute the lateral surface of the temporal lobe. (knee) connecting the rostrum and the body, and a splenium at
The superior, middle, and inferior temporal gyri are separated by the caudal extremity. It consists of fibers that connect the two
the superior and middle sulci (Figure 2–9). The inferior tempo- cerebral hemispheres. Behavioral studies have shown that the
ral gyrus extends over the inferior border of the temporal lobe corpus callosum plays an important role in the transfer of infor-
onto the ventral surface of the brain. The superior temporal mation between the two hemispheres. Lesions in the corpus cal-
gyrus contains on its dorsal border (the bank of the lateral fis- losum, which disconnect the right hemisphere from the left hemi-
sure) the transverse temporal gyri of Heschl (primary auditory sphere, result in the isolation of both hemispheres so that each
area). Caudal to the transverse gyri of Heschl in the superior will have its own learning processes and memories that are inac-
temporal gyrus is Wernicke’s area, which is involved in the com- cessible to the other.
prehension of spoken language. The inferior temporal gyrus is Dorsal to the corpus callosum, separated from it by the peri-
involved with the perception of visual form and color. callosal sulcus, is the cingulate gyrus, which follows the contours
of the corpus callosum and occupies parts of the frontal and pari-
D. OCCIPITAL LOBE etal lobes. The cingulate gyrus is part of the limbic system, which
On the lateral aspect of the brain the occipital lobe (Figure 2–5) affects visceral function, emotion, and behavior. The cingulate
merges with the parietal and temporal lobes, separated from gyrus is separated from the rest of the frontal and parietal lobes
them by an imaginary line drawn between the tip of the parieto- by the cingulate sulcus. Dorsal to the cingulate gyrus, extensions
occipital fissure and the preoccipital notch. The occipital pole of the pre- and postcentral gyri onto the medial aspect of the
contains a portion of the primary visual area, which is more ex- brain form the paracentral lobule. The motor and sensory repre-
tensive on the medial aspect of the occipital lobe. sentations of the contralateral lower extremity are thus located in
Fissures and sulci of the cerebral hemisphere become much the paracentral lobule. The precuneus is the part of the parietal
more prominent in degenerative brain disorders such as Alzhei- lobe that is caudal to the paracentral lobule, between the mar-
mer’s disease because of atrophy of the gyri (Figure 2–10). ginal and parieto-occipital sulci. The parieto-occipital sulcus is
32 / CHAPTER 2
T G
Lateral S
(Sylvian)
Fissure T G
M
Superior
Temporal
Sulcus ITG
Middle
Temporal
Sulcus
Figure 2–9. Lateral view of the brain showing the major sulci and gyri in the temporal lobe. STG, superior tem-
poral gyrus; MTG, middle temporal gyrus; ITG, inferior temporal gyrus. (From N. Gluhbegovic and T. H. Williams:
The Human Brain: A Photographic Guide. Harper & Row, 1980, courtesy of the authors.)
Precentral Central Postcentral

Sulcus Sulcus Sulcus
Intraparietal
Sulcus
Lateral (Sylvian) Superior Temporal

Fissure Sulcus
Figure 2–10. Lateral view of the brain in Alzheimer’s disease showing prominent sulci and atrophy of gyri.
(Courtesy of G. Van Hoesen.)
Parieto-Occipital Marginal Central Cingulate

Sulcus Sulcus Sulcus Sulcus
Pericallosal
P Sulcus
C L
G
Cu
Pre
C G
Cu B
G S FX
Calcarine
Sulcus TH
LG
SP G
A R
Stria Medullaris HT
Thalami
Hypothalamic Lamina
Sulcus Terminalis
Figure 2–11. Midsagittal view of the brain showing major sulci and gyri. PCL, paracentral lobule; Pre Cu G, precuneus gyrus; Cu G,
cuneus gyrus; LG, lingual gyrus; CG, cingulate gyrus; S, splenium of corpus callosum; B, body of corpus callosum; G, genu of corpus
callosum; R, rostrum of corpus callosum; FX, fornix; TH, thalamus; HT, hypothalamus; A, anterior commissure; SP, septum pellucidum.
(From N. Gluhbegovic and T. H. Williams: The Human Brain: A Photographic Guide. Harper & Row, 1980, courtesy of the
authors.)
well delineated on the medial surface of the brain and defines the Extending from the ventral border of the anterior commis-
boundaries between the parietal and occipital lobes. Extending sure to the ventral border of the diencephalon is a thin membrane,
at approximately right angles from the parieto-occipital sulcus in the lamina terminalis. This lamina marks the most anterior
the occipital lobe is the calcarine sulcus, which divides the occip- boundary of the embryologic neural tube.
ital lobe into a dorsal cuneus gyrus and a ventral lingual gyrus. Behind the rostral extremity of the fornix and extending in an
The primary visual area is situated on each bank of the calcarine oblique manner caudally is the hypothalamic sulcus. This sulcus
sulcus. Lesions of the primary visual area produce a loss of vision divides the diencephalon into a dorsal thalamus and a ventral
in the contralateral half of the visual field, a condition known as hypothalamus. The midline area between the two thalami and
hemianopia. hypothalami is occupied by the slit-like third ventricle. In some
Ventral to the corpus callosum is the septum pellucidum, a brains the two thalami are connected across the midline by the in-
thin partition that separates the two lateral ventricles. At the interthalamic adhesion (intermediate mass). The thalamus is the
ferior border of the septum pellucidum is another C-shaped fiber gateway to the cerebral cortex. All sensory inputs except olfaction
bundle, the fornix, which connects the temporal lobe (hippo- pass through the thalamus before reaching the cortex. Similarly,
campal formation) and the diencephalon. Only a small part of motor inputs to the cerebral cortex pass through the thalamus.
the fornix is seen in midsagittal sections of the brain. The hypothalamus is a major central autonomic and endocrine
Rostral to the anterior extent of the fornix is a small bundle of center. It plays a role in activities such as feeding, drinking, sexual
fibers, the anterior commissure, which connects the two tempo- behavior, emotional behavior, and growth.
ral lobes and olfactory or smell structures in both hemispheres. The dorsal border of the thalamus is the stria medullaris thal-
Recent evidence points to a wider distribution of anterior com- ami, a thin band which extends caudally to merge with the habe-
missure fibers than was previously believed. The anterior com- nular nuclei. Above the dorsal and caudal part of the diencephalon
missure in humans has been shown to be composed of an ante- lies the pineal gland, which is assumed to have an endocrine func-
rior limb involved with olfaction and a posterior limb containing tion. The stria medullaris thalami, habenular nuclei, and pineal
neocortical fibers that connect visual and auditory areas in the gland constitute the epithalamus.
temporal lobes. There is strong support for the idea that the an- The continuation of the cingulate gyrus in the temporal lobe
terior commissure plays a role in the interhemispheric transfer of (Figure 2–12) is the parahippocampal gyrus, a component of the
visual information. limbic lobe. The parahippocampal gyrus is continuous with the
34 / CHAPTER 2
Cingulate
Sulcus
G
C
CC
SP
G
SC
PHG
FG
U
Collateral
Sulcus
Figure 2–12. Midsagittal view of the brain showing components of the limbic lobe. CG, cingulate gyrus; CC, corpus callosum; SP, sep-
tum pellucidum; SCG, subcallosal gyrus; PHG, parahippocampal gyrus; U, uncus; FG, fusiform gyrus. (From N. Gluhbegovic and T. H.
Williams: The Human Brain: A Photographic Guide. Harper & Row, 1980, courtesy of the authors.)
uncus (another component of the limbic lobe) in the tip of the A. FRONTAL LOBE
temporal lobe. The collateral sulcus separates the parahippocam- The ventral surface of the frontal lobe shows a longitudinal sulcus—
pal gyrus from the fusiform (occipitotemporal) gyrus. the olfactory sulcus—in which the olfactory tract and bulb are lo-
Extending from the diencephalon caudally are the mesen- cated. Medial to the olfactory sulcus is the gyrus rectus; lateral to
cephalon (midbrain), pons, and medulla oblongata (Figure 2–13). the olfactory sulcus is the orbital gyrus. At the caudal extremity of
The cerebellum occupies a position between the occipital lobe, the olfactory tract is the anterior perforated substance, the site of
pons, and medulla oblongata (Figure 2–13). perforating blood vessels that pass to deeper regions of the brain.
The medial surface of the brain shows the compo-
nents of the limbic lobe (Figure 2–12), including the B. TEMPORAL LOBE
subcallosal gyrus, cingulate gyrus, parahippocampal The ventral surface of the temporal lobe shows the continuation
gyrus, and uncus. The limbic lobe forms the core of the limbic of the inferior temporal gyrus from the lateral surface. Medial
system, which is discussed in Chapter 21. to the inferior temporal gyrus is the occipitotemporal (fusiform)
Parasagittal sections of the brain (Figure 2–14) show deeper gyrus. The collateral sulcus separates the occipitotemporal gyrus
structures that are not seen in midsagittal sections, such as the from the more medial parahippocampal gyrus and uncus, which
basal ganglia (caudate nucleus, putamen, globus pallidus) and constitute parts of the limbic lobe.
the internal capsule. Lateral extension of the thalamus is also
seen in such sections. The caudate nucleus, putamen, and globus Cerebellum and Brain Stem
pallidus are known collectively as the corpus striatum. They are
the basal ganglia of the brain and play a role in the regulation of The ventral surface of the brain also shows the ventral surfaces of the
movement. The caudate nucleus and putamen are collectively cerebellum, pons, medulla oblongata, and diencephalon as well as
known as the striatum and are separated by the anterior limb of the cranial nerves and the circle of Willis (Figures 2–16 and 2–17).
the internal capsule. The putamen and globus pallidus are collec- The ventral surface of the cerebellum (Figure 2–16) shows
tively known as the lenticular nucleus. Both nuclei are separated the cerebellar hemispheres, including the tonsils and flocculus.
from the thalamus by the posterior limb of the internal capsule. Tonsillar herniation (herniation of cerebellar tonsils through the
The internal capsule carries motor and sensory fibers from the foramen magnum) under a marked increase in intracranial pres-
cerebral cortex to lower centers and vice versa. Lesions of the in- sure (from a tumor or intracranial hemorrhage) is a life-threaten-
ternal capsule result in contralateral motor deficits (paralysis) ing condition. The midline cerebellum (vermis) is made visible
and sensory deficits. when the medulla oblongata is lifted.
Cranial nerves and related structures that usually are
Ventral Surface visible on the ventral surface of the brain include the
olfactory tract and bulb, the optic chiasm, and the ocu-
Portions of the frontal and temporal lobes, the cerebellum, and lomotor, trigeminal, abducens, facial, and cochleovestibular
the brain stem appear on this surface of the brain (Figure 2–15). nerves (Figure 2–17).
Occipital
Lobe
Cerebellum
Medulla Pons Mesencephalon Diencephalon

Oblongata
Figure 2–13. Midsagittal view of the brain showing components of the brain stem. (From N. Gluhbegovic and T. H.
Centrum Internal Capsule

Semiovale (Anterior Limb)
Internal Capsule
(Posterior Limb)
Caudate
Nucleus
Thalamus
Occipital
Lobe
Putamen
Cerebellum
Globus Pallidus
Figure 2–14. Parasagittal section of the brain showing the basal ganglia and internal capsule.
36 / CHAPTER 2
Olfactory Bulb
Olfactory Tract
Orbital Gyrus L
TA
N
O
Gyrus Rectus R
F
Anterior Perforated
Substance
Uncus
Collateral Sulcus
AL
Parahippocampal
Midbrain
OR
Gyrus
MP
Occipitotemporal
TE
Gyrus
Inferior Temporal
Gyrus
Figure 2–15. Ventral view of the brain showing major sulci and gyri. (From N. Gluhbegovic and T. H.
Olfactory Bulb Olfactory Sulcus
Olfactory Tract
Optic Nerve
Optic Tract
Cerebral Peduncle Optic Chiasma
Uncus
Pons
Oculomotor Nerve
Facial Nerve Trigeminal Nerve
Cochleovestibular Nerve
Medulla Oblongata Cerebellum (Flocculus)
(Pyramid)
Cerebellum (Tonsil)
Pyramidal
Decussation Medulla Oblongata
(Inferior Olive)
Cerebellum
(Hemisphere) Cerebellum (Vermis)
Occipital Lobe
Figure 2–16. Ventral view of the brain showing the cranial nerves. (From N. Gluhbegovic and T. H. Williams: The
Human Brain: A Photographic Guide. Harper & Row, 1980, courtesy of the authors.)
Figure 2–17. Ventral view of the brain showing cranial nerves and the circle of Willis.
The olfactory tract is located in the olfactory sulcus on the ven- with hearing loss because of early involvement of the cochleo-
tral surface of the frontal lobe. Tumors in this area may encroach vestibular nerve.
on the olfactory tract and present with loss of the sense of smell. The trochlear nerve is slender and often is lost during the
The optic chiasma is ventral to the diencephalon and rostral to the process of brain acquisition from the skull. The glossopharyn-
infundibular stalk. Lesions in this site that encroach on the optic geal, vagus, accessory, and hypoglossal nerves are composed of a
chiasm present with loss of vision in the bitemporal visual fields series of slender filaments aligned along the rostrocaudal surface
(bitemporal hemi-anopia). The oculomotor nerve exits on the of the medulla oblongata.
ventral surface of the brain between the posterior cerebral and Components of the circle of Willis that usually are visible on
superior cerebellar arteries. Aneurysms (saccular dilatations) of the ventral surface of the brain include the following arteries
either of these arteries encroaching on the oculomotor nerve pre- (Figure 2–17): internal carotid, anterior cerebral, anterior com-
sent with oculomotor nerve palsy (drooping of the eyelid, a di- municating, posterior communicating, and posterior cerebral.
lated pupil that is nonresponsive to light stimulation, and devia- These arteries form a circle around the diencephalon. The basilar
tion of the eye down and out). The trigeminal nerve is a robust artery occupies a groove (basilar groove) on the ventral surface of
structure on the ventrolateral surface of the pons. Two compo- the pons. The superior cerebellar, anterior inferior cerebellar, and
nents of the nerve are usually visible: a larger (portio major) sen- paramedian arterial branches of the basilar artery usually are vis-
sory and a smaller (portio minor) motor component. The ab- ible. The two vertebral arteries are visible on the ventral surface
ducens nerve is visible in a paramedian position in the groove of the medulla oblongata. They give rise to the anterior spinal
separating the pons from the medulla oblongata. The facial and artery, which supplies the paramedian medulla and spinal cord,
cochleovestibular nerves are visible in the angle between the cere- and the posterior inferior cerebellar artery (PICA), which has a
bellum, pons, and medulla oblongata (cerebellopontine angle). characteristic S configuration and supplies the dorsolateral part
Tumors arising in this angle (acoustic neuromas) usually present of the medulla and the inferior part of the cerebellum.
38 / CHAPTER 2
INTERNAL TOPOGRAPHY OF THE BRAIN eral retinas. The fornix is dorsal and medial to the optic tracts,
separating the hypothalamus into lateral and medial regions. The
Internal brain topography is presented here in a few selective anterior commissure is seen beneath the putamen. The thalamus
coronal and axial sections. A more complete set of coronal, axial, is larger and is clearly divided into medial and lateral nuclear
and sagittal sections is shown in the Atlas. groups by the internal medullary lamina. The mamillothalamic
tract courses within the thalamus on its way from the mamillary
Coronal Sections body to the anterior nuclear group of the thalamus. The poste-
rior limb of the internal capsule separates the lenticular nucleus
Four representative rostrocaudal coronal sections are considered. (putamen and globus pallidus) from the thalamus. Coursing
A. SECTION AT LEVEL OF ANTERIOR LIMB OF INTERNAL CAPSULE from the globus pallidus to the thalamus is a bundle of fibers, the
(Figure 2–18) ansa lenticularis. Lateral to the putamen is the external capsule,
one of the efferent (corticofugal) cortical bundles. Between the
At this level the anterior limb of the internal capsule separates external and extreme capsules lies the claustrum.
the caudate nucleus medially from the putamen laterally. The
caudate nucleus shows its characteristic bulge into the lateral
ventricle. This bulge is lost in degenerative diseases of the cau- D. SECTION AT LEVEL OF MAMILLARY BODIES (Atlas Figure 4–9)
date nucleus such as Huntington’s chorea. The corpus callosum At this caudal diencephalic level the mamillary bodies occupy
is continuous with the deep white matter of the cerebral hemi- the ventral surface of the brain. Emanating from the mamillary
spheres. The septum pellucidum is ventral to the corpus callo- bodies are the mamillothalamic tracts on their way to the ante-
sum and forms a partition between the two lateral ventricles. rior nucleus of the thalamus. The thalamus at this level is rather
B. SECTION AT LEVEL OF ANTERIOR COMMISSURE (Atlas Figure 4–5) large and is separated from the putamen and the globus pallidus
by the posterior limb of the internal capsule. Medial to the inter-
At this level the anterior commissure courses ventral to the globus
nal capsule and dorsolateral to the mamillary body is the sub-
pallidus. Dorsal to the corpus callosum is the cingulate gyrus.
thalamic nucleus, a component of the diencephalon that is in-
The caudate nucleus is smaller and retains its characteristic rela-
volved with movement. Lesions of the subthalamic nucleus give
tionship to the lateral ventricle. The putamen is larger and is lat-
rise to a characteristic involuntary movement disorder contralat-
eral to the globus pallidus; the two basal ganglia nuclei are sepa-
eral to the lesion known as hemiballismus. The caudate nucleus
rated from the thalamus by the posterior limb of the internal
at this level is small. Between the two diencephalons is the cavity
capsule. The fornix is seen in two sites: ventral to the corpus cal-
of the third ventricle. The insula (island of Reil) is seen deep
losum and ventral to the thalamus.
within the lateral (sylvian) fissure.
C. SECTION AT LEVEL OF OPTIC TRACT (Figure 2–19)
At this level the optic tracts course in the ventral part of the brain Axial Sections
on their way to the lateral geniculate nucleus of the thalamus.
Each optic tract carries fibers from the ipsilateral and contralat- A few representative axial sections are considered.
Corpus Callosum
Lateral Ventricle
Anterior (Frontal)
Horn Caudate Nucleus
Septum Internal Capsule

Pellucidum (Anterior Limb)
Putamen
Figure 2–18. Coronal section of the brain at the level of the anterior limb of the internal capsule.
Lateral Medial Internal Medullary

Thalamus Thalamus Lamina
Internal Capsule
(Posterior Limb) Caudate Nucleus
Putamen Mamillothalamic
Tract
Extreme Capsule
Globus Pallidus
External Capsule
Claustrum
Anterior
Commissure
Ansa Lenticularis
Optic Tract Hypothalamus Fornix
Figure 2–19. Coronal section of the brain at the level of the optic tract.
A. SECTION AT LEVEL OF CORPUS CALLOSUM (Figure 2–20) limb of the internal capsule separates the thalamus from the globus
At this level the corpus callosum interconnects the two halves of pallidus. Dorsomedial to the thalamus is the stria medullaris thal-
the brain and is continuous with the white matter core of both ami. The hippocampus is seen as an involution of the parahip-
hemispheres. The caudate nucleus is shown bulging into the lat- pocampal gyrus into the inferior (temporal) horn of the lateral ven-
eral ventricle. The internal capsule is lateral to the caudate and tricle. The fimbria of the fornix, which contains axons of neurons
continuous with the white matter core of the hemispheres. in the hippocampus, is seen attached to the hippocampus.
B. SECTION AT LEVEL OF THALAMUS AND BASAL GANGLIA D. SECTION AT LEVEL OF BRAIN STEM (Atlas Figure 3–17)
(Figure 2–21) At this level the cerebellum, mesencephalon, mamillary bodies,
At this level the frontal, temporal, and occipital lobes are seen. and optic chiasm are seen. Rootlets of the oculomotor nerve
The insula (island of Reil) is buried deep within the sylvian fis- (cranial nerve III) are seen coursing in the mesencephalon. The
sure. The frontal (anterior) horn, body, and atrium (trigone) of cerebral peduncles, which are continuations of the internal cap-
the lateral ventricle are seen. The atrium of the lateral ventricle sule, are located in the ventral part of the mesencephalon. Dorsal
contains abundant choroid plexus (glomus). The septum pellu- to the cerebral peduncle is the substantia nigra.
cidum separates the two frontal horns. Ventral to the septum is The identification of brain structures in sagittal, axial, and
the fornix. The head of the caudate nucleus is seen bulging into coronal sections assumed more importance with the introduc-
the frontal horn of the lateral ventricle. The tail of the caudate, tion of imaging techniques (magnetic resonance imaging [MRI])
which is much smaller than the head, is seen more caudally over- as a diagnostic tool in neurology. In this procedure computerized
lying the atrium (trigone). The anterior and posterior limbs of the images of the brain are taken at a predetermined angle to detect
internal capsule are both seen. The anterior limb separates the the site and nature of lesions in the brain. This is a highly spe-
caudate and putamen nuclei, whereas the posterior limb sepa- cialized technique that requires a thorough knowledge of the
rates the thalamus and putamen. The rostral part and the caudal anatomy of the brain in sections. For the purpose of this presen-
part (splenium) of the corpus callosum are also seen. tation, only a few representative MRI images will be described.
The first (Figure 2–22) is a midsagittal section of the brain
and brain stem that shows the medial surfaces of the frontal,
C. SECTION AT LEVEL OF ANTERIOR COMMISSURE parietal, and occipital lobes; the rostrum, genu, body, and sple-
(Atlas Figure 3–12) nium of the corpus callosum; and the lateral and fourth ventricles,
At this level the anterior commissure is seen rostral to the putamen, thalamus, mesencephalon, pons, medulla, and cerebellum. Also
the globus pallidus, and the columns of the fornix. The posterior seen in this section are the vertebral, basilar, and anterior cerebral
40 / CHAPTER 2
Lateral Ventricle
Caudate Nucleus
Corpus Callosum Internal Capsule
White Matter Core

(Centrum Semiovale)
Figure 2–20. Axial section of the brain at the level of the corpus callosum.
Frontal Lobe
Corpus Callosum
Lateral Ventricle,
Anterior (Frontal) Horn
Caudate Nucleus
Internal Capsule (Head)
(Anterior Limb)
Septum Pellucidum Insula
Lateral Ventricle, Putamen

(Body) Internal Capsule
(Posterior Limb)
Fornix
Temporal Lobe
Caudate Nucleus
(Tail)
Thalamus
Lateral Ventricle Choroid Plexus

(Atrium, Trigone) Glomus
Occipital Lobe
Corpus Callosum
(Splenium)
Figure 2–21. Axial section of the brain at the level of the basal ganglia and thalamus.
Corpus Callosum Frontal Internal Cerebral Arachnoid Parietal

(Body) Lobe Vein granulations Lobe
Corpus Callosum
(Splenium)
Thalamus
Quadrigeminal
Cistern
Lateral
Ventricle
Great Cerebral
Vein (of Galen)
Corpus Callosum
(Genu) Occipital Lobe
Basal Vein
Corpus Callosum
Mesencephalon
(Rostrum)
Fourth Ventricle
Anterior Cerebral
Artery Medulla oblongata
Suprasellar cistern
Basilar Artery
Cisterna Magna
Pons Medullary Vertebral

Cistern Artery
Figure 2–22. T2-weighted MRI of the brain in midsagittal cut. In this T2 sequence, cerebrospinal fluid spaces appear white,
while brain substance is in shades of gray.
arteries; the internal cerebral vein, basal veins, and great cerebral artery. The third ventricle separates the two thalami. Dorsal to
vein; some of the cerebrospinal fluid cisterns (cisterna magna the third ventricle are the internal cerebral veins. The body of the
and medullary, suprasellar, and quadrigeminal cisterns); and the caudate nucleus is in the lateral wall of the body of the lateral
arachnoid granulations. ventricle. The insula (island of Reil) is deep within the lateral
The second (Figure 2–23) is an axial section through the thal- (sylvian) fissures. Branches of the middle cerebral artery are
amus that shows the frontal, parietal, and occipital lobes. The within the lateral fissure. The inferior (temporal) horns of the
third ventricle is in the midline separating the two thalami. lateral ventricle are dorsal to the temporal lobe.
Within the thalamus the mamillothalamic tract is seen in cross A complete set of MRI images in sagittal, axial, and coronal
section. The caudate nucleus forms the lateral wall of the ante- sections is included in the Atlas.
rior horn of the lateral ventricle. The anterior limb of the inter-
nal capsule separates the caudate nucleus and the putamen. The
posterior limb of the internal capsule separates the putamen and TERMINOLOGY
the thalamus. The genu of the internal capsule lies between the
anterior and posterior limbs. The optic radiation is lateral to the Abducens nerve (Latin, “drawing away”). The sixth cranial
atrium (trigone) of the lateral ventricle. The columns of the fornix nerve, which was discovered by Eustachius in 1564, is so named
are above the third ventricle. In the interhemispheric fissure ros- because it supplies the lateral rectus eye muscle, which directs the
trally are pericallosal branches of the anterior cerebral artery. The eye to the lateral side away from the midline.
internal cerebral veins and the straight and superior sagittal sinuses Accessory nerve. The eleventh cranial nerve (accessory nerve of
are seen caudally. Willis) was described by Thomas Willis in 1664. The name ac-
The third (Atlas Figure 9–7) image is a coronal section cessory was chosen because this nerve receives an additional root
through the thalamus and third ventricle. The body of the cor- from the upper part of the spinal cord (C-2–C-3 spinal roots).
pus callosum interconnects the two hemispheres. Dorsal to the Alzheimer’s disease. A degenerative brain disease (formerly
corpus callosum are pericallosal branches of the anterior cerebral known as senile dementia) characterized by memory loss, corti-
42 / CHAPTER 2
Anterior Cerebral Artery

(Pericallosal Branches)
Corpus Callosum Frontal Lobe
Caudate Nucleus
Internal Capsule
(Anterior Limb)
Lateral Ventricle, Anterior
(Frontal) Horn
Internal Capsule
(Genu) Putamen
Internal Capsule Fornix, Column

(Posterior Limb)
Mamillothalamic Tract
Third Ventricle Thalamus
Basal Vein
Parietal Lobe Lateral Ventricle (Trigone,

Atrium)
Internal Cerebral
Optic Radiation
Veins
Straight Sinus
Superior Sagittal Occipital Lobe

Sinus
Figure 2–23. T2-weighted axial MRI through the thalamus.
cal atrophy, senile plaques, and neurofibrillary tangles. Described Atrium (Greek atrion, “court” or “hall”). The atrium was a
by Alois Alzheimer, a German neuropsychiatrist, in 1907. large area in the center of a Roman house. The term is used in
Aneurysm (Greek aneurysma, “widening”). A sac formed by anatomic nomenclature to refer to a chamber that affords entrance
dilatation of the wall of an artery, a vein, or the heart as a result to another structure. The atrium of the lateral ventricle affords en-
of weakening of the wall. The condition was known to Galen. trance to the occipital and temporal horns of the lateral ventricle.
Aphasia (Greek a, “negative”; phasis, “speech”). A defect in Broca’s area. The motor speech area in the inferior frontal gyrus
language communication, loss of speech. The modern knowl- of the left hemisphere. Named after Pierre-Paul Broca, a French
edge of the condition dates back to its description by Bouillard anthropologist, anatomist, and surgeon who associated lesions of
in 1825. In 1861 Broca associated this condition with lesions in this area with disturbance of speech function (aphasia) in 1861.
the inferior frontal gyrus on the left side of the brain and called Brodmann’s areas. Fifty-two cortical areas defined on the basis
the condition aphemia. The term aphasia was introduced by of cytoarchitecture (cellular organization) by Krobinian Brod-
Armand Trousseau in 1864. mann, a German physician, between 1903 and 1908.
Arachnoid mater (Greek arachnoeides, “like a cobweb”). The Cuneus (Latin, “wedge”). The cuneus gyrus is a wedge-shaped
middle meningeal layer of the brain and spinal cord is so named lobule on the medial surface of the occipital lobe between the
because of weblike trabeculae that extend from the arachnoid to parieto-occipital and calcarine sulci.
the underlying pia mater. The arachnoid mater was described by Dura mater (Latin durus, “hard”; mater, “mother”). The outer-
Bichat in 1800. most hard meningeal covering of the brain. The term is derived
from the Arabic umm al-dimagh (“mother of the brain”). terized by abnormal movements (Greek chorea, “dancing”) and
Believing that the meninges were the mother of all membranes, neuropsychological deficits. Named after George Sumner Hun-
the Arabs called the outermost meningeal layer the thick mother tington, an American general practitioner who described the dis-
and the innermost the thin mother. In 1127 Stephen of Antioch ease in 1872.
translated these terms into Latin as dura mater and pia mater. Hypoglossal nerve (Greek hypo, “beneath”; glossa, “tongue”).
Stephen, a monk, chose pia (pious) rather than tenu to translate The twelfth cranial nerve was named by Winslow. Willis in-
the term thin mother. The arachnoid membrane (middle men- cluded it with the ninth cranial nerve. It was considered the
ingeal layer) was not known to the Arabs. twelfth nerve by Soemmering.
Facial nerve. The seventh cranial nerve. Willis divided the sev- Island of Reil. The insula of the cerebral cortex. It was noted by
enth nerve into the portio dura (facial) and the portio mollis Johann Christian Reil, a Danish physiologist, anatomist, and
(auditory). Soemmering separated the two and numbered them psychiatrist, in 1796 and described by him in 1809.
separately (seventh and eighth cranial nerves).
Limbic lobe (Latin limbus, “border”). The limbic lobe is com-
Falx cerebelli, cerebri (Latin falx, “sickle”). A sickle-shaped posed of structures on the medial surface of the cerebral hemi-
structure. The falx cerebelli and cerebri, dural folds separating sphere bordering the corpus callosum and rostral brain stem.
the two cerebellar and cerebral hemispheres, respectively, are
sickle-shaped. Lingual (Latin, tongue) gyrus. A gyrus in the occipital lobe on
the medial surface of the hemisphere forming the inferior lip of
Flocculus (Latin, “tuft,” “small tangle of wool”). A cerebellar the calcarine sulcus.
lobule that with the nodulus forms the archicerebellum, which is
involved with the maintenance of posture. Flocculus was a vul- Mamillary bodies (Latin, diminutive of mamma, “little
gar Latin word for pubic hair. Its use to name a brain structure breast, nipple”). A pair of small round swellings on the ventral
illustrates the ancient practice of naming parts of the brain for surface of the posterior hypothalamus.
other parts of the body. Oculomotor nerve (Latin oculus, “eye”; motor, “mover”). The
Fornix (Latin, “arch”). An archlike pathway, below the corpus third cranial nerve; affects movements of the eye.
callosum, connecting mainly the hippocampal formation and the Opercular gyrus (Latin operculum, “lid” or “cover”). The op-
mamillary body. The fornix was noted by Galen and described by ercular gyrus of the inferior frontal lobe forms a lid or cover over
Vesalius. It was named by Thomas Willis the fornix cerebri. the lateral (sylvian) fissure.
Fusiform gyrus (Latin fusus, “spindle”; forma, “form”; Greek Optic chiasma (Greek optikos, “of or for sight”; chiasma, “a
gyros, “circle”). The fusiform gyrus of the temporal lobe has a cross,” from the letter chi, ). The site of partial decussation
spindlelike shape, tapering from the middle toward each end. (crossing) of the optic nerves. First described by Rufus of Ephesus
Also called the occipitotemporal gyrus. in the first century A.D. For many years it was thought that the
Globus pallidus (Latin globus, “sphere” or “ball”; pallidus, chiasm was responsible for coordinated eye movements.
“pale”). The medial part of the lentiform nucleus of the basal Orbital gyrus. Located on the inferior surface of the frontal lobe
ganglia. lateral to the olfactory sulcus.
Glomus (Latin, “a ball”). The choroid plexus glomus is a ball- Pia mater (Latin pia, “tender, soft”; mater, “mother”). The
like enlargement of the choroid plexus in the atrium (trigone) of innermost meningeal layer covering the brain and spinal cord.
the lateral ventricle. For further discussion of term, see dura mater (p. 42).
Glossopharyngeal nerve (Greek glossa, “tongue”; pharynx, Putamen (Latin, “shell,” a cutting or paring, that which falls
“throat”). The ninth cranial nerve. Combined by Galen with off in pruning or trimming). The outer part of the lentiform
the sixth nerve. Fallopius distinguished it as a separate nerve in nucleus of the basal ganglia.
1561. Thomas Willis included it as part of the eighth nerve. Rolandic sulcus (central sulcus). The sulcus that separates the
Soemmering listed it as the ninth cranial nerve. frontal and parietal lobes. Described by Luigi Rolando, an
Gyrus rectus (Greek gyros, “circle”; Latin rectus, “straight”). Italian anatomist, in 1825. Named for Rolando by François
The gyrus rectus lies along the ventromedial margin of the Leuret in 1839.
frontal lobe medial to the olfactory sulcus. Septum pellucidum (Latin septum, “dividing wall, parti-
Habenular nuclei (Latin habena, “a bridle rein or strap”). tion”; pellucidus, “translucent”). A thin membrane between
The habenular nuclei in the caudal diencephalon near the pineal the corpus callosum and the fornix, separating the anterior horns
gland constitute part of the epithalamus. The name resulted from of the lateral ventricle. Described by Galen.
the fact that early anatomists considered the pineal gland the Splenium (Greek splenion, “bandlike structure,” a bandage
abode of the soul, likening it to a driver who directed the opera- or compress). The posterior rounded end of the corpus callo-
tions of the mind via the habenula or reins. sum is so named because it is the thick and swollen end of the
Hemianopia (Greek hemi, “half ”; an, “negative”; ops, “eye”). corpus callosum, resembling a compress. Also named because of
Blindness in one-half of the field of vision. The term was intro- its resemblance to the rolled-up leaf of a young fern; splenium
duced by Monoyer. Hirschberg substituted the term hemianopsia. was used by the Romans as the name of a kind of fern.
Heschl’s gyri. The transverse temporal gyri, site of the primary Sylvian fissure (lateral fissure). A prominent fissure on the lat-
auditory cortex. Described by Richard Heschl, an Austrian eral surface of the cerebral hemisphere between the frontal and
anatomist, in 1855. parietal lobes above and the temporal lobe below. Described by
Homunculus (Latin, “a little man”). A cortical representation Francis de la Boe Sylvius, a French anatomist, in 1641.
of body parts in the motor and sensory cortices. Tentorium cerebelli (Latin tentorium, “tent” from tendere,
Huntington’s chorea. A degenerative brain disease caused by “to stretch, something stretched out”). A fold of dura mater
abnormal triplet codon repeats at chromosome 4p16.3 inherited stretched over the cerebellum like a tent. The term was adopted
in an autosomal dominant pattern. The clinical picture is charac- about the end of the eighteenth century.
44 / CHAPTER 2
Thalamus (Greek thalamos, “inner chamber,” the room oc- Wernicke’s area. The posterior part of the superior temporal
cupied in a house by a married couple). A mass of gray matter gyrus, which is involved with comprehension of spoken lan-
on each side of the third ventricle. The name was coined by guage. Lesions in this area are associated with receptive aphasia.
Galen and reaffirmed by Willis in 1664. Named after Karl Wernicke, a German neuropsychiatrist, who
Tonsil (Latin tonsilla, a general term for a small rounded described the area in 1874.
mass). The cerebellar tonsils are rounded masses in the posterior
lobe of the cerebellum. Downward extension of the cerebellar
tonsils into the foramen magnum leads to compression of the
medulla oblongata and is life-threatening. SUGGESTED READINGS
Trigeminal nerve (Latin tres, “three”; geminus, “twin”). The Bergman RA et al: Atlas of Human Anatomy in Cross Section. Baltimore-
fifth cranial nerve was described by Fallopius. So named be- Munich, Urban & Schwarzenberg, 1991.
cause the nerve has three divisions: ophthalmic, maxillary, and Gluhbegovic N, Williams TH: The Human Brain: A Photographic Guide.
mandibular. Hagerstown, Harper & Row, 1980.
Trochlear nerve (Latin trochlearis, “resembling a pulley”). Haines DE: Neuroanatomy: An Atlas of Structures, Sections, and Systems.
Baltimore, MD, Urban & Schwarzenberg, 1983.
The fourth cranial nerve supplies the superior oblique eye
Jouandet ML, Gazzaniga MS: Cortical field of origin of the anterior commis-
muscle, whose tendon angles through a ligamentous sling like a sure of the rhesus monkey. Exp Neurol 1979; 66:381–397.
pulley. Achillini and Vesalius included this nerve with the third Maudgil DD: Changing interpretations of the human cortical pattern. Arch
pair of cranial nerves. It was described as a separate root by Neurol 1997; 54:769–775.
Fallopius and was named the trochlear nerve by William Molins, Naidich TP et al: Anatomic relationships along the low-middle convexity:
an English surgeon, in 1670. I. Normal specimens and magnetic resonance imaging. Neurosurgery
Uncus (Latin “hook, hook-shaped structure”). The medially 1995; 36:517–532.
curved rostral end of the parahippocampal gyrus resembles a Pryse-Phillips W: Companion to Clinical Neurology. Boston, Little, Brown,
hook, hence the name. 1995.
Vagus (Latin vagari, “wanderer”). The tenth cranial nerve is so Risse GL et al: The anterior commissure in man: Functional variation in a
multisensory system. Neuropsychologia 1978; 16:23–31.
named because of its long course and wide distribution. This
Roberts M, Hanaway J: Atlas of the Human Brain in Sections. Philadelphia, Lea
nerve was described by Marinus about A.D. 100. The name vagus & Febiger, 1970.
was coined by Domenico de Marchetti of Padua. Shipps FC et al: Atlas of Brain Anatomy for C.T. Scans, 2nd ed. Springfield, IL,
Vermis (Latin “worm”). The vermis of the cerebellum is named Charles C Thomas, 1977.
for its resemblance to the segmented body of a worm. Galen was Skinner HA: The Origin of Medical Terms, 2nd ed. Baltimore, MD, Williams
the first to liken it to a worm. & Wilkins, 1961.
Spinal Cord 3
External Topography Spinal Cord Neurotransmitters and Neuropeptides

Dermatomes and Myotomes Spinal Reflexes
Meninges Micturition Pathway and Bladder Control
Cross-Sectional Topography Functional Overview of the Spinal Cord
Microscopic Anatomy Blood Supply
Gray Matter
White Matter
KEY CONCEPTS
The spinal cord comprises 31 segments defined by 31 Pain and thermal sensations are conveyed by the lateral
pairs of spinal nerves. Each spinal nerve is formed by and anterior spinothalamic tracts.
union of a dorsal (sensory) and a ventral (motor) root.The
Corticospinal tracts are essential for skilled and precise
first cervical segment has only a ventral root.
movements.
Dermatomes are areas of skin supplied by a single poste-
Autonomic innervation of the urinary bladder is related
rior (dorsal) nerve root. “Myotome” refers to a group of
to specific nerve cells in the lower thoracic, upper lumbar,
muscles innervated by a single spinal cord segment.
and midsacral region of the spinal cord. Somatic inner-
The internal structure of the spinal cord consists of cen- vation of the urinary bladder originates in the nucleus of
tral, H-shaped, gray matter and surrounding white mat- Onufrowicz in the ventral horn of midsacral spinal cord
ter. The former contains neurons, and the latter contains segments. Segmental control of bladder function is modi-
ascending and descending fiber tracts. fied by suprasegmental influences in the pons, midbrain,
hypothalamus, and cerebral cortex.
Autonomic sympathetic neurons are located in thoracic
and upper lumbar spinal cord segments, whereas auto- The blood supply of spinal cord is provided by anterior
nomic parasympathetic neurons are located in sacral and posterior spinal arteries derived from vertebral and
spinal cord segments. segmental (radicular) arteries. Some spinal cord seg-
ments are particularly susceptible to reduction in blood
Alpha motor neurons in the ventral horn are somatotopi-
supply.
cally organized.
Posterior funiculus tracts convey conscious propriocep-
tive sensory modalities, especially those actively explored
by the individual perceived at cortical level.
EXTERNAL TOPOGRAPHY cylindrical shape in the upper cervical and thoracic segments and
an oval shape in the lower cervical and lumbar segments, which
The spinal cord of adult humans extends from the foramen mag- are sites of the brachial and lumbosacral nerve plexuses, respec-
num to the level of the first or second lumbar vertebra. Ap- tively. In the early stages of fetal development, the cord occu-
proximately 45 cm long in males and 42 cm in females, it has a pies the whole length of the vertebral canal; in the term new-
45
46 / CHAPTER 3
born, it extends down to the lower border of the third lumbar the surface of the cord to the dural sheath midway between the
vertebra; in late adolescence, the spinal cord attains its adult dorsal and ventral roots. Denticulate ligaments serve as useful
position, terminating at the level of the intervertebral disk be- landmarks for the neurosurgeon in identifying the anterolateral
tween the L-1 and L-2 vertebrae (Figure 3–1). The level at which segment of the cord when performing operations such as cor-
the cord terminates changes with development because the verte- dotomies for the relief of intractable pain. There are 20 or 21
bral column grows faster than the spinal cord. The length of the pairs of denticulate ligaments extending between the first lumbar
entire adult vertebral column is 70 cm. The spinal cord exhibits and first cervical vertebrae.
two enlargements: cervical (third cervical to second thoracic seg- The human spinal cord comprises 31 segments (8
ments) and lumbar (first lumbar to third sacral segments). These cervical, 12 thoracic or dorsal, 5 lumbar, 5 sacral, and 1
are sites of neurons that innervate the upper and lower extremi- coccygeal), each of which, except the first cervical seg-
ties, respectively. The caudal end of the cord is tapered to form ment, has a pair of dorsal and ventral roots and a pair of spinal
the conus medullaris, from which a pial-glial filament, the filum nerves. The first cervical segment has only a ventral root. The dor-
terminale, extends and attaches to the coccyx to anchor the sal and ventral roots join in the intervertebral foramina to form the
spinal cord. The spinal cord is also anchored to the dura by two spinal nerves. Just proximal to its junction with the ventral root in
lateral series of denticulate ligaments, pial folds that stretch from the intervertebral foramen, each dorsal root has an oval swelling:
the dorsal root (spinal) ganglion containing pseudounipolar sen-
sory neurons. At the point where the dorsal nerve root enters the
spinal cord, glial supporting tissue from the spinal cord extends a
short distance into the nerve root to meet the Schwann cell and
the collagenous supporting tissue of the peripheral nervous sys-
tem. The junction zone between the two types of tissues is quite
sharp histologically. It is called the Obersteiner-Redlich space after
two Austrian neurologists, Heinrich Obersteiner and Emil Redlich.
The 31 pairs of spinal nerves are divided into 8 cervical nerves, 12
thoracic nerves, 5 lumbar nerves, 5 sacral nerves, and 1 coccygeal
nerve (Figure 3–1). The fourth and fifth sacral nerves and the coc-
cygeal nerve arise from the conus medullaris. Spinal nerves leave
the vertebral canal through the intervertebral foramina. The first
cervical nerve emerges above the atlas; the eighth cervical nerve
emerges between the seventh cervical (C-7) and the first thoracic
(T-1) vertebrae. All other spinal nerves exit beneath the corre-
sponding vertebrae (Figure 3–1).
Because of the differential rate of growth of the spinal cord
and vertebral column, spinal cord segment levels do not corre-
spond to those of the vertebral column (Table 3–1). Thus, in the
cervical region, the tip of the vertebral spine corresponds to the
level of the succeeding cord segment; that is, the sixth cervical
spine corresponds to the level of the seventh spinal cord seg-
ment. In the upper thoracic region, the tip of the spine is two
segments above the corresponding cord segment; that is, the
fourth thoracic spine corresponds to the sixth cord segment. In
the lower thoracic and upper lumbar regions, the difference be-
tween the vertebral and cord level is three segments; that is, the
tenth thoracic spine corresponds to the first lumbar cord seg-
ment. Because of this, the root filaments of spinal cord segments
have to travel progressively longer distances from cervical to
sacral segments to reach the corresponding intervertebral foram-
ina from which the spinal nerves emerge (Figure 3–1). The
crowding of lumbosacral roots around the filum terminale is
known as the cauda equina.
Table 3–1. Relationship of Spinal Cord Segments

and Vertebral Spines.
Cord segments Vertebral spines

C-1 C-1
C-7 C-6
Figure 3–1. Schematic diagram showing the relationships of T-6 T-4
L-1 T-10
spinal cord segments and spinal nerves to vertebral column
S-1 T-12 to L-1
levels.
SPINAL CORD / 47
DERMATOMES AND MYOTOMES Table 3–2. Body Landmarks and Corresponding

Dermatomes.
The area of skin supplied by a single posterior (dorsal)
nerve root constitutes a dermatome. Familiarity with Body landmark Dermatome
dermatomal maps (Figure 3–2) is essential for localiza-
tion of the level of lesion in the spinal cord. Few dermatomes are Back of head C-2
particularly useful in localization of lesion (Table 3–2). A viral Shoulder C-4
disorder that characteristically presents with dermatomal distri- Thumb C-6
bution of pain and vesicular lesions is herpes zoster (shingles). Middle finger C-7
Groups of muscles innervated from a single spinal cord segment Small finger C-8
constitute a myotome. Familiarity with clinically relevant myo- Nipple T-4,T-5
tomes is useful in localization of the level of lesion in the spinal Umbilicus T-10
cord (Table 3–3). Inguinal region L-1
Big toe L-4, L-5
Small toe S-1
MENINGES Genitalia and perianal region S-4, S-5
The spinal cord is covered by three meningeal coats; these are the
pia, arachnoid, and dura mater. The pia mater is composed of an
inner membranous layer, the intima pia, and an outer superficial
layer, the epipia. The intima pia is intimately adherent to the sur- within the skull, is firmly attached to bone only at the margin of
face of the spinal cord. The epipia carries blood vessels that sup- the foramen magnum. Elsewhere, the spinal dura is separated
ply and drain the spinal cord. It also forms the denticulate liga- from the vertebral periosteum by the epidural space. The spinal
ments. The arachnoid is closely adherent to the dura mater. The epidural space contains adipose tissue and a venous plexus and is
space between the dura and arachnoid (subdural space) is a very largest at the level of the second lumbar vertebra. The spinal
narrow (potential) space visible with the aid of a microscope in epidural space is used for injection of local anesthetics to pro-
histologic preparations in normal conditions. Bridging veins duce paravertebral nerve block known as epidural anesthesia for
course across this space. Rupture of these veins results in accu- relief of pain during obstetrical delivery. The epidural space is
mulation of blood and expansion of this space, a condition also used to inject drugs (e.g., cortisone) to relieve back pain.
known as subdural hematoma. The space between the arachnoid The spinal dura mater ensheathes the dorsal and ventral roots,
and pia (subarachnoid space), in contrast, is wider and contains the dorsal root ganglia, and proximal portions of spinal nerves,
the cerebrospinal fluid. The spinal dura mater, unlike the dura and then it becomes continuous with the epineurium of spinal
nerves at the level of the intervertebral foramen. The spinal cord
terminates at the level of the L-1 and L-2 vertebrae, whereas the
dura mater extends down to the level of the S-1 and S-2 verte-
brae. Below the site of spinal cord termination (conus medullaris),
a sac filled with cerebrospinal fluid and devoid of spinal cord
forms in the subarachnoid space. This sac is a favorable site for
clinicians to introduce a special spinal needle to obtain cere-
brospinal fluid for examination or to inject drugs or dyes into
the subarachnoid space for purposes of treatment or diagnosis.
This procedure is called lumbar puncture or spinal tap.
CROSS-SECTIONAL TOPOGRAPHY
In cross section, the spinal cord is composed of a cen-
trally placed butterfly- or H-shaped area of gray matter
surrounded by white matter. The two wings of the but-
terfly are connected across the midline by the dorsal and ventral
Table 3–3. Clinically Relevant Myotomes.
Myotome Spinal cord segment
Deltoid C-5
Biceps C-6
Triceps C-7
Hypothenar muscle T-1
Quadriceps femoris L-4
Extensor hallucis L-5
Figure 3–2. Dermatomal map showing body landmarks and Gastrocnemius S-1
Rectal sphincter S-3, S-4
corresponding spinal cord segments.
48 / CHAPTER 3
gray commissures above and below the central canal, respectively fibers on the larger side. It has been shown that more fibers in the
(Figure 3–3). The gray matter of the cord contains primarily the left medullary pyramid cross to reach the right half of the spinal
cell bodies of neurons and glia. The white matter of the cord cord and more fibers from the right medullary pyramid remain
contains primarily fiber tracts. uncrossed to descend in the right half of the spinal cord. These
The two halves of the spinal cord are separated by the dorsal two occurrences result in a larger complement of corticospinal
(posterior) median septum and the ventral (anterior) median fis- fibers in the right half of the cord. In essence, then, the right side
sure (Figure 3–3). The site of entrance of dorsal root fibers is of the spinal cord receives more fibers from the cortex than the
marked by the dorsolateral (posterolateral) sulcus; similarly, the left side. This has no relation to handedness. The amount of un-
site of exit of ventral roots is marked by the ventrolateral (antero- crossed fibers may be related to the occurrence of the ipsilateral
lateral) sulcus (Figure 3–3). These landmarks divide the white hemiplegia (weakness) reported in patients with lesions in the in-
matter of each half of the cord into a dorsal (posterior) funiculus, ternal capsule. If most fibers do not cross, then the hemiplegia
a lateral funiculus, and a ventral (anterior) funiculus (Figure 3–3). will be mostly ipsilateral.
Furthermore, in cervical and upper thoracic spinal cord segments,
the dorsal (posterior) funiculus is divided into two unequal parts MICROSCOPIC ANATOMY
by the dorsal (posterior) intermediate septum (Figure 3–3).
The H-shaped gray matter is also divided into a smaller dor- The microscopic anatomy of the spinal cord varies in the differ-
sal (posterior) horn or column and a larger ventral (anterior) ent regions of the cord. The characteristics of microscopic
horn or column. The thoracic and upper lumbar cord segments, anatomy in the different regions help define the level of section
in addition, exhibit a wedge-shaped intermediolateral horn or (Figure 3–4). As one ascends from low sacral segments to high
column (Figure 3–3). cervical segments, the volume of white matter increases progres-
The spinal cord is asymmetric in about 75 percent of humans, sively because the number of nerve fibers, both ascending to
with the right side being larger in 75 percent of the asymmetries. higher levels and descending to lower levels, is larger in the high
The asymmetry is due to more descending corticospinal tract cervical sections and diminishes progressively at more caudal
Dorsal (posterior)
Dorsal (posterior) intermediate septum
median septum
Dorsolateral (posterolateral) Dorsal (posterior)

sulcus funiculus
Dorsal (posterior)
gray column
Lateral
funiculus
White
matter Intermediolateral
gray column
Gray
matter
Ventral (anterior)
gray column
Ventral
roots
White commissure
Ventrolateral Gray commissure Ventral (anterior) funiculus

(anterolateral)
sulcus Ventral (anterior) fissure
Figure 3–3. Photomicrograph of spinal cord showing division into gray and white matter, the sulci and fissures, gray matter
columns, and white matter funiculi.
SPINAL CORD / 49
C-5
T-7
L-5
S-3
Figure 3–4. Schematic diagram showing

variations in spinal cord segments at different
levels.
levels. Some tracts are not present at certain levels. The dorsal is present in the sacral spinal cord, a dorsal outpouching of
spinocerebellar tract appears first at the second lumbar segment the ventral horn in S-2 to S-4 spinal cord segments contains
and is not present below this segment. This is because neurons preganglionic parasympathetic neurons.
that give rise to this tract first appear at the level of L-2 and are • Ventral horn The ventral horn or column contains multi-
not present below this level. The cuneate tract (fasciculus) ap- polar motor neurons, axons of which constitute the major
pears above the sixth thoracic spinal cord segment and is not pres- component of the ventral root.
ent below this level. It follows that the dorsal (posterior) inter- • Intermediate zone This zone contains the nucleus dorsalis
mediate sulcus, which separates the gracile and cuneate tracts, is of Clarke and a large number of interneurons.
only present above the T-6 segment. Different spinal cord regions
also demonstrate distinctive gray matter features. The intermedio- The preceding organizational pattern is illustrated diagram-
lateral cell column and the nucleus dorsalis of Clarke extend be- matically in Figure 3–5.
tween the C-8 and L-2 segments and are not seen either below or B. REXED TERMINOLOGY
above these levels. The cervical and lumbar enlargements of the
cord are characterized by voluminous ventral horns because of In 1952, Rexed investigated the cytoarchitectonics, or cellular
the presence of motor neurons that supply limb musculature at organization, of the spinal cord in the cat and found that cell
these two levels. clusters in the cord are arranged with extraordinary regularity
into ten zones or laminae. His observations subsequently have
Gray Matter been confirmed in other species, including humans. Figure 3–6
is a diagrammatic representation of the location of the ten lami-
A. OLDER TERMINOLOGY nae of Rexed. Table 3–4 compares the older terminology with
Prior to 1952, the organization of the gray matter of the spinal the more recent Rexed terminology.
cord was presented in the following way. Laminae I to IV are concerned with exteroceptive sensations,
whereas laminae V and VI are concerned primarily with proprio-
• Dorsal horn The dorsal (posterior) horn or column receives ceptive sensations, although they respond to cutaneous stimuli.
axons of the dorsal root ganglia via the dorsal roots and con- Lamina VII acts as a relay between midbrain and cerebellum.
tains cell clusters concerned with sensory function. These Lamina VIII modulates motor activity, most probably via gamma
cell clusters are the posteromarginal nucleus, the substantia neurons. Lamina IX is the main motor area of the spinal cord. It
gelatinosa, and the nucleus proprius. contains large alpha and smaller gamma motor neurons arranged
• Intermediolateral horn The intermediolateral horn or col- in columns (dorsolateral, ventrolateral, ventromedial, and cen-
umn is limited to the thoracic and upper lumbar segments of tral). The axons of these neurons supply extrafusal and intrafusal
the cord. It contains preganglionic neurons of the sym- muscle fibers, respectively. Alpha motor neurons in lamina IX of
pathetic nervous system, the axons of which form the cord segments C-3 to C-5 constitute the phrenic nucleus. Axons
preganglionic nerve fibers and leave the spinal cord via of those neurons innervate the diaphragm and thus are essential
the ventral root. Although no distinct intermediolateral horn for breathing. From segments S-1, S-2 to S-4, a supplementary
50 / CHAPTER 3
Figure 3–5. Cross-sectional dia-

gram of the spinal cord showing
the major nuclear groups within
the gray columns.
column of alpha motor neurons appears in lamina IX. This is the ized by a lower rate of impulse firing and slower axonal conduc-
Onuf ’s (Onufrowicz) nucleus, which lies at the most ventral bor- tion. They innervate the slow muscle fibers. Phasic neurons ex-
der of the ventral horn. The nucleus is divided into a dorsome- hibit fast axonal conduction and innervate the fast muscle fibers.
dial cell group innervating the bulbocavernosus and ischiocaver- No anatomic criteria are available to distinguish tonic from pha-
nosus muscles and a ventrolateral cell group innervating external sic alpha motor neurons.
anal and urethral sphincters. The dorsomedial portion of Onuf ’s Physiologic studies also have demonstrated two types of
nucleus contains significantly more neurons in males than in fe- gamma motor neurons, static and dynamic. The static variety is
males. Motor neurons in Onuf ’s nucleus are characteristically related to the nuclear chain type of intrafusal muscle fiber, which
spared in motor neuron disease (amyotrophic lateral sclerosis), in is concerned with the static response of the muscle spindle,
marked contrast to motor neurons elsewhere in the spinal cord whereas the dynamic variety is related to the nuclear bag type
and brain stem. Alpha motor neurons in lamina IX are so- of intrafusal muscle fiber, which is concerned with the dynamic
matotopically organized in such a way that neurons sup- response of the spindle. As is the case with alpha motor neurons,
plying flexor muscle groups are located dorsally, whereas no anatomic criteria are available to differentiate static from
neurons supplying extensor muscle groups are located ventrally. In dynamic gamma motor neurons.
addition, neurons supplying trunk musculature are placed medi- In addition to alpha and gamma motor neurons, lamina IX
ally whereas neurons supplying extremity musculature are placed contains interneurons. One of these interneurons, the Renshaw
laterally (Figure 3–7). Motor neurons in lamina IX receive direct cell, has received particular attention from neuroscientists. The
input from dorsal roots (for spinal reflexes) as well as from de- Renshaw cell is interposed between the recurrent axon collateral
scending pathways concerned with motor control. of an alpha motor neuron and the dendrite or cell body of the
Physiologic studies have demonstrated two types of alpha same alpha motor neuron. The axon collateral of the alpha mo-
motor neurons, tonic and phasic. Tonic neurons are character- tor neuron excites the Renshaw cell. The axon of the Renshaw
cell inhibits (recurrent inhibition) the parent alpha motor neu-
ron and other motor neurons. Through this feedback loop, an al-
pha motor neuron may influence its own activity. Recent studies
have shown that Renshaw cell axons project to nearby as well as
distant sites, including laminae IX, VIII, and VII. The func-
tional consequences of Renshaw cell inhibition are to curtail the
motor output from a particular collection of motor neurons and
to highlight the output of motor neurons that are strongly acti-
vated. The inhibitory neurotransmitter used by the Renshaw
cells is probably glycine.
Table 3–4. Cellular Organization of Spinal Cord.
Rexed terminology Older terminology
Lamina I Posteromarginal nucleus

Lamina II Substantia gelatinosa
Laminae III, IV Nucleus proprius
Lamina V Neck of posterior horn
Lamina VI Base of posterior horn
Lamina VII Intermediate zone, intermediolateral horn
Lamina VIII Commissural nucleus
Figure 3–6. Schematic diagram of half of the spinal cord show- Lamina IX Ventral horn
ing the location of Rexed laminae. Lamina X Grisea centralis
SPINAL CORD / 51
rise to the spinothalamic tract. In contrast, root neurons have

axons that contribute to the formation of the ventral root. Exam-
ples of such neurons include alpha and gamma motor neurons in
the ventral (anterior) horn and the autonomic (sympathetic and
parasympathetic) neurons in the intermediolateral horn and S-2
to S-4 spinal cord segments, respectively.
White Matter
The white matter of the spinal cord is organized into three funic-
uli (Figure 3–3):
1. Posterior (dorsal) funiculus
2. Lateral funiculus
3. Anterior (ventral) funiculus
Each of these funiculi contains one or more tracts or fasciculi
Figure 3–7. Schematic diagram of the spinal cord showing so- (Tables 3–5 and 3–6). A tract is composed of nerve fibers sharing
matotopic organization of ventral horn (lamina IX) motor neurons. a common origin, destination, and function. In general, the name
of a tract denotes its origin and destination; for example, the spino-
cerebellar tract connects the spinal cord and cerebellum and the
corticospinal tract connects the cerebral cortex and spinal cord.
Quantitative studies of the dendritic organization of spinal
motor neurons have shown that dendrites form approximately
A. POSTERIOR FUNICULUS
80 percent of the receptive area of a neuron. Although dendrites Nerve fibers in this funiculus are concerned with two gen-
extend up to 1000 m from the cell body, the proximal third of eral modalities related to conscious proprioception. These
each dendrite contains most of the synapses and thus is the most are kinesthesia (sense of position and movement) and dis-
effective in the reception and subsequent transmission of incom- criminative touch (precise localization of touch, including two-
ing stimuli. Lamina X surrounds the central canal and contains point discrimination).
neuroglia. Lesions of this funiculus therefore will be manifested clini-
Neurons in the gray matter of the spinal cord are of two cally as loss or diminution of the following sensations:
types, principal neurons and interneurons. The former have been 1. Vibration sense
classified into two general categories on the basis of their axonal 2. Position sense
course. Tract (projection) neurons have axons that contribute to
the formation of a tract. Examples of such neurons include the 3. Two-point discrimination
dorsal nucleus of Clarke, which gives rise to the dorsal spinocere- 4. Touch
bellar tract, and neurons in the dorsal (posterior) horn that give 5. Form recognition
Table 3–5. Spinal Cord Ascending Tracts.
Tract name Origin Location Extent Termination Function
Gracile Ipsilateral Medial in Throughout Ipsilateral Conscious

dorsal root posterior spinal cord gracile nucleus proprioception
ganglion funiculus in medulla
Cuneate Ipsilateral Lateral in Above sixth Ipsilateral Conscious
dorsal root posterior thoracic cuneate nucleus proprioception
ganglion funiculus segment in medulla
Dorsal spino- Ipsilateral Lateral Above second Ipsilateral Unconscious
cerebellar nucleus dorsalis funiculus lumbar cerebellum proprioception
of Clarke segment
Ventral spino- Contralateral Lateral Throughout Contralateral Unconscious
cerebellar dorsal horn funiculus spinal cord cerebellum proprioception
Spinocervical Ipsilateral Lateral Throughout Ipsilateral lateral Conscious
thalamic dorsal root funiculus spinal cord cervical nucleus proprioception
(Morin’s) ganglion
Lateral spino- Contralateral Lateral Throughout Ipsilateral thalamus Pain and thermal
thalamic dorsal horn funiculus spinal cord (ventral posterolateral sensations
nucleus)
Anterior Contralateral Lateral and Throughout Ipsilateral thalamus Light touch
spinothalamic (largely) anterior spinal cord (ventral posterolateral
dorsal horn funiculi nucleus)
52 / CHAPTER 3
Table 3–6. Spinal Cord Descending Tracts
Tract name Origin Location Extent Termination Function
Lateral Contralateral Lateral Throughout Ipsilateral Control of skilled

corticospinal cerebral funiculus spinal cord ventral and movement,
cortex dorsal horns modulation of
sensory activity
Anterior cortico- Ipsilateral Anterior Variable Contralateral Control of skilled
spinal (bundle cerebral funiculus ventral and movement,
of Türck) cortex dorsal horns modulation of
(largely) sensory activity
Tract of Barnes Ipsilateral Lateral Throughout Ipsilateral Control of skilled
cerebral funiculus spinal cord ventral and movement,
cortex dorsal horns modulation of
sensory activity
Rubrospinal Contralateral Lateral Throughout Ipsilateral Control of
red nucleus funiculus spinal cord ventral horn movement
(midbrain)
Lateral vestibulo- Ipsilateral Lateral Throughout Ipsilateral Control of muscles
spinal lateral funiculus spinal cord ventral horn that maintain
vestibular upright posture
nucleus and balance
Medial vestibulo- Ipsi- and Anterior Cervical Ipsilateral Head position in
spinal contralateral funiculus spinal cord ventral horn association with
medial vestibular vestibular
nuclei stimulation
Reticulospinal Medullary and Lateral and Throughout Ipsilateral Control of move-
pontine reticular anterior spinal cord ventral horn ment and posture,
formation, funiculi and inter- modulation of
bilaterally mediate zone sensory activity
Tectospinal Contralateral Anterior Cervical Ipsilateral Head position in
superior funiculus spinal cord ventral horn association with
colliculus eye movement
(midbrain)
Descending Ipsilateral Anterolateral Throughout Ipsilateral Control of smooth
autonomic hypothalamus funiculus spinal cord intermedio- muscles and
lateral cell glands
column and
sacral pre-
ganglionic cell
group
Monoaminergic Raphe nucleus, Lateral and Throughout Ipsilateral Control of pain
locus ceruleus, anterior spinal cord dorsal horn transmission
periaqueductal gray funiculi
The presence or absence of these different sensations is tested The nerve fibers that contribute to the posterior funiculus
by the neurologist as follows: have their cell bodies in the dorsal root ganglia.
1. Vibration is tested by placing a vibrating tuning fork over a Peripheral receptors contributing to this system are (1) cuta-
bony prominence. neous mechanoreceptors (hair follicle and touch pressure receptors)
2. Position sense is tested by moving the tip of the patient’s fin- that convey the sensations of touch, vibration, hair movement, and
ger or toe dorsally and ventrally and asking the patient (with pressure and (2) proprioceptive receptors (muscle spindle, Golgi
eyes closed) to identify the position of the part moved. tendon organ, and joint receptors). Muscle receptors (muscle
spindles and Golgi tendon organs) are the primary receptors
3. Two-point discrimination is tested by simultaneously prick- conveying position sense. Joint receptors may be concerned with
ing or touching the patient in two adjacent areas of skin. signaling joint movement but not joint position.
Under normal conditions, a person is able to recognize these Nerve fibers of the posterior funiculus are thickly myelinated
two simultaneous stimuli as separate stimuli if the distance and occupy the dorsolateral part of the dorsal root. Those that en-
between them is not less than 5 mm on the fingertips using ter the spinal cord below the sixth thoracic segment are located
pins and not less than 10 cm on the shin using fingertips. medially in the posterior funiculus and form the gracile tract (tract
4. Touch is tested by placing a cotton ball gently over the skin. of Goll). Fibers that enter the spinal cord above the sixth thoracic
5. Form recognition is tested by asking the patient to identify segment are located more laterally and form the cuneate tract
an object placed in the hand (with eyes closed) based on (Burdach column). Thus the nerve fibers in the posterior funiculus
weight, size, form, and texture perception. are laminated or layered in such a way that those arising from the
SPINAL CORD / 53
sacral region are most medial, whereas those from the cervical re- the sensory modalities presumably carried by this system. This is
gion are most lateral (Figure 3–8). It should be pointed out that explained by the presence of another system, the spinocervical
the lamination in the posterior funiculus is both segmental (sacral, thalamic, located in the lateral funiculus, which may compensate
lumbar, thoracic, cervical) and modality oriented. Physiologic for some posterior funiculus deficits.
studies have shown that fibers conducting impulses from hair re- The role of the dorsal (posterior) column system in sensory
ceptors are superficial and are followed by fibers mediating tactile transmission and appreciation has been studied extensively in
and vibratory sensations in successively deeper layers. both humans and experimental animals (Table 3–7). Sensory
The fibers forming the posterior funiculus ascend throughout stimuli conducted via the posterior column are generally of three
the spinal cord and synapse on the posterior (dorsal) column types: (1) those that are impressed passively on the organism, (2)
nuclei (nucleus gracilis and nucleus cuneatus) in the medulla those that have temporal or sequential factors added to a spatial
oblongata. Axons of these nuclei then cross in the midline to form cue, and (3) those that cannot be recognized without manipula-
the medial lemniscus, which ascends to the thalamus (ventral tion and active exploration by the digits. The first type, stimuli
posterolateral nucleus) and from there to the primary sensory that are impressed passively on the organism (e.g., vibrating tun-
(somesthetic) cortex (Figure 3–9). ing fork, two-point discrimination, touch with a piece of cot-
Approximately 85 percent of ascending fibers in the posterior ton), are transmitted by the dorsal column. However, much the
funiculus are primary afferents. These have cell bodies in the dor- same information is transmitted by a number of parallel path-
sal root ganglia and are activated by stimulation of mechanore- ways such as the spinocervical thalamic tract. Thus such passive
ceptors (unimodal afferents). Approximately 15 percent of fibers types of sensations remain intact in the absence of the dorsal col-
in the posterior funiculus are nonprimary afferents. These have umn. The second type, stimuli with temporal or sequential fac-
cell bodies in the dorsal root ganglion, establish synapses in lami- tors added to a spatial cue (e.g., determination of the direction of
nae III to V in the posterior (dorsal) horns of the cervical and lines that are drawn on the skin), are detected by the dorsal col-
lumbar enlargements, and are activated by stimulation of both umn. The dorsal column has the inherent function of transmis-
mechanoreceptors and nociceptors (polymodal afferents). sion to higher central nervous system centers information con-
Some of the fibers in the posterior funiculus send collateral cerning the changes in a peripheral stimulus over a period of time.
branches that terminate on neurons in the posterior horn gray The third type, stimuli that cannot be recognized without ma-
matter. Such collaterals give the posterior funiculus a role in nipulation and active exploration by the digits (e.g., detection of
modifying sensory activity in the posterior horn. As discussed shapes and patterns), are appreciated only by the dorsal column.
later, this role is inhibitory to pain impulses. In addition to its role in sensory transmission, the dorsal col-
Lesions in the posterior funiculus decrease the threshold to umn has a role in certain types of motor control. Many move-
painful stimuli and augment all forms of sensations conveyed by ments involving the extremities depend on sensory information
the spinothalamic (pain) pathways. Thus nonpainful stimuli be- that is fed back to the brain from peripheral sensory organs such
come painful, and painful stimuli are triggered by lower stimula- as muscle spindles, joint receptors, and cutaneous receptors.
tion thresholds. Many of these feedback inputs travel via the dorsal column. The
Stimulation of the posterior funiculus has been used in the dorsal column transmits to the motor cortex of the brain (via the
treatment of chronic pain. In one large study, 47 percent of thalamus) information necessary to plan, initiate, program, and
treated patients responded initially to this stimulation, but the monitor tasks that involve manipulative movements by the dig-
percentage dropped to 8 percent after 3 years. None of the pa- its. The thalamic nucleus (ventral posterolateral) that receives in-
tients studied had complete relief from pain. put from the dorsal column system has been shown to project
Reports in the literature describe lesions in the posterior fu- not only to the primary somesthetic (postcentral gyrus) sensory
niculus in humans and animals without concomitant deficit in cortex but also to the primary motor cortex in the precentral
Figure 3–8. Schematic diagram of the spinal

cord showing spatial arrangement of fibers in
the posterior funiculus.
54 / CHAPTER 3
perimental animals it has been shown that cutaneous mechanore-

ceptors in forelimbs and hindlimbs (conveying touch, vibration,
hair movement, and pressure) transmit their impulses via the dor-
sal columns (cuneate and gracile tracts, respectively) and the spino-
cervical thalamic tract (Figure 3–10). In contrast, proprioceptive
sensations (from muscle spindle and Golgi tendon organ [posi-
tion sense] and joint receptors) from the forelimbs utilize the dor-
sal column (cuneate tract), while those from the hindlimb travel
with the gracile tract to the level of the dorsal nucleus of Clarke.
From there they leave the gracile tract, synapse in the nucleus dor-
salis of Clarke, and travel with the dorsal spinocerebellar fibers to
terminate on the nucleus of Z (of Brodal and Pompeiano), a small
collection of cells in the most rostral part of nucleus gracilis in the
medulla. From there the fibers join the medial lemniscus to reach
the thalamus (Figure 3–10).
B. LATERAL AND ANTERIOR FUNICULI
Whereas the posterior funiculus (Table 3–5) contains only one
ascending tract or fiber system (the posterior column system),
the lateral and anterior funiculi contain several ascending and
descending tracts (Tables 3–5 and 3–6). Only those tracts with
established functional or clinical relevance will be discussed.
C. ASCENDING TRACTS
All the following tracts have their cells of origin in dorsal root
ganglia (Table 3–5).
1. Dorsal Spinocerebellar Tract. This ascending fiber system
conveys to the cerebellum proprioceptive impulses from recep-
tors located in muscles, tendons, and joints. The impulses arising
in muscle spindles travel via Ia and II nerve fibers, whereas those
arising in Golgi tendon organs travel via Ib nerve fibers. Central
processes of neurons in dorsal root ganglia enter the spinal cord
via the dorsal root and either ascend or descend in the posterior
funiculus for a few segments before reaching the spinal nucleus,
or they may reach the nucleus directly. Nerve cells, the axons of
which form this tract, are located in the nucleus dorsalis of
Clarke (also known as Clarke’s column, nucleus thoracicus, thoracic
nucleus, Stilling column, or Stilling nucleus) within lamina VII of
Rexed (see Figure 3–12). This nucleus is not found throughout
Figure 3–9. Schematic diagram of the posterior column pathway. the extent of the spinal cord but is limited to the spinal cord seg-
ments between the eighth cervical (C-8) and second lumbar (L-2).
Because of this, the dorsal spinocerebellar tract is not seen below
the second lumbar segment. Nerve fibers belonging to this system
gyrus. In addition, the primary sensory cortex projects to the and entering below L-2 ascend to the L-2 level, where they synapse
primary motor cortex. with cells located in the nucleus. Similarly, nerve fibers entering
A frequently reported observation in lesions of the posterior above the upper limit of the nucleus ascend in the cuneate tract to
column is the discrepancy in loss of vibration and position sense. reach the accessory cuneate nucleus in the medulla oblongata,
A possible explanation for this differential loss is that different which is homologous to the nucleus dorsalis (Figure 3–11). Fibers
pathways are used for transmission of the two modalities. In ex- in this tract are segmentally laminated in such a way that fibers
from lower limbs are placed superficially. The fibers in this tract
reach the cerebellum via the inferior cerebellar peduncle (restiform
body) (Figure 3–12) and terminate on the rostral and caudal por-
Table 3–7. Dorsal Column System Function. tions of the vermis. The dorsal spinocerebellar tract conveys to the
cerebellum information pertaining to muscle contraction, includ-
Dorsal column ing phase, rate, and strength of contraction.
Type of stimulus Transmits Essential for There is evidence to suggest that some of the fibers forming
this tract arise from neurons in laminae V and VI of Rexed, as
Passively impressed (vibration, Yes No well as from the nucleus dorsalis of Clarke.
two-point discrimination, touch) 2. Ventral Spinocerebellar Tract. This fiber system (Figure 3–
Temporal or sequential Yes Yes 12) conveys impulses almost exclusively from Golgi tendon organs
(direction of line drawn on skin) via Ib afferents. Dorsal root fibers destined for this tract synapse
Actively explored and manipulated Yes Yes
with neurons in laminae V to VII of Rexed. Axons arising from
(detection of shapes and patterns)
these neurons then cross to form the ventral spinocerebellar tract,
SPINAL CORD / 55
Figure 3–10. Schematic diagram showing the

different pathways for cutaneous and propriocep-
tive sensations from fore- and hindlimbs.
which ascends throughout the spinal cord, medulla oblongata, and The impulses traveling via the indirect spinocerebellar path-
pons before entering the contralateral cerebellum via the superior ways reach the cerebellum after a longer latency than that ob-
cerebellar peduncle (brachium conjunctivum). Thus the fibers of served with the more direct spinocerebellar pathways. It is postu-
this tract cross twice, once in the spinal cord and again before en- lated that impulses traveling via the classic direct pathway reach
tering the cerebellum. Most fibers in this tract terminate in the the cerebellum sooner and will condition it for the reception of
vermis and intermediate lobe, mostly homolateral to the limb of impulses arriving later via the indirect pathways.
origin but also contralateral. The ventral spinocerebellar tract
transmits, to the cerebellum, information related to interneuronal 3. Spinocervical Thalamic Tract (Morin’s Tract). Nerve fibers
activity and the effectiveness of the descending pathways. destined to form the spinocervical thalamic tract are central
Unlike the posterior column, which conveys conscious pro- processes of dorsal root ganglia. They enter the spinal cord with
prioception to the cerebral cortex, the dorsal and ventral spino- the thickly myelinated fibers of the medial division of the dorsal
cerebellar tracts terminate in the cerebellum and thus convey un- root. They travel within the posterior funiculus for several seg-
conscious proprioception. ments before entering the posterior horn gray matter to synapse
In addition to the preceding classic spinocerebellar pathways, on neurons there. Axons of neurons in the posterior horn ascend
there are at least two other indirect pathways from the spinal in the lateral funiculus to the upper two or three cervical seg-
cord to the cerebellum: ments, where they synapse on neurons of the lateral cervical
nucleus. Axons of this nucleus cross to the opposite lateral
1. The spino-olivo-cerebellar pathway, with an intermediate funiculus and ascend to the thalamus (Figure 3–10). The lateral
station at the inferior olive in the medulla oblongata cervical nucleus is organized somatotopically (similar to the pos-
2. The spino-reticulo-cerebellar pathway, with an intermediate terior column nuclei) and similarly receives an input from the
synapse in the lateral reticular nucleus of the medulla cerebral cortex.
56 / CHAPTER 3
This segmental lamination is useful clinically in differentiating

lesions within the spinal cord from those compressing the spinal
cord from outside. In the former, the cervical fibers are affected
early, whereas the sacral fibers are affected either late or not at all.
This condition, known clinically as sacral sparing, is character-
ized by preservation of pain and temperature sensations in the
sacral dermatomes and their loss or diminution in other der-
matomes. In addition to this segmental lamination, the lateral
spinothalamic tract exhibits modality lamination, in which fibers
conveying pain sensations are located anteriorly and those con-
veying thermal sense are located most posteriorly (Figure 3–14).
This segregation of fibers in a modality pattern, however, is in-
complete. Once formed, this tract ascends throughout the length
of the spinal cord and brain stem to reach the thalamus, where
its axons synapse on neurons in the ventral posterolateral nu-
cleus. Third-order neurons project from there by means of the
posterior limb of the internal capsule to the primary somatosen-
sory cortex (Figure 3–15).
Lesions of this tract result in loss of pain and thermal sensa-
tion in the contralateral half of the body beginning one or two
segments below the level of the lesion. In contrast to this pattern
of pain and thermal loss, lesions of the dorsal root result in seg-
mental (dermatomal) loss of sensation ipsilateral to the lesion,
whereas lesions of the crossing fibers in the anterior white com-
Figure 3–11. Schematic diagram of the spinal cord showing missure result in bilateral segmental loss of pain and temperature
the homology of the accessory cuneate nucleus and the nucleus sensation in dermatomes corresponding to the affected spinal
dorsalis of Clarke. segments. This last pattern is often noted in syringomyelia, a dis-
ease in which the central canal of the spinal cord encroaches on,
among other sites, the anterior white commissure.
The lateral spinothalamic tract may be sectioned surgically for
The spinocervical thalamic tract accounts for the presence of the relief of intractable pain. In this procedure, known as cor-
kinesthesia and discriminative touch after total interruption of dotomy, the surgeon uses the ligamentum denticulatum of the
the posterior funiculus. Although this tract has not been demon- spinal meninges as a landmark and orients the knife anterior to the
strated in humans, its presence has been assumed because of the ligament to reach the tract. Because of the segregation of pain and
persistence of posterior funiculus sensations after total posterior thermal fibers in the lateral spinothalamic tract, cordotomies can
funiculus lesions. Thus the older concept of the necessity of the selectively ablate pain fibers, leaving thermal sensations intact.
posterior funiculus for discriminatory sensation is being chal- There has been increased interest in pain pathways and pain
lenged. Instead, a newer concept is evolving that attributes to the mechanisms in recent years. These extensive studies have shown
posterior funiculus a role in the discrimination of those sensa- that the lateral spinothalamic tract is only one of several path-
tions that an animal must explore actively and to the spinocervi- ways carrying pain impulses. Other pathways conveying this
cal thalamic system a role in the discrimination of sensations that modality include a multisynaptic pathway associated with the
are impressed passively on the organism (Table 3–7). reticular system and a spinotectal pathway. These studies also
have developed the concept of an inhibitory input into the pos-
4. Lateral Spinothalamic Tract. This ascending fiber tract is terior horn from the thickly myelinated fibers of the dorsal root
located medial to the dorsal and ventral spinocerebellar tracts and posterior column. This has led clinicians to stimulate these
(Figure 3–13) and is concerned with transmission of inhibitory fibers traveling in the posterior column in an attempt
pain and temperature sensations. Root fibers contribut- to relieve intractable pain.
ing to this tract (C-fibers and A-delta fibers) have their Out of these studies on pain mechanisms has evolved the
cell bodies in dorsal root ganglia. They are unmyelinated and gate-control theory of pain, proposed by Melzack and Wall
thinly myelinated fibers that generally occupy the ventrolateral (Figure 3–16). According to this theory, two afferent inputs re-
region of the dorsal root as it enters the spinal cord. C-fibers con- lated to pain enter the spinal cord. One input is via small fibers
duct slowly at 0.5 to 2 m/s. A-delta fibers conduct faster at 5 to that are tonic and adapt slowly with a continuous flow of activ-
30 m/s. Incoming root fibers establish synapses in laminae I to ity, thus keeping the gate open. Impulses along these fibers will
VI of Rexed. A-delta and C-fibers terminate in laminae I to III; activate an excitatory mechanism that increases the effect of ar-
A-delta fibers terminate in addition in deep layer V. Axons of riving impulses. The second input is via large, thickly myelinated
neurons in these laminae in turn establish synapses with neurons fibers that are phasic, adapt rapidly, and fire in response to a
in laminae V to VIII. Axons of tract neurons in laminae V to stimulus. Both types of fibers project into lamina II of Rexed,
VIII, as well as some axons arising from neurons in lamina I, which suggests that this lamina is the modular center for pain.
cross to the opposite lateral funiculus in the anterior white com- The thin fibers inhibit, whereas the thick fibers facilitate, neu-
missure within one to two segments above their entry level to rons in this lamina. Both types of fibers also project into lami-
form the lateral spinothalamic tract. A small number of fibers nae I and IV to VIII of Rexed, where tract cells are located. Both
stay uncrossed. Fibers of sacral origin are located most laterally thin and thick fibers facilitate neurons in these laminae.
and those of cervical origin more medially in the crossed tract. Furthermore, axons of neurons in lamina II have a presynaptic
SPINAL CORD / 57
Figure 3–12. Schematic diagram showing the for-

mation, course, and termination of the dorsal (poste-
rior) and ventral (anterior) spinocerebellar tracts.
inhibitory effect on both small and large axons projecting on Since its publication, the gate-control theory has been modi-
tract neurons. These different relationships (Figure 3–16) can fied and further clarified. It is now recognized that inhibition
be summarized as follows: occurs by both presynaptic and postsynaptic inputs from the pe-
riphery, as well as by descending cortical influences. While it is
1. Ongoing activity that precedes a stimulus is carried by the generally agreed that a gate control for pain exists, its functional
tonic, slowly adapting fibers that tend to keep the gate open. role and detailed mechanism need further exploration.
2. A peripheral stimulus will activate both small and large Ongoing research in pain mechanisms has given rise in recent
fibers. The discharge of the latter initially will fire the tract years to much interesting data, some of which are summarized
cells (T cells) through the direct route and then partially below:
close the gate through their action via lamina II (facilitation
of presynaptic inhibition). 1. Two types of pain receptors have been identified: unimodal
3. The balance between large- and small-fiber activation will nociceptors responding to nociceptive stimuli and poly-
determine the state of the gate. If the stimulus is prolonged, modal nociceptors responding to nociceptive, chemical, and
large fibers will adapt, resulting in a relative increase in mechanical stimuli.
small-fiber activity that will open the gate further and in- 2. Three types of spinothalamic neurons have been identified in
crease T-cell activity. However, if large-fiber activity is in- the dorsal horn: low-threshold mechanoreceptors in laminae
creased by a proper stimulus (vibration), the gate will tend to VI to VII, high-threshold, nociceptive-specific nociceptors in
close, and T-cell activity will diminish. lamina I, and wide-dynamic-range neurons in laminae IV
58 / CHAPTER 3
Lateral
spinothalamic A
tract
Tract of
Lissauer
B
Dorsal
root
ganglion
C
Figure 3–13. Schematic diagram showing the formation of the
lateral spinothalamic tract.
and V responding to both mechanoreceptor and nociceptor

stimulation. The wide-dynamic-range neurons receive in-
puts from both low-threshold mechanoreceptors and high-
threshold nociceptors and are probably concerned with vis-
ceral and referred pain.
3. Only the nociceptor neurons are inhibited by serotonergic
fibers from the nucleus raphe magnus of the medulla.
4. Several neurotransmitter substances have been identified in
the dorsal horn: norepinephrine and serotonin in the substan- Figure 3–15. Schematic diagram of the formation, course, and
tia gelatinosa and substance P, somatostatin, and enkephalins
termination of the lateral spinothalamic tract.
in laminae I to III. Substance P has been found to be excita-
tory, whereas enkephalins are inhibitory.
5. C-fibers entering via the dorsal root terminate on lamina I,
lamina II, and lamina III neurons. They excite neurons in all
these laminae via axodendritic synapses. Axons of lamina II
neurons in turn inhibit neurons of lamina I via axosomatic
synapses.
6. A-delta fibers establish excitatory synapses on laminae II and
IV neurons. Some terminate on laminae I, III, and V. Since
lamina II neurons inhibit lamina I neurons, repetitive stimu-
lation of A-delta fibers can inhibit lamina I neurons signifi-
cantly. In common practice, this is probably what happens
when pain from a cut on the finger is reduced by local pres-
sure (stimulation of A-delta fibers).
7. About 24 percent of sacral and 5 percent of lumbar originat-
ing fibers in the lateral spinothalamic tract project to the
ipsilateral thalamus.
5. Anterior Spinothalamic Tract. This tract carries light touch
stimuli. Fibers contributing to this tract in the dorsal root estab-
Figure 3–14. Schematic diagram showing the segmental and lish synapses in laminae VI to VIII. Axons of neurons in these
modality lamination of the lateral spinothalamic tract. S, sacral; laminae cross in the anterior white commissure over several seg-
L, lumbar; T, thoracic (dorsal); C, cervical. Stippled area denotes ments and gather in the lateral and anterior funiculi to form the
thermal fibers. Clear area denotes pain fibers. tract. Somatotopic organization in this tract is similar to that in
SPINAL CORD / 59
spinal cord) (Figure 3–17). Approximately one million axons

compose the corticospinal tract on each side. At the caudal end
of the medulla oblongata, the majority of corticospinal fibers
cross (pyramidal decussation) to form the lateral corticospinal
tract, located in the lateral funiculus of the spinal cord (Figure 3–
18). Fibers in the lateral corticospinal tract are organized soma-
totopically. The cervical fibers are most medial, followed laterally
by the thoracic, lumbar, and sacral fibers (Figure 3–19). The un-
crossed fibers remain in the anterior funiculus as the anterior cor-
ticospinal tract (bundle of Türck) (Figure 3–18). They, in turn,
cross at segmental levels to terminate on contralateral motor
neurons (Figure 3–18). A crossed component of the anterior cor-
ticospinal tract has been described, however. It is located in the
posterolateral part of the anterior funiculus close to the ventral
(anterior) horn. The crossed lateral corticospinal tract extends
throughout the spinal cord. The extent of the uncrossed compo-
nent of the anterior corticospinal tract depends on its size, which
is variable. When large, it extends throughout the spinal cord.
The crossed component of the anterior corticospinal tract ex-
tends to the sixth or seventh cervical segments only. About 2 to
3 percent of the corticospinal fibers remain uncrossed (Figure 3–
18) in the lateral funiculus (tract of Barnes) and influence ipsilat-
eral motor neurons. Most fibers in the corticospinal tract are
Figure 3–16. Schematic diagram of the gate-control theory of
pain.
the lateral spinothalamic tract. The course of this tract in the

spinal cord and brain stem is similar to that of the lateral spino-
thalamic tract. Recent evidence about this tract suggests the
following: (1) It conveys pain impulses in addition to touch.
(2) Some of its fibers ascend ipsilaterally all the way to the mid-
brain, where they cross in the posterior commissure and project
primarily on intralaminar neurons in the thalamus, with some
fibers reaching the periaqueductal gray matter in the midbrain.
(3) It is believed to convey aversive and motivational nondis-
criminative pain sensations, in contrast to the lateral spinotha-
lamic tract, which is believed to convey the well-localized dis-
criminative pain sensations. The existence of this tract as a
separate entity has been questioned. Most authors include this
fiber system with the lateral spinothalamic tract. Physiologists
tend to refer to the two tracts as the anterolateral system.
6. Other Ascending Tracts. Other ascending tracts of less clin-
ical significance include the spino-olivary, spinotectal, and spino-
cortical tracts. The functional significance of these multisynaptic
pathways is not very well delineated; they may play a role in
feedback control mechanisms.
D. DESCENDING TRACTS
Whereas all the ascending tracts originate in dorsal root ganglia
neurons (Table 3–5), the descending tracts, in contradistinction,
originate from several sites (Table 3–6). As with the ascending
tracts, only the descending tracts of clinical or functional signifi-
cance will be discussed.
1. Corticospinal Tract. The corticospinal tract has the highest
level of development in higher primates, especially in humans.
The cells of origin of this tract are located in the cerebral cortex.
The primary motor cortex (Brodmann’s area 4) and the pre-
motor cortex (area 6) contribute 80 percent of the tract. From
their site of origin, axons of the corticospinal tract descend
throughout the whole length of the neuraxis (brain stem and Figure 3–17. Schematic diagram of the corticospinal pathway.
60 / CHAPTER 3
rons located in the lateral part of the ventral horn that supply
distal limb musculature. Anterior (ventral) corticospinal tract
fibers terminate on motor neurons located in the medial part of
the ventral horn that supply neck, trunk, and proximal limb
musculature (Figure 3–18). Stimulation of corticospinal tract
fibers results in co-activation of alpha and gamma motor neu-
rons supplying the same muscle and thus simultaneous co-
contraction of extrafusal and intrafusal muscles. This co-contrac-
tion of the two types of muscles optimizes the sensitivity of the
muscle spindle (intrafusal muscle) to changes in muscle length
even under conditions of muscle shortening. The termination of
the corticospinal tract in laminae IV to VII (which also receive
sensory impulses from the periphery) suggests that this tract
plays a role in modulation of sensory input to the spinal cord.
Evidence for corticospinal tract control of sensory function is
provided by terminations of corticospinal tract fibers on primary
afferent fibers and sensory relay neurons in the posterior (dorsal)
horn of the spinal cord. Corticospinal tract terminals exert pre-
synaptic inhibition on some primary afferents and postsynaptic
inhibition or excitation of sensory relay neurons. The presynap-
tic inhibition of primary afferents determines what type of sen-
sory information is allowed to reach higher levels even before
this information is relayed to sensory relay neurons in the dorsal
horn or elsewhere. The postsynaptic inhibition or excitation of
sensory relay neurons in the dorsal horn modulates activity of
neurons involved in the transmission of somesthetic and proprio-
ceptive information to the thalamus and cerebral cortex.
The corticospinal tract is essential for skill and preci-
Figure 3–18. Schematic diagram showing the three divisions sion in movement and the execution of discrete fine fin-
of the corticospinal tract and their patterns of termination in the ger movements. It cannot by itself, however, initiate these
spinal cord. movements. Other corticofugal (cortically originating) fibers are
needed. An intact corticospinal tract is not essential for produc-
tion of voluntary movement but is necessary for speed and agility
during these movements. It also serves to regulate sensory relay
small in caliber, ranging in diameter from 1 to 4 m. Only processes and thus selects what sensory modality reaches the cere-
about 3 percent of the fiber population consists of large-caliber bral cortex.
fibers (V 10 m in diameter). The large-caliber fibers arise from Lesions of the corticospinal tract result in paralysis. If the le-
the giant cells of Betz in the motor cortex. In the spinal cord, sion occurs above the level of the pyramidal decussation, paraly-
corticospinal fibers project on interneurons in laminae IV to VII sis will be contralateral to the side of the lesion. If the corti-
of Rexed. There is evidence also for a direct projection of a small cospinal tract lesion is below the decussation (i.e., in the spinal
number of fibers on motor neurons (both alpha and gamma) in cord), the paralysis will be homolateral (ipsilateral) to the side of
lamina IX in monkeys and in humans. The impulses conveyed the lesion. In addition to paralysis, lesions in the corticospinal
via the corticospinal tract are facilitatory to flexor motor neu- tract result in a conglomerate of neurologic signs that includes
rons. Lateral corticospinal tract fibers terminate on motor neu- (1) spasticity (resistance to the initial phase of passive movement
of a limb or muscle group), (2) hyperactive myotatic reflexes (ex-
aggerated response of knee-jerk and other deep tendon reflexes),
(3) Babinski sign (abnormal flexor reflex in which stroking the
lateral aspect of the sole of the foot results in dorsiflexion of the
big toe and fanning out of the other toes), and (4) clonus (an al-
ternating contraction of antagonistic muscles resulting in a series
of extension and flexion movements). Collectively, this con-
glomerate of signs is referred to by clinicians as upper motor neu-
ron signs. Usually, there is sparing of muscles of the upper face,
mastication, trunk, and respiration, presumably because these
muscles are innervated bilaterally from the motor cortex.
2. Rubrospinal Tract. Neurons of origin of the rubrospinal
tract are located in the magnicellular posterior two-thirds of the
red nucleus in the midbrain. Fibers forming this tract cross in the
ventral tegmental decussation of the midbrain and descend
throughout the whole length of the neuraxis to reach the lateral
Figure 3–19. Schematic diagram showing somatotopic orga- funiculus of the spinal cord in close proximity to the corti-
nization of fibers in the lateral corticospinal tract. C, cervical; cospinal tract (Figure 3–20). They terminate in the same laminae
T, thoracic; L, lumbar; S, sacral. as the corticospinal tract and similarly facilitate flexor motor
SPINAL CORD / 61
MIDBRAIN
Red
nucleus
Lateral
vestibular
nucleus
Ventral tegmental Sites of termination of lateral

Site of termination
decussation vestibulospinal tract
of rubrospinal
tract Lateral
vestibulospinal
Rubrospinal tract
tract
SPINAL CORD
Figure 3–21. Composite schematic diagram of the origin,
course, and termination of the lateral vestibulospinal tract.
Figure 3–20. Composite schematic diagram of the origin,

course, and termination of the rubrospinal tract. 5. Reticulospinal Tracts (Figure 3–23). The neurons of origin
of these tracts are located in the reticular formation of the pons
and medulla oblongata. The pontine reticulospinal tract is lo-
cated in the anterior funiculus of the spinal cord, whereas the
neurons. Because of the similarity in the site of termination of medullary reticulospinal tract is located in the lateral funiculus.
both tracts, and because the red nucleus receives an input from Both tracts descend predominantly ipsilaterally, but both have,
the cortex, the rubrospinal tract has been considered by some as in addition, some crossed components. The pontine reticulo-
an indirect corticospinal tract. The two tracts constitute the dor- spinal tract facilitates extensor motor neurons, whereas the
solateral pathway for movement, in which the corticospinal tract medullary reticulospinal tract facilitates flexor motor neurons.
initiates movement and the rubrospinal corrects errors in move-
ment. In most mammals, the rubrospinal tract is the major out-
put of the red nucleus. The significance of the rubrospinal tract
has diminished with evolution. In humans, the major output of
the red nucleus is to the inferior olive.
3. Lateral Vestibulospinal Tract. The neurons of origin of this
tract lie in the lateral vestibular nucleus located in the pons.
From their site of origin, fibers descend uncrossed and occupy a
position in the lateral funiculus of the spinal cord (Figure 3–21).
The fibers in this tract terminate on interneurons in laminae VII
and VIII, with some direct terminations on alpha motor neuron
dendrites in the same laminae. The impulses conducted in this Medial longitudinal
system facilitate extensor motor neurons that maintain upright fasciculus
posture.
4. Medial Vestibulospinal Tract. The neurons of origin of the
medial vestibulospinal tract are located in the medial vestibular
nucleus. From their neurons of origin, fibers join the ipsilateral
and contralateral medial longitudinal fasciculi, descend in the
anterior funiculus of the cervical cord segments, and terminate
on neurons in laminae VII and VIII (Figure 3–22). They exert a
facilitatory effect on flexor motor neurons. The tract plays a role Figure 3–22. Schematic diagram of origin, course, and termi-
in control of head position. nation of the medial vestibulospinal tract.
62 / CHAPTER 3
Dorsal tegmental
decussation
Figure 3–24. Schematic diagram of the origin and termination

of the tectospinal tract.
known as Horner’s syndrome, or Bernard-Horner syndrome, will

result. This syndrome is manifested by (1) miosis (small pupil),
(2) pseudoptosis (minimal drooping of the eyelid), (3) anhidro-
sis (absence of sweating) of the face, and (4) enophthalmos
(slight retraction of the eyeball). All these signs occur on the
same side as the lesion and are due to interruption of sympa-
thetic innervation to the dilator pupillae, tarsal plate, sweat
glands of the face, and retro-orbital fat, respectively.
8. Descending Monoaminergic Pathways. Serotonergic fibers
Figure 3–23. Schematic diagram of the origins and termina- from the raphe nucleus of the medulla oblongata, noradrenergic
tions of the pontine and medullary reticulospinal tracts.
fibers from the nucleus locus ceruleus in the rostral pons and
caudal midbrain, and enkephalinergic fibers from the periaque-
ductal gray matter in midbrain descend in the lateral and ante-
rior funiculi. They descend both ipsilateral and contralateral to
Pontine originating fibers terminate in laminae VII and VIII their site of origin.
of Rexed, whereas medullary originating fibers terminate primar-
ily in lamina VII. Some medullary originating fibers interact Spinal Cord Neurotransmitters
with motor neuron dendrites in laminae VII and VIII. In addi- and Neuropeptides
tion to influencing motor neurons, reticulospinal fibers modify
sensory activity through their interaction with spinothalamic Most primary sensory neurons in the dorsal horn release gluta-
neurons in the dorsal horn. mate as a rapidly acting excitatory neurotransmitter irrespective
of the sensory modality conveyed by the afferent fiber. In addi-
6. Tectospinal Tract (Figure 3–24). From their neurons of ori- tion to glutamate, many small-diameter neurons in the dorsal
gin in the superior colliculus of the midbrain, fibers of this tract horn also release neuropeptide transmitters, notably substance P,
cross in the dorsal tegmental decussation in the midbrain and somatostatin, and vasoactive intestinal peptides. These are be-
descend throughout the neuraxis to occupy a position in the an- lieved to mediate slow synaptic transmission. Other neurotrans-
terior funiculus of the cervical spinal cord. Fibers of this tract mitters and neuromodulators (peptide neurotransmitters) in the
terminate on neurons in laminae VI, VII, and VIII. The func- spinal cord include norepinephrine, serotonin, enkephalin, neu-
tion of this tract is not well understood; it is believed to play a ropeptide Y, peptide histidyl isoleucine, and cholecystokinin.
role in the turning of the head in response to light stimulation. Neuropeptides are most abundant in the dorsal horn, followed
7. Descending Autonomic Pathway. Fibers belonging to this in decreasing intensity by the intermediate zone and the anterior
descending system originate predominantly from the hypothala- (ventral) horn. The lumbosacral region has more neuropeptides
mus. They are small-caliber fibers that follow a polysynaptic compared with other regions of the spinal cord. While the exact
route and are scattered diffusely in the anterolateral funiculus of function of most neuropeptides is not established with absolute
the spinal cord. They project on neurons in the intermediolateral certainty, the following observations have been reported: Sub-
cell column. Lesions of this system result in autonomic distur- stance P is the neurotransmitter of primary nociceptive and non-
bances. If the lesion involves the sympathetic component of this nociceptive afferents in the dorsal horn. The marked reduction
system at or above the T-1 level, a characteristic syndrome of substance P immunoreactivity in lamina II in patients with
SPINAL CORD / 63
profound analgesia in the familial dysautonomia (Riley-Day) In humans, myotatic stretch reflexes can be elicited in the fol-
syndrome supports a role for this neuropeptide in pain transmis- lowing sites and are part of a neurologic examination:
sion. Met-enkephalin and somatostatin (SST) in the dorsal horn Biceps jerk. This reflex is elicited by tapping the tendon of
inhibit release of substance P from primary afferents and inhibit the biceps muscle. The biceps muscle will contract, flexing
activity in dorsal horn neurons. Vasoactive intestinal peptide the elbow.
(VIP) is the major neurotransmitter in visceral (especially pelvic)
afferents and is found abundantly in lumbosacral segments Triceps Jerk. This reflex is elicited by tapping the tendon of
of the cord. Substance P, Met-enkephalin, and cholecystokinin the triceps muscle. As a result, the triceps will contract and
(CCK) in the intermediate zone are terminals from caudal raphe extend the elbow joint.
nuclei of the brain stem. Substance P and serotonin from the Radial jerk. Tapping the tendon of the brachioradialis mus-
caudal raphe nuclei participate in the modulation of motor neu- cle at the wrist will contract the brachioradialis muscle and
ron activity in the anterior horn. Norepinephrine from the locus flex the wrist joint.
ceruleus has an inhibitory effect on nociceptive activity in the Knee jerk (quadriceps myotatic reflex). This reflex is
dorsal horn. elicited by tapping the tendon of the quadriceps femoris mus-
cle at the patella. The quadriceps muscle contraction extends
Spinal Reflexes the knee joint.
Ankle jerk. Tapping the tendon of the gastrocnemius muscle
Motor neurons in the spinal cord are activated by (1) impulses at the Achilles tendon will contract the gastrocnemius and
from the periphery as part of reflex mechanisms and (2) impulses plantar flex the ankle.
from higher levels (cortical and subcortical) that modify local re-
flex mechanisms. The spinal reflexes discussed below are of clini- B. INVERSE MYOTATIC REFLEX (Figure 3–26)
cal significance. Severe tension in a muscle produced by stretch or contraction
A. MYOTATIC (STRETCH) REFLEX (Figure 3–25) will stimulate nerve endings in its tendon (Golgi tendon organ).
Impulses from Golgi tendon organs travel via Ib nerve fibers. In
Stretching a muscle (by tapping its tendon) will activate the the spinal cord, they project upon inhibitory neurons, which in
muscle spindle of the intrafusal muscle fiber (primary annulospi- turn inhibit alpha motor neurons supplying the muscle under
ral endings). Impulses from the activated muscle spindle will ac- tension (homonymous motor neurons). The result is relaxation
tivate monosynaptically, via Ia fibers, the homonymous (corre- of the muscle (lengthening reaction, autogenic inhibition). At
sponding, ipsilateral) alpha motor neurons in the anterior horn the same time, the Ib activity facilitates motor neurons that sup-
of the spinal cord. Impulses traveling via the axons of such alpha ply the antagonistic muscle.
motor neurons will then reach the stretched skeletal muscle and In reviewing the myotatic and inverse reflexes and their role
result in contraction of the muscle. Ia afferents will also make di- in muscular activity, it becomes evident that there are three con-
rect monosynaptic excitatory connections with alpha motor neu- trolling mechanisms.
rons, which innervate muscles that are synergistic in action to One is a length-controlling mechanism subserved by the an-
the muscle from which the Ia fiber originated. The activity in the nulospiral endings of the intrafusal fiber. This mechanism is sen-
Ia fibers will, in addition, inhibit disynaptically the motor neu- sitive to changes in length and mediates its effects via the Ia
rons that supply the antagonistic muscle (reciprocal inhibition). nerve fibers.
This obviously facilitates contraction of the homonymous muscle. A second is a tension-controlling mechanism subserved by
the Golgi tendon organ. This mechanism is sensitive to tension
in the muscle developed by either stretch or contraction of the
muscle and is mediated via the Ib nerve fibers.
Inhibitory interneuron
Figure 3–25. Schematic diagram of the components of the

stretch reflex. Muscle stretch (1) will activate Ia sensory nerve
fibers (2), which will monosynaptically activate motor neurons.
Axons of activated motor neurons (3) will synapse on skeletal Figure 3–26. Schematic diagram of the components of the in-
muscle fibers and produce contraction. verse myotatic reflex.
64 / CHAPTER 3
A third is a follow-up control system in which extrafusal muscle nerve, (2) parasympathetic supply via the pelvic nerve, and (3) so-
fiber length follows intrafusal muscle fiber length and is medi- matic supply via the pudendal nerve. The sympathetic pregan-
ated through the gamma loop. glionic neurons are in the intermediolateral cell column in the
upper lumbar cord. Preganglionic axons leave the cord via the
C. FLEXOR REFLEX (Figure 3–27) ventral root and synapse in paravertebral and preaortic sympa-
The proper stimulus for eliciting this reflex is a nociceptive or thetic ganglia. Postganglionic fibers travel in the hypogastric
painful one, such as pin prick, or one that inflicts injury or dam- nerve to smooth muscles of bladder wall and internal urethral
age to the skin or deeper tissues. The primary receptors for this sphincter. Parasympathetic preganglionic neurons are in the inter-
reflex are the pain (free nerve endings) receptors, although light mediolateral-like cell column between the second and fourth
touch receptors elicit a weaker and less sustained flexor reflex. sacral segments (S-2 and S-4). Preganglionic axons join the
The purpose of this reflex is withdrawal of the injured part from pelvic splanchnic nerves (nervi erigentes) to terminal (vesical)
the stimulus, thus the reflex is also called the withdrawal reflex. ganglia and innervate smooth muscles in the bladder wall and
From the stimulated receptors, impulses travel by means of internal urethral sphincter. Somatic neurons are motor neurons
group III nerve fibers to the spinal cord, where they establish in the ventral-ventromedial part of the anterior (ventral) horn of
polysynaptic relations (at least three or four interneurons) with a S-2 to S-4 (nucleus of Onufrowicz). Axons travel with the ven-
number of motor neurons. The net effect of this circuitry is tral root, join the pudendal nerve, and innervate the external
twofold: (1) facilitation of ipsilateral flexor motor neurons and urethral sphincter.
(2) inhibition of ipsilateral extensor motor neurons. Afferent impulses from the bladder enter the cord via the
Efferent outflow of the activated motor neurons will effect same three nerves. Sympathetic afferents travel via the hypogas-
contraction of flexor muscles (flexion) and relaxation of antago- tric nerve, enter the cord at the upper lumbar level, and may ex-
nist extensor muscles in the stimulated part of the body. tend rostrally up to the fourth thoracic segment (T-4), but most
D. CROSSED EXTENSION REFLEX (Figure 3–28) are in the upper lumbar and low thoracic levels. Parasympathetic
afferents travel via the pelvic nerves and enter the cord between
This reflex is actually a byproduct of the flexion reflex. The in- S-2 and S-4. Somatic afferents travel via the pudendal nerves and
coming impulses from a nociceptive stimulus will cross in the an- enter the cord at S-2 to S-4 levels.
terior commissure of the spinal cord and establish multisynaptic Bladder filling is associated with tonic activity in the sympa-
relationships with both flexor and extensor motor neurons. Their thetic neurons and Onuf ’s nucleus. The former results in relax-
effect on these motor neurons, however, is the reverse of that de- ation of the detrusor muscle directly and indirectly (by inhibit-
scribed ipsilaterally: (1) facilitation of extensor motor neurons ing parasympathetic ganglion cells in the vesical wall) and in
and (2) inhibition of flexor motor neurons. As a result, the limb contraction of the internal urethral sphincter. The latter results
contralateral to the stimulated part of the body will be extended. in contraction of the external sphincter.
Thus, in response to a nociceptive stimulus, the ipsilateral Bladder emptying (micturition) is associated with inhibition
limb will flex and the contralateral limb will extend in prepara- of sympathetic outflow, activation of parasympathetic outflow
tion for withdrawal. Very strong nociceptive stimuli will spread (contraction of detrusor muscle), and inhibition of Onuf ’s nu-
activity in the spinal cord through intersegmental reflexes to in- cleus (relaxation of external sphincter).
volve all four extremities. In response to a stimulus applied to Table 3–8 is a summary of the effects of the sympathetic,
one extremity (hindlimb), a spinal cat will withdraw the stimu- parasympathetic, and somatic (Onuf ’s) neurons on detrusor
lated limb, extend the opposite hindlimb and ipsilateral fore- muscle, internal sphincter, vesical ganglion cells, and external
limb, and flex the contralateral forelimb. sphincter.
Descending pathways for micturition travel in the lateral fu-
Micturition Pathway and Bladder Control niculus just ventral to the denticulate ligament and lateral corti-
cospinal tract. They play a role in starting and stopping micturi-
The urinary bladder receives efferent innervation from tion and in inhibiting the independent reflex activity of the
three sources: (1) sympathetic supply via the hypogastric sacral bladder center. The role of the corticospinal tracts in con-
Figure 3–27. Schematic diagram of the

components of the flexor reflex.
SPINAL CORD / 65
Figure 3–28. Schematic diagram of the components of the crossed extensor reflex.
trolling the external sphincter and bladder contractions remains M-region). Another pontine area (L-region), ventral and lateral
uncertain. In motor neuron disease (amyotrophic lateral sclero- to the Barrington area, was found to project to Onuf ’s nucleus
sis), patients retain bladder control until very late in the disease (nucleus of Onufrowicz). This area is important during the fill-
despite the degeneration in the corticospinal tract. Furthermore, ing phase of the bladder and is called the pontine continence
the nucleus of Onufrowicz (Onuf ’s nucleus) is spared in motor center.
neuron disease. Information about degree of bladder filling is conveyed by the
Ascending pathways related to micturition also travel in the hypogastric (sympathetic) and pelvic (parasympathetic) nerves
lateral funiculus ventral to the denticulate ligament, in the re- (primary afferents) to autonomic (sympathetic and parasympa-
gion of the spinothalamic tract. They play a role in the conscious thetic) neurons in the lumbosacral spinal cord, which in turn
appreciation of the desire to micturate. send secondary afferents that travel in the lateral funiculus and
Although the motor neuronal cell groups of bladder and lateral brain stem tegmentum to the periaqueductal gray area in
sphincter are located in the spinal cord, the coordination of the midbrain (mesencephalon). When the bladder is filled to a
urine storage and voiding takes place in the pons. This brain degree that voiding is appropriate, the periaqueductal gray area
stem coordination is best seen in patients with spinal cord injury activates neurons in the pontine micturition center (Barrington
above the sacral level. Such patients have great difficulty empty- nucleus), which in turn excites the sacral (S-2 to S-4) pregan-
ing the bladder, because when the bladder contracts, the urethral glionic parasympathetic neurons and simultaneously inhibits (via
sphincter also contracts (detrusor–sphincter dyssynergia). Such a GABA-ergic interneurons) Onuf ’s nucleus. The combined effect
disorder never occurs in lesions rostral to the pons. In 1925, on these two nuclear groups (parasympathetic preganglionic and
Barrington showed in the cat that lesions in the dorsolateral pon- Onuf ’s) results in bladder wall contraction, relaxation of external
tine tegmentum result in inability to empty the bladder (urinary urethral sphincter, and bladder emptying (micturition).
retention). Tracing studies in the cat undertaken in 1979 showed Besides the pons and midbrain, the hypothalamus (medial
that the Barrington area in the pons projects to sacral autonomic preoptic area) and the cerebral cortex are involved in micturi-
neurons (parasympathetic bladder motor neurons between S-2 tion. Cortical areas involved in micturition are the right inferior
and S-4). The pontine area described by Barrington is now rec- frontal gyrus and the right anterior cingulate gyrus. Positron
ognized as the pontine micturition center (Barrington nucleus, emission tomography scanning has shown increased blood flow
Table 3–8. Spinal Cord Control of Urinary Bladder.
Neural system Detrusor muscle Internal urethral Vesical External

sphincter parasympathetic sphincter
ganglion cells
Sympathetic (T-11 to L-2)

Parasympathetic (S-2 to S-4)
Somatic (Onuf nucleus) +
(S-2 to S-4)
, facilitatory; , inhibitory.
66 / CHAPTER 3
in the right dorsal pontine tegmentum and the right inferior ious peripheral inputs received, as well as by descending in-
frontal gyrus with micturition. Decreased blood flow was found fluences from the cerebral cortex and subcortical areas. The
in the right anterior cingulate gyrus during urine withholding. sum total of this interaction in the dorsal horn is then medi-
These studies have shown that cortical and pontine micturition ated to motor neurons in lamina IX, to interneurons, or to
sites are more active on the right side than on the left. A schema ascending tracts.
of the segmental and suprasegmental control of micturition is 2. The intermediate zone similarly receives a variety of inputs
shown in Figure 3–29. from the dorsal root and dorsal horn, as well as from cortical
and subcortical areas. The information received here is inte-
FUNCTIONAL OVERVIEW grated and modified before being projected to other zones.
OF THE SPINAL CORD 3. The ventral horn receives inputs from the dorsal root
(monosynaptic reflex connections), the dorsal horn, the in-
The spinal cord is organized into three major functional zones: termediate zone, and the descending tracts. The descending
the dorsal horn, the intermediate zone, and the ventral horn. tracts influence motor neurons either directly or indirectly
1. The dorsal horn receives several varieties of sensory informa- through interneurons in the intermediate zone. They selec-
tion from receptors in the skin surface (exteroceptive), as tively facilitate flexor motor neurons (corticospinal, rubro-
well as from deeper-lying receptors in joints, tendons, and spinal, medial vestibulospinal, and medullary reticulospinal
muscles (interoceptive). Cell characteristics in the dorsal tracts) or extensor motor neurons (lateral vestibulospinal and
horn vary greatly with respect to the extent of their receptive pontine reticulospinal tracts). The output from the ventral
fields and the degree of specificity of the modality received. horn is via either alpha motor neurons to influence striated
Information received from the periphery is not merely re- musculature or gamma motor neurons to influence intra-
layed in the dorsal horn but is modified by virtue of the var- fusal muscle fibers.
NEUROANATOMY OF MICTURITION AND CONTINENCE
HYPOTHALAMUS
Medial Preoptic Area
MIDBRAIN
PAG
+ +
PONS
Pontine Pontine Micturition

Secondary Center
Continence
Afferents Barrington Nucleus
Center
L-Region M-Region
2 1 1
SPINAL CORD (S2 - S4)

+ + +
Onuf's 1 GABAergic Parasympathetic
Nucleus Interneurons Motor Neurons
−
Primary
Afferents 1
Pelvic
Pelvic BLADDER +
Nerve
Nerve
Pudendal 2
Nerve Ext. Urethral Sphincter
+
Figure 3–29. Schema of segmental and supra-
1. Micturition Pathways segmental control of micturition and continence.
2. Continence Pathways + facilitatory; {–} inhibitory; (1) micturition path-
blue lines - Efferent ways; (2) continence pathways. Blue lines, efferent
black lines - Afferent pathways; black lines, afferent pathways.
SPINAL CORD / 67
BLOOD SUPPLY
The spinal cord receives its blood supply from the following
arteries.
1. Subclavian via the following branches: vertebral, as-
cending cervical, inferior thyroid, deep cervical, and supe-
rior intercostal
2. Aorta via the following branches: intercostal and lumbar
arteries
3. Internal iliac via the following branches: iliolumbar and lateral
sacral
Branches of the subclavian artery supply the cervical spinal Figure 3–30. Schematic diagram of segmental blood supply of
cord and the upper two thoracic segments; the rest of the thoracic spinal cord.
spinal cord is supplied by the intercostal arteries. The lumbosacral
cord is supplied by the lumbar, iliolumbar, and lateral sacral arter-
ies. Intercostal arteries supply segmental branches to the spinal Certain segments of the spinal cord are more vulnerable than
cord down to the level of the first lumbar cord segment. The others to a compromise in blood flow. The segments that are par-
largest of these branches, the great ventral radicular artery, enters ticularly vulnerable are T-1 to T-4 and L-1. These are regions of
the spinal cord between the eighth thoracic and fourth lumbar the spinal cord that derive their blood supply from two different
cord segments. This large artery, also known as the arteria radicu- sources. At the level of T-1 to T-4, for example, the anterior
laris magna or artery of Adamkiewicz, usually arises on the left side spinal artery becomes small, and its sulcal branches are not ade-
and may be responsible for most of the arterial blood supply of quate to provide the necessary blood supply. These segments are
the lower half of the spinal cord in some people. dependent for their blood supply on the radicular branches of
The vertebral arteries give rise to anterior and posterior spinal the intercostal arteries. If one or more of the intercostal vessels
arteries in the cranial cavity. The two anterior spinal arteries are compromised, the T-1 to T-4 spinal segments could not be
unite to form a single anterior spinal artery that descends in the supplied adequately by the small sulcal branches of the anterior
anterior median fissure of the spinal cord. The posterior spinal spinal artery. As a result, a segment or several segments affected
arteries, smaller than the anterior, remain paired and descend in would be damaged.
the posterolateral sulci of the spinal cord. All other arteries send Venous drainage of the spinal cord corresponds to the arterial
branches that enter the intervertebral foramina, penetrate the supply with the following differences:
dural sheath, and divide into anterior and posterior branches
(radicular arteries) that accompany the anterior and posterior 1. The venous network is denser on the posterior side of the
nerve roots. These radicular arteries contribute to the three ma- cord compared with the arterial network, which is more
jor spinal cord arteries: the anterior spinal and the paired poste- dense anteriorly.
rior spinal arteries. Since most of the radicular arteries contribut- 2. There is only one posterior spinal vein.
ing to the anterior spinal artery are small, blood supply is mainly 3. Anastomoses between the anterior and posterior spinal veins
dependent on the 4 to 10 of these that are large, of which one or are more frequent than between the arteries.
two are located in the cervical region usually at C-6, one or two 4. The territorial drainage from the anterior two-thirds of the
in the upper thoracic region, and one to three in the inferior tho- spinal cord by the anterior spinal vein and from the posterior
racic and lumbosacral region, one of which form the artery of one-third by the posterior spinal vein is generally maintained
Adamkiewicz. In contrast, the posterior spinal arteries receive but not immutable.
from 10 to 20 well-developed radicular arteries. In the lum-
bosacral cord, the posterior radicular arteries are vestigial and of 5. Venous tributaries within and around the spinal cord are
no clinical significance. Anastomoses between the anterior and much more numerous than arterial tributaries, so venous ob-
posterior spinal arteries occur caudally around the cauda equina. struction rarely damages the spinal cord. From the perispinal
There are very few anastomoses at each segmental level. venous network, blood drains into anterior and posterior
The anterior spinal artery gives off a sulcal branch in the an- radicular veins and then into dense longitudinal vertebral
terior median fissure. This branch turns either right or left to en- plexuses located posteriorly and anteriorly in the epidural
ter the spinal cord; only in the lumbar and sacral cords are there space. Blood then reaches the external vertebral venous plexus
both right and left branches. The sulcal arteries are most numer- through the intervertebral and sacral foramina.
ous in the lumbar region and fewest in the thoracic region. Sulcal
arteries supply the anterior and intermediolateral gray horns, the TERMINOLOGY
central gray matter, and Clarke’s column, that is, all the gray
matter except the dorsal horn. They also supply the bulk of the Afferent (Latin afferre, “to carry to”). Conveying impulses in-
white matter of the anterior and lateral funiculi. Thus the ante- ward to a part or organ. Toward the spinal cord.
rior two-thirds of the spinal cord is fed from the anterior spinal Arachnoid (Greek arachne, “like a cobweb, spider’s web”).
artery; the remaining third, including the posterior funiculus The middle layer of the meninges between the outer dura and
and posterior horn, is supplied by the two posterior spinal arter- inner pia. Attached to the pia by a spider web–like delicate net-
ies. The outer rim of the spinal cord is supplied by coronal work of fibers.
branches that arise from the anterior spinal artery, pass laterally Autonomic (Greek autos, “self ”; nomos, “law”). Self-govern-
around the cord, and form imperfect anastomoses with the posing. The part of the nervous system concerned with visceral (in-
terior spinal artery branches (Figure 3–30). voluntary) processes.
68 / CHAPTER 3
Axon (Greek axon, “axis”). The process of the nerve cell that Ipsilateral (Latin ipse, “self ”; latus, “side”). Pertaining or pro-
transmits impulses away from the nerve cell. jecting to the same side.
Babinski, Josef-François-Felix (1857–1932). French neurolo- Kinesthesia (Greek kinesis, “motion”; aisthesis, “sensation”).
gist who described the Babinski sign in 1896 as the “phenome- Sense of perception of movement.
non of the toes.” The sign or components of it were noted earlier Lamina (Latin “thin layer”). As in column of nerve cells in
by Marshall Hall and Remak, but Babinski is credited with in- Rexed laminae.
vestigating the phenomenon in depth, principally to differenti- Lesions (Latin laesia, laedere, “to hurt or injure”). Morbid
ate organic from hysterical weakness. Babinski regarded his work changes in tissue due to disease or injury.
on spinal cord compression (not the “phenomenon of the toes”)
to be his best. Meninges (Greek plural of meninx, “membrane”). The mem-
branes covering the spinal cord and brain.
Burdach column. Cuneate tract, described in 1819 by Karl
Frederich Burdach, German anatomist and physiologist. Myotatic (Greek myo, “muscle”; teinein, “to stretch”).
Performed or induced by stretching or extending muscle.
Cauda equina (Latin “horse’s tail”). Bundle of lumbosacral
Nociceptive (Latin noceo, “to injure”; capio, “to take”).
nerve roots beyond the tip of the spinal cord that forms a cluster
Responds to painful injurious stimuli.
in the spinal canal that resembles the tail of a horse.
Nucleus (Latin nux, “a nut”). Aggregation of nerve cells con-
Caudal (Latin “tail”). Pertaining to cauda, toward the tail or
cerned with a particular function.
posterior end.
Paralysis (Greek paralusis, “to disable”). Loss of voluntary
Clarke’s column. After Jacob Clarke, English anatomist and movement.
neurologist who described the nucleus dorsalis in 1851.
Pia mater (Latin “soft, tender mother”). The thin, delicate in-
Commissure (Latin “joining together”). Axons that connect nermost meningeal layer.
the two halves of the spinal cord or the two cerebral hemispheres.
Proprioception (Latin proprius, “one’s own”; perception,
Contralateral (Latin contra, “opposite”; latus, “side”). Per- “perception”). The sense of position and movement.
taining to or projecting to the opposite side.
Receptor (Latin recipere, “to receive”). The sensory nerve end-
Cordotomy. Sectioning of the lateral spinothalamic tract for re- ing or sensory organ that receives sensory stimuli.
lief of intractable pain. The procedure was introduced by Spiller
in 1910. Since then the technique has been modified and im- Rubro (Latin ruber, “red”). Rubrospinal tract originates from
proved. Percutaneous and open cordotomies continue to be used the red nucleus.
to relieve pain in the contralateral side. Somatic (Greek somatikos, “of the body”). Pertaining to body
Cuneatus (Latin “wedge”). The fasciculus cuneatus is so named as distinct from visceral; pertaining to viscera. Includes neurons
because of its wedge shape and because it is short. and neural processes related to skin, muscles, and joints.
Decussation (Latin decussare, “to cross like an X”). X-shaped Spinal cat. An experimental cat preparation in which the spinal
crossing of nerve fiber tracts in the midline, as in pyramidal cord is disconnected from the brain stem and cerebral cortex.
decussation. Stilling nucleus (column). Described by Benedict Stilling (1810–
Dendrite (Latin dendron, “a tree”). The numerous processes of 1879), a German anatomist and surgeon who reported that it ex-
a nerve cell that branch like a tree and that transmit impulses to- tended from C-8 to L-3, L-4. Stilling published detailed accounts
ward the nerve cell. of the anatomy of the spinal cord, medulla, and pons, including
the solitary tract in the medulla. In his detailed anatomic studies,
Denticulate (Latin denticulus, “a small tooth”). The toothlike he used serial tissue sections in three dimensions using the micro-
lateral projections of the pia mater in the spinal cord. tome, which he introduced in 1824. Stilling also described and dif-
Dorsal (Latin dorsalis, from dorsum, “back”). Pertaining to or ferentiated almost all the cranial nerve nuclei recognized today.
situated near the back of an animal. Sulcus (Latin “groove”). As in posterolateral and anterolateral
Dura mater (Latin “hard mother”). The thick and hard outer- sulci of the spinal cord.
most layer of the meninges, so named because the Arabs believed Sympathetic (Greek sympathein, “self-responsive”). Sympa-
the meninges were the “mother” of all body tissues. thetic division of the autonomic nervous system.
Exteroceptive (Latin “to take outside”). To receive from out- Synapse (Greek synapsis, “contact”). Site of contact between
side. Exteroceptive receptors receive impulses from the outside. processes of nerve cells (axon to axon, axon to dendrite), between
Fasciculus (Latin “a small bundle”). Small bundle of nerve neural process and nerve cell, or between neural process and
fibers forming a tract, with a common origin and termination. muscle.
Funiculus (Latin funis, “cord”). A bundle of white matter con- Syndrome (Greek syndromos, “running together”). A group
taining one or more fasciculi (tracts). of symptoms and signs that characterize a disease.
Ganglion (Greek “swelling, knot”). A collection of nerve cells Syringomyelia (Greek syrinx, “a tube”; myelos, “marrow”).
outside the central nervous system, as in dorsal root ganglia or Tubelike cavitation within the spinal cord.
autonomic ganglia. Tactile (Latin tactilis, “touching”). Pertaining to touch.
Gracilis (Latin “slender, thin”). The fasciculus gracilis is so Tract of Goll. Gracile tract, described in 1860 by the Swiss
named because it is slender and long. anatomist and neurologist, Goll.
Inhibition (Latin inhibere, “to restrain or check”). Arrest or Türck, Ludwig (1810–1868). Austrian anatomist who de-
restraint of a process. scribed the anterior corticospinal tract in 1849. Other contribu-
Interoceptive. Internal surface field of distribution of receptor tions include description of the corticopontine fiber tract and
organs. the principle that nerve fiber degeneration occurs in the direc-
SPINAL CORD / 69
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Clinical Correlates of Spinal 4

Cord Anatomy
Clinically Important Spinal Cord Structures Anterior Horn and Lateral Corticospinal Tract Syndrome
Motor Signs of Spinal Cord Disorders (Motor Neuron Disease)
Sensory Signs of Spinal Cord Disorders Lesions around Central Canal (Syringomyelia)
Dorsal (Posterior) Column Signs Combined System Degeneration Syndrome
Lateral Spinothalamic Tract Signs Anterior Spinal Artery Syndrome
Sacral Sparing Transection
Dorsal Root Signs Conus Medullaris Syndrome
Anterior White Commissure Signs Cauda Equina Syndrome
Spinal Cord Syndromes Autonomic Syndromes
Segmental Lower Motor Neuron Syndrome
Hemisection (Brown-Séquard Syndrome)
KEY CONCEPTS
Lesions in the thoracolumbar autonomic (sympathetic) Spinal cord lesions around the central canal characteris-
neurons at or above T-2 result in ipsilateral Horner’s tically present early with bilateral segmental pain and
syndrome. thermal sensory loss.
Lesions in the sacral autonomic (parasympathetic) neurons Ascending and descending tracts in the posterior and lat-
between S-2 and S-4 result in bladder and bowel dysfunction. eral funiculi are affected in Vitamin B12 deficiency states
as well as in a hereditary progressive disorder, Friedreich’s
Lesions of the dorsal (posterior) column result in ipsilat-
ataxia.
eral loss of kinesthesia and discriminative touch at and
below the level of spinal cord lesion. The anterior two-thirds of the spinal cord is characteristi-
cally preferentially involved in ischemic lesions.
Lesions of the lateral spinothalamic tract result in con-
tralateral loss of pain and temperature sensations begin- Lesions of the conus medullaris are characterized by early
ning in dermatomes one or two segments below the spinal sphincter dysfunction and saddle anesthesia.
cord lesion.
Lesions of the cauda equina manifest with ipsilateral sen-
Sacral sparing helps differentiate intrinsic from extrinsic sory and lower motor neuron–type signs of the affected
cord lesions. nerve roots.
CLINICALLY IMPORTANT SPINAL 2. Ascending tracts (sensory function)

CORD STRUCTURES a. Dorsal (posterior) column (kinesthesia and discrimina-
tive touch)
The following structures (Figure 4–1) are useful in clinical local- b. Lateral spinothalamic tract (pain and temperature)
ization of spinal cord disorders: 3. Neuronal populations
a. Anterior horn cells (somatic motor function)
1. Descending tracts (motor function): Lateral corticospinal b. Intermediolateral cell column (autonomic sympathetic
(pyramidal) tract function)
70
CLINICAL CORRELATES OF SPINAL CORD ANATOMY / 71
Figure 4–1. Schematic diagram of clinically important spinal cord structures and effects of lesions in each.
c. Sacral autonomic neurons (autonomic parasympathetic 3. Autonomic neuron signs

function) a. Intermediolateral (sympathetic) cell column (T-1 to
L-2): Lesions in the intermediolateral cell column at or
MOTOR SIGNS OF SPINAL CORD DISORDERS above T-2 spinal cord segment are associated with the
following conglomerate of signs collectively known as
(Figure 4–1) the Horner’s syndrome: miosis (small pupil), pseudopto-
It is customary to classify motor signs of spinal cord disease into sis (minimal drooping of eyelids), anhidrosis (absence of
upper and lower motor neuron signs: sweating over the face), and enophthalmos (slight retrac-
tion of eyeball)
1. Upper motor neuron signs (lesion of corticospinal tract)
a. Loss (paralysis) or diminution (paresis) of voluntary All these signs occur ipsilateral to the lesion in the spinal cord.
movement Johann Friedrich Horner, a Swiss ophthalmologist, is credited
b. Increase in muscle tone (spasticity) with the first complete description of this syndrome in humans,
c. Hyperreflexia (exaggerated deep tendon [myotatic] reflexes) although Claude Bernard described the same ocular changes in an-
d. Clonus (repetitive involuntary alternating contractions imals 7 years earlier. (The syndrome is also known as the Bernard-
of agonist and antagonist muscle groups in response to Horner syndrome.)
sudden maintained stretching force) b. Sacral autonomic (parasympathetic) neurons (S-2
e. Abnormal superficial plantar reflex (Babinski sign). The to S-4): Lesions in the sacral autonomic area are
Babinski sign, described by the French neurologist associated with urinary incontinence and bowel
Josef-François-Felix Babinski as “the phenomenon of incontinence.
the toes,” consists of dorsiflexion of the hallux and fan-
ning of the toes in response to painful stimulation of
the sole of the foot. SENSORY SIGNS OF SPINAL
All these signs occur ipsilateral and below the level of the spinal CORD DISORDERS
cord lesion.
Dorsal (Posterior) Column Signs
2. Lower motor neuron signs (lesion of anterior horn cells) (Figures 4–1 and 4–2)
a. Loss (paralysis) or diminution (paresis) of voluntary
movement Lesions in the dorsal column are usually associated with diminu-
b. Decrease in muscle tone (hypotonia) tion or loss of
c. Hyporeflexia (decrease) or areflexia (absence) of deep 1. Vibration sense
tendon (myotatic) reflexes
d. Fibrillations and/or fasciculations (spontaneous activity 2. Position sense
of muscle fibers at rest) 3. Two-point discrimination
e. Muscle atrophy 4. Deep touch
All these signs occur ipsilateral and in muscles (myotomes) sup- All these signs occur ipsilateral to the affected posterior column
plied by the affected motor neurons. in dermatomes at and below the level of the spinal cord lesion.
72 / CHAPTER 4
T-10 T-8
Left Right Left
Right Left g Left
Figure 4–2. Schematic diagram showing the pattern of sen- Figure 4–3. Schematic diagram showing the pattern of sen-
sory deficit resulting from a lesion in the posterior column. sory deficit resulting from a lesion in the lateral funiculus involv-
ing the lateral spinothalamic tract.
Lateral Spinothalamic Tract Signs lateral and in dermatomes supplied by the involved dorsal
(Figures 4–1 and 4–3) root(s).
Lesions affecting the lateral spinothalamic tract are asso- Anterior White Commissure Signs (Figure 4–5)
ciated with diminution or loss of
Lesions in the anterior white commissure are associated with
1. Pain sensations
bilateral diminution or loss of pain and temperature (sensory
2. Temperature sensations modalities that cross in the anterior white commissure) sen-
Deficits in pain and temperature sensations occur contralateral to sations in dermatomes supplied by the involved spinal cord seg-
the affected tract in dermatomes beginning one or two segments ments. Although fibers carrying light touch also travel in the
below the level of the spinal cord lesions. anterior white commissure, no deficit in light touch occurs be-
cause this sensory modality is also represented in the posterior
Sacral Sparing column.
Because of the pattern of lamination of nerve fibers in the spino- SPINAL CORD SYNDROMES
thalamic tract (sacral fibers lateral, cervical fibers medial), extrinsic
cord lesions (such as a tumor in the meninges that compresses the The following clinicopathologic syndromes are encountered in
spinal cord from the outside) will affect sacral fibers early, clinical practice.
whereas intrinsic spinal cord lesions (such as a tumor aris-
ing within the spinal cord) will affect cervical fibers early Segmental Lower Motor Neuron Syndrome
and sacral fibers late or not at all (sacral sparing). (Figure 4–6)
Dorsal Root Signs (Figure 4–4) Lesions of spinal motor neurons in the anterior horn are associ-
ated with a lower motor neuron syndrome (paralysis, hypotonia,
Lesions affecting one or more dorsal roots are associated with areflexia, muscle atrophy, fasciculations) ipsilateral to the cord
diminution or loss of all sensory modalities (anesthesia) ipsi- lesion and in muscles (myotomes) supplied by the affected spinal
T-10 T-8
Right Left Right Left
Right Left
Right Left
Figure 4–4. Schematic diagram showing the distribution of Figure 4–5. Schematic diagram showing the distribution
sensory deficit resulting from a lesion in the dorsal root. of sensory deficit resulting from a lesion in the anterior white
commissure.
cord segments. This syndrome is commonly seen in the disease c. Ventral horn signs. The following lower motor neuron
poliomyelitis. signs are found in muscles (myotomes) supplied by the
affected spinal cord segment(s):
Hemisection (Brown-Séquard Syndrome) (1) Muscle paralysis
(Figure 4–7) (2) Muscle atrophy
This syndrome is named after the neurologist Charles Edouard

Brown-Séquard, who first described the syndrome. The follow-
ing signs will be detected in hemisection of the spinal cord. The
nuclear groups or tracts giving rise to these signs are listed.
1. Ipsilateral signs. Signs ipsilateral to the spinal cord lesion are
a. Corticospinal tract signs. The following upper motor neu-
ron signs occur at and below the level of the hemisection:
(1) Muscle paralysis
(2) Spasticity
(3) Hyperactive myotatic reflexes
(4) Babinski sign
(5) Clonus
b. Posterior column signs. These include loss of the fol-
lowing sensations at and below the level of the hemi-
section:
(1) Vibration
(2) Position Figure 4–6. Schematic diagram showing the site of the lesion
(3) Two-point discrimination in segmental lower motor neuron syndrome and associated
(4) Deep touch neurologic signs.
74 / CHAPTER 4
Figure 4–7. Schematic diagram showing the

site of the lesion in spinal cord hemisection and
associated neurologic signs.
(3) Loss of myotatic reflexes horn and the lateral corticospinal tract bilaterally. It is thus
(4) Fibrillations and fasciculations manifested by a combination of lower and upper motor neuron
(5) Hypotonia signs, including paralysis, muscular atrophy, fasciculation and
2. Contralateral signs. Signs contralateral to the spinal cord le- fibrillation, exaggerated myotatic reflexes, and a Babinski sign.
sion are lateral spinothalamic tract signs. Loss of pain and This is a progressive condition that involves the spinal cord as
thermal sense in the contralateral half of the body in der- well as motor nuclei of cranial nerves in the brain stem. For un-
matomes beginning one or two segments below the level of explained reasons, motor neurons in the brain stem controlling
hemisection. eye movements and sacral neurons controlling sphincter func-
3. Bilateral signs. Segmental loss of pain and thermal sense in tion are usually spared. Life expectancy is usually three to five
dermatomes one or two segments below the level of the hemi- years after onset.
section due to interruption of spinothalamic fibers crossing
in the anterior white commissure.
Lesions Around Central Canal (Syringomyelia)
(Figure 4–9)
Anterior Horn and Lateral Corticospinal Tract
Syndrome (Motor Neuron Disease) (Figure 4–8) Lesions in or around the central canal will encroach initially on
the fibers conveying pain and temperature in the anterior white
This syndrome is known clinically as motor neuron disease or commissure. The effect of such encroachment will be
amyotrophic lateral sclerosis. This disorder is also known as Lou segmental and bilateral loss of temperature and pain
Gehrig’s disease. It is a degenerative disease affecting the anterior sensations in the corresponding dermatomes. Such a
Figure 4–8. Schematic diagram showing the spinal

cord structures involved in motor neuron disease and
associated neurologic signs.
Anterior Spinal Artery Syndrome (Figure 4–11)

This syndrome is due to occlusion of the anterior spinal
artery that supplies the anterior two-thirds of the spinal
cord. The syndrome is characterized by abrupt onset
of symptoms and signs. Flaccid (lower motor neuron) paralysis
(spinal shock) occurs within minutes or hours below the level of
the lesion and is associated with impaired bowel and bladder func-
tions. Dissociated sensory loss characterized by loss of pain and
temperature sensations (lateral spinothalamic tract lesion) and
preservation of kinesthesia and discriminative touch sensations
(sparing of posterior column) occurs below the level of the spinal
cord lesion. With time, upper motor neuron signs predominate
(withdrawal of supraspinal inhibition). Some patients develop
painful dysesthesia about 6 to 8 months after onset of neurologic
symptoms. This is attributed either to sparing of spinoreticulo-
thalamic tract or to alteration of central nervous system interpre-
tation of sensory input as a result of the imbalance produced by
an intact posterior column and impaired lateral spinothalamic
sensory input.
Figure 4–9. Schematic diagram showing the site of the lesion
in syringomyelia and associated neurologic signs. Transection
The following signs will be detected in transection of the spinal
cord, as occurs in transverse myelitis due to a demyelinating lesion
lesion is characteristic of the clinical condition known as as in multiple sclerosis or to trauma, inflammation, or ischemia.
syringomyelia. This type of lesion usually affects the cervical
spinal segments but may affect other segments of the spinal cord A. SPINAL SHOCK
as well. In some patients, the lesion (syrinx) may extend to the Complete transection of the spinal cord results in disturbances of
brain stem (syringobulbia). In most instances, the original lesion motor, sensory, and autonomic functions. The manifestations of
may progress to involve, in addition to the anterior white com- such a lesion in the immediate and early stages (2 to 3 weeks)
missure, the anterior, lateral, and/or posterior columns of the differ from those in later stages.
spinal cord, with symptoms and signs corresponding to the af- 1. Motor manifestations. In the immediate and early stages fol-
fected structures. lowing transection, there is flaccid and bilateral paralysis of
all muscles (myotomes) innervated by segments of the spinal
Combined System Degeneration Syndrome cord affected by the transection, as well as those myotomes
below the level of the transection. The flaccid paralysis of
In this syndrome, there is bilateral but selective degener- muscles below the level of the lesion, however, will change
ation of some of the posterior and lateral column tracts into the spastic (upper motor neuron) variety in later stages.
with loss of kinesthesia and discriminative touch, as well Flaccid paralysis of muscles innervated by the affected spinal
as upper motor neuron signs (Figure 4–10). It is seen in patients cord segments is attributed to injury of motor neurons in the
with pernicious anemia (vitamin B12 deficiency). In a hereditary anterior horn or their ventral roots. The early flaccid paralysis
form of this syndrome, known as Friedreich’s ataxia (after the below the level of the lesion is attributed to the sudden with-
German pathologist Nikolaus Friedreich, who described the drawal of a predominantly facilitating or excitatory influence
condition), the spinocerebellar tracts are also involved bilaterally from supraspinal centers. The spastic type of paralysis that
in the degenerative process. follows later is attributed to release of segmental reflexes below

the affected spinal cord tracts in combined
system degeneration and associated neuro-
logic signs.
76 / CHAPTER 4
Figure 4–11. Schematic diagram showing the extent of the spinal cord lesion in the anterior spinal artery
syndrome and associated neurologic signs.
the level of the lesion from supraspinal inhibitory influences. addition, constipation and impairments in erection and ejacula-
This spastic paralysis results in the development of flexor tion occur. Symmetric loss of sacral sensations (saddle anesthe-
spasms that eventually change into extensor spasms. During sia) along the distribution of S-2 to S-4 dermatomes is found.
the stage of flexor spasm, the patient’s paralyzed limbs are Pain is unusual, but dull aching pain may occur over the region
kept in almost permanent hip and knee flexion (paraplegia- of the tumor. Usually there is no motor deficit until S-1 and L-
in-flexion). In the extension spasm stage, the limbs are kept 5 roots are involved. Loss of ankle jerk may then be the early
extended at the knee and ankle (paraplegia-in-extension). sign.
Experience with war victims has shown that paraplegia-in-
flexion occurs in complete (whole segment[s]) cord transec-
tion, whereas paraplegia-in-extension occurs in incomplete
Cauda Equina Syndrome
(partial) cord lesion. Lesions of the cauda equina give rise to symptoms and signs re-
2. Sensory manifestations. All sensations are lost bilaterally at lated to the affected nerve roots. In general, there is early occur-
and below the level of the transection. In addition, there is a rence of radicular pain in dermatomes supplied by the affected
hyperpathic zone at the border of the lesion and for one or roots. Lower motor neuron–type paresis or paralysis oc-
two dermatomes above it. In this hyperpathic zone, the pa- curs in muscles supplied by the affected nerves. In high
tient complains of pain of a burning character. cauda equina lesions, for example, affecting the L-2 to
3. Bladder function. In the immediate and early stages following L-4 nerves, on the right side, the patient will have ipsilateral
transection, all volitional or reflex functions of the urinary wasting and weakness of quadriceps and adductor thigh muscles
bladder are lost, resulting in urinary retention. This may last and absent knee jerk. Sensory loss will be evident in L-2 to L-4
from 8 days to 8 weeks. Subsequently, a state of automatic dermatomes. If the tumor compresses the spinal cord, upper mo-
bladder emptying develops. In this state, once a sufficient tor neuron–type signs will be present. For example, in L-2 to L-
degree of bladder distension occurs, sensory receptors in the 4 tumor, there will be ipsilateral Babinski sign, ankle clonus, and
bladder wall evoke reflex contraction of the detrusor muscle, weakness of dorsiflexion of foot. Sphincter disturbances are usu-
thus emptying the bladder. ally late occurrences in cauda equina lesions.
4. Bowel function. Similar to bladder function, the immediate Clinical differentiation between lesions of the conus medullaris
and early effect of cord transection is paralysis of bowel func- and cauda equina is often difficult. In general, however, lesions
tion and fecal retention. This is changed in later stages to in- of the conus medullaris are associated with early sphincter dis-
termittent automatic reflex defecation. turbance and symmetric loss of sacral sensations. Pain is unusual
in conus lesions. In contrast, cauda equina lesions are associated
5. Sexual function. Erection and ejaculatory functions are lost in with early radicular pain and late sphincter disturbance.
males in the immediate and early stages. Later on, reflex erec-
tion and ejaculation appear as a component of the automatic
activity of the isolated cord and are evoked by extrinsic and in- Autonomic Syndromes
trinsic stimuli. In the female, there may be temporary cessa-
tion of menstruation and irregularities in the menstrual cycle. A. RESPIRATORY DYSFUNCTION
Three patterns of respiratory insufficiency may occur in spinal
Conus Medullaris Syndrome cord lesions. The first is reduction in respiratory vital capacity
due to weakness of the diaphragm and intercostal muscles as a
Lesions of the conus (usually tumors) are characterized by early result of interruption of the descending motor pathways. The
sphincter dysfunction, urinary incontinence, loss of vol- second is reduction in CO2 responsivity without reduction in vi-
untary emptying of the bladder, increased residual urine tal capacity and without overt weakness of the diaphragm or
volume, and absent sensation of the urge to urinate. In chest wall muscles. The basis of this phenomenon is presumed to
be interruption of ascending ventrolateral quadrant nerve fibers, Horner’s syndrome. Drooping of the eyelid (ptosis), constric-
which augment the response of the respiratory center to CO2. tion of the pupil (miosis), retraction of the eyeball (enophthal-
The third is a combination of the preceding two syndromes, mos), and loss of sweating on the face (anhidrosis) comprise a
namely, reduced vital capacity from muscle weakness as well as syndrome described by Johann Friedrich Horner, Swiss ophthal-
reduced responsivity to CO2. This deficit may indicate interrup- mologist, in 1869. The syndrome is due to interruption of de-
tion of both ascending and descending pathways. scending sympathetic fibers. The syndrome was described in
animals by Francois du Petit in 1727. Claude Bernard in France
B. AUTONOMIC RESPIRATORY DYSFUNCTION SYNDROME in 1862, and E. S. Hare in England in 1838 gave precise ac-
Interruption of the ventrolateral white matter of the cervical re- counts of the syndrome before Horner.
gion causes a distinct autonomic respiratory dysfunction syn- Hyperpathic (Greek hyper, “above or excessive”; pathia, “pain”).
drome. The full syndrome consists of (1) respiratory arrest or Abnormally exaggerated subjective response to painful stimuli.
sleep apnea (core sign) and variable onset of one or more of the
Hypohidrosis (Greek hypo, “below”; hidros, “sweat”). Decreased
following: (2) hypotension, (3) hyponatremia, (4) inappropriate
sweating, as seen in the face in those with Horner’s syndrome.
antidiuretic hormone secretion, (5) hypohidrosis, and (6) uri-
nary retention. The syndrome may appear suddenly or within Inappropriate antidiuretic hormone secretion. Excessive secre-
hours following cordotomy. It may last days to weeks. tion of antidiuretic hormone (ADH) by the posterior pituitary
gland leading to excessive urine output, and hyponatremia asso-
C. AUTONOMIC DYSFUNCTION SYNDROME ciated with serum hypoosmolarity and urine hyperosmolarity.
This is an episodic autonomic dysreflexia syndrome seen in the Kinesthesia (Greek kinesis, “motion”; aisthesis, “sensation”).
chronic stages after cord section rostral to T-5. In this syndrome, Sense of perception of movement.
a specific stimulus (usually distension of bladder or rectum) sets Lou Gehrig. Renowned first base player for the New York Yankees
off excessive sweating (especially rostral to the level of the lesion), from 1923–1939. Had a lifetime batting average of .340 with a
cutaneous flushing, hypertension, pounding headache, and re- record 23 grand slams. Died of amyotrophic lateral sclerosis.
flex bradycardia. Other famous personalities afflicted with the disease include ac-
tor David Niven, senator Jacob Javits, heavyweight boxer Ezzard
TERMINOLOGY Charles, physicist Stephen Hawking, photographer Eliot Porter,
and composer Dmitri Shostakovich.
Amyotrophic lateral sclerosis. Progressive degenerative central Paraplegia (Greek para, “beside”; plege, “stroke”). Paralysis of
nervous system disorder characterized by muscle weakness and the legs.
wasting combined with pyramidal tract signs. The pathology Saddle anesthesia. Sensory deficit in the anal, perianal, and gen-
primarily affects spinal and cranial nerve motor neurons and the ital regions; buttocks; and posterior upper thighs due to a lesion
corticospinal (pyramidal) tract. The condition is also known as in the second to the fourth sacral segments of the spinal cord or
motor neuron disease, Charcot syndrome, progressive muscular their roots.
atrophy, Aran-Duchenne disease, and Lou Gehrig’s disease. Syringobulbia (Greek syrinx, “pipe, tube”; bolbos, “bulb”).
Babinski sign. An upper motor neuron sign consisting of dorsi- Extension of syringomyelic cavity from the spinal cord to the
flexion of the big toe and fanning out of the rest of the toes in re- brain stem.
sponse to stimulation of the sole of the foot. Described in detail Syringomyelia (Greek syrinx, “pipe, tube”; myelos, “marrow”).
by Josef-François-Felix Babinski, French neurologist, in 1896. Longitudinal cystic cavitation within the spinal cord of develop-
Brown-Séquard syndrome. A spinal cord syndrome character- mental or acquired etiology. Clinical signs were described by Sir
ized by ipsilateral loss of pyramidal and posterior column signs William Withey Gull, English physician, in 1862. The term was
and contralateral spinothalamic signs, due to cord hemisection. introduced by Hans Chiari, Austrian pathologist in 1888.
Described by Charles Edouard Brown-Séquard, Eurasian and Syrinx (Greek syrinx, “pipe, tube”). Fluid-filled space longitu-
Irish American neurologist, in 1850. dinal cavitation of the spinal cord or brain stem of developmen-
Clonus (Greek klonos, “turmoil”). Repetitive involuntary con- tal or acquired etiology.
tractions of agonist and antagonist muscles in response to stretch.
A sign of upper motor neuron disease.
Fasciculations. Local, spontaneous, contraction of a group of
SUGGESTED READINGS
muscle fibers, usually visible under the skin due to denervation. The Biller J, Brazis PW: The localization of lesions affecting the spinal cord. In
term was introduced by Derek Denny Brown, English neurologist. Brazis PW, et al (eds): Localization in Clinical Neurology. Boston, Little,
Brown, 1985:63.
Fibrillations. Spontaneous contraction of a single muscle fiber
not visible by the naked eye but recorded by electromyography. Guttman L: Clinical symptomology of spinal cord lesions. In Vinken RJ,
Bruyn GW (eds): Handbook of Clinical Neurology, vol 2. Amsterdam,
A sign of denervation. North-Holland, 1978:178.
Friedreich’s ataxia. Progressive hereditary degenerative central Nathan PW et al: Sensory effects in man of lesions of the posterior columns
nervous system disorder characterized by combination of poste- and of some other afferent pathways. Brain 1986; 109:1003–1041.
rior column, lateral corticospinal, and spinocerebellar tracts signs. Triggs WJ, Beric A: Sensory abnormalities and dysaesthesias in the anterior
Described by Nikolaus Friedreich, German pathologist in 1863. spinal artery syndrome. Brain 1991; 115:189–198.
Medulla Oblongata 5
Gross Topography Vagus Nerve (Cranial Nerve X)

Ventral (Anterior) Surface Glossopharyngeal Nerve (Cranial Nerve IX)
Dorsal (Posterior) Surface Vestibulocochlear Nerve (Cranial Nerve VIII)
Fourth Ventricle Nucleus Solitarius
Internal Structure The Medulla and Cardiovascular Control
Level of Motor (Pyramidal) Decussation The Medulla and Respiratory Function
Level of Sensory (Lemniscal) Decussation Neurogenic Pulmonary Edema
Area Postrema The Medulla and Sneezing
Level of Inferior Olive The Medulla and Swallowing
Medullary Reticular Formation Neuroanatomy of Vomiting
Inferior Cerebellar Peduncle (Restiform Body) Neuroanatomy of Yawning
Cranial Nerve Nuclei of the Medulla Neurotransmitters and Neuropeptides
Hypoglossal Nerve (Cranial Nerve XII) Blood Supply of the Medulla
Accessory Nerve (Cranial Nerve XI)
KEY CONCEPTS
The ventral surface of the medulla oblongata shows the tralateral body) described in patients with medullary
pyramids, the pyramidal decussation, and the inferior lesions.
olives.
The medial lemniscus conveys dorsal column sensations
The dorsal surface of the medulla shows the clava (gracile (kinesthesia and discriminative touch) to the thalamus.
nucleus), the cuneate tubercle (cuneate nucleus), and
The accessory (lateral) cuneate nucleus is homologous to
the hypoglossal and vagal trigones (surface markings of
the nucleus dorsalis (Clarke’s nucleus) in the spinal cord
the hypoglossal nucleus and dorsal motor nucleus of the
and thus is part of the spinocerebellar system of uncon-
vagus, respectively).
scious proprioception.
At the pyramidal decussation, 75 to 90 percent of corti-
The area postrema in the caudal fourth ventricle belongs
cospinal fibers decussate to form the lateral corticospinal
to the group of circumventricular organs devoid of blood-
tract.
brain barrier.
Dorsal column nuclei receive input from the dorsal col-
The inferior olivary complex serves as a relay between
umn (gracile and cuneate tracts) as well as from the cere-
cortical and subcortical areas and the cerebellum.
bral cortex and other suprasegmental sites.
The inferior cerebellar peduncle (restiform body) links the
The output of the dorsal column nuclei projects to the
spinal cord and medulla with the cerebellum.
thalamus via the medial lemniscus.
Lesions of the hypoglossal nucleus or nerve result in ipsilat-
The proximity of the spinal trigeminal nucleus to the
eral tongue atrophy, fasciculations, and weakness.The pro-
spinothalamic tract in the medulla is responsible for
truded tongue deviates toward the weak atrophic side.
the crossed sensory deficit (ipsilateral face and con-
78
MEDULLA OBLONGATA / 79
(continued from previous page) The glossopharyngeal nerve has two motor nuclei (the
nucleus ambiguus and the inferior salivatory nucleus)
Vascular occlusion of the anterior spinal artery in the and two sensory nuclei (the nucleus solitarius and the
medulla produces crossed motor or sensory syndromes spinal trigeminal nucleus).
characterized by ipsilateral tongue paralysis and contra-
Two regions in the medulla are concerned with respira-
lateral loss of kinesthesia and discriminative touch (me-
tory function: dorsal in the nucleus solitarius and ventral
dial lemniscus) and/or the contralateral upper motor neu-
in the nuclei ambiguus and retroambiguus.
ron syndrome (pyramid).
Two regions in the medulla oblongata are linked to swal-
The accessory nerve has two components: the spinal,
lowing: a dorsal region in and near the nucleus solitarius
which supplies the sternocleidomastoid and the upper
and a ventral region around the nucleus ambiguus.
part of the trapezius muscles, and the cranial, which
forms the recurrent laryngeal nerve of the vagus and sup- A vomiting center has been identified in the dorsolat-
plies the intrinsic muscles of the larynx. eral medullary reticular formation, and a chemorecep-
tor trigger zone for vomiting has been identified in the
The vagus nerve has two motor nuclei (the dorsal motor
area postrema.
nucleus and the nucleus ambiguus) and two sensory
nuclei (the nucleus solitarius and the spinal trigeminal The medulla oblongata is divided into four vascular terri-
nucleus). tories: paramedian, olivary, lateral, and dorsal.
GROSS TOPOGRAPHY laterally by the anterolateral (ventrolateral) sulcus, a continua-

tion of the same structure in the spinal cord. Lateral to this sul-
Ventral (Anterior) Surface cus, approximately in the middle of the medulla, are the inferior
olives. Lateral to each olive is the posterolateral (dorsolateral)
The anterior median fissure of the spinal cord continues on the sulcus. Rootlets of the hypoglossal nerve (cranial nerve XII) exit
ventral (anterior) surface of the medulla (Figure 5–1). On each between the pyramids and olives in the anterolateral sulcus.
side of this fissure are the medullary pyramids. These pyramids Rootlets of the accessory (cranial nerve XI), vagus (cranial nerve
carry descending corticospinal fibers from the cerebral cortex to X), and glossopharyngeal (cranial nerve IX) cranial nerves exit
the lateral and anterior corticospinal tracts in the spinal lateral to the olives.
cord and carry corticobulbar fibers to cranial nerve nu-
clei in the brain stem. In the lower part of the medulla, Dorsal (Posterior) Surface
the corticospinal fibers in the pyramid partly cross to the oppo-
site side to form the lateral corticospinal tract. This decussation, The posterior (dorsal) median sulcus and the posterolateral
or crossing, forms the basis for the motor control of one cerebral (dorsolateral) sulcus of the spinal cord continue on the dorsal
hemisphere over the contralateral half of the body and is known surface of the medulla (Figure 5–2). Between these two sur-
as the motor or pyramidal decussation. The pyramids are bounded face landmarks are the rostral prolongations of the gracile and
Pons
Inferior olive Glossopharyngeal nerve
Hypoglossal nerve Vagus nerve
Medulla Accessory nerve Pyramid
Pyramidal decussation
Anterior median sulcus

Anterior lateral sulcus (preolivary)
Figure 5–1. Schematic diagram showing the major structures seen on the ventral surface of the
medulla oblongata.
80 / CHAPTER 5
Pineal body 2. Hypoglossal Trigone. This trigone is a protuberance of the

nucleus of the hypoglossal nerve (cranial nerve XII) into the
Superior colliculus
floor of the fourth ventricle.
Inferior colliculus 3. Vagal Trigone. Lateral to the hypoglossal trigone is a protu-
Midbrain
Trochlear nerve berance of the dorsal motor nucleus of the vagus nerve (cranial
nerve X) into the floor of the fourth ventricle.
Trigonum hypoglossi The pontine part of the floor contains the facial colliculus,
Restiform body Pons which represents the surface markings of the subependymal bundle
of the facial nerve (cranial nerve VII), making a loop around the
Trigonum vagi
nucleus of the abducens nerve (cranial nerve VI).
Clava Between the rostral (pontine) and caudal (medullary) parts of
Medulla the floor of the fourth ventricle is an intermediate zone contain-
Cuneate tubercle
ing the stria medullaris, a fiber bundle which courses laterally.
Tuberculum
culum
lum cinereum
cinereu
cine This is the surface landmark of the arcuatocerebellar bundle of
fibers running from the arcuate nucleus of the medulla oblon-
Posteromedian
edian Posterolateral gata to the cerebellum.
sulcus sulcus
B. ROOF
Posterointermediate Three structures form the roof of the fourth ventricle: the anterior
sulcus
medullary velum, the cerebellum, and the tela choroidea (Figure
Figure 5–2. Schematic diagram showing the major structures 5–4). The tela choroidea is formed by the neural ependyma (the
seen on the dorsal surface of the brain stem. original posterior [inferior] medullary velum) covered by a meso-
dermal pia mater.
From the tela choroidea in the posterior part of the roof of
cuneate tracts and their nuclei. On the dorsal surface of the fourth ventricle, the choroid plexus projects as two vertical and
the medulla, the gracile and cuneate nuclei form protu- two lateral ridges, forming a T-shaped structure with a double
berances known as the clava and cuneate tubercles, re- vertical stem.
spectively. Lateral to the cuneate tubercle, between it and the C. LATERAL BOUNDARIES
posterolateral sulcus, is the tuberculum cinereum, which repre-
sents the surface marking of the spinal nucleus of the trigeminal The lateral boundaries of the fourth ventricle (see Figure 5–3)
nerve (cranial nerve V). are formed from rostral to caudal by the following structures.
1. Brachium Conjunctivum. This structure connects the cere-
Fourth Ventricle bellum and the midbrain.
2. Restiform Body. This structure connects the medulla oblon-
A. FLOOR gata and the cerebellum.
The caudal part of the floor of the fourth ventricle is formed by 3. Clava and Cuneate Tubercles. These are the surface mark-
the dorsal surface of the medulla oblongata (Figure 5–3). The ings of the gracile and cuneate nuclei, respectively.
rostral part of the floor is formed by the pons. The medullary The lateral angles of the fourth ventricle are the lateral recesses.
and pontine parts of the floor form a diamond-shaped struc-
ture. The medullary part of the floor has the following surface
landmarks. INTERNAL STRUCTURE
1. Posterior Median Fissure. This fissure is a continuation of The internal structure of the medulla is best understood when
the posterior median sulcus of the spinal cord. examined at three caudorostral representative levels: the level of
Cerebellum
Anterior
Brachium
medullary velum
conjunctivum
Midbrain
Fourth ventricle
Facial colliculus Choroid plexus

Pons
Restiform
body Pons
Hypoglossal
Fourth ventricle trigone
Clava Medulla Medulla
Cuneate tubercle Vagal Posterior

trigone medullary velum
Figure 5–3. Schematic diagram showing the major structures Figure 5–4. Schematic diagram showing structures that form
seen in the floor of the fourth ventricle. the roof and floor of the fourth ventricle.
motor (pyramidal) decussation, the level of sensory (lemniscal) bears no relationship to the handedness of an individual. The cor-
decussation, and the level of the inferior olive. ticospinal fibers that convey impulses to the neck and upper ex-
tremity musculature cross first. These fibers are separate from and
Level of Motor (Pyramidal) Decussation rostral to those conveying impulses to the lower extremities; they
are also more superficially located and are identified in the lower
The two main distinguishing features of this level (Figure 5–5) medulla in close proximity to the odontoid process of the second
are the pyramidal decussation and the dorsal column nuclei. cervical vertebra. Because of this anatomic location, fractures of
the odontoid process or mass lesions in that location result in
A. PYRAMIDAL DECUSSATION paralysis of the muscles of the upper extremities but may spare the
Although the concept of the control of one side of the body by muscles of the lower extremities. By contrast, paralysis of an ipsi-
the contralateral hemisphere (law of cruciate conduction) has lateral arm and a contralateral leg (hemiplegia cruciata) can result
existed since the time of Hippocrates, the actual crossing of the from a lesion in the lower medulla that injures the crossed fibers to
pyramids was not observed until 1709; it was described in the the arm as well as the uncrossed fibers to the leg (Figure 5–6).
following year. This description was ignored, however, until The pyramidal decussation constitutes the anatomic basis for
Gall and Spurzheim called attention to it in 1810. Many anat- the voluntary motor control of one-half of the body by the oppo-
omists denied the existence of the pyramidal decussation until site cerebral hemisphere. As the pyramidal fibers decussate, the
1835, when Cruveilhier traced the pyramidal bundles to the fibers of the medial longitudinal fasciculus are displaced laterally.
opposite side.
The pyramids contain two types of descending cortical fibers: B. DORSAL COLUMN NUCLEI
corticospinal and corticobulbar. The corticospinal fibers are so- In the dorsal (posterior) column two nuclei appear: the nucleus
matotopically organized. The fibers of the lower extremities are gracilis in the tractus gracilis and the nucleus cuneatus in the trac-
more lateral than are those of the upper extremities. As they de- tus cuneatus. They are collectively referred to as the dorsal col-
scend in the medulla oblongata, corticobulbar fibers leave the umn nuclei. The gracile nucleus appears and disappears caudal to
pyramid to project on the nuclei of cranial nerves. Near the cuneate nucleus. Caudally, both the nuclei and the tracts cap-
the caudal border of the medulla, roughly 75 to 90 per- ping them are seen; rostrally, only the nuclei are seen. The surface
cent of the corticospinal fibers in the pyramid decussate projections of these two nuclei into the dorsal (posterior) surface
to the opposite side to form the lateral corticospinal tract. The of the medulla form the clava and cuneate tubercles.
rest of the corticospinal fibers descend homolaterally to form the The dorsal column nuclei are organized for the spatial origin
anterior corticospinal tract. It has been observed that the left of afferent fibers. Afferent fibers from C-1 to T-7 project to the
pyramid decussates first in 73 percent of humans; this, however, nucleus cuneatus, whereas fibers below T-7 project to the nu-
Cuneate
Gracile
Gracile Nucleus
Tract
Nucleus
Cuneate
Tract
Tract of Spinal
Trigeminal Nucleus
Spinal Trigeminal
Nucleus
Spinocerebellar
Spinothalamic Tracts
Tract
Rootlets of Spinal
Accessory Nerve
Medial
Longitudinal Pyramidal
Fasciculus Decussation
Pyramid
Figure 5–5. Photograph of caudal medulla oblongata at the level of the motor (pyramidal) decussation showing
major structures seen at this level.
82 / CHAPTER 5
Peripheral afferent inputs from cutaneous mechanoreceptors

that are activated by mechanical stimulation (touch, pressure,
vibration, hair movement) in both forelimbs and hind-
limbs are transmitted to the core region of the dorsal
column nuclei by primary afferents in the dorsal col-
umn. From the dorsal column nuclei, this information reaches
the thalamus (ventral posterolateral [VPL] nucleus) via the
medial lemniscus. This primary pathway accounts for roughly
20 percent of the fibers in the dorsal column. Collateral branches
from these primary afferents in the dorsal column synapse on
second-order sensory neurons in the posterior horn of the spinal
cord. The second-order (sensory) neurons then travel in
the spinocervical thalamic tract, synapse on neurons in
the lateral cervical nucleus, and from there join the me-
dial lemniscus to reach the VPL nucleus of the thalamus. The ex-
istence of two pathways by which information from peripheral
mechanoreceptors reaches the thalamus (dorsal column and
spinocervical thalamic tract) explains the preservation of sensa-
tions related to these mechanoreceptors (touch, pressure, vibra-
tion) after a dorsal column lesion.
Proprioceptive pathways from joint (Golgi tendon organ) and
muscle (spindle) receptors convey joint movement and position
sense, respectively, and are more complicated than the cutaneous
mechanoreceptor pathways. Afferents from upper extremity pro-
prioceptors travel in the dorsal column (cuneate tract) and synapse
on relay cells in the cuneate nucleus and from there travel via the
medial lemniscus to the thalamus. Afferents from lower extrem-
ity proprioceptors, in contrast, reach the thalamus via two path-
ways. Those from some joint receptors (rapidly adapting) travel
through the dorsal column (gracile tract) to the dorsal column
nuclei (gracile nucleus) and from there project to the thalamus
via the medial lemniscus. Afferents from muscle spindles and
slowly adapting joint receptors leave the gracile tract and synapse
on cells of the dorsal (Clarke’s) nucleus in the spinal cord. Second-
order neurons then travel via the dorsolateral fasciculus to nu-
cleus of Z, a small collection of cells situated in the medulla in
the most rostral part of the nucleus gracilis. Fibers from this nu-
cleus cross the midline to join the medial lemniscus to reach the
thalamus. The differential channeling of cutaneous and proprio-
Figure 5–6. Schematic diagram of the pattern of motor decus- ceptive information presumably is responsible for the differential
sation to the upper and lower extremity motor neurons showing loss of vibration and position senses in some patients with spinal
how a rostral lesion A can result in bilateral upper extremity paral- cord lesions.
ysis without lower extremity paralysis, whereas a more caudal Descending afferents to the dorsal column nuclei arise mainly
lesion B can result in hemiplegia cruciata. A, arm; T, trunk; L, leg. from the primary somatosensory cortex with contributions from
the secondary somatosensory cortex and the primary motor and
premotor cortices. This input is somatotopically organized so
cleus gracilis. It has been shown in animal experiments that over- that forelimb cortical areas project on the cuneate nucleus and
lapping terminations are more extensive and irregular in the hindlimb cortical areas project on the gracile nucleus. Cortical
gracile nucleus than in the cuneate nucleus, with less au- inputs to the dorsal column nuclei travel via the internal capsule
tonomous terminal representation of individual dorsal roots. and reach the nuclei via the pyramid. They project on inter-
The dorsal column nuclei are not homogeneous cell masses. neurons in the reticular zone. Activation of descending cortical
They contain several different types of nerve cells, and on the basis input generally inhibits, via interneurons, the excitation of relay
of the distribution of these cells and their afferent and efferent neurons.
connections, the dorsal column nuclei are divided into two dis- Neurons in the dorsal column nuclei are influenced by facili-
tinct areas (Table 5–1): a core region and a reticular zone. The core tatory as well as inhibitory inputs (Figure 5–7). Inhibition is me-
region includes the middle and caudal parts of each dorsal column diated by reticular zone interneurons and is both presynaptic and
nucleus. The reticular zone surrounds the core region and consists postsynaptic. Presynaptic inhibition is mediated by interneurons
of the rostral and deeper portions of the dorsal column nuclei. that form axoaxonic synapses on the terminals of dorsal column
Activity in the dorsal column nuclei is controlled by periph- afferents. These terminals in turn form excitatory synapses on re-
eral afferent inputs and is modulated by input from the cerebral lay neurons. Postsynaptic inhibition, in contrast, is mediated by
cortex and other suprasegmental sites (reticular formation, cau- interneurons that form axodendritic and axosomatic synapses on
date nucleus, cerebellum). In general, descending afferents are relay neurons. Interneurons in the reticular zone are excited by
restricted in their distribution to the reticular zone. primary as well as postsynaptic fibers in the dorsal column. In
Table 5–1. Dorsal Column Nuclei
Core region Reticular zone
Location Middle and caudal Rostral and deeper

Neuron Type Relay Interneurons and relay
Input Posterior column (long ascending primary fibers) Posterior column (second-order postsynaptic fibers,
and dorsolateral fasciculus)
Output Ventral posterolateral nucleus of thalamus Diffusely to thalamus, brain stem nuclei, cerebellum
Primary receptors Cutaneous (distal extremities) Cutaneous (distal and proximal extremities and axial)
Other receptors Joint and muscle proprioceptors (minority) Muscle and joint
Receptive fields Small Large
Other Selective response to activation of a particular Input from cortical areas and reticular formation
cutaneous receptor excited by specific stimuli
turn, interneurons modulate the transmission of impulses from cord. It is continuous caudally with the substantia gelatinosa of
dorsal column afferents to relay neurons. the spinal cord and rostrally with the main sensory nucleus of
The main efferent projection of the dorsal column nuclei is the trigeminal nerve in the pons. The spinal tract and nucleus
the medial lemniscus, which terminates in the thalamus. Other of the trigeminal nerve are concerned with exteroceptive sensa-
projections, which have been confirmed recently, include those tions (pain, temperature, and light touch) from the ipsilateral
to the inferior olive, tectum, spinal cord, and cerebellum. The face. The spinal nucleus is divided into three parts along its ros-
cerebellar fibers originate mainly from the cuneate nucleus with trocaudal extent. The caudal part, the caudal nucleus, extends
minor contributions from the gracile nucleus. The function of from the obex of the medulla oblongata rostrally to the substan-
these extrathalamic connections is not well understood. tia gelatinosa of the spinal cord, with which it is continuous
caudally. It mediates pain and temperature sensations from the
C. SPINAL TRIGEMINAL NUCLEUS ipsilateral side of the face. Rostral to the obex is the nucleus in-
Another feature seen at the level of the motor decussation is the terpolaris, which is distinct cytologically from the nucleus cau-
spinal nucleus of the trigeminal nerve. This nuclear mass occu- dalis; it mediates dental pain. Rostral to the interpolar nucleus
pies a dorsolateral position in the medulla and is capped by the and just caudal to the main sensory nucleus of the trigeminal is
descending (spinal) tract of the trigeminal nerve. The spinal the nucleus oralis, which mediates tactile sensations from the
trigeminal nucleus extends throughout the medulla oblongata oral mucosa.
and descends caudally to the level of C-3 in the cervical spinal Fibers of the spinal tract of the trigeminal nerve that originate
from the mandibular region of the face project down to the third
and fourth cervical segments. Those from the perioral region of
the face project to lower medullary levels. Those originating be-
tween the mandible and the perioral region terminate in the up-
Descending
afferent per cervical region. Evidence in support of this “onion-skin” dis-
tribution pattern is found in patients in whom the spinal tract of
the trigeminal nerve is cut (tractotomies) to relieve pain. Thus,
Medial lemniscus tractotomies that spare the lower medulla spare pain and tem-
to thalamus
perature sensations around the mouth. In contrast to the onion-
skin pattern of distribution of exteroceptive sensations on the
face described by Dejerine in 1914, some observations suggest
Relay
neuron that all fibers carrying pain impulses from the face, not only
– those from the mandible, reach lower cervical levels. Pain neu-
+ Dorsal
rons in the spinal trigeminal nucleus, like their counterparts in
Interneuron column the spinal cord, have been classified physiologically into high-
– – nuclei threshold (HT), low-threshold (LT), and wide-dynamic-range
+ (WDR) neurons. Specific thermoreceptive neurons have been
Interneuron Dorsal localized on the outer rim of the nucleus. Axons of neurons in
column the spinal trigeminal nucleus cross the midline to form the ven-
tral trigeminothalamic tract which projects on neurons in the
Dorsal root
ventral posteromedial (VPM) nucleus of the thalamus. From
ganglion there, facial sensations are transmitted to the face area of the pri-
mary somatosensory cortex. Within the trigeminothalamic tract,
fibers from the ophthalmic branch (V1) of the trigeminal nerve
Receptors are located most lateral and those from the mandibular branch
(V3) are most medial. In addition to the major input from ex-
Figure 5–7. Schematic diagram depicting the major input and teroreceptors in the face, the spinal trigeminal nucleus has been
output of the posterior column nuclei, as well as their internal shown to receive an input from the nucleus locus ceruleus in the
circuitry. pons and to send fibers back to the locus ceruleus. The input
84 / CHAPTER 5
from the locus ceruleus is inhibitory. It should be pointed out that Other ascending and descending tracts encountered in the
the spinal tract of the trigeminal conveys, in addition to extero- spinal cord traverse the medulla on their way to higher or lower
ceptive sensations from the face, general somatic fibers belonging levels.
to the facial (cranial nerve VII), glossopharyngeal (cranial nerve
IX), and vagus (cranial nerve X) nerves. Level of Sensory (Lemniscal) Decussation
D. OTHER TRACTS A. MEDIAL LEMNISCUS
The following ascending tracts are also seen at the level of the The distinguishing feature of the level of sensory decussation
motor decussation. The spinothalamic tracts traverse the medulla (Figure 5–8) is the crossing of second-order neurons of the dorsal
in close proximity to the spinal nucleus and tract of the column system. Axons of relay neurons in the dorsal column nu-
trigeminal nerve (Figure 5–5). Lesions of the medulla in clei course ventromedially (internal arcuate fibers) and cross to the
this location therefore produce sensory loss of pain and opposite side (sensory decussation) above the pyramids to form
temperature sensation on the face ipsilateral to the medullary le- the medial lemniscus. In the decussation, fibers derived from the
sion (spinal tract and nucleus of the trigeminal nerve) as well as gracile nucleus come to lie ventral to those derived from the cu-
loss of the same sensations on the body contralateral to the neate nucleus. The medial lemniscus thus carries the same
medullary lesion (spinothalamic tract). Although the lateral and modalities of sensation carried by the dorsal column. The
anterior spinothalamic tracts retain their spinal cord positions in medial lemniscus projects on neurons in the VPL nucleus
the caudal medulla, the position of the anterior spinothalamic of thalamus. VPL, in turn, projects to the primary somatosensory
tract in the rostral medulla has not been definitively delineated cortex. Lesions in the medial lemniscus result in a loss of kinesthe-
in humans, and its fibers probably run along with the lateral sia and discriminative touch contralateral to the side of the lesion
spinothalamic tract. As in the spinal cord, several lines of evidence in the medulla. The sensory decussation provides part of the
support segregation of pain and thermal fibers within the lateral anatomic basis for the sensory representation of half of the body in
spinothalamic tract in the medulla oblongata. Thus, a superficial the contralateral hemisphere. The other part is provided by the
lesion in the medulla that only involves the dorsal portion of the crossing of the spinothalamic system in the spinal cord.
lateral spinothalamic tract could result in isolated loss of thermal
sensation. B. MEDIAL LONGITUDINAL FASCICULUS
The spinal cord positions of the dorsal and ventral spinocere- The medial longitudinal fasciculus (MLF), displaced dorso-
bellar tracts remain unchanged in the medulla (Figure 5–5). laterally by the pyramidal decussation, is pushed farther upward
Gracile
Gracile Nucleus
Tract
Cuneate Cuneate
Nucleus Tract
Medial
Longitudinal
Accessory
Fasciculus
Cuneate Nucleus
Tract of Spinal
Trigeminal
Internal Nucleus
Arcuate
Fibers
Spinal Trigeminal
Nucleus
Sensory
(Lemniscal) Medial
Decussation Lemniscus
Pyramid
Arcuate
Nucleus
Figure 5–8. Photograph of medulla oblongata at the level of sensory (lemniscal) decussation showing major
structures seen at this level.
by the sensory decussation so that it comes to lie dorsal to the

medial lemniscus (Figure 5–8). It retains this position through-
out the extent of the medulla oblongata. Descending fibers in
this bundle are derived from various brain stem nuclei. Vestib-
ular fibers in the bundle are derived from the medial and infe-
rior vestibular nuclei. The pontine reticular formation contrib-
utes the largest number of descending fibers. Smaller groups
of fibers arise from Cajal’s interstitial nucleus in the rostral
midbrain.
C. ACCESSORY CUNEATE NUCLEUS
A group of large neurons situated dorsolateral to the cuneate
nucleus is known as the accessory (lateral or external) cuneate
nucleus. Although this nucleus shares its name with the
cuneate nucleus, it does not belong functionally to the
dorsal column system; it is part of the dorsal spinocere-
bellar system. Fibers of the dorsal spinocerebellar system enter-
ing the spinal cord above the level of C-8 (upper extent of the
dorsal [Clarke’s] nucleus) ascend with the posterior column fibers
and terminate on neurons of the accessory cuneate nucleus.
Second-order neurons from the accessory cuneate nucleus course Figure 5–9. Schematic diagram illustrating the course of arcu-
dorsolaterally as dorsal external arcuate fibers and reach the cere- atocerebellar fibers within the medulla oblongata.
bellum (cuneocerebellar fibers) via the restiform body. Like the
spinocerebellar system, the cuneocerebellar tract is concerned with
unconscious proprioception. Neurons in the accessory cuneate
nucleus have been shown to receive fibers from the glossopha- Level of Inferior Olive
ryngeal (cranial nerve IX) and vagus (cranial nerve X) nerves as
well as from the vasopressor and cardioacceleratory areas of the The distinguishing feature of the level of the inferior olive
posterior hypothalamus. Stimulation of the accessory cuneate (Figure 5–10) of the medulla is the appearance of the inferior
nucleus has been shown to produce bradycardia and hypoten- olivary nuclei, which are convoluted laminae of gray matter
sion. This response has been shown to be due to vagal stimulation. dorsal to the pyramids. They project from the ventrolateral
It has been suggested that hypertension triggers the accessory surface of the medulla as olive-shaped structures (Figure 5–1).
cuneate nucleus, via cardiovascular reflexes, to produce bradycar- The inferior olivary nuclear complex consists of three nuclear
dia and hypotension. groups:
1. Principal olive (the largest of the complex)
D. ARCUATE NUCLEI
2. Dorsal accessory olive
A group of neurons on the anterior (ventral) aspect of the pyra-
mid is known as the arcuate nucleus. The arcuate nuclei increase 3. Medial accessory olive
in size significantly in rostral levels of the medulla and become The olivary complex in humans is estimated to contain 0.5
continuous with the pontine nuclei in the pons. The afferent and million neurons. The complex is surrounded by a mass of fibers
efferent connections of the arcuate nuclei are identical to those of known as the amiculum olivae.
the pontine nuclei. Their major input is from the contralateral The inferior olives receive fibers from the following sources
cerebral cortex; their major output is to the homolateral and con- (Figure 5–11):
tralateral cerebellum via the restiform body. The arcuatocerebellar
fibers reach the restiform body via two routes (Figure 5–9). One 1. Cerebral cortex via the corticospinal tract to both principal
route courses along the outer surface of the medulla (ventral ex- olives.
ternal arcuate fibers); the other route courses along the midline of 2. Basal ganglia to both principal olives via the central tegmen-
the medulla and turns laterally in the floor of the fourth ventricle, tal tract.
forming the stria medullaris of the floor of the fourth ventricle. 3. Mesencephalon from the periaqueductal gray matter of the
midbrain and the red nucleus to the homolateral principal
Area Postrema olive via the central tegmental tract.
4. In the medulla oblongata, the dorsal column nuclei project
In the floor of the caudal fourth ventricle, just rostral to to the contralateral accessory olive. The inferior and medial
the obex, is the area postrema, which is formed of as- vestibular nuclei project to both inferior olives. The two in-
troblast-like cells, arterioles, sinusoids, and some apolar ferior olives are interconnected.
or unipolar neurons. It is one of several central nervous system 5. In the cerebellum, the deep cerebellar nuclei (dentate and
areas that lack a blood-brain barrier. Collectively referred to as the interposed nuclei) project to the principal and accessory in-
circumventricular organs, they include, in addition to the area ferior olives via the superior cerebellar peduncle.
postrema, the subfornical organ, subcommissural organ, pineal
gland, median eminence, neurohypophysis, and organum vascu- 6. From the spinal cord, to the accessory olives of both sides via
losum. All except the area postrema are unpaired midline struc- the spino-olivary tract.
tures that are related to the diencephalon. Stimulation of the area The major output of the inferior olivary complex is to the
postrema in experimental animals induces vomiting, suggesting cerebellum (olivocerebellar tract). Olivocerebellar fibers arise
the presence of a chemosensitive emetic center in this area. from both olivary complexes but come primarily from the
86 / CHAPTER 5
Dorsal Motor
Hypoglossal Nucleus of
Medial Longitudinal Vagus
Nucleus
Fasciculus
Inferior
Vestibular
Restiform Nucleus
Body
Medial
Lemniscus
Dorsal Accessory
Olive
Amiculum
Olivae
Principal
Olive
Pyramid Medial Accessory

Olive
Figure 5–10. Photograph of medulla oblongata at the inferior olive level showing major structures seen at this level.
contralateral complex. They pass through the hilum of the olive, medial parts of the principal olives project onto the vermis of the
traverse the medial lemniscus, and course through the opposite cerebellum, whereas fibers originating from the rest of the prin-
olive to enter the restiform body on their way to the cerebellum. cipal olive project to the cerebellar hemispheres. The deep cere-
Olivocerebellar fibers constitute the major component of the res- bellar nuclei also receive fibers from the olivocerebellar tract.
tiform body and are localized in the ventromedial part. Olivo- Thus, the inferior olivary complex is a relay station
cerebellar fibers originating from the accessory olives and the between the cortex, subcortical structures, the spinal
cord, and the cerebellum.
The ascending and descending fiber tracts, as well as the
nuclear complexes encountered in more caudal levels of the
Cerebral medulla, are present at this level. The cranial nerve nuclei of
cortex the medulla are discussed in “Cranial Nerve Nuclei of the
Medulla,” below.
Basal
ganglia
MEDULLARY RETICULAR FORMATION
Midbrain
Red nucleus The medullary reticular formation is characterized by a great
Periaqueductal number of neurons of various sizes and shapes intermingled
gray with a complex network of fibers. It spans the area between the
pyramids (ventrally) and the floor of the fourth ventricle (dor-
sally). It is phylogenetically old and in lower forms constitutes
Cerebellum
INFERIOR OLIVARY Medulla the major part of the central nervous system. Caudally, the
COMPLEX Dorsal column reticular formation appears at about the level of the pyramidal
nuclei decussation. Rostrally, it is continuous with the reticular forma-
Vestibular tion of the pons. Physiologically, the reticular formation is a
Spinal cord nuclei polysynaptic system that is rich in collateral fibers for the dis-
persion of impulses. The cellular organization, connections, and
Figure 5–11. Schematic diagram showing major sources of in- functions of the medullary reticular formation are discussed in
put to the inferior olive. Chapter 32.
INFERIOR CEREBELLAR PEDUNCLE 4. Cuneocerebellar tract from the accessory cuneate nucleus to
(RESTIFORM BODY) the cerebellum (homologous to the dorsal spinocerebellar
tract)
The brain stem and cerebellum are connected by three peduncles: 5. Arcuatocerebellar tract from the arcuate nucleus to the
1. The inferior cerebellar peduncle (Figures 5–3 and 5–12) be- cerebellum
tween the medulla and the cerebellum 6. Cerebello-olivary tract from the cerebellum to the inferior
2. The middle cerebellar peduncle (brachium pontis) between olive
the pons and the cerebellum 7. Trigeminocerebellar tract from the spinal nucleus of the
3. The superior cerebellar peduncle (brachium conjunctivum) trigeminal nerve (medulla) and the principal nucleus of the
between the cerebellum and the midbrain trigeminal nerve (pons) to the cerebellum
8. Fibers from the perihypoglossal nuclei (concerned with eye
The inferior cerebellar peduncle (restiform body) is located movement) to the cerebellum
on the dorsolateral border of the medulla oblongata. It appears
rostral to the clava and cuneate tubercles and forms a distinct A small inner (medial) part of the restiform body is known as
bundle at about the midolivary level. The fiber tracts the juxtarestiform body. It contains the following fiber tracts:
contained within the inferior cerebellar peduncle include 1. Cerebelloreticular tract from the cerebellum to the reticular
the following afferent and efferent (medullary and spinal formation
originating or destined) tracts:
2. Cerebellovestibular tract from the cerebellum to the vestibu-
1. Olivocerebellar tract (the largest component of this peduncle) lar nuclei
connecting the inferior olive and cerebellum 3. Vestibulocerebellar, secondary vestibular fibers form the ves-
2. Dorsal spinocerebellar tract from the nucleus dorsalis (Clarke’s tibular nuclei to the cerebellum
nucleus) to the cerebellum 4. Direct vestibular nerve fibers to the cerebellum (with no
3. Reticulocerebellar tract connecting the reticular formation synapse in the vestibular nuclei)
with the cerebellum 5. Cerebellospinal tract (from the cerebellum to motor neurons
of the cervical spinal cord)
Lesions in the inferior cerebellar peduncle result in the fol-
lowing symptoms and signs:
1. Ataxia (lack of coordination of movement) with a tendency
Restiform body to fall toward the side of the lesion
2. Nystagmus (involuntary rapid eye movement)
Paramedian 3. Muscular hypotonia
reticular nucleus
Lateral reticular
nucleus CRANIAL NERVE NUCLEI OF THE MEDULLA
Inferior olive The following cranial nerves have their nuclei in the medulla
oblongata: (1) hypoglossal (cranial nerve XII), (2) accessory
Arcuate nucleus (cranial nerve XI), (3) vagus (cranial nerve X), (4) glossopha-
ryngeal (cranial nerve IX), and (5) vestibulocochlear (cranial
nerve VIII).
Accessory Hypoglossal Nerve (Cranial Nerve XII)

cuneate
nucleus The hypoglossal nerve contains primarily somatic motor nerve
fibers that innervate the intrinsic and extrinsic muscles of the
tongue. It also contains afferent proprioceptive fibers from the
muscle spindles of tongue muscles. The central termination of
Pyramid afferent proprioceptive fibers in the hypoglossal nerve is not
known with certainty. The nucleus of the solitary tract and the
hypoglossal nucleus have been reported to receive these afferents.
The nucleus of the hypoglossal nerve extends throughout the
medulla oblongata except for its most rostral and caudal levels. It
Dorsal is divided into cell groups that correspond to the tongue muscles
spinocerebellar
tract they supply. The surface markings of the nucleus in the floor of
the fourth ventricle are known as trigonum hypoglossi. The nu-
cleus receives both crossed and uncrossed corticoreticulobulbar
Nucleus dorsalis
of Clarke
fibers. The root fibers of the nerve course in the medulla oblon-
gata lateral to the medial lemniscus and emerge on the ventral
Figure 5–12. Composite schematic diagram of the compo- surface of the medulla between the pyramid and the inferior olive
nents of the inferior cerebellar peduncle (restiform body). (Figure 5–13).
88 / CHAPTER 5
receive input from the (1) cerebral cortex, (2) vestibular nuclei,
(3) accessory oculomotor nuclei, and (4) paramedian pontine
reticular formation.
The output of these nuclei terminates in (1) cranial nerve
nuclei involved in extraocular movement (oculomotor, trochlear,
abducens), (2) the cerebellum, and (3) the thalamus.
The perihypoglossal nuclei and their connections are part of a
complex circuitry related to eye movements.
Lesions in the hypoglossal nerve or nucleus result in lower
motor neuron paralysis of the tongue musculature ho-
molateral to the lesion (Figure 5–14A), which is mani-
fested by the following symptoms:
1. Decrease or loss of movement of the homolateral half of the
tongue
2. Atrophy of muscles in the homolateral half of the tongue
3. Fasciculations of muscles in the homolateral half of the
Figure 5–13. Schematic diagram of the origin and intra- tongue
medullary course of rootlets of the hypoglossal nerve.
4. Deviation of the protruding tongue to the atrophic side (by
action of the normal genioglossus muscle)
A number of nuclear masses in close proximity to the hypo- Lesions involving the rootlets of the hypoglossal nerve and
glossal nerve (cranial nerve XII) nucleus are believed to be retic- the adjacent medial lemniscus within the medulla result in the
ular neurons; they do not contribute fibers to the hypoglossal signs of hypoglossal nerve lesion detailed above and contralateral
nerve. They are known as perihypoglossal or satellite nuclei (nu- hemisensory loss of kinesthesia and discriminative touch (Figure
cleus intercalatus, nucleus prepositus, and Roller’s nucleus). They 5–14B). Extremely rare, sensory loss follows a dermatomal pat-
DEFICIT
Ipsilateral Contralateral
Loss of movement, None

decreased tone,
muscular atrophy
of denervated half
of tongue
Deviation of protruded
A tongue to the atrophic
side
Loss of movement, Loss of kinesthesia

decreased tone, and discriminative
muscular atrophy touch
of denervated half
of tongue
tongue to the atrophic
side
Loss of movement, Spastic paralysis

decreased tone,
muscular atrophy
of denervated half
of tongue
tongue to the atrophic Figure 5–14. Schematic diagram illus-
side trating lesions of the hypoglossal nerve
in its extra- and intramedullary course,
C and the resulting clinical deficits of each.
tern reflecting the arrangement of posterior column fibers in Some scholars argue that the function of the recurrent laryngeal
the medial lemniscus (sacral fibers most ventral, cervical fibers nerve was described centuries before Galen.
most dorsal). The following are manifestations of unilateral lesions of the
Lesions involving the rootlets of the hypoglossal nerve and accessory nerve:
the adjacent pyramid within the medulla are manifested
by the signs and symptoms of a hypoglossal nerve lesion 1. Downward and outward rotation of the scapula ipsilateral to
and contralateral upper motor neuron paralysis (Figure the lesion
5–14C ). 2. Moderate sagging of the ipsilateral shoulder
Intramedullary vascular lesions or tumors that involve the 3. Weakness on turning the head to the side opposite the lesion
hypoglossal, cranial accessory, vagus, and glossopharyngeal nerves 4. No observable abnormality of head position in repose
and contralateral hemiparesis constitute Jackson’s syndrome.
Intra- or extramedullary lesions that involve the hypoglossal, The first two signs are due to impaired function of the tra-
vagus, and glossopharyngeal nerves constitute Tapia’s syndrome. pezius muscle, and the third is due to impaired function of the
sternocleidomastoid muscle.
Accessory Nerve (Cranial Nerve XI)
Vagus Nerve (Cranial Nerve X)
The accessory nerve (Figure 5–15) has two roots: spinal and
cranial. The spinal root arises from the accessory nucleus, a The vagus nerve (Figure 5–16), a mixed nerve containing both
collection of motor neurons in the anterior horn of the upper afferent and efferent fibers, is associated with four nuclei in the
five or six cervical spinal segments and the caudal part of the medulla oblongata. The efferent components of the nerve are
medulla. From their cells of origin, the rootlets course related to two medullary nuclei.
dorsolaterally and exit from the lateral part of the spinal
cord between the dorsal and ventral roots. The spinal A. DORSAL MOTOR NUCLEUS OF THE VAGUS
root of the accessory nerve enters the cranial cavity through the The dorsal motor nucleus of the vagus is a column of cells dor-
foramen magnum and leaves it through the jugular foramen. solateral or lateral to the hypoglossal nucleus and extending
The spinal root contains somatic motor fibers that supply the both rostrally and caudally a little beyond the hypoglossal nu-
sternocleidomastoid and trapezius (upper part) muscles. cleus. Axons of neurons in this column course ventrolaterally
The cranial root arises from the caudal pole of the nucleus in the medulla and emerge from the lateral surface of the
ambiguus in the medulla oblongata. This root emerges from the medulla between the inferior olive and the inferior cerebellar
lateral surface of the medulla, joins rootlets of the vagus nerve peduncle. Axons arising from this nucleus are preganglionic
(forming its recurrent laryngeal branch), and supplies the intrin- parasympathetic fibers that convey general visceral effer-
sic muscles of the larynx. Thus, the cranial root of the accessory ent impulses to the viscera in the thorax and abdomen.
nerve is in essence part of the vagus nerve. Postganglionic fibers arise from terminal ganglia situ-
The recurrent laryngeal nerve is also known as Galen’s nerve ated within or on the innervated viscera in the thorax and ab-
after Galen of Pergamon (A.D. 130–200), who took pride in his domen. The dorsal motor nucleus of the vagus receives fibers
discovery that the recurrent laryngeal nerves control the voice. from the vestibular nuclei; thus, excessive vestibular stimulation
Nucleus ambiguus
MEDULLA
Intrinsic muscle
of larynx
Cranial root
SPINAL CORD
pinal root
Figure 5–15. Schematic diagram illustrat-

Sternocleidomastoid muscle
ing the neurons of origin of the accessory
nerve, and muscles supplied by the nerve. Accessory nucleus Trapezius muscle
90 / CHAPTER 5
Dorsal motor nucleus

Spinal trigeminal Nucleus of vagus
nucleus solitarius Nucleus
ambiguus Nucleus solitarius
Superior
ganglion
General
sensations Inferior Peripheral
ganglion autonomic
ganglion Abdominal and
thoracic viscera
Ear
Taste sensation
Epiglottis
Pharynx, larynx,
trachea, esophagus,
abdominal and
thoracic viscera, Branchiomeric muscle
baro- and chemoreceptor of pharynx and larynx
SENSORY COMPONENT MOTOR COMPONENT
Figure 5–16. Schematic diagram of the components of the vagus nerve and the areas they supply.
(e.g., motion sickness) results in nausea, vomiting, and a change 2. Nucleus solitarius. This nucleus receives two types of visceral
in heart rate. afferent fibers.
a. General visceral afferent fibers. These fibers convey gen-
B. NUCLEUS AMBIGUUS eral visceral sensations from the pharynx, larynx, tra-
The nucleus ambiguus is also known as the ventral motor nu- chea, and esophagus as well as the thoracic and abdomi-
cleus of the vagus. It is a column of cells situated about halfway nal viscera.
between the inferior olive and the nucleus of the spinal tract of b. Special visceral afferent fibers. These fibers convey taste
the trigeminal nerve. Axons of neurons in this nucleus course sensations from the region of the epiglottis.
dorsomedially and then turn ventrolaterally to emerge from the
The neurons of origin of both types of afferent fibers reside
lateral surface of the medulla between the inferior olive and the
in the inferior (nodosum) ganglion of the vagus. The central
inferior cerebellar peduncle. These axons convey special vis-
processes of neurons in this ganglion enter the lateral surface of
ceral efferent impulses to the branchiomeric muscles of the
the medulla oblongata, course dorsomedially, and form the trac-
pharynx and larynx (pharyngeal constrictors, cricothyroid, in-
tus solitarius, which projects on cells of the nucleus solitarius.
trinsic muscles of the larynx, levator veli palatini, palatoglossus,
Neurons in the latter nucleus are organized so that those receiving
palatopharyngeus, and uvula). In addition to the vagus nerve,
general visceral afferent fibers are located in the caudal and medial
the nucleus ambiguus contributes efferent fibers to the glosso-
part of the nucleus, whereas those receiving special visceral affer-
pharyngeal (cranial nerve IX) and accessory (cranial nerve XI)
ent fibers (taste) are located in the rostral and lateral part. Cau-
nerves.
dally, the two solitary nuclei merge to form the commissural
The afferent components of the vagus nerve are related to
nucleus of the vagus nerve. In addition to the vagus nerve, the
two medullary nuclei:
nucleus solitarius receives general visceral afferent fibers from the
1. Nucleus of the spinal tract of the trigeminal nerve. This glossopharyngeal nerve (cranial nerve IX) and special visceral
nucleus receives general somatic afferent fibers from the ex- (taste) afferent fibers from the glossopharyngeal (cranial nerve IX)
ternal ear, external auditory canal, and external surface of and facial (cranial nerve VII) nerves.
the tympanic membrane. The neurons of origin of these The vagus nerve emerges from the medulla in a series of
fibers are in the superior (jugular) ganglion of the vagus rootlets lateral to the inferior olive. The rootlets come to form a
nerve. The general somatic afferent component of the vagus single root that leaves the skull through the jugular foramen.
nerve is small, and its ganglion contains relatively few neu- Bilateral lesions of the vagus nerve are fatal as a result of com-
rons. Somatic afferent fibers in the vagus nerve descend in plete laryngeal paralysis and asphyxia.
the spinal trigeminal tract and synapse in the nucleus of the Unilateral vagal lesions result in ipsilateral paralysis of the soft
spinal tract of the trigeminal nerve. palate, pharynx, and larynx. This is manifested by hoarseness of
the voice, dysphagia (difficulty swallowing), and dyspnea (diffi- in response to food odor reflect inputs to the inferior salivatory
culty breathing). nucleus from the hypothalamus and olfactory system, respectively.
The afferent components of the glossopharyngeal nerve are
related to the same two nuclei associated with the vagus nerve:
Glossopharyngeal Nerve (Cranial Nerve IX)
1. Nucleus of the spinal tract of the trigeminal nerve. This nu-
The glossopharyngeal nerve (Figure 5–17), which is also a mixed cleus receives general somatic afferent fibers from the retro-
nerve (containing both afferent and efferent components), is asso- auricular region. Neurons of origin of these fibers are located
ciated with four nuclei in the medulla. The efferent com- in the superior ganglion within the jugular foramen.
ponents of the glossopharyngeal nerve are related to two 2. Nucleus solitarius. This nucleus receives two types of visceral
nuclei. afferent fibers.
A. NUCLEUS AMBIGUUS a. General visceral afferent fibers. These fibers convey tactile,
pain, and thermal sensations from the mucous mem-
Axons that travel with the glossopharyngeal nerve arise from
branes of the posterior third of the tongue, the tonsils,
neurons in the rostral part of the nucleus ambiguus and supply
and the eustachian tube.
special visceral efferent fibers to the stylopharyngeus muscle,
b. Special visceral afferent fibers. These fibers convey taste
which elevates the pharynx during swallowing and speech. This
sensations from the posterior third of the tongue.
efferent component of the glossopharyngeal nerve is small.
Neurons of origin of the visceral afferent fibers are located in
B. INFERIOR SALIVATORY NUCLEUS the inferior (petrosal) ganglion. Within the medulla, they form
The inferior salivatory nucleus is a group of neurons that are dif- the tractus solitarius and project on the nucleus solitarius in a
ficult to distinguish from reticular neurons in the dorsal aspect of manner similar to that described above for the vagus nerve.
the medulla. The axons of neurons in this nucleus leave the The glossopharyngeal nerve also contains a special afferent
medulla from its lateral surface. They are preganglionic general branch, the carotid sinus nerve. This branch innervates the carotid
visceral efferent fibers that convey secretomotor impulses to the body and carotid sinus, which are chemoreceptor and barorecep-
parotid gland. They travel via the lesser petrosal nerve to the otic tor centers. Elevation of carotid arterial pressure stimulates the
ganglion, from which postganglionic fibers supply the parotid carotid sinus nerve, which upon reaching the medulla sends col-
gland. Dry mouth in response to fear and anxiety, and salivation laterals to the dorsal motor nucleus of the vagus. General visceral
General sensations Nucleus ambiguus
Inferior salivatory nucleus

Superior ganglion
Nucleus solitarius
Spinal trigeminal nucleus

Inferior ganglion
Otic Parotid
ganglion gland
uricular
Eustachian
tube
Taste sensation
Posterior third of tongue
Stylopharyngeus
Posterior third muscle
of tongue
Tonsils
SENSORY MOTOR
COMPONENT COMPONENT
Figure 5–17. Schematic diagram of the components of the glossopharyngeal nerve and the
structures they supply.
92 / CHAPTER 5
efferent components of the vagus nerve then reach ganglion cells NUCLEUS SOLITARIUS
in the wall of the heart to slow the heart rate and reduce blood
pressure. This glossopharyngeal-vagal reflex is especially sensi- Amygdala \ hypothalamus Gustatory cortex
tive in elderly people. Therefore, extreme care should be taken
in manipulating the carotid sinus region in the neck of an elderly
person.
Parabrachial pontine nucleus VPM
Unilateral lesions of the glossopharyngeal nerve are mani-
fested by the following signs: Nucleus ambiguus
DMN CN X
1. Loss of the pharyngeal (gag) reflex homolateral to the nerve
lesion. This reflex is elicited by stimulation of the posterior Medullary Reticular
pharyngeal wall, the tonsillar area, or the base of the tongue. Formation
CV centers
Normally, tongue retraction is associated with elevation and Respiratory centers
constriction of the pharyngeal musculature.
Rostral
2. Loss of the carotid sinus reflex homolateral to the nerve lesion.
3. Loss of taste in the homolateral posterior third of the tongue.
4. Deviation of the uvula to the unaffected side. Medial Taste
CN IX Lateral
Glossopharyngeal neuralgia (Reichert syndrome, tympanic Cardio-
plexus neuralgia) due to a lesion in the glossopharyngeal nerve is respiratory CN X
CN X
characterized by paroxysms of severe pain in the throat, posterior CN IX
tongue, and ear triggered by swallowing or tongue movements. Caudal
CN VII
Vestibulocochlear Nerve (Cranial Nerve VIII) Intermediolateral

Cell Column
The vestibular component of the vestibulocochlear nerve is dis- Spinal Cord
cussed in Chapter 7. The two vestibular nuclei that appear at ros-
tral levels of the medulla are the inferior vestibular nucleus and Figure 5–18. Schematic diagram showing major inputs and
the medial vestibular nucleus. outputs of the nucleus solitarius.
The inferior vestibular nucleus is located medial to the resti-
form body and is characterized in histologic preparations by the
presence of dark-staining bundles of fibers coursing through it. animals with a change in feeding behavior characterized by early
The medial vestibular nucleus, which is located medial to the in- satiety and poor appetite. The nucleus solitarius is coextensive
ferior nucleus, is poorly stained in myelin preparations because with the physiologically defined medullary respiratory center,
of the relatively few fibers it contains. which includes the nucleus ambiguus and surrounding portions
of the reticular formation. Cells of the medullary respiratory cen-
Nucleus Solitarius ter are activated by vagal impulses and by changes in their chem-
ical environment (CO2 accumulation). The caudal zone of the nu-
The nucleus solitarius is divided into two zones (Figure 5–18). cleus solitarius, along with the dorsal motor nucleus of the vagus
The caudal and medial zone is concerned with general visceral and the medial reticular formation, has been implicated in the
sensation and primarily cardio-respiratory function. The rostral genesis of neurogenic pulmonary edema.
and lateral zone is concerned with special visceral (taste) func-
tion. Caudally, the two medial parts of the solitary nuclei merge
to form the commissural nucleus. The Medulla and Cardiovascular Control
The gustatory (taste) zone receives taste sensations via three The nucleus solitarius, along with the dorsal motor nucleus of
cranial nerves: The facial nerve (cranial nerve VII) conveys taste the vagus, the caudal, and the rostral ventrolateral medulla,
sensations from the anterior two-thirds of the tongue, the glos- comprise the brain stem nuclei involved in cardiovascular control.
sopharyngeal nerve (cranial nerve IX) conveys taste sensations They receive direct projections from the sensorimotor cortex.
from the posterior third of the tongue, and the vagus nerve (cra- The cortical input to these nuclei provides the basis for cortical
nial nerve X) conveys taste sensations from the epiglottis. The out- influences on the baroreceptor reflex and sympathetic vasomo-
put of the gustatory zone is to the posterior thalamus (ventral tor mechanisms for control of blood pressure. Lesions in the nu-
posterior medial nucleus), which in turn projects to the primary cleus solitarius have been shown to result in arterial blood pres-
gustatory cortex. sure elevation. Neurons in the caudal ventrolateral medulla
The zone concerned with general visceral sensations receives receive baroreceptor input and send inhibitory projections to the
input via two cranial nerves: the glossopharyngeal (cranial nerve rostral ventrolateral medulla. Lack of activity in caudal ventrolat-
IX) and the vagus (cranial nerve X). Neurons in this zone project eral medullary neurons has been associated with development of
to the nucleus ambiguus, the dorsal motor nucleus of the vagus, hypertension. The rostral ventrolateral medulla is critical for the
centers within the medullary reticular formation concerned with tonic and reflexic regulation of blood pressure.
cardiovascular and respiratory function, the intermediolateral
cell column in the spinal cord, and the parabrachial pontine nu- The Medulla and Respiratory Function
cleus. From the parabrachial pontine nucleus, visceral sensory in-
formation is relayed to the amygdala and hypothalamus. Lesions Experimental studies have identified two medullary regions re-
in the nucleus or tractus solitarius and their connections with the lated to respiratory function. The dorsal respiratory group
area postrema have been associated in humans and experimental in the nucleus solitarius contains primary inspiratory
neurons that project to the nucleus ambiguus and to spinal cord nial nerve VII), which innervate glands and blood vessels in the
neurons that supply the diaphragm. The ventral respiratory group nose, resulting in nasal secretion and edema, further stimulation
in the nucleus ambiguus and nucleus retroambiguus contains in- of the nasal mucosa, and more impulses to the sneezing center.
spiratory and expiratory neurons. The inspiratory neurons are The respiratory phase of the sneezing reflex commences when
driven by the nucleus solitarius. Neurons in the ventral respira- a critical number of inspiratory and expiratory neurons are re-
tory group project to spinal cord neurons that supply the inter- cruited by the sneezing center. Recruitment of these neurons in-
costal and abdominal muscles. creases activity in the vagus, phrenic, and intercostal nerves to
There is a paucity of information about centers of respiration the appropriate musculature. Manifestations of this phase con-
in the brain stem in humans. Structures implicated in apnea in sist of the following sequence of events: eye closure, deep inspi-
humans include the nucleus solitarius, the nucleus ambiguus, the ration, pharyngeal closure, forceful expiration, dilation of the
nucleus retroambiguus, the dorsal motor nucleus of the vagus, the glottis, explosive air release through the mouth and nose, and ex-
region of the medial lemniscus, the region of the spinothalamic pulsion of mucus and irritants.
tract, and the medullary reticular formation, all bilaterally. Sneezing disorders consist of those of excessive sneezing (more
Discrete unilateral lesions in the nucleus ambiguus and the common) and the inability to sneeze (less common). Inability to
adjacent reticular formation in humans have been reported to re- sneeze has been reported in psychiatric disorders and in medullary
sult in failure of automatic respiratory function (sleep apnea, neoplasms affecting the sneezing center.
Ondine’s curse). Lesions that also involve the nucleus solitarius
result in failure of both automatic and voluntary respiration. The Medulla and Swallowing
Swallowing is a complex motor sequence that involves more than
Neurogenic Pulmonary Edema 25 pairs of muscles in the mouth, pharynx, larynx, and esopha-
The specific pathways for neurogenic pulmonary edema have gus. Swallowing is a primitive reflex. The human fetus can
not been identified with certainty. Based primarily on experimen- swallow by the twelfth week of gestation, before cortical and
tal data, hypothalamic and medullary sites have been reported to subcortical structures have developed. Swallowing has even been
be the origin of neurogenic pulmonary edema. reported to occur in anencephalic fetuses. The process of swal-
Clinical reports of neurogenic pulmonary edema from focal lowing involves three functionally distinct phases: oral, pharyn-
lesions support a caudal brain stem site for the induction of pul- golaryngeal, and esophageal. In the oral phase, food is broken
monary edema. These cases include focal puncture wounds of the into sufficiently small pieces for transport through the pharynx
medulla, posterior fossa stroke, localized brain stem hemorrhage, and esophagus and the food is propelled into the pharynx after
bulbar poliomyelitis, and multiple sclerosis. Recent high-resolution mastication. The oral phase is entirely voluntary and can be in-
brain imaging studies have suggested an anatomic substrate for terrupted at any time. The pharyngolaryngeal phase propels the
neurogenic pulmonary edema in the caudal brain stem that in- bolus to the esophagus while coordinating the protection of the
cludes the nucleus solitarius, the dorsal motor nucleus of the va- respiratory tract by means of inhibition of respiration, closure of
gus, and the medial medullary reticular formation. Both indirect the palatopharyngeal isthmus, and constriction of the larynx.
evidence and direct evidence support the nucleus solitarius as the The esophageal phase involves both striated and smooth
effector site inducing neurogenic pulmonary edema. The caudal esophageal muscles and propels the food to the stomach. The
portion of the nucleus solitarius appears phylogenetically only in pharyngolaryngeal and esophageal phases are controlled invol-
air-breathing animals and contains the neuronal pools involved untarily, by neurons in the medullary reticular formation.
in the regulation of ventilation. The nucleus is also the site of ter- Stimulation studies suggest that two regions in the
mination of afferent fibers from the lung (via cranial nerves IX medulla are involved in swallowing: both areas consti-
and X) and from chemoreceptors and baroreceptors of the carotid tute the central pattern generator (CPG). The dorsal
sinus. Efferent fibers from the ventral lateral zone of the nucleus swallowing group (DSG), located within the nucleus solitarius
solitarius terminate in the thoracic region of the spinal cord. The and the adjacent reticular formation, contains the generator neu-
caudal zone of the nucleus plays well-defined roles in the regula- rons which trigger, shape, and time the sequential or rhythmic
tion of other peripheral cardiovascular functions, particularly swallowing pattern. The ventral swallowing group (VSG), lo-
systemic vascular pressure. cated in the ventrolateral medulla adjacent to the nucleus am-
biguus, contains the switching neurons, which distribute the
The Medulla and Sneezing swallowing drive to the various motor neuronal pools involved in
swallowing. The ventral swallowing group of neurons is driven
The sneezing reflex is triggered by a variety of stimuli, the most by the dorsal swallowing group (Figure 5–19). The swallowing
common of which is stimulation of the nasal mucosa (trigeminal centers in the medulla are influenced by peripheral stimuli from
nerve sensory endings) by mechanical or chemical stimuli. Other sensory receptors and by descending suprasegmental input. The
stimuli include exposure to bright or blue light (solar sneeze) and peripheral fields from which swallowing can be evoked include
male orgasm. The latter two stimuli elicit sneezing via pathways the posterior tongue and the oropharyngeal region. The most
that converge on the sneezing center. The sneezing center is in important afferent impulses are carried in the glossopharyngeal
the medulla oblongata at the ventromedial margin of the descend- and vagus nerves. Descending pathways that modify swallowing
ing tract and nucleus (spinal nucleus) of the trigeminal nerve arise from the prefrontal cortex, the limbic system, the hypothal-
and includes the adjacent reticular formation and nucleus soli- amus, the midbrain, and the pons. Descending influences can be
tarius. The sneezing reflex has two phases: nasal and respiratory. either excitatory or inhibitory. Descending pathways are impor-
The afferent limb of the nasal phase consists of the ethmoidal tant in the process of learning to integrate orofacial movements
(cranial nerve V) and olfactory (cranial nerve I) nerves, which in the oral phase but are not essential in the coordination of the
project to the sneezing center in the medulla oblongata. The ef- pharyngeal and esophageal phases. Swallowing continues in hu-
ferent limb consists of preganglionic fibers to the greater petrosal mans and experimental animals with lesions in the descending
nerve (cranial nerve VII) and the sphenopalatine ganglion (cra- pathways.
94 / CHAPTER 5
of the presence of a group of loosely organized neuronal groups

Supramedullary Input
that may be activated in sequence by a central pattern generator.
Neuroanatomy of Yawning
Yawning is a phylogenetically old, stereotyped event that occurs
Central DSG
Pattern Generator Neurons
IX, X Peripheral alone or in association with stretching, penile erection, or both.
Input It is characterized by gaping and facial mimics that are accompa-
Generator Nucleus Solitarius
X nied by a long inspiration followed by a shorter expiration. The
V
XII neural structures necessary for yawning are presumably located
VII VSG in the medulla oblongata close to respiratory and vasomotor cen-
Switching Neurons ters. Yawning can be triggered by a variety of stimuli, including
C-1–C-3
seeing someone yawn, being involved in a boring task, and think-
ing about it. Yawning is influenced by several neurotransmitters
Nucleus Ambiguus and neuropeptides. Oxytocinergic neurons in the paraventricular
nucleus of the hypothalamus mediate the expression of yawning
Figure 5–19. Schematic diagram of the swallowing central via connections to the hippocampus, pons, and medulla oblon-
pattern generator and its afferent and efferent connections. gata. Yawn-producing neurons in the paraventricular nucleus are
Roman numerals indicate cranial nerves. DSG, dorsal swallowing activated by dopamine, excitatory amino acids, and oxytocin.
group; VSG, ventral swallowing group; C-1–C-3, motor neurons at They are inhibited by opioid peptides. Several links exist among
cervical spinal segments 1–3. neurotransmitters and neuropeptides involved in yawning, sug-
gesting that multiple pathways influence yawning. The details of
these pathways are not yet worked out.
Neuroanatomy of Vomiting Neurotransmitters and Neuropeptides
Vomiting or emesis is an instinctive defense reaction caused by The following neurotransmitters and neuropeptides have been
somatoautonomic reflexes integrated in the medulla oblongata. identified in the medulla oblongata: acetylcholine, norepineph-
Vomiting may be induced by a variety of triggers: motion, adverse rine, serotonin, enkephalin, substance P, somatostatin, cholecys-
drug reactions, trauma, toxin ingestion, among others. A tokinin, and neuropeptide Y (Table 5–2).
chemoreceptor trigger zone for vomiting is present in the
area postrema, an area in the floor of the fourth ventricle
devoid of blood-brain barrier. Chemoreceptors in the area BLOOD SUPPLY OF THE MEDULLA
postrema detect emetic agents in the blood and relay the infor- The medulla oblongata receives its blood supply from the follow-
mation to the adjacent nucleus solitarius. Ablation of the area ing arteries:
postrema abolishes the response to emetic agents in the blood
stream. In addition to the input from area postrema, the nucleus 1. Vertebral
solitarius receives inputs from taste receptors via cranial nerves 2. Anterior spinal
VII, IX, and X; autonomic input from the intestine via cranial 3. Posterior spinal
nerve X (parasympathetic) and splanchnic nerves (sympathetic);
4. Posterior inferior cerebellar artery (PICA)
and from the vestibular system. The nucleus solitarius projects to a
central pattern generator, which coordinates the sequence of be- The medulla is divided into the following four vas-
haviors during vomiting, to a group of cranial nerve nuclei that cular territories: paramedian, olivary, lateral, and dorsal
control jaw, mouth, and tongue movements (trigeminal, facial, (Figure 5–20).
and hypoglossal), to nuclei that control respiratory and abdominal The paramedian territory receives its blood supply from the
muscles that participate in the expulsive phase of vomiting (dorsal vertebral and/or anterior spinal arteries. It includes the pyramid,
motor nucleus of vagus, nucleus ambiguus, anterior horn of spinal the medial lemniscus, the medial longitudinal fasciculus, and the
cord), and to the hypothalamus. The previous concept of a “vom- hypoglossal nucleus and nerve. The olivary territory receives an
iting center” in the medulla has now been replaced by the concept inconstant blood supply from the vertebral artery. It includes
Table 5–2. Medulla Oblongata: Neurotransmitters and Neuropeptides
Hypoglossal Dorsal motor Nucleus Nucleus Spinal Reticular Raphe

nucleus nucleus of vagus ambiguus solitarius trigeminal nucleus formation nucleus
Acetylcholine X X X
Norepinephrine X
Serotonin X
Enkephalin X X X X
Substance P X X X
Somatostatin X
Cholecystokinin X
Neuropeptide Y X
Hypoglossal nucleus Dorsal motor nucleus

of vagus
Nucleus solitarius
Medial longitudinal
fasciculus Inferior and medial
vestibular nuclei
Restiform body
Dorsal territory
Spinal trigeminal
nucleus and tract
Lateral territory Nucleus ambiguus

Spinothalamic tract
Spinocerebellar tract
Olivary territory
Inferior olive
Hypoglossal nerve
Figure 5–20. Schematic diagram of vas-

Medial lemniscus Pyramid
cular territories of the medulla oblongata. Paramedian territory
most of the inferior olivary complex. The lateral territory re- Cruveilhier, Jean (1791–1874). A French surgeon and pathol-
ceives a constant blood supply from the vertebral artery and a ogist who traced the crossing of the pyramids at the pyramidal
variable supply from the posterior inferior cerebellar artery. It in- decussation.
cludes the dorsal motor nucleus of the vagus, the nucleus solitar- Cuneate (Latin, “wedge”). The cuneate fasciculus and cuneate
ius and tract, vestibular nuclei, the nucleus ambiguus, the spinal tubercle are so called because of their wedgelike shape.
trigeminal nucleus and tract, the lateral spinothalamic tract, the Dejerine, Joseph-Jules (1849–1917). A French neurologist
restiform body, and the olivocerebellar pathway. The dorsal terri- who increased knowledge about cerebral localization, clinical
tory is supplied rostrally by the posterior inferior cerebellar neurology, and the alexias.
artery and caudally by the posterior spinal artery. This includes
the vestibular nuclei, the dorsal column nuclei and tracts, and Dysphagia (Greek dys, “difficult”; phagien, “to eat”). Difficulty
part of the restiform body. swallowing.
Dyspnea (Greek dyspnoia, “difficulty breathing”). Difficulty
breathing.
TERMINOLOGY Galen, Claudius (A.D. 130–200). Founder of Galenic medicine.
Described the Great Vein of Galen and several cranial nerves. He
Accessory nerve. The eleventh cranial nerve (accessory nerve of described the function of the recurrent laryngeal nerve by cut-
Willis) was described by Thomas Willis in 1664. The name acting the nerve in the pig. His many contributions guided med-
cessory was used because this nerve receives an additional root ical practice for over a thousand years.
from the upper part of the spinal cord. Gall, F. J. (1758–1828). A Viennese physician and neuroanat-
Arcuate nucleus (Latin arcuatus, “bow-shaped”). The arcuate omist who founded the discipline of phrenology and cerebral
nucleus in the medulla oblongata is an archlike structure lateral localization.
and inferior to the pyramid. Glossopharyngeal (Greek glossa, “tongue”; pharynx, “throat”).
Area postrema. One of the circumventricular organs devoid of a The ninth cranial nerve. Included by Galen with the sixth nerve.
blood-brain barrier. Located in the floor of the fourth ventricle. Fallopius distinguished it as a separate nerve in 1561. Thomas
Ataxia (Greek a, “negative”; taxis, “order”). Without order, Willis included it as part of the eighth nerve. Soemmering listed
disorganized. Incoordination of movement frequently seen in it as the ninth cranial nerve.
cerebellar disease. The term was used by Hippocrates and Galen Gracile (Latin, “slender, thin”). The fasciculus gracilis and nu-
for disordered action of any type, such as irregularity of pulse. cleus gracilis are so named because they are slender and long.
Brachium (Latin, Greek brachion, “arm”). Any structure re- Gustatory (Latin gustatorius, “pertaining to the sense of taste”).
sembling an arm. Hemiplegia cruciata (alternate brachial diplegia). Paralysis of
Brachium conjunctivum (Latin, Greek brachion, “arm”; con- one arm and the contralateral leg caused by a lesion within the
junctiva, “connecting”). An armlike bundle of fibers that con- pyramidal decussation at a point below the decussation of fibers
nect the cerebellum and midbrain. destined for the arm and above the decussation of fibers destined
Brachium pontis. An armlike bundle of fibers that link the pons for the leg.
and the cerebellum. Hypoglossal nerve (Greek hypo, “beneath”; glossa, “tongue”).
Cinereum (Latin cinerius, “ashen-hued,” for the gray matter The twelfth cranial nerve was so named by Winslow. Willis in-
of the brain). The term tuberculum cinereum refers to the spinal cluded it with the ninth cranial nerve. It was named the twelfth
trigeminal nucleus. nerve by Soemmering.
Clava (Latin, “stick”). The surface marking of the nucleus gra- Jackson’s Syndrome. Paralysis of the hypoglossal, cranial acces-
cilis on the dorsal surface of the medulla oblongata. sory, vagus, glossopharyngeal nerves and contralateral hemiparesis,
96 / CHAPTER 5
associated with intramedullary lesions. First described by John Tractotomy. A surgical operation that involves severing a spe-
Hughlings in a case of tongue paralysis from intramedullary cific nerve fiber tract in the central nervous system, usually to re-
hemorrhage. lieve pain.
Lemniscal decussation. Crossing of axons of the posterior col- Trigeminal nerve (Latin tres, “three”; geminus, “twin”). The fifth
umn nuclei in the medulla oblongata to form the medial lemnis- cranial nerve was described by Fallopius. So named because the
cus. Also known as sensory decussation. nerve has three divisions: ophthalmic, maxillary, and mandibular.
Locus ceruleus (Latin, “place, dark blue”). A pigmented norad- Trigone (Latin, “triangular area”). The hypoglossal and vagal
renergic nucleus in the rostral pons that is dark blue in sections. trigones are so named because of their triangular shape.
Motor decussation. The crossing of most of the pyramidal Vagus (Latin vagari, “wanderer”). The tenth cranial nerve is so
fibers in the caudal medulla oblongata to form the lateral corti- named because of its long course and wide distribution. The
cospinal tract. Also called the pyramidal decussation. nerve was described by Marinus in about A.D. 100. The name
Nucleus ambiguus (Latin, “changeable or doubtful”). The vagus was coined by Domenico de Marchetti of Padua.
boundaries of the nucleus ambiguus are indistinct. Velum (Latin, “curtain or veil”). A term used for various thin
Nystagmus (Greek nystagmos, “drowsiness, nodding”). Nod- membranes or veils in the brain, such as the superior medullary
ding or closing of the eyes in a sleepy person. Today the term velum and inferior medullary velum, that constitute the roof of
refers to involuntary rhythmic oscillation of the eyes. the fourth ventricle.
Ondine’s curse. A syndrome characterized by the cessation of
breathing in sleep because of failure of the medullary automatic
respiratory center. Named after the story of the 1939 play
“Ondine” by the French playwright Jean Giraudoux in which a SUGGESTED READINGS
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Medulla Oblongata: Clinical Correlates 6
Medial Medullary Syndrome (Dejerine’s Anterior Bulbar Dorsal Medullary Syndrome

Syndrome) Collet-Sicard Syndrome
Lateral Medullary Syndrome Pseudobulbar Palsy
Babinski-Nageotte Syndrome
KEY CONCEPTS
Vascular lesions of the medulla oblongata are designated ataxia, vertigo, ipsilateral Horner’s syndrome, nystagmus,
by the anatomic region affected rather than by the arte- and ocular lateropulsion.
rial supply.
The clinical signs of combined lateral and medial medul-
The clinical signs of the medial medullary syndrome in- lary syndromes constitute the Babinski-Nageotte syndrome.
clude contralateral weakness of the upper motor neuron
The clinical signs of the dorsal medullary syndrome in-
type, contralateral loss of kinesthesia and discriminative
clude ipsilateral ataxia, nystagmus, vomiting, and vertigo.
touch, and ipsilateral tongue weakness of the lower mo-
tor neuron type. The Collet-Sicard syndrome results from an extra-axial le-
sion affecting cranial nerves IX to XII.
The clinical signs of the lateral medullary syndrome in-
clude loss of pain and temperature sense in the ipsilateral Bilateral interruption of the corticobulbar or corticoretic-
face and the contralateral half of the body, ipsilateral loss ulobulbar fibers results in the pseudobulbar syndrome.
of the gag reflex, hoarseness, dysphagia, dysarthria,
Vascular lesions in the medulla oblongata are best suited to 3. Rootlets of the hypoglossal nerve or its nucleus within the
anatomicoclinical correlation. In the past, these syndromes were medulla
designated by the artery of supply (e.g., anterior spinal artery
syndrome, posterior inferior cerebellar artery syndrome, The neurologic signs resulting from the involvement of these
vertebral artery syndrome). Because of variations in the areas are as follows:
source of blood supply, however, these syndromes are
1. Contralateral loss of kinesthesia and discriminative
currently designated by the anatomic region affected by the le-
touch resulting from involvement of the medial lemniscus
sion. Two such syndromes are particularly illustrative: the medial
medullary syndrome and the lateral medullary syndrome. 2. Contralateral paralysis of the upper motor neuron
type (weakness, hyperactive reflexes, Babinski’s sign, clonus,
and spasticity) with sparing of the face caused by involve-
MEDIAL MEDULLARY SYNDROME ment of the pyramid
(DEJERINE’S ANTERIOR BULBAR SYNDROME) 3. Lower motor neuron paralysis of the homolateral half of the
The medial medullary syndrome (Figure 6–1) is caused by oc- tongue (weakness, atrophy, and fibrillation) and deviation of
clusion of the anterior spinal artery or the paramedian branches the protruded tongue to the atrophic side caused by involve-
of the vertebral artery. The affected area usually includes the fol- ment of the hypoglossal nucleus or nerve
lowing structures: The medial medullary syndrome may occur bilaterally, resulting
in bilateral upper motor neuron weakness or paralysis (with facial
1. Medial lemniscus sparing), bilateral paralysis of the tongue of the lower motor neuron
2. Pyramid type, and bilateral loss of kinesthesia and discriminative touch.
98
MEDULLA OBLONGATA: CLINICAL CORRELATES / 99
Hypoglossal nucleus
s
MEDIAL MEDULLARY SYNDROME
Paralysis of homolateral half of

tongue (lower motor neuron
type)
Medial lemniscus Contralateral paralysis (upper

motor neuron type)
Figure 6–1. Schematic diagram of Contralateral loss of kines-

thesia and discriminative
medullary structures involved in the me- touch
dial medullary syndrome, and the result-
ing clinical manifestations. Pyramid
LATERAL MEDULLARY SYNDROME The neurologic signs and symptoms resulting from the in-
volvement of these areas include the following:
The lateral medullary syndrome (Figure 6–2) is caused by occlu-
sion of the vertebral artery or, less frequently, the medial branch 1. Loss of pain and temperature sensations from the ip-
of the posterior inferior cerebellar artery when this artery sup- silateral face as a result of involvement of the spinal nu-
plies the lateral medulla. It is also known as the posterior inferior cleus of the trigeminal nerve and its tract.
cerebellar artery (PICA) syndrome or Wallenberg’s syndrome. 2. Loss of pain and temperature sensation over the contralateral
The affected area usually includes the following structures: half of the body because of involvement of the spinothalamic
tract.
1. Spinal nucleus of the trigeminal nerve and its tract 3. Loss of the gag reflex, difficulty swallowing (dysphagia),
2. Adjacent spinothalamic tract hoarseness, and difficulty in articulation (dysarthria) caused
3. Nucleus ambiguus or its axons by paralysis of muscles supplied by the nucleus ambiguus
ipsilateral to the medullary lesion.
4. Base of the inferior cerebellar peduncle (restiform body)
4. Ipsilateral loss of coordination (ataxia) resulting from in-
5. Vestibular nuclei volvement of the base of the inferior cerebellar peduncle.
6. Descending sympathetic fibers from the hypothalamus 5. Hallucination of turning (vertigo) resulting from involve-
7. Olivocerebellar fibers ment of the vestibular nuclei.
LATERAL MEDULLARY SYNDROME

Vestibular nuclei
Restiform body Loss of pain and temperature
sensations over the ipsilat-
eral face and contralateral
Spinal trigemin half of the body
nucleus
Ataxia (loss of coordination)
Spinothalamic
Vertigo (hallucination of
tract
movement)
Nucleus ambiguus Loss of gag reflex, difficulty in
swallowing, and difficulty in
articulation
Ipsilateral Horner’s syndrome
Vomiting, nausea, and

nystagmus
Hiccups
Ocular lateropulsion
Figure 6–2. Schematic diagram of medullary structures involved in the lateral medullary syn-
drome, and the resulting clinical manifestations.
100 / CHAPTER 6
6. Horner’s syndrome caused by involvement of the descending tent of the lesion. The following sensory patterns (Figure 6–3)
sympathetic fibers from the hypothalamus. This syndrome have been described (Table 6–1):
consists of a small pupil (miosis), slight drooping of the up- 1. Loss of pain and thermal sense in the ipsilateral face and con-
per eyelid (ptosis), and warm dry skin of the face (anhidro- tralateral body (classical pattern). This pattern has been re-
sis), all ipsilateral to the lesion. ported in 26 percent of patients. The lesion is in the postero-
7. Vomiting, nystagmus, and nausea resulting from involve- lateral part of the caudal-middle medulla and involves the
ment of the vestibular nuclei. spinothalamic tract and spinal trigeminal tract and nucleus.
8. Hiccuping that is of uncertain cause but usually is attributed 2. Loss of pain and thermal sense in the face bilaterally and in the
to involvement of the respiratory center in the reticular for- contralateral body. This pattern occurs in 24 percent of pa-
mation of the medulla. tients. The lesion is usually large in the posterolateral and ven-
9. Ocular lateropulsion occurs almost universally in this syn- tromedial parts of the middle-rostral medulla. In addition to
drome. It consists of a tendency toward saccadic eye move- the spinothalamic tract and spinal trigeminal tract and nucleus,
ment overshoot or hypermetria toward the side of the lesion the trigeminothalamic tract (secondary trigeminal) is involved.
and a tendency toward hypometria away from the lesion. 3. Loss of pain and thermal sense in the contralateral face and
Ocular lateropulsion is believed to result from involvement body. This pattern reportedly occurs in 18 percent of pa-
of olivocerebellar fibers related to ocular movement traveling tients. The lesion spares most of the posterolateral part of the
in the lateral medulla or to a concomitant cerebellar lesion. medulla and selectively involves the spinothalamic and tri-
10. Difficulty pursuing contralateral moving targets as a result of geminothalamic tracts.
involvement of the vestibular pathways to nuclei of extra- 4. Loss of pain and thermal sense in the contralateral body. The
ocular movement. face is spared. This pattern occurs in 20 percent of patients.
The lesion is small and superficial in the lateral medulla, in-
Although credit for the description of the lateral medullary volving only the spinothalamic tract.
syndrome in 1895 is often given to Adolph Wallenberg, as evi- 5. Loss of pain and thermal sense in the ipsilateral face. This
denced by the term Wallenberg’s syndrome, the Swiss physician pattern has been reported to occur in 8 percent of patients.
Gaspard Vieusseux provided an account in 1810, reporting in The lesion is usually small, more posteriorly localized, and
detail his own stroke to the Medical and Surgical Society of involves only the spinal trigeminal tract and nucleus.
London.
6. No sensory loss. This pattern has been reported in 4 percent of
Clinical manifestations of the lateral medullary syndrome may
patients. The lesion is small and spares all sensory structures.
vary depending on the caudal-rostral level of the lesion. Dys-
phagia, hoarseness, and ipsilateral facial paresis are more common Dissociation of spinothalamic sensation (loss of thermal sense
in patients with lesions in the rostral medulla. Gait ataxia, vertigo, and maintenance of pain sensation) in the contralateral body has
and nystagmus are more common in patients with caudal medul- been reported in the lateral medullary syndrome. This pattern is
lary lesions. The ipsilateral facial paresis reported in rostral me- attributed to a small superficial lesion that transects the lateral
dullary lesions is attributed to involvement of aberrant cortico- spinothalamic tract, thus affecting thermal fibers and sparing
bulbar fibers in the medulla or extension of the medullary lesion pain fibers.
to the pons. Proprioceptive (vibration, position) deficits have been re-
The sensory pattern in the lateral medullary syndrome has ported in lateral medullary syndrome when the lesion is in the
been shown to vary with the rostral-caudal and lateral-medial ex- caudal medulla and involves the posterior column nuclei.
Figure 6–3. Lateral medullary syndrome patterns.

MEDULLA OBLONGATA: CLINICAL CORRELATES / 101
Table 6–1. Lateral Medullary Syndrome Patterns of Sensory Deficits (Pain and Thermal Sense)
Face Body Involved structures
Pattern Ipsilateral Contralateral Bilateral Ipsilateral Contralateral Spinothalamic Spinal trigeminal Trigeminothalamic
tract tract and nucleus tract
1 X X X X
2 X X X X X
3 X X X X
4 ` X X
5 X X
Chronic facial pain has been reported in some patients with ogist and neurologist Jean-Athenase Sicard, this syndrome consists
lateral medullary syndrome. This rare manifestation has been at- of loss of taste in the posterior third of the tongue, paralysis of
tributed to a lesion that affects the rostral spinal trigeminal nu- vocal cords and palate, weakness of sternomastoid and trapezius
cleus (pars oralis and interpolaris) and tract, and that spares the muscles, and hemianesthesia of palate, tongue, and pharyngeal
caudal spinal trigeminal nucleus (pars caudalis), where most no- wall, all ipsilateral to the lesion. The syndrome is associated with
ciceptor neurons are located. Deafferentation of the pars caudalis unilateral extra-axial injury of the glossopharyngeal (cranial
results in abnormal neuronal activity, which is transmitted to the nerve IX), vagus (cranial nerve X), accessory (cranial nerve XI),
thalamus and beyond, leading to chronic neuropathic pain. and hypoglossal (cranial nerve XII) nerves.
Besides Wallenberg’s syndrome, occlusion of the medial branch
of PICA can present with a pseudolabyrinthine syndrome char- PSEUDOBULBAR PALSY
acterized by cerebellar and vestibular signs (vertigo, dysmetria,
ataxia, and axial lateropulsion) that overshadow the medullary Pseudobulbar palsy is a clinical syndrome caused by the inter-
signs. Occlusion of the medial branch of the posterior inferior ruption of the corticobulbar fibers to motor nuclei of the cranial
cerebellar artery also may result in a silent infarct that is detected nerves. Most cranial nerve nuclei in the brain stem receive bilat-
only at autopsy. There are no clinical reports of occlusion of the eral inputs from the cerebral cortex arising primarily from the
lateral branch of the posterior inferior cerebellar artery. Silent in- precentral cortex. The majority of these fibers reach cra-
farcts have been reported as a chance autopsy finding. nial nerve nuclei via the reticular formation (corti-
coreticulobulbar system). Some cranial nerve nuclei,
BABINSKI-NAGEOTTE SYNDROME however, receive corticobulbar fibers directly. These nuclei in-
clude the sensory and motor trigeminal nuclei, the nucleus soli-
The Babinski-Nageotte syndrome, also known as medullary tarius, the facial motor nucleus, the spinal accessory (supraspinal)
tegmental paralysis, is a combined lateral and medial medullary nucleus, and the hypoglossal nucleus.
syndrome. The lesion is at the pontomedullary junction. Bilateral interruption of the indirect corticoreticulobulbar or
Manifestations include ipsilateral Horner’s syndrome direct corticobulbar fibers in the brain stem results in the syn-
(autonomic sympathetic fibers); ipsilateral weakness of drome of pseudobulbar palsy. The neurologic manifestations of
the soft palate, pharynx, larynx (nucleus ambiguus), and tongue this syndrome include the following:
(hypoglossal nucleus); loss of taste in the posterior third of the 1. Weakness (upper motor neuron variety) of muscles supplied
tongue (nucleus solitarius); cerebellar ataxia (restiform body)
by the corresponding cranial nerve nuclei
and nystagmus (vestibular nuclei); and contralateral hemiparesis
(pyramid) and hemianesthesia (medial lemniscus). 2. Inappropriate outbursts of laughter and crying
DORSAL MEDULLARY SYNDROME TERMINOLOGY

The dorsal medullary syndrome is caused by occlusion Anhidrosis (Greek an, “negative”; hidros, “sweat”). Absence
of the medial branch of the posterior inferior cerebellar or deficiency of sweating.
artery. Affected structures include the vestibular nuclei Babinski’s sign. An upper motor neuron lesion sign character-
and the restiform body (inferior cerebellar peduncle). The associ- ized by dorsiflexion of the big toe and fanning out of the rest of
ated neurologic signs include the following: the toes upon painful stimulation or stroking of the sole. The
1. Ipsilateral limb or gait ataxia resulting from involvement of sign was described “as the phenomenon of the toes” by Josef-
the restiform body François-Felix Babinski (1857–1932), a French neurologist, in
2. Vertigo, vomiting, and ipsilateral gaze-evoked nystagmus re- 1896. The phenomenon had previously been noted by Hall and
sulting from involvement of the vestibular nuclei Remak. Babinski investigated the phenomenon in depth in pa-
pers published between 1896 and 1903.
COLLET-SICARD SYNDROME Clonus (Greek klonos, “turmoil”). Alternate muscular contrac-
tion of agonist and antagonist muscle groups in rapid succession
Described by the French otolaryngologist Frederick in response to sudden stretching of the muscle tendon. Usually
Collet in 1915 and two years later by the French radiol- seen in an upper motor neuron lesion caused by the loss of
102 / CHAPTER 6
suprasegmental inhibition of the local spinal reflex arc. The term lateral bulbar syndrome and the posterior inferior cerebellar
was originally used by Greek physicians for the convulsing move- artery syndrome. A syndrome consisting of vertigo, vomiting,
ments of epileptics. hiccups, dysarthria, dysphagia, hoarseness, ataxia, Horner’s syn-
Dejerine, Joseph-Jules (1849–1917). A French neurologist drome, and crossed sensory loss. The syndrome was described in
who described, among other syndromes, the medial medullary detail by Adolph Wallenberg, a German neurologist, in 1895.
syndrome. An earlier account of the syndrome was provided by the Swiss
Dysmetria (Greek dys, “difficult”; metron, “measure”). physician Gaspard Vieusseux in 1810.
Improper measuring of distance, disturbed control of range of
movement. A sign of cerebellar disease. SUGGESTED READINGS
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Hemianesthesia (Greek hemi, “half ”; an, “negative”; aisthe-
Brazis PW: The localization of lesions affecting the brainstem. In Brazis PW
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mos), and loss of sweating on the face (anhidrosis) constitute a Clinical–MRI correlation. Neurology 1997; 49:1557–1563.
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Pons 7
Gross Topography Cranial Nerve Nuclei

Ventral Surface Cochleovestibular Nerve (Cranial Nerve VIII)
Dorsal Surface Facial Nerve (Cranial Nerve VII)
Microscopic Structure Abducens Nerve (Cranial Nerve VI)
Basis Pontis (Ventral) Trigeminal Nerve (Cranial Nerve V)
Tegmentum (Dorsal)
Pontine Reticular Formation
Parabrachial and Pedunculopontine Nuclei
Parabrachial Nucleus
Pedunculopontine Nucleus
KEY CONCEPTS
The ventral surface of the pons shows the basilar artery Reciprocal feedback circuits exist throughout the extent
in the pontine sulcus and four cranial nerves: the ab- of the auditory pathways.
ducens at the medullary pontine junction, the facial and
Reflex eye and neck movements to sound are carried out
cochleovestibular in the cerebellopontine angle, and the
via two pathways: from the inferior colliculus to the supe-
trigeminal at the midpontine level.
rior colliculus and then via the tectobulbar and tectospinal
The dorsal surface of the pons forms the rostral floor tracts to the nuclei of eye and neck muscles and from the
of the fourth ventricle, in which the facial colliculi are superior olive to the abducens nucleus and then via the
seen. Coronal sections of the pons reveal two compo- medial longitudinal fasciculus to the nuclei of extraocular
nents: a ventral and phylogenetically newer basis pontis movements.
and a dorsal and phylogenetically older tegmentum.
Vestibular nerve fibers terminate selectively on four ves-
The basis pontis contains pontine nuclei and the follow- tibular nuclei: medial (Schwalbe’s principal), inferior
ing nerve fiber bundles: corticospinal, corticobulbar, and (spinal), lateral (Deiters’), and superior (Bechterew’s).
corticopontocerebellar (the largest). Some fibers project directly to the cerebellum.
The tegmentum contains the following nerve fiber bundles: The output of vestibular nuclei is to the following
medial lemniscus,trigeminal lemniscus,spinothalamic,trap- areas: spinal cord, cerebellum, thalamus, nuclei of
ezoid body, central tegmental tract, medial longitudinal extraocular movement, vestibular cortex, and vestibu-
fasciculus, tectospinal, and descending sympathetic fibers. lar end organ.
The parabrachial nucleus plays an important role in auto- Vestibular projections to the nuclei of extraocular move-
nomic regulation. The pedunculopontine nucleus plays ment play important roles in controlling conjugate eye
roles in locomotion,motor learning,reward system,arousal, movements.
and saccadic eye movements.
The sensory facial nuclei are the spinal trigeminal nu-
Cochlear nerve fibers terminate selectively on neurons in cleus (exteroceptive sensation) and the nucleus solitarius
the dorsal or ventral cochlear nuclei. (taste).
103
104 / CHAPTER 7
(continued from previous page) The motor nucleus of the trigeminal nerve supplies the
muscles of mastication, the tensor tympani, the tensor
The motor facial nuclei are the facial motor nucleus (so- palati, the mylohyoideus, and the anterior belly of the
matic motor) and the superior salivatory nucleus (visceral digastric.
motor).
The sensory nuclei of the trigeminal nerve are the spinal
Cortical input to the facial motor nucleus is bilateral to (pain,temperature,touch),principal (main) sensory (touch),
the upper face motor neurons and only contralateral to and mesencephalic (proprioception).
the lower face motor neurons.
Dorsal and ventral trigeminothalamic tracts link the main
Characteristic conglomerate clinical signs occur in lesions sensory and spinal trigeminal nuclei, respectively, with
of the facial nerve at or distal to the stylomastoid fora- the thalamus.
men, distal to the geniculate ganglion, and proximal to
Blood supply to the pons is provided by the basilar artery
the geniculate ganglion.
via three branches: paramedian, short circumferential,
Lesions of the abducens nerve outside the neuraxis result in and long circumferential.
ipsilateral lateral rectus paralysis. Lesions of the abducens
nucleus result in paralysis of ipsilateral lateral gaze.
GROSS TOPOGRAPHY angle between the caudal pons, the rostral medulla, and the cere-
bellum (the cerebellopontine angle), the facial (cranial nerve VII)
The pons is the part of the brain stem that lies between the and cochleovestibular (cranial nerve VIII) nerves appear. From
medulla oblongata caudally and the midbrain rostrally. The cere- the lateral and rostral parts of the pons emerge the two compo-
bral peduncles and the superior pontine sulcus mark its rostral nents of the trigeminal nerve (cranial nerve V): the larger sensory
boundary, the middle cerebellar peduncles (brachium pontis) portion (portio major) and the smaller motor portion (portio mi-
mark its lateral boundary, and the inferior pontine sulcus marks nor). The crowding of the facial and cochleovestibular nerves in
its caudal boundary. The dorsal surface of the pons is covered by the cerebellopontine angle explains the early involvement of these
the cerebellum. two nerves in tumors (acoustic neuromas) that arise in this angle.
Ventral Surface Dorsal Surface

The ventral surface (Figure 7–1) of the pons forms a The dorsal surface (see Figure 5–3) of the pons forms
bulge known as the pontine protuberance. In the middle the rostral portion of the floor of the fourth ventricle.
of this protuberance is the pontine sulcus, which contains This part of the floor features the facial colliculi, one on
the basilar artery. Several cranial nerves leave the ventral surface of each side of the midline sulcus (median sulcus). These colliculi
the pons. The abducens nerve (cranial nerve VI) emerges from the represent the surface landmarks of the genu of the facial nerve
boundary between the pons and the medulla oblongata. In the and the underlying nucleus of the abducens nerve.
Figure 7–1. Schematic diagram

of the ventral surface of the brain
stem showing the major structures
on the ventral surface of the pons.
PONS / 105
MICROSCOPIC STRUCTURE cerned with the rapid correction of movements. The func-
tional significance of the cingulopontine fiber connection is
Coronal sections of the pons reveal a basic organizational pattern not known, but it may represent the anatomic substrate for
made of two parts: a ventral basis pontis and a dorsal tegmentum. the effect of emotion on motor function. The input from the
association cortices suggests a role for this fiber system in be-
Basis Pontis (Ventral) havioral and cognitive processes. A cortical region usually
projects to more than one cell column of the pontine nuclei,
The basis pontis (Figure 7–2) corresponds to the pontine protu- and some pontine columns receive projections from more
berance described in “Gross Topography,” earlier. It contains the than one cortical region. Like the corticoolivocerebellar sys-
pontine nuclei and multidirectional nerve fiber bundles. tem, the corticopontocerebellar system is somatotopically
The multidirectional nerve fiber bundles in the basis organized. Thus, the prerolandic cortex (primary motor cor-
pontis belong to three fiber systems. tex) projects to medial pontine nuclei, the postrolandic cor-
1. Corticospinal fibers from the cerebral cortex to the tex (primary somatosensory cortex) to lateral pontine nuclei,
spinal cord pass through the basis pontis and continue cau- the arm area of the sensorimotor cortex to dorsal pontine
dally as the pyramids of the medulla oblongata. nuclei, and the leg area to ventral pontine nuclei. The pro-
2. Corticobulbar fibers from the cerebral cortex to the cranial jection from the cingulate gyrus also has been shown to be
nerve nuclei of the brain stem. Some of these fibers project somatotopically organized, with the anterior cingulate cortex
directly on the nuclei of cranial nerves (corticobulbar); the projecting to the medial pontine nuclei and the posterior
majority, however, synapse on an intermediate reticular nu- cingulate cortex projecting to the lateral pontine nuclei.
cleus before reaching the cranial nerve nucleus (corticoretic- The pontocerebellar projection is primarily crossed; however,
ulobulbar). Corticobulbar and corticoreticulobulbar fibers it has been estimated that 30 percent of the pontine projection
usually arise from both cerebral hemispheres. to the cerebellar vermis and 10 percent of the projection to the
3. Corticopontocerebellar fibers constitute the largest group of cerebellar hemisphere are ipsilateral. The density of projection to
fibers in the basis pontis. This fiber system originates from the cerebellar hemispheres is three times that to the vermis. Like
wide areas of the cerebral cortex, projects on ipsilateral pon- the corticopontine projection, the pontocerebellar projection is
tine nuclei, and crosses the midline on its way to the cerebel- somatotopically organized, with the caudal half of the pons pro-
lum via the middle cerebellar peduncle. It is estimated that jecting to the anterior lobe of the cerebellum and the rostral half
in humans this fiber system contains approximately 19 mil- projecting to the posterior lobe.
lion fibers on each side. The number of pontine neurons in The basilar portion of the pons is the phylogenetically newer
humans is estimated to be approximately 23 million in each part and is present only in animals with well-developed cerebel-
half of the pons. Thus, the ratio of corticopontine fibers to lar hemispheres.
pontine neurons is approximately 1:1. Although the cortico-
pontine projection is believed to arise from wide areas of Tegmentum (Dorsal)
the cerebral cortex, it arises principally from the prerolandic
and postrolandic sensorimotor cortices with minor to mod- The tegmentum is the phylogenetically older part of the pons and
erate contributions from the parietal and temporal associa- is composed largely of the reticular formation. Lesions that de-
tion cortices, the premotor and prefrontal association cor- stroy more than 25 percent of the tegmentum may result in loss
tices, and the cingulate gyrus. The fact that cortical input to of consciousness. In the basal part of the tegmentum, the medial
the pontine nuclei arises chiefly from primary cortical areas lemniscus (which maintains a vertical orientation on each side of
suggests that the corticopontocerebellar fiber system is con- the midline in the medulla) becomes flattened in a mediolateral
Abducens nucleus Corticobulbar tract
Corticoreticulobulbar tract
Pontine reticular nucleus

TEGMENTUM
Brachium pontis
(middle cerebellar
peduncle) BASIS PONTIS
of the pons showing its major divi-
sions into tegmentum and basis
pontis, and types of fiber bundles
traversing the basis pontis. Corticospinal tract Corticopontocerebellar tract
106 / CHAPTER 7
direction (Figure 7–3). Fibers originating from the cuneate nu- and ventral), and a small posterior and dorsal nucleus. The nu-
cleus are located medially; gracile fibers are laterally placed. cleus spans a rostral-caudal distance of 11 to 14 mm. Rostrally,
Lateral to the medial lemniscus lies the trigeminal tract, which the nucleus begins at the level of the inferior colliculus (mid-
conveys sensations of pain, temperature, touch, and propriocep- brain), where it is situated ventral and lateral to the cerebral
tion from the contralateral face. The spinothalamic tract is lateral aqueduct (aqueduct of Sylvius) in the periaqueductal gray matter
to the trigeminal tract and carries pain and temperature sensa- of the midbrain. Caudally, at the junction of the cerebral aque-
tions from the contralateral half of the body. Thus, in the basal duct and the fourth ventricle, the nucleus is displaced laterally.
part of the tegmentum lies the specific sensory lemniscal The number of cells in the nucleus increases from rostral to cau-
system, which includes the medial lemniscus, trigeminal dal. Two projection bundles emanate from the nucleus: a dorsal
lemniscus, and spinotha-lamic tract. ascending bundle to the hypothalamus, hippocampus, neocor-
Intermingled with the ascending fibers of the lemniscal sys- tex, and cerebellum and a descending bundle to the spinal cord.
tem are transversely oriented fibers of the trapezoid body. These Cell loss in the nucleus is generalized in Parkinson’s disease,
fibers arise from the cochlear nuclei, course through the tegmen- whereas it is limited to the rostral portion of the nucleus (which
tum, and gather in the lateral portion of the pons to form the lat- projects mainly to the cerebral cortex) in Alzheimer’s disease and
eral lemniscus. This fiber system will be discussed later in con- Down syndrome.
nection with the cochlear division of the cochleovestibular nerve
(cranial nerve VIII). PONTINE RETICULAR FORMATION
Dorsal to the medial lemniscus is the central tegmental tract,
which originates in the basal ganglia and midbrain and projects The pontine reticular formation constitutes the major part of the
on the inferior olive. It shifts position in the tegmentum of the tegmental portion of the pons and is a rostral continuation of the
pons and lies dorsal to the lateral part of the medial lemniscus in medullary reticular formation. The organization and connections
the caudal pons (Figure 7–3). of the pontine reticular formation are discussed in Chapter 32.
The medial longitudinal fasciculus and the tectospinal tract Lesions involving the pontine reticular nuclei in the tegmentum
retain the same dorsal and paramedian positions they occupied and corticospinal fibers in the basis pontis are associated with the
in the medulla just beneath the floor of the fourth ventricle syndrome of anosognosia for hemiplegia in which the patients
(Figure 7–3). are unaware of their motor deficit. A similar syndrome occurs in
Other tracts coursing through the tegmentum of the pons lesions of the nondominant parietal lobe.
include the rubrospinal tract medial to the spinal trigeminal nu-
cleus and the ventral spinocerebellar tract medial to the restiform PARABRACHIAL AND
body. The ventral spinocerebellar tract enters the superior cere-
bellar peduncle to reach the cerebellum. The tegmentum of the PEDUNCULOPONTINE NUCLEI
pons also contains descending sympathetic fibers from the hypo- Parabrachial Nucleus
thalamus; these fibers are located in the lateral part of the
tegmentum. Interruption of these fibers produces Horner’s syn- At the level of the isthmus, in the dorsolateral pons, between
drome (Chapter 5). Corticobulbar fibers and corticoreticulo- the lateral edge of the brachium conjunctivum (superior cere-
bulbar fibers on their way from the basis pontis to cranial nerve bellar peduncle) and the lateral lemniscus, is the parabrachial
nuclei also pass through the tegmentum (Figure 7–2). nucleus, a synaptic station for gustatory (taste) pathways. In hu-
In the rostral pons, lying dorsally in the tegmentum, is the mans the parabrachial nucleus has been shown to have neu-
nucleus locus ceruleus (group A-6 of primates). It contains on romelanin-containing catecholamine neurons. The pigmented
each side an average of 16,000 to 18,000 melanin-containing neurons in the nucleus are rather small (compared with neu-
neurons that are involved in Parkinson’s disease, Alzheimer’s dis- romelanin-containing neurons in the locus ceruleus or the sub-
ease, and Down syndrome. It is the major source of the wide- stantia nigra), and their granules have a very delicate appear-
spread noradrenergic innervation to most central nervous system ance; this may explain why pigmented neurons in this nucleus
regions. This nucleus is subdivided into four subnuclei: central have been overlooked in reports on the distribution of cate-
(largest), anterior (rostral end), the nucleus subceruleus (caudal cholamine neurons in the human brain. In humans the para-
Medial longitudinal fasciculus
Tectospinal tract
TEGMENTUM Central tegmental tract
SPECIFIC
LEMNISCAL
SYSTEM
Spinothalamic tract
BASIS PONTIS
Trigeminal tract Figure 7–3. Schematic diagram

of the pons showing the major
Trapezoid body Medial lemniscus tracts traversing the tegmentum.
PONS / 107
brachial nucleus is subdivided into lateral and medial segments. Frontal

CORTEX
Pigmented neurons are more abundant in the lateral segment. Cortex
Pigmented neurons in the parabrachial nucleus undergo a sig-
nificant reduction in number in patients with Parkinson’s dis- BASAL GANGLIA
ease. The parabrachial nucleus has fiber connections with the +
hypothalamus, amygdala, stria terminalis, and brain stem nu- GPi SNr
THALAMUS −
clei, including the nucleus of the solitary tract and the dorsal + +
raphe nucleus. It is believed that the parabrachial nucleus plays Intralaminar PPN STN SNc
nuclei
an important role in autonomic regulation, and its involvement
+
in parkinsonism may explain the autonomic disturbances that GPi GPe
occur in that disease. Studies in animals and man suggest that
the parabrachial nucleus is a relay station in the brainstem path-
way for taste.
+
Pedunculopontine Nucleus MEDULLA
Gigantocellular
reticular nucleus
Between the spinal lemniscus, brachium conjunctivum, and me-
dial lemniscus is the parabrachial pedunculopontine nucleus.
The pedunculopontine nucleus is the brain stem control cen-
ter for somatic motor and cognitive behaviors, including loco- +
motion, motor learning, and the reward system. Accumulated evi- SPINAL CORD
dence points to a role for the nucleus in the sleep–wake arousal
system and the muscle coordination mechanism as well as in ocu- Figure 7–4. Afferent and efferent connections of the peduncu-
lomotor function including initiation of saccadic eye movements. lopontine nucleus. PPN, pedunculopontine nucleus; GPi, internal
The nucleus contains two populations of neurons, cholinergic segment of globus pallidus; SNr, substantia nigra pars reticulata;
and glutamatergic. The complex and widely distributed efferents STN, subthalamic nucleus; SNc, substantia nigra pars compacta;
of the cholinergic population allow the nucleus to participate in GPe, external segment of globus pallidus.
a variety of functions. The glutamatergic population projects
caudally to the pontine and medullary reticular formation respon-
sible for locomotion. It receives direct excitatory cortical input
from multiple motor-related areas of the frontal lobe and an in- lateral surface caudal and lateral to the vestibular divi-
hibitory input from the basal ganglia (internal segment of globus sion and project on the dorsal and ventral cochlear nu-
pallidus and substantia nigra pars reticulata). The nucleus sends clei. The dorsal cochlear nucleus, situated on the dorso-
direct excitatory output to the basal ganglia (mainly to subtha- lateral surface of the restiform body, receives fibers originating in
lamic nucleus and substantia nigra pars compacta, with a smaller the basal turns of the cochlea (mediating high-frequency sound).
projection to both segments of globus pallidus) and to the in- The ventral cochlear nucleus, situated on the ventrolateral aspect
tralaminar nuclei of thalamus. The nucleus sends indirect output of the restiform body, receives fibers from apical turns of the
to the spinal cord (via the gigantocellular reticular nucleus of the cochlea (mediating low-frequency sound). The total number of
medulla oblongata) (Figure 7–4). The nucleus is believed to pos- neurons in the cochlear nuclei far exceeds the total number of
sibly have two functional roles: (1) relay between the cerebral cochlear nerve fibers, and so each fiber is believed to project on
cortex and spinal cord serving as control center for interlimb co- several neurons.
ordination in locomotion and (2) modulatory center that receives Second-order neurons from the cochlear nuclei course through
excitatory drive from the cerebral cortex and governs activity of the tegmentum of the pons to form the three acoustic striae: dor-
dopaminergic neurons in the substantia nigra pars compacta, sal, ventral, and intermediate. The dorsal acoustic stria is formed
thus influencing motor learning and the reward system as well as by axons of neurons in the dorsal cochlear nucleus, the ventral
voluntary motor control. acoustic stria (trapezoid body) is formed by axons from the infe-
rior cochlear nucleus, and the intermediate acoustic stria origi-
nates in the inferior and superior cochlear nuclei.
CRANIAL NERVE NUCLEI The ventral acoustic stria (the trapezoid body) is the largest
of the three striae. Fibers in this stria project on neurons in the
Cochleovestibular Nerve (Cranial Nerve VIII) superior olivary complex and the nucleus of the trapezoid body.
The cochleovestibular nerve has two divisions: cochlear and ves- The superior olivary nuclear complex is embedded in the trape-
tibular. The two divisions travel together from the peripheral end zoid body. It includes the lateral and medial superior olivary
organs in the inner ear to the pons, where they separate; each nuclei. The olivary nuclei are elongated cell masses of which the
then establishes its own distinct connections. medial superior olivary nucleus is much better developed in hu-
mans, whereas the lateral superior olivary nucleus and the nu-
A. COCHLEAR DIVISION cleus of the trapezoid body are poorly developed. The nucleus
The cochlear division (Figure 7–5) of the cochleovestibular nerve of the trapezoid body consists of small cells situated at the cau-
is the larger of the two divisions. Nerve fibers in the cochlear dal half of the superior olivary nucleus. The two superior oli-
nerve are central processes of bipolar neurons in the spiral gan- vary nuclei and the nucleus of the trapezoid body are sur-
glion located in the modiolus of the inner ear. The peripheral rounded by a zone of cells of varying sizes and shapes known
processes of these bipolar neurons are linked to the hair cells of collectively as the periolivary nuclei. It was originally believed
the auditory end organ in the organ of Corti. As fibers of the that the periolivary nuclei are exclusively involved in descend-
cochlear nerve reach the caudal part of the pons, they enter its ing auditory pathways, but it has been established that these
108 / CHAPTER 7
Medial geniculate nucleus

AUDITORY
CORTEX
Inferior colliculus
Nucleus of lateral lemniscus
Lateral lemniscus
COCHLEAR
NUCLEI
Dorsal
Cochlear nerve
Ventral
ORGAN
OF CORTI
Restiform body
Superior olive SPIRAL GANGLION
Intermediate
Nucleus of ACOUSTIC STRIAE
trapezoid body Dorsal
Trapezoid body
Figure 7–5. Schematic diagram of the auditory pathways.
cells are involved in descending as well as ascending auditory a large compact central nucleus and a more diffuse laterally situ-
projections. Functions of the superior olivary complex include: ated zone. The majority of ascending auditory fibers to the infe-
(1) processing of cochlear signals via the ascending auditory rior colliculus terminate in the central nucleus. The lateral zone
pathway, (2) detection of interaural sound intensity, and (3) of the inferior colliculus receives afferents from the central nucleus
providing feedback control of cochlear mechanism through the as well as from the nucleus of the lateral lemniscus. There is evi-
olivocochlear bundle. dence that the ipsilateral medial superior olivary nucleus and the
Afferents to the superior olivary complex from nonauditory contralateral lateral superior olivary nucleus send excitatory pro-
areas have been described from serotoninergic and noradrenergic jections to the central nucleus of the inferior colliculus, whereas
brain stem nuclei. Compared to the auditory afferents, the sero- the ipsilateral lateral superior olivary nucleus sends inhibitory
toninergic and noradrenergic afferents are sparse. An input from projections to the central nucleus. Only a limited number of
the trigeminal ganglion to the superior olivary nuclear complex fibers belonging to the ascending auditory projection bypass the
has also been described. Third-order neurons from the superior inferior colliculus to reach the medial geniculate body directly.
olivary complex, the nucleus of the trapezoid body, and the peri- These fibers usually arise from the cochlear nuclei and the nucleus
olivary nuclei contribute mainly to the contralateral lateral lem- of the lateral lemniscus. The two inferior colliculi are connected
niscus, with some projection to the homolateral lateral lemnis- to each other by the commissure of the inferior colliculus and to
cus. The lateral lemniscus also receives fibers from the dorsal and the medial geniculate nucleus by the brachium of the inferior
intermediate acoustic striae. Fibers in the lateral lemniscus pro- colliculus (inferior quadrigeminal brachium).
ject on the nucleus of the lateral lemniscus. The nucleus of the The final station is the primary auditory cortex (transverse
lateral lemniscus is an elongated strand of cells embedded within Heschl’s gyri) in the temporal lobe. The auditory projection (au-
the lateral lemniscus at the isthmus level. Two subnuclei are rec- ditory radiation) from the medial geniculate body to the primary
ognized: dorsal and ventral. Subsequent stations in the auditory auditory cortex traverses the sublenticular portion of the internal
system include synapses in the inferior colliculus and the medial capsule. From the level of the inferior colliculus onward to the
geniculate body. primary auditory cortex, the auditory projection is subdivided
The inferior colliculus is the most important relay station in into “core” and “belt” projections. The core projection terminates
the ascending and descending auditory projections. It consists of in the primary auditory cortex; the belt projection terminates
PONS / 109
in cortical areas surrounding the primary auditory cortex. The Superior olive Olivocochlear bundle Organ
core and belt projections also have distinct zones of origin within of Corti
the inferior colliculus, where the central nucleus is related to the Vestibular nerve
core projection, whereas the lateral zone is related to the belt
projection. Tonotopic localization exists throughout the audi-
tory system.
In addition to this “classic” auditory pathway, evidence suggests
the existence of another multisynaptic auditory pathway through Cochlear nerve
the reticular formation. The evidence for a reticular pathway is
based on several experimental observations. Abducens nucleus
1. Reticular thalamic neurons project to the medial geniculate

nucleus.
2. The nucleus of the lateral lemniscus and the inferior collicu- Periolivary area Basis pontis
lus are connected with the mesencephalic reticular formation. Tegmentum
3. Auditory-responding cells have been identified in the mesen-
cephalic reticular formation and the pretectum. Figure 7–6. Schematic diagram showing the origins and course
4. An increase in 2-deoxy-D-glucose metabolism throughout of the olivocochlear bundle.
the auditory pathways has been obtained by means of elec-
tric stimulation of the mesencephalic reticular formation.
leave it and travel with the cochlear division as far as the hair cells
Several fiber bundles of the auditory system decussate at vari- of the organ of Corti. Stimulation of the olivocochlear bundle
ous levels: suppresses the receptivity of the organ of Corti, and thus activity
in the auditory nerve. A variety of functions have been proposed
1. In the pontine tegmentum, the superior, middle, and inferior for the olivocochlear bundle. These include: (1) a protective ef-
acoustic striae decussate and link the right and left cochlear fect on the cochlea against loud sound, (2) frequency selectivity,
nuclear complexes. (3) selective auditory attention that permits detection of new sig-
2. The olivocochlear bundle (efferent bundle of Rasmussen), nals and understanding of speech in a noisy background.
which will be discussed below, also decussates in the pontine The hair cells of the organ of Corti transduce mechanical en-
tegmentum. ergy into nerve impulses and exhibit a graded generator poten-
3. The nuclei of the lateral lemniscus are connected via Probst’s tial. Spike potentials appear in the cochlear nerve.
commissure, which passes through the brachium conjunc- Cochlear nerve fibers respond to both displacement and ve-
tivum and the most rostral part of the pontine tegmentum. locity of the basilar membrane of the organ of Corti. Displace-
Probst’s commissure also carries fibers from the nuclei of the ment of the basilar membrane toward the scala vestibuli produces
lateral lemniscus to the contralateral inferior colliculus. inhibition, whereas displacement toward the scala tympani pro-
4. At the midbrain level, the two inferior colliculi communi- duces excitation. A single fiber in the cochlear nerve may respond
cate via the commissure of the inferior colliculus. This com- to both displacement and velocity.
missure also carries fibers passing from the inferior colliculus Reflex movements of the eyes and neck toward a sound source
to the medial geniculate body. are mediated via two reflex pathways. The first runs from the in-
ferior colliculus to the superior colliculus and from there via tecto-
The auditory system is characterized by the presence of sev- bulbar and tectospinal pathways to the nuclei of eye muscles and
eral inhibitory feedback mechanisms that consist of descending the cervical musculature. The other pathway runs from
pathways linking the different cortical and subcortical auditory the superior olive to the abducens nerve (cranial nerve
nuclei. Thus, a system of descending fibers links the pri- VI) nucleus and then via the medial longitudinal fasci-
mary auditory cortex, the medial geniculate body, the culus to the nuclei of cranial nerves of extraocular muscles.
inferior colliculus, the nucleus of the lateral lemniscus, Other reflex pathways include those between cochlear nuclei
the superior olivary nuclear complex, and the cochlear nuclei. and the ascending reticular activating system, which give rise to
However, the most important feedback mechanism is served by the auditory-evoked startle response, and those between the ven-
the olivocochlear bundle, also known as the efferent bundle of tral cochlear nuclei and the motor nuclei of the trigeminal and
Rasmussen (Figure 7–6). This bundle of fibers arises from cholin- facial nerves. The latter pathways constitute reflex arcs that link
ergic neurons of the periolivary nuclei and projects on hair cells the organ of Corti with the tensor tympani and stapedius mus-
in the organ of Corti. It has both crossed and uncrossed compo- cles. Thus, in response to sounds of high intensity, these muscles
nents which differentially innervate the two types of hair cells. reflexly contract and dampen the vibration of the ear ossicles.
The crossed bundle originates from large cells in the ventro-
medial part of the periolivary area, courses dorsally in the pon- B. VESTIBULAR DIVISION
tine tegmentum, bypasses the nucleus of the abducens nerve, Vestibular nerve fibers are central processes of bipolar cells in
and crosses to the contralateral side to terminate by large synap- Scarpa’s ganglion. Peripheral processes of these bipolar cells are
tic terminals abutting the basal parts of the outer hair cells. The distributed to the vestibular end organ in the three semicircular
uncrossed component is smaller and originates from small neu- canals, the utricle, and saccule. The semicircular canals are con-
rons in the vicinity of the lateral superior olivary nucleus. It ter- cerned with angular acceleration (detecting a simultaneous in-
minates by en passant synapses on primary afferent cochlear crease in velocity and direction when one is rotating or turning);
fibers just beneath the inner hair cells. Both components initially the utricle and saccule are concerned with linear acceleration
join the vestibular division of the cochleovestibular nerve (cra- (detecting a change in velocity without a change in direction,
nial nerve VIII), but at the vestibulocochlear anastomosis, they the gravitational effect). The superior portion of Scarpa’s gan-
110 / CHAPTER 7
glion receives fibers from the anterior and horizontal semicircu- The vestibular projection to the spinal cord (Figure 7–9) is
lar canals, the utricle and saccule. The inferior portion of the through the lateral vestibulospinal tract (from the lateral vestibu-
ganglion receives fibers from the posterior semicircular canal and lar nucleus) and the medial vestibulospinal tract (from the me-
the saccule (Figure 7–7). The vestibular nerve accompanies the dial vestibular nucleus) via the descending component of the
cochlear nerve from the internal auditory meatus to the pons, medial longitudinal fasciculus. The lateral vestibulospinal tract
where it enters the lateral surface at the pontomedullary junction facilitates extensor motor neurons, whereas the medial tract facil-
medial to the cochlear nerve. itates flexor motor neurons. The medial vestibulospinal tract sends
Within the pons, vestibular nerve fibers course in the tegmen- fibers to the dorsal motor nucleus of the vagus. This explains the
tum between the restiform body and the spinal trigeminal com- nausea, sweating, and vomiting that occur after stimulation of
plex. The major portion of these fibers projects on the four the vestibular end organ.
vestibular nuclei; a smaller portion goes directly to the cerebellum Projections from the vestibular nuclei to the cerebellum (Figure
via the juxtarestiform body. In the cerebellum, these fibers termi- 7–9) travel via the juxtarestiform body along with the primary
nate as mossy fibers on neurons in the flocculonodular vestibulocerebellar fibers. These projections arise from the supe-
lobe and the uvula. There are four vestibular nuclei: me- rior, inferior, and medial vestibular nuclei and terminate mainly
dial, inferior, lateral, and superior. The medial nucleus ipsilaterally (but also bilaterally) on neurons in the flocculonodu-
(principal nucleus [Schwalbe’s nucleus]) appears in the medulla lar lobe, the uvula, and the nucleus fastigii. Cerebello-
oblongata at the rostral end of the inferior olive and extends to vestibular connections are much more abundant than
the caudal part of the pons. The inferior nucleus (spinal nucleus) are vestibulocerebellar connections.
lies between the medial nucleus and the restiform body. The in- Vestibulothalamic projections arise from the medial, lateral,
ferior nucleus, which is characterized in histologic sections by and superior vestibular nuclei and project bilaterally on several
myelinated fibers that traverse it from the vestibular nerve, ex- thalamic nuclei (ventral posterolateral, centrolateral, lateral genic-
tends from the rostral extremity of the gracile nucleus to the ulate, and posterior group). They reach their destinations via sev-
pontomedullary junction. The lateral nucleus (Deiters’ nucleus), eral pathways (lateral lemniscus, brachium conjunctivum, retic-
which is characterized in histologic sections by the presence of ular formation), with a few traveling via the medial longitudinal
large multipolar neurons, extends from the pontomedullary junc- fasciculus.
tion to the level of the abducens nerve (cranial nerve VI) nucleus. Vestibular projections to the nuclei of extraocular muscles travel
The superior nucleus (Bechterew’s nucleus) is smaller than the via the ascending component of the medial longitudinal fasciculus.
other nuclei and lies dorsal and medial to the medial and lateral They arise from all four vestibular nuclei and project on nuclei of
nuclei. The number of neurons in the vestibular nuclei far ex- the oculomotor (cranial nerve III), trochlear (cranial nerve IV), and
ceeds the number of vestibular nerve fibers. Vestibular nerve fibers abducens (cranial nerve VI) nerves. The crossed component of this
project only to limited regions within each vestibular nucleus. In system exerts an excitatory effect, whereas the uncrossed compo-
addition to input from the vestibular nerve, the vestibular nuclei nent exerts an inhibitory effect, on nuclei of extraocular movement.
receive fibers from: (1) the spinal cord, (2) the cerebellum, and A projection from the vestibular nuclei to the primary vestibu-
(3) the vestibular cortex (Figure 7–8). The output from the ves- lar cortex in the temporal lobe probably reaches the vestibular
tibular nuclei is to: (1) the spinal cord, (2) the cerebellum, (3) the cortex via relays in the thalamus.
thalamus, (4) the nuclei of the extraocular muscles, (5) the ves- A projection to the vestibular end organ has been described.
tibular cortex, and (6) the vestibular end organ. Axons travel with the vestibular nerve and terminate in a bilateral
Juxtarestiform CEREBELLUM
body
Restiform body
Vestibular nuclei
Anterior and
horizontal canals
Utricle
Saccule
Posterior canal
Figure 7–7. Schematic diagram Saccule
showing the origin and termina- Spinal trigeminal nucleus Vestibular Scarpa’s
tion of the vestibular nerve. nerve ganglion
PONS / 111
mary oculomotor responses. Nystagmus, however, can still result

from labyrinthine stimulation, confirming that pathways essen-
tial for nystagmus probably pass via the reticular formation.
Stimulation of the superior vestibular nucleus produces vertical
Vestibular cortex nystagmus.
Lesions of the medial longitudinal fasciculus (MLF) rostral to
the abducens nucleus interfere with normal conjugate eye move-
ments. In this condition, which is known as internuclear ophthal-
moplegia or the MLF syndrome, there is paralysis of adduction
ipsilateral to the MLF lesion and horizontal monocular nystagmus
of the abducting eye (Figure 7–10). This condition is known to
Cerebellum
occur in multiple sclerosis and vascular disorders of the pons.
Experimental evidence has shown that this type of lesion inter-
rupts MLF fibers destined for the part of the oculomotor nuclear
complex that innervates the medial rectus; this explains the loss
of adduction.
Vestibular There is no satisfactory explanation for the monocular hori-
nuclei Vestibular zontal nystagmus of the abducting eye. Two theories have been
nerve proposed to explain this phenomenon. The first suggests that
nystagmus is due to the utilization of convergence mechanisms
to adduct the ipsilateral eye. This induces adduction of the
contralateral eye, which then jerks back to the position of fixa-
tion. The second theory suggests that the medial longitudinal
Spinovestibular fasciculus carries facilitatory fibers to the ipsilateral medial rec-
Spinal
cord
tract tus neurons and inhibitory fibers to the contralateral medial rec-
tus neurons. In lesions of the medial longitudinal fasciculus, fail-
ure of inhibition of adduction in the contralateral eye thus
Figure 7–8. Schematic diagram showing the major inputs to

the vestibular nuclei. Nuclei of
extraocular
movement
fashion on hair cells in cristae of the semicircular canal and the

maculae of the utricle and saccule. In contrast to the olivo- Cerebellum
cochlear bundle, which exerts an inhibitory effect on the cochlear – +
end organ, this bundle is excitatory to the vestibular end organ.
The vestibular output to the nuclei of extraocular muscles MLF
plays an important role in the control of conjugate eye
movements (Figure 7–9). This control is mediated via
two pathways: the ascending component of the medial
longitudinal fasciculus and the reticular formation.
Reflex conjugate deviation of the eyes in a specific direction, Vestibular
which is known as nystagmus, has two components: a slow com- nuclei Juxtarestiform
body
ponent away from the stimulated vestibular system and a fast
component toward the stimulated side. In clinical medicine, the
term nystagmus refers to the fast component. Although the mech-
anism of the slow component is fairly well understood in terms of
neuronal connections, the same cannot be said of the fast com-
ponent, which is believed to represent a corrective attempt to re- Medial Lateral
turn the eyes to a neutral position. Stimulation of the right hori- vestibulospinal vestibulospinal
zontal semicircular canal (turning to the right in a Bárány chair or tract tract
pouring warm water in the right ear) or the right medial, lateral,
or inferior vestibular nucleus results in a reflex conjugate horizon- Spinal cord
tal deviation of the eyes (horizontal nystagmus) with a slow com-
ponent to the left and a fast component to the right. Bilateral
stimulation of the anterior semicircular canal results in upward
movement of the eyes, while stimulation of the posterior canal
produces downward movement. Sectioning of the medial longitu- Figure 7–9. Schematic diagram showing the efferent connec-
dinal fasciculus rostral to the abducens nuclei abolishes these pri- tions of the vestibular nuclei. MLF, medial longitudinal fasciculus.
112 / CHAPTER 7
Lesion Direction The exteroceptive fibers from the external ear are peripheral
of gaze Convergence processes of neurons in the geniculate ganglion. Central processes
project on neurons in the spinal trigeminal nucleus (similar to
Right MLF fibers from the same area carried by the glossopharyngeal [cranial
nerve IX] and vagus [cranial nerve X] nerves).
The taste fibers have their neurons of origin in the geniculate
ganglion. Peripheral processes of these neurons reach the taste
Left MLF buds in the anterior two-thirds of the tongue; central processes
enter the brain stem with the nervus intermedius and project on
neurons in the gustatory part of the nucleus solitarius, along
Bilateral MLF with fibers carried by the glossopharyngeal (from the posterior
third of the tongue) and vagus (from the epiglottic region) nerves.
The sensory and gustatory fibers, along with the visceral motor
Figure 7–10. Schematic diagram showing the effects of le- component, form a separate lateral root of the facial nerve, the
sions in the medial longitudinal fasciculus (MLF) on conjugate nervus intermedius (Wrisberg’s nerve).
eye movements. Zigzag arrows indicate nystagmus.
B. MOTOR COMPONENTS
The facial nerve carries two types of motor fibers: so-
causes an abducting (corrective) nystagmus in that eye. The term matic and secretomotor.
“internuclear ophthalmoplegia” (ataxic nystagmus, Lhermitte
syndrome, Bielschowsky-Lutz-Cogan syndrome) was coined by 1. Somatic Motor Fibers. Somatic motor fibers supply
Lhermitte, a French neurologist. Lutz, a Cuban ophthalmolo- the muscles of facial expression and the stapedius, the stylohy-
gist, defined two varieties of this syndrome: (1) anterior, in oid, and the posterior belly of the digastric. These fibers arise
which the lateral rectus functions normally but the medial rectus from the facial motor nucleus in the pontine tegmentum. From
is paralyzed on the side of the MLF lesion and (2) posterior, in their neurons of origin, fibers course dorsomedially and then ros-
which the lateral rectus is paralyzed but the medial rectus func- trally in the tegmentum and form a compact bundle near the ab-
tions normally. The validity of this division of the syndrome is ducens (cranial nerve VI) nucleus in the floor of the fourth ven-
not certain. tricle (the facial colliculus). They bend (genu) laterally over the
abducens nucleus and turn ventrolaterally to emerge at the lat-
eral border of the pons. This peculiar course of the somatic mo-
Facial Nerve (Cranial Nerve VII) tor component of the facial nerve fibers in the tegmentum results
The facial nerve (Figure 7–11) is a mixed nerve with both sen- from the migration of facial motor neurons from a dorsal posi-
sory and motor components. This nerve is responsible for our tion in the floor of the fourth ventricle caudally and ventrally,
individuality, the facial expressions that characterize each of us. pulling their axons with them. The migration of the facial motor
nucleus is explained by neurobiotaxis, in which neurons tend to
A. SENSORY COMPONENTS migrate toward major sources of stimuli. In the case of the facial
The facial nerve carries two types of sensory afferents: motor nucleus, this migration brings it closer to the trigeminal
exteroceptive fibers from the external ear and taste fibers spinal nucleus and its tract. Visceral motor and sensory compo-
from the anterior two-thirds of the tongue. nents of the facial nerve do not make a loop around the ab-
SENSORY COMPONENTS MOTOR COMPONENTS
Spinal Superior Facial

trigeminal Nucleus Abducens salivatory motor
nucleus solitarius nucleus nucleus nucleus
Geniculate ganglion
Chorda tympani and

lingual nerves
Submandibular
gland
Tongue Chorda tympani
Greater superficial
petrosal nerve Sublingual Figure 7–11. Schematic diagram
gland showing the nuclei of origin,
Pterygopalatine Lacrimal Submandibular course, and areas of supply of the
ganglion gland ganglion facial nerve (cranial nerve VII).
PONS / 113
ducens nucleus. Instead, they form a separate lateral root of the can produce mimetic central facial paralysis without voluntary
facial nerve, the nervus intermedius. central facial paralysis. More extensive lesions produce combined
The motor nucleus of the facial nerve is organized into longi- voluntary and mimetic central facial paralysis.
tudinally oriented motor columns (subnuclei) concerned with Recent experimental evidence provides an alternative expla-
specific facial muscles: the medial, dorsal, intermediate, and lat- nation for the sparing of the upper facial musculature in patients
eral subnuclei. Motor neurons that supply upper facial muscles with central (hemispheral) lesions. Sparse data from human stud-
are located in the dorsal part of the nucleus, those innervating ies coupled with the results of experimental studies in a variety of
lower facial muscles are primarily located in the lateral part of mammals, including monkeys, have shown that (1) the bilateral
the nucleus, and those supplying the platysma and the posterior cortical input to facial motor neurons that innervate upper facial
auricular muscles are in the medial part of the nucleus. muscles is sparse, (2) motor neurons of the facial nucleus that in-
The facial motor nucleus receives fibers from the following nervate the lower facial muscles receive significant and bilateral
sources: cortical input which is threefold heavier on the contralateral side,
a. Cerebral cortex. Corticofacial fibers originate from areas of and (3) cortical innervation of the ipsilateral lower facial motor
face representations in the primary motor, supplementary motor, subnucleus is considerably heavier than that of the ipsilateral up-
premotor, rostral, and caudal cingulate cortices. These fibers travel per facial motor subnucleus. On the basis of these findings, it has
as direct corticobulbar or indirect corticoreticulobulbar been proposed that the deficit of facial muscles seen after unilat-
fibers. The cortical input to the facial nucleus is bilateral eral hemispheral lesions reflects the extent to which direct corti-
to the part of the nucleus that supplies the upper facial cal innervation of facial motor neuron is lost. Thus, motor neu-
muscles and only contralateral to the part that innervates the peri- rons innervating the upper face would be little affected because
oral musculature. In lesions affecting one hemisphere, only the they do not receive much direct cortical input. Also, lower facial
lower facial muscles contralateral to the lesion are affected (Figure motor neurons contralateral to the lesion would suffer loss of
7–12). This is referred to as central (supranuclear) facial paresis, in function because they are most dependent on direct contralateral
contradistinction to peripheral facial paralysis or paresis (resulting cortical innervation and because the remaining ipsilateral corti-
from lesions of the facial motor nucleus or the facial nerve), in cal projection apparently is insufficient to drive them. The small
which all the muscles of facial expression ipsilateral to the lesion loss of cortical input to lower facial motor neurons ipsilateral to
are affected. Two types of central facial paresis (palsy) have been the lesion is compensated by the remaining, much more intense,
described: voluntary and involuntary (mimetic). Voluntary central input from the intact hemisphere. Alternately, it is possible that
facial palsy results from lesions involving the contralateral corti- the lower facial muscles ipsilateral to the lesion display some
cobulbar or corticoreticulobulbar fibers. Mimetic or emotional in- mild weakness, but this is obscured by the much more profound
nervation of the muscles of facial expression is involuntary and of contralateral weakness. The course of corticobulbar fibers to the
uncertain origin. It allows contraction of the lower facial muscles facial nucleus in humans remains uncertain. Histologic studies in
in response to genuine emotional stimuli. Certain neural lesions human autopsy material at the turn of the 20th century described
Right Left
LEFT
HEMISPHERE
LESION
Intact corticobulbar fibers Degenerated corticobulbar fibers
Right Left
RIGHT FACIAL NUCLEUS FACE
Partial interruption of Upper facial muscles
corticobulbar fibers to part unaffected
of nucleus supplying
upper facial muscles
Complete interruption of
corticobulbar fibers to part Paretic lower facial
Figure 7–12. Schematic diagram of nucleus innervating muscles
illustrating the concept of central lower facial muscles
facial paresis.
114 / CHAPTER 7
an “aberrant bundle” separating from the corticospinal tract at 2. Secretomotor (Visceral Motor) Fibers. These fibers arise
the midbrain and upper pons and coursing along the tegmental from the superior salivatory nucleus in the tegmentum of the
border adjacent to the lemniscal fibers. These observations were pons. They are preganglionic fibers that leave the brain stem
subsequently confirmed using more reliable staining methods. with the nevus intermedius (Wrisberg’s nerve) and synapse in
Recent studies have described three possible trajectories for the collateral ganglia. Fibers destined for the lacrimal gland leave the
corticofacial fibers: (1) via the “aberrant bundle,” (2) separating nervus intermedius and travel in the greater superficial petrosal
from the corticospinal tract in the caudal basis pontis and cours- and the nerve of the pterygoid canal (vidian nerve) before synapse
ing dorsally to the facial nucleus in the pontine tegmentum, and in the pterygopalatine ganglion, from which postganglionic
(3) forming a loop into the medulla oblongata before reaching parasympathetic fibers travel in the maxillary, zygomatic, zygo-
the facial nucleus. These trajectories would explain the occur- maticotemporal, and lacrimal nerves to reach the lacrimal gland.
rence of central facial palsy in lesions affecting the pontine Fibers destined for the submandibular and sublingual glands
tegmentum and basis pontis and those associated with the lateral join the chorda tympani and the lingual nerves and synapse in
medullary syndrome. the submandibular ganglion, from which postganglionic parasym-
pathetic fibers arise. Because fibers for the lacrimal, submandibu-
b. Basal ganglia. This input to the facial motor nucleus ex- lar, and sublingual glands leave the brain stem together, lesions
plains the movement of paretic facial muscles in response to of the facial nerve proximal to the geniculate ganglion may re-
emotional stimulation. Patients with central facial paralysis who sult in aberrant growth of regenerating fibers so that fibers des-
are unable to move the lower facial muscles voluntarily may be tined to innervate the lacrimal glands reach the submandibular
able to do so reflexly in response to emotional stimulation. and sublingual salivary glands. This aberrant growth is respon-
c. Superior olive. This input is part of a reflex involving the sible for the phenomenon of “crocodile tears,” in which the pres-
facial and auditory nerves. It explains the grimacing of facial ence of food in the mouth is followed by lacrimation rather than
muscles that occurs in response to a loud noise. salivation.
d. Trigeminal system. This input is also reflex in nature, C. FACIAL NERVE LESIONS
linking the trigeminal and facial nerves. It underlies the blinking
of the eyelids in response to corneal stimulation. Signs of facial nerve paralysis (Bell’s palsy) vary with the loca-
tion of the lesion (Figure 7–13). Bell’s palsy is named after Sir
e. Superior colliculus. This input via tectobulbar fibers is Charles Bell (1774–1842), a British anatomist, physiologist,
reflex in nature and provides for closure of the eyelids in response surgeon, and neurologist who was also a pioneer in the study of
to intense light or a rapidly approaching object. facial expression.
Paralysis of muscles of facial expression, Paralysis of muscles of facial expression,

loss of taste, impaired salivation, loss of taste, impaired salivation,
hyperacusis, and loss of lacrimation and hyperacusis
Lacrimal
Superior salivatory nucleus gland
Nucleus Tongue
solitarius
Submandibular
Geniculate gland
region
Sublingual
gland
Motor facial nucleus
Stylomastoid
foramen Stapedius
muscle
Paralysis of
muscles of
facial expression
Figure 7–13. Schematic diagram showing lesions in the facial nerve at different sites and the
resulting clinical manifestations of each.
PONS / 115
1. Proximal to Geniculate Ganglion. Lesions of the facial Left Right

nerve proximal to the geniculate ganglion result in the follow-
ing signs:
1. Paralysis of all the muscles of facial expression
Direction of gaze
2. Loss of taste in the anterior two-thirds of the ipsilat-
eral half of the tongue
3. Impaired salivary secretion
4. Impaired lacrimation
5. Hyperacusis (hypersensitivity to sound as a result of paralysis
of the stapedius muscle) Right abducens
nerve lesion
6. Crocodile tears in some patients with aberrant growth of re- A
generating fibers
2. Distal to Geniculate Ganglion. Lesions of the facial nerve
distal to the geniculate ganglion but proximal to the chorda tym- L f Right Right abducens
pani result in the following ipsilateral signs: nucleus lesion
1. Paralysis of all the muscles of facial expression Direction of gaze

2. Loss of taste in the anterior two-thirds of the tongue
3. Impaired salivary secretion
4. Hyperacusis
Lacrimation is not affected by this type of lesion, since the
fibers destined for the lacrimal gland leave the nerve proximal to
the level of the lesion.
3. Stylomastoid Foramen. Lesions of the facial nerve at the sty- B
lomastoid foramen (where the motor fibers destined for the mus-
cles of facial expression leave the cranium) result only in paralysis of Figure 7–15. Schematic diagram showing the clinical manifes-
the muscles of facial expression that are ipsilateral to the lesion. tations resulting from lesions in the abducens nucleus (B) and
nerve (A).
Abducens Nerve (Cranial Nerve VI)

that supply the medial rectus muscle (medial rectus subnucleus).
The abducens nerve (Figure 7–14) is a purely motor nerve that
Axons of the abducens nerve course through the tegmentum and
innervates the lateral rectus muscle. The abducens nucleus is lo-
basis pontis and exit on the ventral surface of the pons in the
cated in a paramedian site in the tegmentum of the pons, in the
groove between the pons and the medulla oblongata (Figure
floor of the fourth ventricle. It extends from the rostral limit of
7–14). The abducens nucleus (Figure 7–14) receives fibers from
the lateral vestibular nucleus to the rostral portion of the descend-
(1) the cerebral cortex (corticoreticulobulbar fibers), (2) the me-
ing vestibular nucleus. The abducens nucleus has two popula-
dial vestibular nucleus via the medial longitudinal fasciculus,
tions of neurons: large (motor neurons) and small (interneurons).
(3) the paramedian pontine reticular formation (PPRF), and
Axons of the large neurons (motor neurons) form the abducens
(4) the nucleus prepositus hypoglossi. The corticobulbar input is
nerve and supply the lateral rectus muscles. Axons of the small
bilateral, the inputs from the PPRF and the nucleus prepositus
neurons (interneurons) join the contralateral medial longitudinal
are uncrossed, and the input from the medial vestibular nucleus
fasciculus and terminate on neurons in the oculomotor nucleus
is predominantly uncrossed. Direct afferent fibers from Scarpa’s
ganglion to the abducens nucleus have been described.
Lesions of the abducens nerve result in paralysis of the ipsi-
Abducens nucleus Vestibular nuclei lateral lateral rectus muscle and diplopia (double vision) on at-
tempted horizontal gaze toward the side of the paralyzed muscle
Reticular nucleus (Figure 7–15A); the two images are horizontal, and the distance
between them increases as the eyes move in the direction of ac-
Corticospinal tract
tion of the paralyzed muscle. The abducens nerve has a
long intracranial course and therefore is commonly af-
fected in intracranial diseases of varying etiologies and
sites. In contrast to lesions of the abducens nerve, lesions of the
abducens nucleus do not result in paralysis of abduction but in-
stead in paralysis of horizontal gaze ipsilateral to the lesion; this
is manifested by the failure of both eyes to move on attempted
ipsilateral horizontal gaze (Figure 7–15).
Abducens
nerve Paralysis of lateral gaze after abducens nucleus lesions is ex-
plained by involvement of the large neurons that supply the ipsi-
Figure 7–14. Schematic diagram showing sources of modu- lateral lateral rectus muscle and the small neurons (interneurons)
lating inputs into the abducens (cranial nerve VI) nucleus and that supply the contralateral medial rectus neurons (medial rectus
intrapontine course of the abducens nerve. subnucleus) within the oculomotor nucleus (Figure 7–16). The
116 / CHAPTER 7
Direction of gaze Abducens nucleus
Oculomotor nerve Abducens nerve

Corticospinal tract
to medial rectus muscle to lateral
rectus muscle
Abducens nerve
Oculomotor nucleus
A Ipsilateral paralysis of lateral

rectus and diplopia
Medial longitudinal
Contralateral upper motor
fasciculus
neuron signs
Abducens Abducens
nucleus nucleus lesion
Medial lemniscus
Figure 7–16. Schematic diagram illustrating the basis of lateral Abducens nerve
gaze paralysis in abducens nucleus lesions.
B Ipsilateral paralysis of lateral

rectus and diplopia
notion that pontine reticular neurons are responsible for paraly-
Contralateral loss of kinesthesia
sis of adduction no longer appears tenable. Tritiated amino acids and discriminative touch
injected into the paramedian pontine reticular formation do not
reveal terminations in the oculomotor nucleus but instead in the
abducens nucleus and the interstitial nucleus of the medial lon-
gitudinal fasciculus, which is believed to be involved in vertical
(downward) gaze. The pontine center for lateral gaze and the ab-
ducens nucleus probably constitute a single entity. The PPRF Facial nerve
(pontine center for lateral gaze) is a physiologically defined neu-
ronal pool that is rostral to the abducens nucleus. It is composed
of caudal and rostral parts. The caudal part is connected to the
ipsilateral abducens nucleus. Stimulation of the caudal part re- Facial motor
nucleus
sults in conjugate horizontal deviation of the eyes. The rostral
part is connected to the rostral interstitial nucleus of the MLF Abducens nerve
(RiMLF), which in turn projects to the ipsilateral oculomotor
nucleus by pathways other than the MLF. Stimulation of the ros-
tral PPRF results in vertical gaze. Lesions in the caudal PPRF
C Ipsilateral paralysis of
abolish conjugate lateral gaze, whereas lesions in the rostral horizontal gaze
PPRF abolish vertical gaze. Extensive lesions in PPRF result in
paralysis of both horizontal and vertical gaze. Ipsilateral peripheral
Abducens nerve rootlets along their course within the pons facial paralysis
may be involved in a variety of intraaxial vascular lesions.
Figure 7–17. Schematic diagram of lesions of the abducens
1. Lesions in the basis pontis involving the corticospinal fibers nerve (cranial nerve VI) and nucleus and the resulting clinical
and the rootlets of the abducens nerve result in alternating manifestations.
hemiplegia manifested by ipsilateral lateral rectus paralysis
(and diplopia) as well as an upper motor neuron paralysis of
the contralateral half of the body (Figure 7–17A). nerve produce paralysis of horizontal gaze and peripheral-type
facial paralysis, both ipsilateral to the lesion (Figure 7–17C).
2. Lesions in the pontine tegmentum involving the abducens
rootlets and the medial lemniscus result in ipsilateral lateral 4. Small lacunar infarct involving sixth nerve fascicles within
rectus paralysis (and diplopia) and contralateral loss of kines- the pons produce isolated abducens nerve palsy.
thesia and discriminative touch (Figure 7–17B). Unilateral and bilateral duplications of the abducens nerve
3. More dorsal lesions involving the abducens nucleus, the medial have been reported. In some cases, the nerve emerged from the
longitudinal fasciculus, and the curving rootlets of the facial brain stem as a single trunk and split into two branches in the
PONS / 117
subarachnoid space before reaching the cavernous sinus. In other Dorsal secondary tract
cases, the nerve exited the brain stem as two separate branches.
In both situations, the two branches usually merge within the Main sensory nucleus
cavernous sinus.
Trigeminal Nerve (Cranial Nerve V)

The trigeminal nerve is the largest of the twelve cranial nerves. Semilunar Ventral
secondary
It transmits sensory information from the head and neck and ganglion
tract
provides innervation to the muscles of mastication, the tensor
tympani, tensor palati, myelohyoid, and anterior belly
of the digastric. The trigeminal nerve has two roots: a
smaller (portio minor) efferent root and a larger (portio
major) afferent root. The motor root is composed of as many as
14 separately originating rootlets that are joined about 1 cm Spinal
from the pons. At the pons, the first division of the trigeminal trigeminal
tract
sensory root (V1) usually is located in a dorsomedial position ad-
jacent to the motor root and the third division (V3) is in a cau-
dolateral position. V3, however, may vary from being directly
lateral to directly caudal to V1. Aberrant sensory roots exist in
about 50 percent of individuals and may explain the persistence
of facial pain (trigeminal neuralgia) after surgical sectioning of
the sensory root. Aberrant sensory rootlets enter the sensory root
within 1 cm of the pons and contribute mainly to V1. Some Spinal trigeminal nucleus
rootlets between the motor and sensory roots may join either
Figure 7–18. Schematic diagram showing the cells of origin and
root farther away from the pons. Anastomosis between the mo-
course of the sensory root of the trigeminal nerve (cranial nerve V).
tor and sensory roots has been described and may explain the
failure of sensory root sectioning to relieve facial pain.
A. EFFERENT ROOT ganglion. The peripheral processes of neurons in the ganglion are
The efferent root of the trigeminal nerve arises from the motor distributed in the three divisions of the trigeminal nerve: oph-
nucleus of the trigeminal nerve in the tegmentum of the pons. thalmic, maxillary, and mandibular. The central processes of these
The efferent root supplies the muscles of mastication and the unipolar neurons enter the lateral aspect of the pons and distrib-
tensor tympani, the tensor palati, the mylohyoid, and the ante- ute themselves as follows.
rior belly of the digastric. The motor nucleus receives fibers from Some of these fibers descend in the pons and medulla and
the cerebral cortex (corticobulbar) and the sensory nuclei of the run down to the level of the second or third cervical spinal seg-
trigeminal nerve. The cortical projections to trigeminal motor ment as the descending (spinal) tract of the trigeminal nerve.
neurons are bilateral and symmetric via direct corticobulbar and They convey pain and temperature sensations. Throughout their
indirect corticoreticulobulbar fibers. Lesions affecting the motor caudal course these fibers project on neurons in the adjacent
nucleus or efferent root result in paralysis of the lower motor nucleus of the descending tract of the trigeminal nerve (spinal
neuron type of the muscles supplied by this root. trigeminal nucleus). The spinal trigeminal nucleus is divided
into three parts on the basis of its cytoarchitecture: (1) an oral
B. AFFERENT ROOT part, which extends from the entry zone of the trigeminal nerve
The afferent root (Figure 7–18) of the trigeminal nerve in the pons to the level of the rostral third of the inferior olivary
contains two types of afferent fibers. nucleus in the medulla oblongata and receives tactile sensibility
from oral mucosa, (2) an interpolar part, which extends from the
1. Proprioceptive Fibers. Proprioceptive fibers from caudal extent of the oral part to just rostral to the pyramidal de-
deep structures of the face travel via the efferent and afferent cussation in the medulla oblongata and receives dental pain, and
roots. They are peripheral processes of unipolar neurons in the (3) a caudal part, which extends from the pyramidal decussation
mesencephalic nucleus of the trigeminal nerve located at the ros- down to the second or third cervical spinal segments and receives
tral pontine and caudal mesencephalic levels. This nucleus is pain and temperature sensations from the face.
unique in that it is homologous to the dorsal root ganglion yet is Axons of neurons in the spinal trigeminal nucleus cross the
centrally placed. Proprioceptive fibers to the mesencephalic nu- midline and form the ventral secondary ascending trigeminal tract,
cleus convey pressure and kinesthesia from the teeth, periodon- which courses rostrally to terminate in the thalamus. During their
tium, hard palate, and joint capsules as well as impulses from rostral course these second-order fibers send collateral branches
stretch receptors in the muscles of mastication. The output from to several motor nuclei of the brain stem (hypoglossal [cranial
the mesencephalic nucleus is destined for the cerebellum, the nerve XII], vagus [cranial nerve X], glossopharyngeal [cranial nerve
thalamus, the motor nuclei of the brain stem, and the reticular IX], facial [cranial nerve VII], and trigeminal [cranial nerve V])
formation. The mesencephalic nucleus is concerned with mech- to establish reflexes. The spinal tract of the trigeminal nerve is
anisms that control the force of the bite. concerned mainly with the transmission of pain and temperature
2. Exteroceptive Fibers. Exteroceptive fibers are general somatic sensations. It sometimes is cut surgically at a low level (trigemi-
sensory fibers that convey pain, temperature, and touch sensations nal tractotomy) to relieve intractable pain. These operations may
from the face and the anterior aspect of the head. The neurons relieve pain but leave touch sensation intact. The spinal tract of
of origin of these fibers are situated in the semilunar (gasserian) the trigeminal nerve also carries somatic afferent fibers traveling
118 / CHAPTER 7
with other cranial nerves (facial [cranial nerve VII], glossopharyn- in response to unilateral corneal stimulation. The reflex is
geal [cranial nerve IX], and vagus [cranial nerve X]), as was out- elicited by gently touching the cornea (usually with a cotton
lined previously. wisp). The afferent limb of the reflex is the trigeminal nerve
Other incoming fibers of the trigeminal nerve bifurcate on en- and the descending (spinal) tract of the trigeminal nerve.
try into the pons into ascending and descending branches. These Collateral branches of the spinal tract synapse in the oral or
fibers convey touch sensation. The descending branches join the interpolar parts of the spinal nucleus of the trigeminal nerve.
spinal tract of the trigeminal nerve and follow the course that was Connections are then made via the reticular formation with
outlined above. The shorter ascending branches project on the the facial nuclei bilaterally. Trigeminal fibers establish three
main sensory nucleus of the trigeminal nerve. From the main sen- types of synapses with facial nuclei: (1) disynaptic with the
sory nucleus, second-order fibers ascend ipsilaterally and ipsilateral facial nerve nucleus, (2) polysynaptic with the
contralaterally as the dorsal ascending trigeminal tract to ipsilateral facial nucleus, and (3) indirect and polysynaptic
the thalamus. Some crossed fibers also travel in the ventral with the contralateral facial nerve nucleus.
ascending trigeminal tract. Once they are formed, both secondary 3. The nucleus ambiguus, the respiratory center of the reticular
trigeminal tracts (dorsal and ventral) lie lateral to the medial lem- formation, and the spinal cord (phrenic nerve nuclei and an-
niscus between it and the spinothalamic tract. Since fibers that con- terior horn cells to intercostal muscles), resulting in the sneez-
vey touch sensation bifurcate on entry to the pons and terminate ing reflex in response to stimulation of the nasal mucous
on both the spinal and the main sensory trigeminal nuclei, touch membrane
sensations are not abolished when the spinal trigeminal tract is cut 4. The dorsal motor nucleus of the vagus as part of the vomit-
(trigeminal tractotomy). A schematic summary of the afferent and ing reflex
efferent trigeminal roots and their nuclei is shown in Figure 7–19.
Studies of trigeminothalamic fibers have revealed that the bulk of 5. The inferior salivatory nucleus for the salivatory reflex
these fibers arise from the main sensory nucleus and the interpolaris 6. The hypoglossal nucleus for reflex movements of the tongue
segment of the spinal nucleus. Most of these fibers terminate in the in response to tongue stimulation
contralateral thalamus (ventral posterior medial [VPM] nucleus) 7. The superior salivatory nucleus, resulting in tears in response
with few terminations ipsilaterally. Other efferents of the trigeminal to corneal irritation, the tearing reflex
nuclei include projections to the ipsilateral cerebellum via the infe-
rior cerebellar peduncle (from the spinal and main sensory nuclei), D. BLOOD SUPPLY
the spinal cord dorsal horn (bilaterally) from the spinal nucleus,
and the cerebellum (from the mesencephalic nucleus). The blood supply of the pons (Figures 7–20 and 7–21) is
Trigeminal neuralgia (tic douloureux) is a disabling painful sen- derived from the basilar artery. Three groups of vessels
sation in the distribution of the branches of the trigeminal nerve. provide blood to specific regions of the pons: the para-
The pain is paroxysmal, stabbing, or like lightning in nature and median and the short and long circumferential.
usually is triggered by eating, talking, or brushing the teeth. Several The paramedian vessels (four to six in number) arise from the
methods of treatment, including drugs, alcohol injection of the basilar artery and enter the pons ventrally, supplying the medial
nerve, electrocoagulation of the ganglion, and surgical interrup- basis pontis and the tegmentum. Pontine nuclei, corticospinal
tion of the nerve or spinal tract in the medulla oblongata (trigem- tract bundles within the basis pontis, and the medial lemniscus
inal tractotomy), have been tried with varying degrees of success. are among the structures supplied by these vessels.
Short circumferential arteries arise from the basilar artery, en-
C. TRIGEMINAL REFLEXES ter the brachium pontis, and supply the ventrolateral region of
Collaterals from the secondary ascending trigeminal tracts estab- the basis pontis.
lish synapses with the following cranial nerve nuclei to establish Long circumferential arteries include the anterior inferior
reflex responses: cerebellar artery (AICA), the internal auditory artery, and the su-
perior cerebellar artery. The AICA supplies the lateral tegmentum
1. The motor nucleus of the trigeminal to elicit the jaw reflex of the lower two-thirds of the pons as well as the ventrolateral
2. The facial motor nuclei on both sides, resulting in a bilat- cerebellum. The internal auditory artery, which may arise from
eral blink reflex, the corneal reflex (direct and consensual), the AICA or the basilar artery, supplies the auditory, vestibular,
Afferent Efferent
Mesencephalic
nucleus
Main sensory
nucleus
Semilunar ganglion
Motor nucleus
Spinal nucleus Figure 7–19. Composite schematic diagram of

the afferent and efferent roots of the trigeminal
nerve (cranial nerve V) and their nuclei.
PONS / 119
Long circumferential
branches of basilar and
Fourth ventricle anterior inferior cerebellar
Brachium conjunctivum artery
Reticular formation
Long circumferential
branches of basilar
Brachium pontis artery and superior
cerebellar artery
Spinal lemniscus
Medial lemniscus
Trigeminal nerve
Short circumferential
branches of basilar artery
Pontocerebellar tract
Paramedian branches
Corticospinal and of basilar artery
corticobulbar tracts
Rostral pons
Figure 7–20. Schematic diagram of vascular territories in the rostral pons.
Vermis of cerebellum
Abducens nucleus Fourth ventricle
Trigeminal nucleus Long circumferential

branches of basilar and
Brachium pontis inferior cerebellar
Facial
motor
nucleus
Spinal
lemniscus
Medial
lemniscus
Facial nerve Short circumferential
branches of basilar artery
Pontocerebellar fibers Abducens nerve Paramedian branches

of basilar artery
Corticospinal and
corticobulbar tracts
Caudal pons
Figure 7–21. Schematic diagram of vascular territories in the caudal pons.

120 / CHAPTER 7
and facial cranial nerves. The superior cerebellar artery supplies Deiters’ nucleus. The lateral vestibular nucleus. Described by
the dorsolateral pons, brachium pontis, brachium conjunctivum, Otto Friedrich Karl Deiters, a German anatomist, in 1865.
and dorsal reticular formation. Occasionally the ventrolateral Diplopia (Greek diplos, “double”; ops, “eye”). The perception
pontine tegmentum is also supplied by this vessel. of two images of a single object. Double vision resulting from
extraocular muscle weakness.
Down syndrome. A genetic syndrome caused by trisomy of chro-
TERMINOLOGY mosome 21 or translocation of chromosomal material. Charac-
terized by unique facial features, mental retardation, skeletal
Abducens nerve (Latin, “drawing away”). The sixth cranial
abnormalities, congenital cardiac lesions, and a single transverse
nerve, discovered by Eustachius in 1564, is so named because it
palmar crease. Described by James Langdon Haydon Down, an
supplies the lateral rectus muscle, whose function is to direct the
English physician, in 1866.
eye to the lateral side away from the midline.
Acoustic neuroma. A tumor of the eighth cranial nerve charac- Efferent bundle of Rasmussen. The olivocochlear efferent bun-
terized by deafness and vertigo. May involve adjacent structures dle in the pons extends from the periolivary nuclei to the hair cells
in the brain stem. Described by Harvey Cushing, an American of the organ of Corti. Suppresses the receptivity of the cochlear
neurosurgeon, in 1917. end organ. Described by Theodor Rasmussen, a Canadian neuro-
surgeon, in 1946.
Alternating hemiplegia. Paresis of the cranial nerves ipsilateral
to a brain stem lesion and of the trunk and limbs contralateral to Facial colliculus (Latin colliculus, “small elevation”). An ele-
the lesion. vation in the floor of the fourth ventricle overlying the genu of
the facial nerve and the abducens nucleus.
Alzheimer’s disease. A degenerative disease of the brain formerly
known as senile dementia. Characterized by memory loss, cortical Facial nerve. The seventh cranial nerve. Willis divided the
atrophy, senile plaques, and neurofibrillary tangles. Described by seventh nerve into a portio dura (facial) and a portio mollis
Alois Alzheimer, a German neuropsychiatrist, in 1907. (auditory). Soemmering separated the two and numbered them
Bárány chair test. A test of labyrinthine function in which the separately.
subject, wearing opaque lenses, is rotated while seated on a chair Gasserian ganglion. The sensory trigeminal (semilunar) gan-
with the head tilted 30 degrees forward to bring the horizontal glion was named after Johann Gasser, an Austrian anatomist, by
semicircular canal into the true horizontal plane. Rotation nor- one of his students in 1765. Gasser had described the ganglion
mally elicits horizontal nystagmus opposite to the direction of in his thesis.
rotation. Heschl’s gyri (Greek gyros, “circle”). The transverse gyri in the
Bechterew’s nucleus. The superior nucleus of the vestibular temporal lobe are the sites of the primary auditory cortex. Named
nerve. Described by Vladimir Bechterew, a Russian neurologist, after Richard Heschl, an Austrian anatomist who described them
in 1908. in 1855.
Bell’s palsy. Facial paralysis ipsilateral to a facial nerve lesion. Horner’s syndrome. Drooping of the eyelids (ptosis), constric-
Described by Sir Charles Bell, a Scottish anatomist and surgeon, tion of the pupil (miosis), retraction of the eyeball (enophthal-
in 1821. mos), and loss of sweating on the face (anhidrosis) constitute this
Brachium conjunctivum (Latin, Greek brachion, “arm”; con- syndrome described by Johann Friedrich Horner, a Swiss oph-
junctiva, “connecting”). An armlike bundle of fibers that con- thalmologist, in 1869. The syndrome is due to interruption of
nect the cerebellum and midbrain. descending sympathetic fibers. Also known as Bernard-Horner
Brachium pontis (Latin, Greek, brachion, “arm”; pontis, syndrome and oculosympathetic palsy. Described in animals by
“bridge”). An armlike bundle of fibers that connect the pons Francois du Petit in 1727. Claude Bernard in France in 1862
and cerebellum. and E. S. Hare in Great Britain in 1838 gave precise accounts of
the syndrome before Horner did.
Central facial palsy. Weakness of the lower facial muscles
contralateral to a lesion in the cerebral cortex or corticobulbar Hyperacusis (Greek hyper, “above”; akousis, “hearing”). Ab-
fibers. normal sensitivity to loud sounds. Commonly seen in persons
Cerebellopontine angle. The angle between the medulla oblon- with facial nerve lesions and subsequent paralysis of the stapedius
gata, pons, and cerebellum. Contains the seventh (facial) and muscle.
eighth (cochleovestibular) cranial nerves. Internuclear ophthalmoplegia (MLF syndrome). A condition
Cochlea (Latin, “snail shell”). So named because it has a spiral characterized by paralysis of ocular adduction ipsilateral to the
form resembling a snail shell. medial longitudinal fasciculus lesion and monocular nystagmus
in the contralateral abducting eye.
Conjugate eye movement (Latin conjugatus, “yoked together”).
The lateral deviation of the two eyes in parallel. Isthmus (Greek isthmos, “a narrow connection between two
Corneal reflex. Blinking in response to corneal stimulation. The large bodies or spaces”). The narrowest portion of the hind-
afferent limb of the reflex is via the trigeminal nerve, and the ef- brain. It is situated between the pons and the midbrain.
ferent limb is via the facial nerve. Jaw reflex. Contraction of the masseter and the temporalis mus-
Crocodile tears (Bogorad syndrome). Shedding of tears while cle in response to a tap just below the lower lip. The afferents and
eating as a result of aberrant innervation of facial nerve fibers so efferent limbs of the reflex are via the trigeminal nerve. The re-
that fibers destined to innervate the lacrimal glands reach the sub- flex is evident in upper motor neuron lesions.
mandibular and sublingual glands. Named after F. A. Bogorad, a Juxtarestiform body (Latin juxta, “near, close by”; restis,
Russian physiologist who suggested the name and the physiologic “rope”; forma, “shape”). A bundle of nerve fibers in close prox-
mechanism in 1928. The phenomenon had been described by imity to the restiform body (inferior cerebellar peduncle). Carries
Hermann Oppenheim, a German neurologist, in 1913. vestibular and reticular fibers from and to the cerebellum.
PONS / 121
Lateral lemniscus (Latin from Greek lemniskos, “ribbon”). A Tegmentum (Latin, a “covering”). The dorsal parts of the pons
fiber bundle carrying second- and third-order auditory fibers in and midbrain.
the brain stem. Trapezoid body (Latin trapezoides, “table-shaped”). The ven-
Locus ceruleus (Latin, “place, dark blue”). A pigmented tral acoustic stria in the tegmentum of the pons constitutes the
noradrenergic nucleus in the rostral pons that is dark blue in trapezoid body.
sections. Trigeminal nerve (Latin tres, “three”; geminus, “twin”). The
Modiolus (Latin, “nave, hub”). The central pillar (axis) of the fifth cranial nerve was described by Fallopius. So named because
cochlea. Described and named by Eustachius in 1563. Its struc- it has three divisions: ophthalmic, maxillary, and mandibular.
ture suggests the hub of the wheel with radiating spokes (lamina Trigeminal neuralgia (tic douloureux, Fothergill’s syndrome).
spiralis) attached to it. Paroxysmal attacks of severe facial pain in the trigeminal sensory
Nervus intermedius (Wrisberg’s nerve). Lateral root of the fa- distribution. Described by John Fothergill, an English physician,
cial nerve containing visceral motor and sensory components. in 1773.
Named by Heinrich August Wrisberg, a German anatomist. Trigeminal tractotomy. Cutting of the spinal trigeminal tract in
Nucleus prepositus. One of the perihypoglossal reticular nuclei the brain stem to relieve severe intractable facial pain.
in the medulla oblongata. Related to ocular movement. Utricle (Latin utriculus, “small sac”). A sensory vestibular end
Nystagmus (Greek nystagmos, “drowsiness, nodding”). Nod- organ that detects linear displacement of the body.
ding or closing of the eyes in a sleepy person. The term now Vomiting reflex. Vomiting in response to stimulation of the
refers to involuntary rhythmic oscillation of the eyes. pharyngeal wall. The afferent limb of the reflex is via the trigem-
Organ of Corti. The cochlear receptor organ in the inner ear. inal nerve; the efferent limb is via the vagus nerve.
Described by Marchese Alfonso Corti, an Italian histologist, in
1851.
Parkinson’s disease. A degenerative disease of the brain charac-
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Pons: Clinical Correlates 8
Basal Pontine Syndromes Caudal Tegmental Pontine Syndromes

Caudal Basal Pontine Syndromes Mid-Tegmental Pontine Syndrome (Grenet Syndrome)
Rostral Basal Pontine Syndrome Rostral Tegmental Pontine Syndrome
Pure Motor and Ataxic Hemiparesis (Raymond-Cestan-Chenais Syndrome)
Dysarthria–Clumsy Hand Syndrome Extreme Lateral Tegmental Pontine Syndrome
The Locked-in Syndrome (Marie-Foix Syndrome)
Crying and Laughter Ocular Bobbing and Dipping
Tegmental Pontine Syndromes REM Sleep
The Medial Tegmental Syndrome Central Neurogenic Hyperventilation
The One-and-a-Half Syndrome The Pons and Respiration
Dorsolateral Tegmental Pontine Syndrome
KEY CONCEPTS
Manifestations of the Millard-Gubler syndrome consist of The dorsolateral pontine tegmental syndrome is mani-
ipsilateral facial nerve palsy and contralateral hemiple- fested by dissociated sensory loss (loss of pain and tem-
gia. In some patients the abducens nerve may be involved perature sense with preservation of kinesthesia and dis-
ipsilateral to the lesion. criminative touch) over the ipsilateral face and
contralateral trunk and extremities.
Manifestations of the Gellé syndrome consist of ipsilateral
deafness and vertigo, with or without facial palsy, and Foville syndrome is manifested by ipsilateral facial nerve
contralateral hemiparesis. palsy, ipsilateral horizontal gaze paralysis, and contra-
lateral hemiparesis.
Manifestations of the Brissaud-Sicard syndrome consist
of ipsilateral facial hemispasm and contralateral hemi- Manifestations of the Grenet syndrome consist of bilat-
paresis. eral facial and contralateral trunk thermoanalgesia, ipsi-
lateral paralysis of muscles of mastication, ataxia and
Manifestations of the rostral basal pontine syndrome
tremor, and contralateral hemiparesis.
consist of ipsilateral trigeminal nerve palsy (motor and sen-
sory) and contralateral hemiplegia. The Raymond-Cestan-Chenais syndrome is manifested
by ipsilateral internuclear ophthalmoplegia and ataxia
The medial tegmental syndrome is manifested by ipsilat-
and contralateral hemiparesis and hemisensory loss.
eral abducens and facial nerve palsies and contralateral
loss of kinesthesia and discriminative touch. The Marie-Foix syndrome is manifested by ipsilateral
ataxia and contralateral hemiparesis with or without
The one-and-a-half syndrome is manifested by ipsilat-
hemisensory loss.
eral horizontal gaze paralysis and internuclear ophthal-
moplegia.
123
124 / CHAPTER 8
Medial lemniscus nerve VIII) nerve and corticospinal tract fibers with variable in-
volvement of the facial nerve.
Abducens nucleus
C. BRISSAUD-SICARD SYNDROME
Facial nerve Described in 1906, the Brissaud-Sicard syndrome consists of
ipsilateral facial hemispasm and contralateral hemiparesis. The
lesion is in the caudal ventral pons involving facial nerve
(cranial nerve VII) rootlets and corticospinal tract fibers.
Rostral Basal Pontine Syndrome

If the basal pontine lesion occurs more rostrally, at the level of
the trigeminal nerve (Figure 8–3), the manifestations
include ipsilateral trigeminal signs (sensory and motor)
and a contralateral hemiplegia of the upper motor neu-
ron variety.
Pure Motor and Ataxic Hemiparesis

Discrete lesions in the basis pontis have been reported to result
Corticospinal tract
in pure motor hemiparesis or ataxic hemiparesis. Pure motor
hemiparesis is secondary to involvement of corticospinal tract
BASAL PONTINE SYNDROME fascicles within the basis pontis. Ataxic hemiparesis is due to in-
volvement of corticospinal tract fascicles along with pontocere-
Ipsilateral facial muscle paralysis bellar fascicles in the basis pontis.
Contralateral limb paralysis
Dysarthria–Clumsy Hand Syndrome
Figure 8–1 Schematic diagram of the structures involved in
the caudal pontine syndrome (Millard-Gubler) and the resulting Vascular lesions of the basis pontis at the junction of the upper
clinical manifestations. third and lower two-thirds of the pons have been associated
Medial lemniscus
Vascular lesions of the pons are best suited to anatomicoclinical
correlations. The following syndromes are particularly illustrative. Abducens nucleus
Facial nerve
BASAL PONTINE SYNDROMES
Basal pontine syndromes are caused by lesions in the basal part
of the pons, affecting the rootlets of cranial nerves and cortico-
spinal tract bundles in the basis pontis.
Caudal Basal Pontine Syndromes

A. MILLARD-GUBLER SYNDROME
The manifestations of this syndrome, as originally described by
Millard and Gubler in 1856, include ipsilateral facial
paralysis of the peripheral type and contralateral hemi-
plegia of the upper motor neuron type (Figure 8–1).
Frequently, the lesion may extend medially and rostrally to in- Abducens
clude the rootlets of the sixth nerve (Figure 8–2). In this situa- nerve
tion, the patient also manifests signs of ipsilateral sixth nerve
paralysis. Current textbook definitions of the Millard-Gubler Corticospinal tract
syndrome concur on the presence of contralateral hemiplegia of
the upper motor neuron type in association with ipsilateral facial BASAL PONTINE SYNDROME
nerve or abducens nerve paresis or both and with occasional in- Ipsilateral paralysis of facial muscle
volvement of the medial lemniscus.
Ipsilateral paralysis of ocular abduction
B. GELLÉ SYNDROME Contralateral limb paralysis
Described in 1901, the Gellé syndrome consists of ipsilateral
deafness, vertigo, variable facial nerve palsy, and con- Figure 8–2 Schematic diagram of the structures involved in
tralateral hemiparesis. The lesion is in the caudal ventromedial and rostral extensions of the caudal basal pontine syn-
lateral pons involving the cochleovestibular (cranial drome and the resulting clinical manifestations.
PONS: CLINICAL CORRELATES / 125
TEGMENTAL PONTINE SYNDROMES

Tegmental pontine syndromes are caused by lesions in the teg-
mentum of the pons that affect cranial nerve nuclei or rootlets
Trigeminal and long tracts in the tegmentum.
nerve
The Medial Tegmental Syndrome

Structures affected in the medial tegmental syndrome include
the nucleus and rootlets of the abducens nerve (cranial
nerve VI), the genu of the facial nerve, and the medial
lemniscus (Figure 8–4). The manifestations of the lesion
therefore include ipsilateral sixth nerve paralysis and a lateral
gaze paralysis, ipsilateral facial paralysis of the peripheral variety,
and contralateral loss of kinesthesia and discriminative touch.
The One-and-a-Half Syndrome

Corticospinal tract
The one-and-a-half syndrome is characterized by ipsilateral lateral
gaze paralysis resulting from involvement of the abducens nucleus
Basal pontine syndrome
and internuclear ophthalmoplegia (paralysis of adduc-
Ipsilateral paralysis of muscles tion of the eye ipsilateral to the lesion and nystagmus of
supplied by trigeminal nerve the abducting eye) as a result of involvement of the me-
Ipsilateral loss dial longitudinal fasciculus. The vascular lesion is discrete in the
of facial sensation dorsal paramedian tegmentum, involving the abducens nucleus
Contralateral limb paralysis and the medial longitudinal fasciculus (type I one-and-a-half
syndrome, Figure 8–5). Type II one-and-a-half syndrome is asso-
Figure 8–3 Schematic diagram showing structures involved in ciated with cavernous sinus thrombosis that affects two of its
the rostral basal pontine syndrome and the resulting clinical contents: abducens nerve and internal carotid artery. The clinical
manifestations.
with the dysarthria–clumsy hand syndrome. This syndrome is Abducens nucleus

characterized by central (supranuclear) facial weakness, severe
dysarthria and dysphagia, hand paresis, and clumsiness. Medial
lemniscus
The Locked-in Syndrome
The locked-in syndrome is a severely disabling basal pontine
syndrome that is due to an infarct in the ventral half of the pons.
In this syndrome there is paralysis of all motor activity as a result
of involvement of corticospinal tracts in the basis pontis and
aphonia (loss of voice) caused by the involvement of corticobul-
bar fibers coursing in the basis pontis. Vertical gaze and blinking
are spared and are the only means by which such patients com-
municate. Such patients have been described as “corpses with liv-
ing eyes.”
Abducens Corticospinal
Crying and Laughter nerve tract
Discrete unilateral or bilateral vascular lesions in the basis pontis

have been associated with pathologic crying and, rarely, laughter.
These episodes consist of a sudden onset of involuntary crying TEGMENTAL PONTINE SYNDROME
(rarely laughter) lasting about 15 to 30 seconds. Such emotional
Ipsilateral paralysis of lateral gaze
“incontinence” may herald a brain stem stroke, be part of it, or
follow the onset of a stroke by a few days. The anatomic basis for Ipsilateral paralysis of ocular abduction
the emotional incontinence in pontine lesions has not been es- Contralateral loss of kinesthesia and
tablished. Most cases of pathologic crying or laughter are associ- discriminative touch
ated with bilateral frontal or parietal lesions with pseudobulbar Ipsilateral facial muscle paralysis
palsy. Some investigators have postulated that lesions in the basis
pontis interrupt an inhibitory corticobulbar pathway to the pon- Figure 8–4 Schematic diagram showing structures involved
tine tegmental center for laughing and crying, essentially releas- in the tegmental pontine syndrome and the resulting clinical
ing that center from cortical inhibition. manifestations.
126 / CHAPTER 8
Figure 8–5 One-and-a-half syndrome, type I. MLF, medial longitudinal fasciculus.
picture is that of abducens nerve palsy and cerebral hemisphere B. MUSICAL HALLUCINOSIS
(gaze center) infarction (Figure 8–6) Lateral or paramedian lesions in the tegmentum of the caudal
pons have been associated with musical hallucinosis. The musical
Dorsolateral Tegmental Pontine Syndrome melodies or sounds are usually familiar. The lesion usually involves
one or more of the following auditory structures: acoustic striae
Vascular lesions in the dorsolateral pontine tegmentum that (including the trapezoid body), superior olivary nucleus, lateral
affect structures supplied by the anterior inferior cere- lemniscus. In addition, the lesion involves trigeminal nerve fibers
bellar artery (AICA) on one side coupled with a vascular destined to the tensor tympani muscle and facial nerve fibers to
lesion in the dorsolateral medulla that affects structures the stapedius muscle, both of which travel in caudal pons. The
supplied by the posterior inferior cerebellar artery (PICA) on the hallucinations are attributed to release of auditory memories by
other side have been reported to produce dissociated sensory disinhibition of reticular pathways from nucleus raphe pontis to
loss (loss of pain and temperature sense with preservation of sensory centers in the thalamus and cerebral cortex.
vibration and position sense) enveloping the entire body, accom-
panied by truncal and limb ataxia without weakness. The disso-
ciated sensory loss is due to simultaneous and bilateral involve- Mid-Tegmental Pontine Syndrome
ment of the spinothalamic tracts and the trigeminal system with (Grenet Syndrome)
sparing of the lemniscal system. The ataxia is due to involvement Described by Grenet in 1856, this syndrome consists
of cerebellar-destined fibers coursing in the tegmentum or, alter- of thermoanalgesia in both sides of the face and the
natively, the cerebellum itself. contralateral trunk, ipsilateral trigeminal (cranial nerve
V) nerve motor involvement (paralysis of muscles of mastica-
Caudal Tegmental Pontine Syndromes tion), ataxia and tremor, and contralateral hemiparesis. The le-
sion is in mid-pons tegmentum and involves the trigeminal nu-
A. FOVILLE’S SYNDROME (RAYMOND-FOVILLE SYNDROME) cleus and trigeminothalamic fibers, superior cerebellar peduncle,
Foville’s syndrome is characterized by an ipsilateral pe- and spinothalamic tract, and it extends ventrally to involve corti-
ripheral type of facial nerve palsy and horizontal gaze cospinal fibers.
palsy and contralateral hemiparesis. The lesion usually is
in the caudal pons and involves the corticospinal tract (contra- Rostral Tegmental Pontine Syndrome
lateral hemiparesis), the paramedian pontine reticular formation (Raymond-Cestan-Chenais Syndrome)
(PPRF), and/or the abducens nucleus (conjugate gaze palsy), as
well as the nucleus or fascicles of the facial nerve (facial muscle In the Raymond-Cestan-Chenais syndrome the lesion is in the ros-
weakness). tral pons and involves the medial lemniscus, medial longitudinal
PONS: CLINICAL CORRELATES / 127
Figure 8–6 One-and-a-half syndrome, type II.
fasciculus, spinothalamic tract, and cerebellar fibers. The Central Neurogenic Hyperventilation
manifestations are internuclear ophthalmoplegia (me-
dial longitudinal fasciculus), ipsilateral ataxia (cerebellar Reports in humans suggest that medial tegmental pontine lesions,
fibers), and hemisensory loss (medial lemniscus and spinotha- possibly affecting the PPRF bilaterally, are associated with the
lamic tract). With ventral extension, there may be contralateral syndrome of central neurogenic hyperventilation. This syndrome
hemiparesis due to corticospinal tract involvement. is characterized by sustained tachypnea that persists despite an
elevated arterial PO2 and pH and a low arterial PCO2. It has been
hypothesized that a pontine lesion of this type disinhibits in-
Extreme Lateral Tegmental Pontine Syndrome hibitory pontine influences on medullary respiratory neurons.
(Marie-Foix Syndrome)
In the Marie-Foix syndrome there is ipsilateral cerebellar ataxia The Pons and Respiration
and contralateral hemiparesis with or without hemisen- Respiration is of two types: voluntary and automatic. Selective
sory loss. The lesion in the rostral extreme lateral pons loss of voluntary respiration occurs in patients with lesions of the
involves the brachium pontis (ataxia), the spinothalamic basis pontis. Selective loss of voluntary or automatic respiration
tract (hemisensory loss), and the corticospinal tract (hemi- also has been described as part of the locked-in syndrome.
paresis). The full clinical picture of the Marie-Foix syndrome has Automatic respiratory pathways are presumed to be initiated
rarely been reported and includes ipsilateral cranial nerve palsies, in limbic cortex and involve diencephalic structures, the reticular
Horner’s syndrome, hemiataxia, palatal myoclonus, and contra- system of the brain stem, the lateral or dorsal pons, the medullary
lateral spinothalamic sensory loss. nuclei mediating automatic respirations, and respiratory neurons
of the spinal cord. Selective loss of automatic respiration occurs
Ocular Bobbing and Dipping in patients with Ondine’s curse, lesions of the medulla oblon-
gata, or bilateral high cervical cord lesions.
A variety of oscillatory eye movement abnormalities have been de-
scribed in patients with pontine vascular lesions. These abnormal- TERMINOLOGY
ities have been referred to as ocular bobbing, inverse ocular bob-
bing, ocular dipping, and inverse ocular dipping on the basis of Ataxia (Greek an, “negative”; taxis, “order”). Without order,
the predominant oscillatory abnormality. disorganized. Incoordination of movement seen in cerebellar dis-
ease. The term was used by Hippocrates and Galen for disordered
action of any type, such as irregularity of pulse.
REM Sleep
Brissaud, Edward (1852–1909). French neuropsychiatrist who
The pons is also necessary and sufficient to generate rapid eye trained under Charcot and later deputized for him at the Sal-
movement (REM) sleep. In humans, bilateral pontine damage pêtrière hospital in Paris. He described the Brissaud-Sicard pon-
may prevent REM sleep. tine syndrome and many other syndromes. Died of brain tumor.
128 / CHAPTER 8
Dysarthria (Greek dys, “difficult”; arthroun, “to utter dis- SUGGESTED READINGS
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ysis. Arch Neurol 1971; 24:431–440.
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Jaeckle KA et al: Central neurogenic hyperventilation: Pharmacologic inter-
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Millard and Adolphe-Marie Gubler, French physicians, in 1856. Kushida CA et al: Cortical asymmetry of REM sleep EEG following unilateral
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1995.
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rapidity of respiration.
Mesencephalon (Midbrain) 9
Gross Topography Accommodation-Convergence Reflex

Ventral View Mesencephalic Reticular Formation
Dorsal View Vertical Gaze
Microscopic Structure Control of Saccadic Eye Movement
General Organization Smooth Pursuit Eye Movements
Inferior Colliculus Level Blood Supply
Superior Colliculus Level Inferior Colliculus Level
Light Reflex Superior Colliculus Level
Afferent Pathway Pretectal Level
Efferent Pathway
KEY CONCEPTS
In cross section the mesencephalon is divided into three re- On the basis of its projection sites, the mesencephalic
gions: the tectum, the tegmentum, and the basal portion. dopaminergic system is subdivided into mesostriatal,
mesoallocortical, and mesoneocortical subdivisions.
The inferior colliculus receives inputs from the lateral lem-
niscus, medial geniculate body, primary auditory cortex, The superior colliculus receives inputs from the cerebral
and cerebellar cortex. cortex, retina, spinal cord, and inferior colliculus.
The output of the inferior colliculus is to the medial genic- The output of the superior colliculus is to the spinal cord,
ulate body, nucleus of the lateral lemniscus, superior col- pontine nuclei, reticular formation of the midbrain, and
liculus, and cerebellum. thalamus.
Axons of trochlear neurons form the trochlear nerve, the The pretectal area is involved in the pupillary light reflex
smallest cranial nerve and the only one that decussates and vertical gaze.
before exiting the neuraxis from the dorsal surface of the
Input to the red nucleus comes mainly from the deep cere-
midbrain.
bellar nuclei and the cerebral cortex.
In the cerebral peduncle, corticospinal fibers occupy the
The output of the red nucleus is mainly to the spinal cord,
middle three-fifths, flanked on each side by corticopon-
cerebellum, reticular formation, and inferior olive.
tine fibers.
Somatic motor neurons of the oculomotor nucleus are
The substantia nigra receives inputs from the neostriatum,
organized into subnuclei that correspond to the eye
cerebral cortex, globus pallidus, subthalamic nucleus, and
muscles supplied by the oculomotor nerve. All these sub-
midbrain reticular formation.
nuclei supply ipsilateral muscles except the superior rec-
The output of the substantia nigra is to the neostriatum, tus subnucleus, which supplies the contralateral superior
limbic cortex, globus pallidus, red nucleus, subthalamic rectus muscle, and the levator palpebrae subnucleus,
nucleus, thalamus, superior colliculus, midbrain reticular which supplies both levator palpebrae muscles.
formation, and amygdala.
129
130 / CHAPTER 9
(continued from previous page) The midbrain reticular formation is involved in wakeful-
ness and sleep.
Lesions of the oculomotor nerve within the midbrain re-
The neural substrates for vertical gaze consist of the
sult in oculomotor nerve palsy and either contralateral
ocular motor neurons of cranial nerves III and IV, the ros-
tremor (if the red nucleus is concomitantly involved) or
tral interstitial nucleus of the medial longitudinal fasci-
contralateral upper motor neuron paralysis (if the cere-
culus, interstitial nucleus of Cajal, nucleus of the posterior
bral peduncle is involved).
commissure, the posterior commissure, the mesen-
Accessory oculomotor nuclei include Cajal’s interstitial cephalic reticular formation, and the medial longitudinal
nucleus, rostral interstitial nucleus of the medial longitu- fasciculus.
dinal fasciculus (RiMLF), Darkschewitsch’s nucleus, and
Saccadic eye movements are controlled by cortical inputs
nucleus of the posterior commissure.
to the brain stem pulse generators either directly or indi-
The periaqueductal (central) gray region is concerned rectly via the superior colliculus. Brain stem pulse genera-
with modulation of pain, vocalization, control of repro- tors for horizontal saccades are in the paramedian pon-
ductive behavior, modulation of medullary respiratory tine reticular formation, and for vertical saccades they are
centers, aggressive behavior, and vertical gaze. in the midbrain (RiMLF).
Constriction of the pupil ipsilateral to light stimulation Smooth pursuit eye movements are controlled by input
constitutes the direct light reflex; constriction of the pupil from cortical areas 8, 19, 37, and 39 to the dorsolateral
contralateral to light stimulation constitutes the consen- pontine nucleus and the nucleus reticularis tegmenti pon-
sual light reflex. tis and cerebellum.
In an Argyll Robertson pupil, light reflex is lost while ac- The midbrain receives the bulk of its blood supply from
commodation convergence is preserved. the basilar artery via the paramedian, superior cerebellar,
and posterior cerebral branches.
GROSS TOPOGRAPHY inferior colliculi (quadrigeminal plates). The term quadrigem-

inal plate was coined by Vesalius to refer to the tectum.
Ventral View Anatomists of that time wanted to name the superior and in-
ferior colliculi after the Latin equivalents for the testes and
The inferior surface of the mesencephalon (midbrain) is marked
buttocks. The overlying pineal gland, which looked like a
by the divergence of two massive bundles of fibers—the cerebral
pinecone to the Greeks, was mistaken for a penis. This was
peduncles—which carry corticofugal fibers to lower levels (Figure
too explicit for Vesalius, who renamed the tectum the quad-
9–1). Caudally, the cerebral peduncles pass into the basis pontis;
rigeminal plate.
rostrally, they continue into the internal capsule. Between the
cerebral peduncles lies the interpeduncular fossa, from which ex-
its the oculomotor nerve (cranial nerve III). The trochlear nerve
(cranial nerve IV) emerges from the dorsal aspect of the mesen-
cephalon, curves around, and appears at the lateral borders of the Cerebral cortex Optic nerve
cerebral peduncles. The optic tract passes under the cerebral pe-
duncles before the peduncles disappear into the substance of the Interpeduncular
fossa Optic tract
cerebral hemispheres.
Dorsal View
The dorsal surface of the mesencephalon features four elevations
(corpora quadrigemina) (see Figure 5–2). The rostral and larger Oculomotor
Cerebral
two are the superior colliculi; the caudal and smaller two are the nerve
peduncle
inferior colliculi. The trochlear nerves emerge just caudal to the
inferior colliculi. Trochlear
nerve
Pons
MICROSCOPIC STRUCTURE Trigeminal
nerve
General Organization
Three subdivisions are generally recognized in sections
of the mesencephalon (Figure 9–2). Figure 9–1. Schematic diagram of the ventral surface of the
1. The tectum is a mixture of gray and white matter midbrain and pons showing major midbrain structures encoun-
dorsal to the central gray matter. It includes the superior and tered on this surface.
MESENCEPHALON (MIDBRAIN) / 131
Aqueduct Tectum 1. Afferent Connections (Figure 9–3). Fibers come from the
of Sylvius following sources.
Central 1. Lateral lemniscus. These fibers terminate on the ipsi- and
Tegmentum (periaqueductal) contralateral inferior colliculi. Some lateral lemniscus
gray
fibers bypass the inferior colliculus to reach the medial
geniculate body.
2. Contralateral inferior colliculus.
3. Ipsilateral medial geniculate body. This connection serves as a
feedback mechanism in the auditory pathway.
4. Cerebral cortex ( primary auditory cortex).
5. Cerebellar cortex via the anterior medullary velum.
Substantia Cerebral
nigra peduncle 2. Efferent Connections. The inferior colliculus projects to the
following areas (Figure 9–4).
Figure 9–2. Cross-sectional diagram of the midbrain showing 1. Medial geniculate body via the brachium of the infe-
its major subdivisions. rior colliculus. This pathway is concerned with audition.
2. Contralateral inferior colliculus.
3. Superior colliculus. This pathway establishes reflexes for turn-
2. The tegmentum, the main portion of the mesencephalon, ing the neck and eyes in response to sound.
lies inferior to the central gray matter and contains ascending 4. Nucleus of the lateral lemniscus and other relay nuclei of the
and descending tracts, reticular nuclei, and well-delineated auditory system for feedback.
nuclear masses. 5. Cerebellum. The inferior colliculus is a major center for the
3. The basal portion includes the cerebral peduncles, a massive transmission of auditory impulses to the cerebellum via the
bundle of corticofugal fibers on the ventral aspect of the anterior medullary velum. The inferior colliculus thus is a
mesencephalon, and the substantia nigra, a pigmented nu- relay nucleus in the auditory pathway to the cerebral cortex
clear mass that lies between the dorsal surface of the cerebral and cerebellum. In addition, the inferior colliculus plays a
peduncle and the tegmentum. The term basis pedunculi role in the localization of the source of sound.
has been used to refer to the basal portion of the mesen-
cephalon, which includes the cerebral peduncle and sub-
stantia nigra. The term crus cerebri has been used to refer to
the massive bundle of corticofugal fibers (cerebral peduncle)
on the ventral aspect of the mesencephalon. Not frequently,
the term cerebral peduncle is erroneously used to refer to the
mesencephalon below the tectum (tegmentum and basal
portion).
The components of these subdivisions are discussed below
under two characteristic levels of the mesencephalon: the inferior
colliculus and the superior colliculus. The inferior colliculus level
is characterized in histologic sections by the decussation of the
superior cerebellar peduncle and by the fourth nerve (trochlear) Cerebellum
nucleus. The superior colliculus level is characterized by the red Primary auditory
nucleus, the third nerve (oculomotor) nucleus, and the posterior cortex
commissure.
Inferior Colliculus Level

A. TECTUM Inferior colliculus
The nucleus of the inferior colliculus occupies the tectum at the

level of the inferior colliculus. This nucleus is an oval mass of small
and medium-size neurons organized into three parts: (1) main Lateral lemniscus
laminated mass of neurons, called the central nucleus, (2) a thin
dorsal cellular layer, the pericentral nucleus, and (3) a group of
neurons that surround the central nucleus laterally and ventrally,
the external nucleus. The central nucleus is the major relay nu-
cleus in the auditory pathway. High-frequency sounds are repre- geniculate
body
sented in the ventral part, and low-frequency sounds in the dorsal
part of the nucleus (similar to that in the cochlea). The pericen-
tral nucleus receives only contralateral monaural input and serves
to direct auditory attention. The external nucleus is related pri-
marily to acousticomotor reflexes. The inferior colliculus has the Figure 9–3. Schematic diagram showing the major afferent
following afferent and efferent connections. connections of the inferior colliculus.
132 / CHAPTER 9
the body and lies lateral to the medial lemniscus. Mingled with
the spinothalamic fibers are the spinotectal fibers on their way to
Superior colliculus the tectum. Fibers in the spinothalamic tract are somatotopically
organized, with cervical fibers being most medial and sacral
fibers most lateral.
e. Lateral lemniscus. The lateral lemniscus conveys audi-
tory fibers and occupies a position lateral and dorsal to the
spinothalamic tract.
f. Medial longitudinal fasciculus. The medial longitudinal
fasciculus maintains its position dorsally in the tegmentum in a
Cerebellum
paramedian position.
g. Central tegmental tract. The central tegmental tract
conveys fibers from the basal ganglia and midbrain to the infe-
Inferior rior olive and occupies a dorsal position in the tegmentum, ven-
colliculus trolateral to the medial longitudinal fasciculus.
h. Rubrospinal tract. The rubrospinal tract conveys fibers
Nucleus of
lateral from the red nucleus to the spinal cord and inferior olive and is
lemniscus located dorsal to the substantia nigra.
Medial
geniculate C. NUCLEAR GROUPS
body The following nuclei are seen at the level of the inferior collicu-
lus (Figure 9–6).
1. Mesencephalic Nucleus. The mesencephalic nucleus of the
trigeminal nerve is homologous in structure to the dorsal root
ganglion but is uniquely placed within the central nervous sys-
tem. It contains unipolar neurons with axons (the mesencephalic
root of the trigeminal nerve) which convey proprioceptive im-
pulses from the muscles of mastication and the periodontal
membranes. As these fibers approach the nucleus, they gather in
a bundle close to the nucleus: the mesencephalic tract.
2. Nucleus of the Trochlear Nerve (Cranial Nerve IV). The
Figure 9–4. Schematic diagram showing the major efferent nucleus of the trochlear nerve lies in the V-shaped ventral part of
connections of the inferior colliculus. the central gray matter. Axons of this nerve arch around the cen-
tral gray matter, cross in the anterior medullary velum, and
emerge from the dorsal aspect of the mesencephalon
B. TEGMENTUM (Figure 9–7). These axons supply the superior oblique
At the level of the inferior colliculus, the tegmentum of the mes-
encephalon contains fibers of passage (ascending and descending
tracts) and nuclear groups. Lateral lemniscus
1. Fibers of Passage. The following fiber tracts pass through Medial longitudinal
the mesencephalon (Figure 9–5). fasciculus
a. Brachium conjunctivum (superior cerebellar pe- Central
duncle). The brachium conjunctivum is a massive bundle of tegmental tract
fibers arising in the deep cerebellar nuclei. These fibers decussate
Spinothalamic
in the tegmentum of the midbrain at this level. A few proceed tract
rostrally to terminate on the red nucleus; the others form the
capsule of the red nucleus and continue rostrally to terminate on Medial
the ventrolateral nucleus of the thalamus. lemniscus
b. Medial lemniscus. The medial lemniscus lies lateral to Trigeminal
the decussating brachium conjunctivum and above the substan- lemniscus
tia nigra. This fiber system, which conveys kinesthesia and dis-
criminative touch from more caudal levels, continues its course Substantia
nigra
toward the thalamus. Fibers in the medial lemniscus are somato-
topically organized, with cervical fibers being most medial and Cerebral
sacral fibers most lateral. peduncle
c. Trigeminal lemniscus. The trigeminal lemniscus is com- Brachium
posed of the ventral secondary trigeminal tracts and travels close conjunctivum Rubrospinal tract
to the medial lemniscus on its way to the thalamus. Figure 9–5. Schematic diagram of the midbrain at the inferior
d. Spinothalamic tract. The spinothalamic tract conveys colliculus level, showing the major ascending and descending
pain and temperature sensations from the contralateral half of tracts.
Mesencephalic Dorsal tegmental Parabigeminal

nucleus of trigeminal nucleus area
Locus ceruleus Pedunculopontine

nucleus
Trochlear nucleus Spinothalamic

tract
Medial
lemniscus
Lateral dorsal
tegmental nucleus Trigeminal
lemniscus
Substantia
nigra
Cerebral
peduncle
Figure 9–6. Schematic diagram Medial longitudinal Nucleus parabrachialis Interpeduncular Nucleus
of the midbrain at the inferior col- fasciculus pigmentosus nucleus supratrochlearis
liculus level showing major nuclear Ventral tegmental
groups seen at this level. nucleus
eye muscle. The trochlear nerve is thus unique in two respects: It normal nerve) to compensate for the action of the paralyzed
is the only cranial nerve that crosses before emerging from the muscle. Tilting the head toward the paretic nerve increases double
brain stem, and it is the only cranial nerve that emerges on the vision. The trochlear nucleus receives contralateral and probably
dorsal aspect of the brain stem. Because of decussation, lesions of some ipsilateral corticobulbar fibers and vestibular fibers from
the trochlear nucleus result in paralysis of the contralateral supe- the medial longitudinal fasciculus that are concerned with coor-
rior oblique muscle, whereas lesions of this nerve after it dination of eye movements. Vestibular fibers to the trochlear nu-
emerges from the brain stem result in paralysis of the ipsilateral cleus originate from the superior and medial vestibular nuclei.
superior oblique muscle. The superior oblique muscle has three The fibers from the superior vestibular nucleus are ipsilateral and
actions: primary of intorsion, secondary of depression, and ter- inhibitory; those from the medial vestibular nucleus are con-
tiary of abduction. It thus acts by intorsion of the abducted eye tralateral and excitatory.
and depression of the adducted eye. Patients with trochlear nerve 3. Interpeduncular Nucleus. The interpeduncular nucleus,
lesions complain of vertical diplopia (double vision) that is espe- which is indistinct in humans, is a poorly understood nuclear
cially marked in looking contralaterally downward while de- group in the base of the tegmentum between the cerebral pedun-
scending stairs and usually is corrected by head tilt (toward the cles. It receives fibers mainly from the habenular nuclei (in the
diencephalon) through the habenulointerpeduncular tract and
sends fibers to the dorsal tegmental nucleus through the pedun-
culotegmental tract.
4. Nucleus Parabrachialis Pigmentosus. The nucleus parabra-
Superior
oblique
chialis pigmentosus, which lies between the substantia nigra and
Trochlear
muscle nerve the interpeduncular nucleus, is a ventral extension of the ventral
tegmental area of Tsai.
5. Dorsal Tegmental Nucleus. The dorsal tegmental nucleus
lies dorsal to the medial longitudinal fasciculus (MLF) in the
central gray matter in close proximity to the dorsal raphe nu-
cleus. It receives fibers from the interpeduncular nucleus and
projects on autonomic nuclei of the brain stem and the reticular
Trochlear formation.
nucleus 6. Ventral Tegmental Nucleus. The ventral tegmental nucleus
lies ventral to the MLF in the midbrain tegmentum. Cells in this
nucleus are rostral continuations of the superior central nucleus
of the pons. This nucleus receives fibers from the mamillary bod-
ies in the hypothalamus. The dorsal and ventral tegmental nuclei
are part of a circuit concerned with emotion and behavior.
7. Pedunculopontine (Nucleus Tegmenti Pedunculopontis)
Figure 9–7. Schematic diagram of the midbrain showing ori- and Lateral Dorsal Tegmental Nuclei. These two cholinergic
gin, intra-axial course of the trochlear nerve, and the extraocular nuclei lie within the tegmentum of the caudal mesencephalon
muscle supplied by the nerve. (inferior colliculus level) and rostral pons dorsolateral to and
134 / CHAPTER 9
overlapping the lateral margin of the rostral superior cerebellar pe-

duncle, between that peduncle and the lateral lemniscus. Neurons
of the pedunculopontine nucleus are affected in patients with pro-
gressive supranuclear palsy, a degenerative central nervous system Corticopontin
disease. It projects to the thalamus and the pars compacta of the fibers
substantia nigra. This nucleus lies in a region from which walking
movements can be elicited on stimulation (locomotor center).
8. Nucleus Supratrochlearis (Dorsal Raphe Nucleus). The
nucleus supratrochlearis lies in the ventral part of the periaque-
ductal (central) gray matter between the two trochlear nuclei. It
sends serotonergic fibers to the substantia nigra, neostriatum
Cerebral
(caudate and putamen), and neocortex. peduncle
9. Parabigeminal Area. The parabigeminal area is an oval col-
lection of cholinergic neurons ventrolateral to the nucleus of the Corticospinal and Corticopontine
inferior colliculus and lateral to the lateral lemniscus. It receives corticobulbar fibers fibers
fibers from superficial layers of the superior colliculus and pro- Figure 9–8. Schematic diagram of the midbrain showing the
jects bilaterally back into superficial layers of the superior col-
major subdivisions of the cerebral peduncle.
liculus. Cells in this area play a role, along with the superior col-
liculus, in processing visual information. They respond to visual
stimuli and are activated by both moving and stationary visual
stimuli.
cerebral cortex, synapse on pontine nuclei, and enter the contra-
10. Nucleus Pigmentosus (Locus Ceruleus). The nucleus lateral cerebellar hemisphere via the middle cerebellar peduncle
pigmentosus is seen in the rostral pons and caudal mesencepha- (brachium pontis). The corticobulbar fibers destined for cranial
lon. It contains 30,000 to 35,000 neurons. At the level of the in- nerve nuclei occupy a dorsomedial position among the corti-
ferior colliculus it is situated at the edge of the central gray mat- cospinal fibers. According to some studies, the cerebral peduncle
ter. It is made up of four subnuclei: central (largest); anterior in humans has two groups of corticobulbar tracts. Those in the
(rostral end); ventral (caudal and ventral), also known as the nu- medial portion of the peduncle descend to the pontine neurons
cleus subceruleus; and posterior dorsal (small). Its pigmented responsible for gaze; those in the lateral portion descend to the
cells contain melanin granules, which are lost in patients with motor nuclei of cranial nerves V, VII, and XII and the nucleus
Parkinson’s disease. The neurons of the locus ceruleus provide ambiguus.
noradrenergic innervation to most central nervous system re-
gions. Axons of the neurons in the locus ceruleus are elaborately 2. Substantia Nigra. The substantia nigra was first identified by
branched and ramify practically throughout the brain. These ax- Felix Vicq d’Azyr, a French physician in 1786. It was then con-
ons reach their destinations via three major ascending tracts: the sidered to be part of the oculomotor nerve because of its prox-
central tegmental tract, the dorsal longitudinal fasciculus, and imity to oculomotor nerve rootlets. The substantia nigra is a
the medial forebrain bundle. Through these tracts, the locus pigmented mass of neurons sandwiched between the cerebral pe-
ceruleus innervates the thalamus, hypothalamus, and basal telen- duncles and the tegmentum. It is composed of two zones: a dor-
cephalon. In addition, the locus ceruleus projects to the cerebel- sal zona compacta containing melanin pigment and a ventral
lum (via the brachium conjunctivum), to the spinal cord and to zona reticulata containing iron compounds. Dendrites of neu-
sensory nuclei of the brain stem. This nucleus is believed to play rons in the zona compacta arborize in the zona reticulata. The
a role in the regulation of respiration as well as in the rapid eye pars lateralis represents the oldest part of this nucleus. The neu-
movement (REM) stage of sleep. ronal population of the substantia nigra consists of pigmented
and nonpigmented neurons. Pigmented neurons outnumber
D. BASAL PORTION nonpigmented neurons two to one. The neurotransmitter in pig-
mented neurons is dopamine. Nonpigmented neurons are either
At the level of the inferior colliculus, the basal portion of the cholinergic or GABAergic. There is a characteristic pattern of
mesencephalon includes the cerebral peduncles and the substan- neuronal loss in the substantia nigra in different disease states
tia nigra. (Table 9–1). Both pigmented and nonpigmented neurons are lost
1. Cerebral Peduncle. The cerebral peduncle (Figure 9–8) is a in patients with Huntington’s chorea. Only pigmented (dopamin-
massive fiber bundle that occupies the most ventral part of the ergic) neurons, especially those in the center of the substantia
mesencephalon. It is continuous with the internal capsule ros- nigra, are lost in idiopathic Parkinson’s disease. In the posten-
trally and merges caudally into the basis pontis. This massive cephalitic type of Parkinson’s disease, pigmented (dopaminergic)
fiber bundle carries corticofugal fibers from the cerebral cortex to neurons are lost uniformly. In Parkinson’s disease–dementia com-
several subcortical centers. The middle three-fifths of the cere- plex, there is a uniform loss of both pigmented and nonpigmented
bral peduncle is occupied by the corticospinal tract, which is neurons. Finally, in multiple system atrophy, pigmented neurons
continuous caudally with the pyramids. Fibers destined to the are lost in medial and lateral nigral zones. Nigral neurons (vari-
arm are medially located, those to the leg are laterally placed, and able number) show abnormal (reduced) immunostaining for
trunk fibers lie in between. The corticopontine fibers occupy the complex I of the mitochondrial electron transport system in pa-
areas of the cerebral peduncle on each side of the corti- tients with Parkinson’s disease. This reduction is believed to be
cospinal tract. The medially located corticopontine fibers related to the pathogenesis of the disease. The neural connectiv-
constitute the frontopontine projection; the laterally ity of the substantia nigra suggests an important role in the regu-
located fibers constitute the parieto-occipito-temporo-pontine lation of motor activity. Lesions of the substantia nigra are al-
projections. Corticopontine fibers originate in wide areas of the most always seen in Parkinson’s disease, which is characterized by
Table 9-1. Substantia Nigra: Pattern of Cell Loss in Disease.
Type of cell Huntington’s disease Idiopathic Postencephalitic Parkinson’s Multiple

Parkinson’s disease Parkinson’s disease dementia complex system atrophy
Pigmented neurons X X X X X
Nonpigmented neurons X X
Distribution
Uniform loss X X
Central loss X
Medial X
Lateral X
tremor, rigidity, and slowness of motor activity. The known af- composed of GABAergic fibers that terminate mainly on pars
ferent and efferent connections of the substantia nigra are out- reticulata, with some in the pars compacta.
lined below. (4) Subthalamic Nucleus —The subthalamic nucleus pro-
a. Afferent connections (Figure 9–9). jects in a patchy manner to pars reticulata. The transmitter is
(1) Neostriatum —The neostriatal input to the substantia ni- glutamine.
gra is the largest and projects primarily to the pars reticulata with (5) Tegmentonigral Tracts —The tegmentonigral tracts arise
a smaller input to the pars compacta. It arises from the associa- from the midbrain raphe nuclei, which have serotonin and
tive region of the neostriatum primarily from the caudate nu- cholecystokinin, and from the pedunculopontine nucleus, which
cleus. The neurotransmitter is gamma-aminobutyric acid (GABA). is cholinergic.
The striatonigral fibers are topographically organized so b. Efferent connections (Figure 9–9).
that the head of the caudate nucleus projects to the ros- (1) Nigrostriate Fibers —Nigrostriate fibers from the pars
tral third of the substantia nigra, while the putamen pro- compacta project to the neostriatum (caudate and putamen) and
jects to all the other parts of the nigra. are dopaminergic. The nigrostriate projection is somato-
(2) Cerebral Cortex —The corticonigral projection is not as topically organized so that neurons in the lateral part of
massive as was previously believed. Most of these fibers are fibers the pars compacta of the substantia nigra project to the
of passage, and relatively few of them terminate on nigral neurons. putamen, whereas the caudate nucleus receives its nigral input
(3) Globus Pallidus —The input to the substantia nigra from mainly from the medial part. The nigrostriate projections ter-
the globus pallidus arises from the external (lateral) segment. It is minate on the associative sensorimotor and limbic striatum. The
sites of origin of the projections to the caudate and putamen
are segregated in the pars compacta. Cells in the pars compacta
Afferents Efferents project to the caudate nucleus or the putamen but not to both.
Dopaminergic nigral projections to the neostriatum terminate
Cerebral cortex Cerebral cortex on distal dendrites of medium spiny (projection) neurons. They
facilitate neostriatal neurons that project to the pars reticulata of
Amygdaloid the substantia nigra and the internal (medial) segment of the
nucleus globus pallidus and inhibit neostriatal neurons that project to
the external (lateral) segment of the globus pallidus.
(2) Nigrocortical Tract —The nigrocortical fibers originate
Basal ganglia Basal ganglia
neostriatum neostriatum
in the medial zona compacta and the adjacent ventral tegmental
pallidum pallidum area, course through the medial forebrain bundle, and terminate
in the limbic cortex. The involvement of this pathway in parkin-
sonism may explain the akinesia seen in that disease. Another
Subthalamic Subthalamic projection from the substantia nigra and the ventral tegmental
nucleus nucleus area terminates in the neocortex. The function of this projection
is not known but may be related to cognition.
(3) Nigropallidal Tract —Nigropallidal projections are more
Thalamus
abundant in the associative pallidal territory compared with the
sensorimotor territory.
SUBSTANTIA Superior (4) Nigrorubral Tract—A projection to the red nucleus from
NIGRA colliculus the substantia nigra has been described in experimental animals.
(5) Nigrosubthalamic Tract —The connections between the
substantia nigra and subthalamic nucleus are reciprocal.
Raphe nuclei Red nucleus
(6) Nigrothalamic Tract —The nigrothalamic GABAergic
tract runs from the pars reticulata to the ventral anterior, ventral
Pedunculopontine Midbrain lateral, and dorsomedial nuclei of the thalamus.
nucleus tegmentum (7) Nigrotegmental Tract and Nigrocollicular Tract —The
nigrotegmental and nigrocollicular tracts originate from separate
Figure 9–9. Schematic diagram showing the major afferent regions of the pars reticularis of the substantia nigra. They are
and efferent connections of the substantia nigra. both GABAergic. The nigrotegmental tract links the substantia
136 / CHAPTER 9
nigra with the reticular formation and with the spinal cord via crease in dopamine in the visual cortex has been implicated in
the reticulospinal projection. The nigrocollicular tract links the photosensitive epilepsy (Table 9–2).
substantia nigra with the superior colliculus and secondarily with Two types of response mode have been demonstrated in mes-
the control of ocular movement as well as with the spinal cord encephalic dopamine neurons: (1) a phasic mode response to re-
(tectospinal tract). Through its connections with the basal ganglia ward and reward-predicting stimuli that have to be processed by
and the superior colliculus and reticular formation, the substan- the subject with high priority and (2) a tonic mode response in-
tia nigra acts as a link through which the basal ganglia exert an volved in maintaining states of behavioral alertness. Thus, the
effect on spinal and ocular movements. dopamine system is involved in both the setting and the mainte-
(8) Nigroamygdaloid Tract—The nigroamygdaloid tract nance of levels of alertness through the phasic and tonic mode
originates from dopaminergic neurons in the zona compacta and responses.
the pars lateralis of the substantia nigra and projects on the lat-
eral and central amygdaloid nuclei. Superior Colliculus Level
The nigral origin of many of these efferent fiber systems re-
quires further exploration. The GABAergic outputs from the pars A. TECTUM
reticulata of the substantia nigra to the thalamus, superior col- The nucleus of the superior colliculus occupies the tectum at the
liculus, and reticular formation are believed to play a role in sup- level of the superior colliculus. The superior colliculus is a lami-
pressing the progression of epileptic discharge. A marked increase nated mass of gray matter that plays a role in visual reflexes and
in metabolic activity in the substantia nigra has been reported to control of eye movement. The laminated appearance results
occur during epileptic discharge. Nigrothalamic, nigrotectal, and from alternating strata of white and gray matter. Superficial lay-
nigrotegmental pathways originate from separate regions in the ers of the superior colliculus contain cells aligned in an orderly
pars reticulata. fashion with well-defined visual receptive fields and apparently
represent a map of visual space. In contrast, the deep layers con-
E. MESENCEPHALIC DOPAMINERGIC CELL GROUPS
tain cells whose activity is related to the goal points of saccadic
Besides the pars compacta of the substantia nigra, two other cell eye movements. It thus appears that a sensory map of the visual
groups in the mesencephalic tegmentum are dopaminergic: the space in the superficial layers is transformed in the deeper layers
ventral tegmental area of Tsai in close proximity to the medial into a motor map on which a vector from an initial eye position
substantia nigra and the retrorubral cell group (substantia nigra, to a goal eye position is represented. The vector is then translated
pars dorsalis) in close proximity to the red nucleus. The pars into command signals for saccade generators such as the parame-
compacta of the substantia nigra in humans (area A-9 of pri- dian pontine reticular formation (PPRF).
mates) is closely associated, and merges with the immediately ad-
1. Afferent Connections. Afferent connections to the superior
jacent dopamine cell groups of the ventral tegmental area, the
colliculus (Figure 9–10) come from the following sources.
most prominent of which is the nucleus parabrachialis pigmen-
tosus. The ventral tegmental area corresponds to area A-10, and a. Cerebral Cortex. Corticocollicular fibers arise from all over
the retrorubral nucleus corresponds to area A-8. the cerebral cortex, but most abundantly from the occipital (vi-
Studies in primates and humans have identified three subdi- sual) cortex. Fibers originating from the frontal lobe are concerned
visions of the mesencephalic dopaminergic system on the basis with conjugate eye movements and reach the superior col-
of their projection sites. One subdivision is related to the stria- liculus by a transtegmental route. Occipitotectal fibers are
tum (mesostriatal subdivision) and terminates on the caudate concerned with reflex scanning eye movements in pursuit
nucleus, putamen, globus pallidus, and nucleus accumbens. The of a passing object and reach the colliculus via the brachium of
second subdivision is related to the allocortex (mesoallocortical the superior colliculus. Corticotectal fibers are ipsilateral. Occip-
subdivision) and terminates on the amygdala, olfactory itotectal and frontotectal fibers terminate in the superficial and
tubercle, septal area, and piriform cortex. The third sub- middle layers of the superior colliculus. Temporotectal fibers (from
division is related to the neocortex (mesoneocortical) the auditory cortex), in contrast, project into deep collicular layers.
and terminates in all neocortical areas (frontal, temporal, pari- b. Retina. Retinal fibers project on the same layer of the supe-
etal, and occipital cortices). Recently, a dopaminergic projection rior colliculus as do those of the cerebral cortex. In contrast to cor-
to the cerebellar cortex from the ventral tegmental area of Tsai tical fibers, fibers from the retina are bilateral, with a preponderance
was described, possibly as part of the hypothalamo-tegmental- of contralateral input. Retinal fibers reach the superior colliculus by
cerebellar hypothalamic loop. way of the brachium of the superior colliculus; they leave the optic
The term mesostriatal is used to describe the first subdivision
in preference to the term nigrostriatal system, since evidence sug-
gests that both the ventral tegmental area and the substantia ni-
gra contribute to this projection. A reduction in dopaminergic Table 9-2. Disorders of the Mesencephalic Dopaminergic
neurotransmission in this system is associated with parkinson- System
ism. Hyperactivity of this system has been implicated in
Huntington’s chorea. Hyperactivity in the mesoallocortical sub- Subdivision Hypoactivity Hyperactivity
division is believed to play a role in the symptomatology of psy-
chotic disorders, whereas a reduction in function may contribute Mesostriatal Parkinson’s disease Huntington’s chorea
to the cognitive abnormalities found in patients with Parkinson’s Mesoallocortical Cognitive impairment
disease. (Parkinson’s disease) Psychotic disorders
Very little is known about the functional role of the mesoneo- Mesoneocortical Cognitive impairment
cortical system. Some researchers have suggested a role in human (Parkinson’s disease) Undetermined
cognition. A decrease in dopamine in this system may explain Photosensitive epilepsy
cognitive impairments in patients with Parkinson’s disease. A de- (visual cortex)
rants are in the lateral parts of the colliculus. Peripheral visual fields
are represented in the caudal superior colliculus, and central visual
fields are rostrally placed in the colliculus.
EBRAL
TEX c. Spinal cord. Spinotectal fibers ascend in the anterolateral
part of the cord (with the spinothalamic tract) to reach the supe-
rior colliculus. They belong to a multisynaptic system that con-
veys pain sensation.
d. Inferior colliculus. The input from the inferior colliculus
and a number of other auditory relay nuclei is part of a reflex arc
that turns the neck and eyes toward the source of a sound.
Other inputs to the superior colliculus have been reported to
arise from the midbrain tegmentum, central (periaqueductal)
gray matter, substantia nigra (pars reticulata), and spinal trigem-
Corticotectal inal nucleus.
tract
2. Efferent Connections. Efferent connections (Figure 9–11)
RETINA leave the superior colliculus via the following tracts.
Retinotectal MESENCEPHALON
tract THALAMUS
(Superior colliculus)
Tectothalamic
tract
Tectoreticular
tract
Tectotectal Dorsal
tract MESENCEPHALON
(Inferior colliculus) tegmental
decussation
CEREBELLUM
MESENCEPHALON
Spinotectal
tract
Tectopontocerebellar
SPINAL CORD tract
PONS
Figure 9–10. Schematic diagram showing the major afferent
connections of the superior colliculus. Tectospinal
tract
tract proximal to the lateral geniculate body. Retinotectal fibers

arise from homonymous portions of the retina of each eye, but
crossed fibers are the most numerous. The contralateral homony-
mous halves of the visual field are thus represented in each superior SPINAL CORD
colliculus. The retinotectal fibers are retinotopically organized so
that upper retinal quadrants of the contralateral visual fields are in Figure 9–11. Schematic diagram showing the major efferent
the medial parts of the superior colliculus and lower retinal quad- connections of the superior colliculus.
138 / CHAPTER 9
a. Tectospinal tract. From their neurons of origin in the su- the pineal syndrome, and Parinaud’s syndrome. The conglomerate
perior colliculus, fibers of the tectospinal tract system cross in the signs and symptoms that constitute this syndrome include ver-
dorsal tegmental decussation in the midbrain tegmentum and tical gaze palsies, pupillary abnormalities (anisocoria, light-near
descend as part of or in close proximity to the medial longitudi- dissociation), conversion retraction nystagmus, lid retraction
nal fasciculus to reach the cervical spinal cord and termi- (Collier’s sign), inappropriate conversion (pseudoabducens palsy),
nate on Rexed’s laminae VII and VIII. They are con- impaired convergence, skewed eye deviation in the neutral posi-
cerned with reflex neck movement in response to visual tion, papilledema, and lid flutter. This syndrome has been reported
stimuli. in a variety of clinical states, including brain tumors (pineal,
b. Tectopontocerebellar tract. The tectopontocerebellar thalamic, midbrain, third ventricle), hydrocephalus, stroke, in-
tract descends to the ipsilateral pontine nuclei, which also receive fection, trauma, and tentorial herniation.
fibers from visual and auditory cortex. This tract is believed to C. TEGMENTUM
convey visual impulses from the superior colliculus to the cere-
bellum via the pontine nuclei. At the level of the superior colliculus, the tegmentum contains
fibers of passage and nuclear groups.
c. Tectoreticular tract. The tectoreticular tract projects pro-
fusely and bilaterally on reticular nuclei in the midbrain as well 1. Fibers of Passage. The fibers of passage include all the fiber
as on the accessory oculomotor nuclei. tracts encountered at the level of the inferior colliculus except the
lateral lemniscus, which terminates on inferior colliculus neurons
d. Tectothalamic tract. The tectothalamic tract projects to and is not seen at superior colliculus levels. The brachium con-
the lateral posterior nucleus of the thalamus, the lateral genicu- junctivum fibers, which decussate at inferior colliculus levels,
late, and the pulvinar. The pulvinar receives extensive projections terminate in the red nucleus at this level or form the capsule of
from superficial layers of the superior colliculus and relays them the red nucleus on their way to the thalamus. The other tracts
to extrastriate cortical areas 18 and 19. Input to the lateral genic- discussed under “Inferior Colliculus Level” above maintain ap-
ulate nucleus arises from superficial layers of the superior collicu- proximately the same positions at this level.
lus and is relayed to the striate cortex.
As with the afferent connections of the superior colliculus, 2. Nuclear Groups. The nuclear groups include the red nu-
the efferent connections originate from different laminae of the cleus, the oculomotor nucleus, and accessory oculomotor nuclei
superior colliculus. In general, the ascending tectothalamic pro- (Figure 9–12).
jections originate from superficial laminae, whereas the descend- a. Red nucleus. The red nucleus, so named because in fresh
ing tectospinal, tectopontine, and tectoreticular projections orig- preparations its rich vascularity gives it a pinkish hue, is a promi-
inate in deeper laminae. nent feature of the tegmentum at this level. It is composed of a
Unilateral lesions of the superior colliculus in animals have rostral, phylogenetically recent small cell part (parvicellular) and
been associated with the following functional deficits: relative a caudal, phylogenetically older large cell part (magnicellular).
neglect of visual stimuli in the contralateral visual field, height- The rostral part is well developed in humans. The nucleus is tra-
ened responses to stimuli in the ipsilateral visual field, and deficits versed by the following fiber systems: (1) the superior cerebellar
in perception involving spatial discrimination and the tracking peduncle (brachium conjunctivum), (2) the oculomotor nerve
of moving objects. (cranial nerve III) rootlets, and (3) the habenulointerpeduncular
Stimulation of the superior colliculus results in contralateral tract. Of the three systems, only the brachium conjunctivum
conjugate deviation of the eyes. Since there are no demonstrable projects on this nucleus; the other two are related to the red nu-
direct connections of the superior colliculus to the nuclei of extra- cleus only by proximity. The red nucleus has the following affer-
ocular movement, this effect may be mediated via connections to ent and efferent connections.
the rostral interstitial nucleus of the medial longitudinal fascicu- (1) Afferent Connections—Afferent connections that are
lus (RiMLF) and the PPRF. most documented come from two sources (Figure 9–13).
Most collicular neurons respond only to moving stimuli, and (a) Deep Cerebellar Nuclei —The cerebellorubral fibers arise
most also show directional selectivity. from the dentate, globose, and emboliform nuclei of the cerebel-
lum. They travel via the brachium conjunctivum, decussate in
B. PRETECTAL AREA the tegmentum of the inferior colliculus, and project partly to
Rostral to the superior colliculus at the mesencephalic-dien- the contralateral red nucleus. Fibers from the dentate
cephalic junction is the pretectal area (pretectal nucleus). This nucleus terminate on the rostral (parvicellular) part of
area is an important station in the reflex pathway for the pupil- the red nucleus which projects to the inferior olive,
lary light reflex and vertical gaze. It receives fibers from while fibers from the globose and emboliform nuclei project on
the retinas and projects fibers bilaterally to both oculo- the caudal part (magnicellular) of the nucleus, which projects to
motor nuclei. Several nuclei in the pretectal region have the spinal cord. Interruption of the cerebellorubral fiber system
been identified, including the nucleus of the optic tract, results in a volitional type of tremor that is manifested when the
along the dorsolateral border of the pretectum at its junction extremity is in motion (e.g., attempting to reach for an object).
with the pulvinar, and the pretectal olivary nucleus, which is The triangular area bounded by the red nucleus, the inferior
seen best at the level of the caudal posterior commissure. olive (in the medulla oblongata), and the dentate nucleus of the
Experiments in which the pretectal area and/or the posterior cerebellum is known as Mollaret’s triangle. Lesions that interrupt
commissure were ablated suggest strongly that these structures are connectivity among these three structures result in spontaneous
essential for vertical gaze. This may explain the paralysis of verti- rhythmic movement of the palate (palatal myoclonus).
cal gaze in patients with pineal tumors, which compress these (b) Cerebral Cortex —Corticorubral fibers arise mainly from
structures. In humans, a group of signs and symptoms resulting the motor and premotor cortices and project mainly to the ipsi-
from a lesion in the pretectal area are referred to as the pretectal lateral red nucleus. This projection is somatotopically organized.
syndrome. Synonyms include the sylvian aqueduct syndrome, the Projections from the medial part of area 6 (supplementary motor
dorsal midbrain syndrome, Koerber-Salus-Elschnig syndrome, area MII) are crossed and end in the magnicellular region of the
Superior colliculus
Posterior commissure Nucleus of
posterior commissure
Nucleus of Oculomotor nucleus

Darkschewitsch Edinger-Westphal nucleus
Somatic motor nucleus
Interstitial
nucleus of Cajal
Substantia nigra Red nucleus
of the midbrain at the superior
colliculus level, showing its major
nuclear groups.
nucleus. Projections from the precentral (motor) cortex are ipsi- input to the red nucleus establishes axosomatic synapses to re-
lateral to the magnicellular part of the nucleus and correspond place the deafferented cerebellar input.
to the somatotopic origin of the rubrospinal fibers. The corti- The two afferent connections mentioned above are the best es-
corubral and rubrospinal tracts are considered an indirect corti- tablished. Other possible afferent tracts include tectorubral from the
cospinal fiber system. The corticorubral input to the red nucleus superior colliculus and the pallidorubral from the globus pallidus.
establishes primarily axodendritic synapses. Deafferentation ex- (2) Efferent Connections—Efferent connections project to
periments have shown that after cerebellar ablation the cerebral the following areas (Figure 9–14).
(a) Spinal Cord —Rubrospinal fibers arise from the caudal
part (magnicellular) of the nucleus, cross in the ventral
tegmental decussation, and descend to the spinal cord.
CEREBRAL They project on the same spinal cord laminae as does
CORTEX
the corticospinal tract. Like the corticospinal tract, the rubro-
spinal tract facilitates flexor motor neurons and inhibits extensor
motor neurons. Because of their common termination and the
MESENCEPHALON
Red
nucleus
Corticorubral Central
tract tegmental
tract
MESENCEPHALON
Red Brachium Inferior
nucleus conjunctivum olive
CEREBELLUM
Brachium
conjunctivum
Restiform Rubrospinal
DEEP body tract
CEREBELLAR
NUCLEI
Lateral SPINAL CORD
reticular
nucleus
Figure 9–13. Schematic diagram showing the major afferent Figure 9–14. Schematic diagram showing the major efferent
connections of the red nucleus. connections of the red nucleus.
140 / CHAPTER 9
fact that the red nucleus receives cortical input, the rubrospinal (3) Pons and Medulla—Pontine and medullary projections
tract has been considered an indirect corticospinal tract. In most to the oculomotor nucleus arise from the vestibular nuclei, the
mammals, the red nucleus sends its major output to the spinal nucleus prepositus, and the abducens nucleus. The vestibular pro-
cord and clearly subserves a motor function. The projection to jections originate in the superior and medial vestibular nuclei.
the spinal cord has diminished with evolution, and in humans Projections from the medial vestibular nuclei via the MLF are bi-
the red nucleus sends its major output to the inferior olive. In lateral, while those from the superior vestibular nucleus, via the
turn, the inferior olive is connected to the cerebellum. MLF, are ipsilateral. Other fibers from the superior vestibular nu-
(b) Cerebellum —In most mammals the rubrocerebellar fibers cleus that are not contained in the MLF cross in the caudal mid-
are collaterals from the rubrospinal tract. In the upper pons some brain and project to the superior rectus and the inferior oblique
rubrospinal fibers leave the descending tract and accompany the subnuclei of the oculomotor complex. The projection from the
superior cerebellar peduncle to the cerebellum. In the cerebellum abducens nucleus arises from interneurons, is crossed, and reaches
these fibers terminate on cells of the interposed nuclei (embo- the oculomotor nucleus via the MLF along with vestibular fibers.
liform and globose). The connection between the abducens and oculomotor nuclei
(c) Reticular Formation —Rubroreticular fibers are also off- provides the anatomic substrate for the coordination between the
shoots from the rubrospinal tract. They separate from the de- lateral rectus and medial rectus muscles in conjugate horizontal
scending tract in the medulla oblongata and terminate in the gaze. The nucleus prepositus projects ipsilaterally to the oculomo-
ipsilateral lateral reticular nucleus. The lateral reticular nucleus tor complex and may be involved in vertical eye movement.
in turn projects to the cerebellum. Thus, a feedback circuit is es- (4) Cerebellum—Cerebello-oculomotor fibers to the somatic
tablished between the cerebellum, the red nucleus, the lateral motor cell column arise from the contralateral dentate nucleus
reticular nucleus, and back to the cerebellum. and are concerned with the regulation of eye movements. In ad-
(d) Inferior Olive—The rubro-olivary tract arises in the ros- dition, the cerebellum exerts an influence on autonomic neurons
tral small cell part (parvicellular) of the nucleus and projects to of the oculomotor nucleus. Short-latency (direct) as well as long-
the ipsilateral inferior olive via the central tegmental tract. The in- latency (indirect) responses have been elicited in the Edinger-
ferior olive in turn projects to the cerebellum, thus establishing Westphal nucleus after stimulation of the interposed and fastigial
another feedback circuit between the cerebellum, the red nucleus, cerebellar nuclei. This connection is believed to course in the
the inferior olive, and back to the cerebellum. The rubro-olivary brachium conjunctivum and plays a role in pupillary constriction
tract in humans is more important than is the rubrospinal tract. and accommodation. The short-latency connection is facilitatory,
(e) Other Projections —Other efferent projections include whereas the long-latency connection is inhibitory.
fibers to Darkschewitsch’s nucleus, the Edinger-Westphal nucleus, The somatic motor cell column is organized into subgroups
the mesencephalic reticular formation, the tectum, the pretectum, (Figure 9–15) for each of the eye muscles supplied by the oculo-
principal sensory and spinal trigeminal nuclei, and the facial mo- motor nerve. From the most rostral extension of the oculomotor
tor nucleus. nucleus to its middle third are the Edinger-Westphal
Thus, the red nucleus is a synaptic station in neural systems nuclei and the inferior rectus subnuclei. Inferior rectus
concerned with movement, linking the cerebral cortex, cerebel- subnuclei extend rostrally like a peninsula and are the
lum, and spinal cord. only subnuclei seen in the most rostral part of the nucleus. A dis-
Lesions of the red nucleus result in contralateral tremor. crete lesion of the oculomotor nucleus at its most rostral level
may result in an isolated inferior rectus paresis with or without
b. Oculomotor nucleus. The oculomotor nucleus lies dor- pupillary abnormalities.
sal to the medial longitudinal fasciculus (MLF) at the level of the The inferior oblique subnuclei are the most laterally placed
superior colliculus. It is composed of a lateral somatic motor cell subnuclei in the middle and caudal thirds of the nuclear com-
column and a medial visceral cell column. It is approximately 10
mm in length. This nucleus receives fibers from the following
sources.
(1) Cerebral Cortex —Corticoreticulobulbar fibers are bilat-
eral but come mainly from the contralateral hemisphere. Rostral
(2) Mesencephalon—Mesencephalic projections to the ocu- Third
lomotor nucleus originate from Cajal’s interstitial nucleus, the
rostral interstitial nucleus of the medial longitudinal fasciculus
(RiMLF), and the pretectal olivary nucleus. Fibers from Cajal’s Middle
interstitial nucleus course in the posterior commissure and pro- Third
ject mainly on the contralateral oculomotor nucleus. Interruption
of these fibers results in paralysis of upward gaze. The RiMLF is
just rostral to Cajal’s interstitial nucleus. The projection from the Caudal
RiMLF to the oculomotor nucleus is mainly ipsilateral. Lesions Third
of the RiMLF lead to paralysis of downard gaze. Physiologic
studies have shown that neurons in Cajal’s interstitial nucleus and
the RiMLF are active just before vertical eye movements. Cajal’s
interstitial nucleus and the RiMLF project fibers to the somatic MLF MLF
motor cell column of the oculomotor nucleus, whereas the pre-
tectal area projects mainly to the Edinger-Westphal nucleus of Figure 9–15. Simplified schematic diagram of the rostrocaudal
the visceral cell column. The pretectal area receives fibers from arrangement of oculomotor subnuclei. EW, Edinger-Westphal;
both retinas and projects to both oculomotor nuclei. This con- IR, inferior rectus; SR, superior rectus; L, levator; IO, inferior
nection plays a role in the pupillary light reflex. oblique; MR, medial rectus; MLF, medial longitudinal fasciculus.
plex. Superior rectus subnuclei are medially located in the mid- and superior rectus muscles. The inferior division innervates the
dle and caudal thirds of the nucleus and are the only subnuclei in inferior rectus, medial rectus, and inferior oblique muscles and
the third nuclear complex that supply contralateral eye muscles the iris sphincter. The inferior oblique muscle lowers the eye
(superior rectus muscle). All other subnuclei supply correspond- when one is looking medially, and the superior and inferior rec-
ing ipsilateral eye muscles. The superior rectus subnucleus is tus muscles elevate and lower the eye, respectively, when one is
adjacent to and caudal to the inferior rectus subnucleus. A lesion looking laterally. The medial rectus adducts the eye. The levator
slightly caudal to a lesion that produces an isolated inferior rec- palpebrae elevate the lid.
tus palsy can affect the inferior and superior rectus subnuclei, The visceral cell column includes the Edinger-Westphal nu-
producing an ipsilateral inferior rectus and contralateral superior cleus and Perlia’s nucleus. The Edinger-Westphal nucleus is con-
rectus paresis. The medial rectus subnuclei are located primarily cerned with the light reflex. Perlia’s nucleus is probably concerned
in the ventral oculomotor nuclear complex in close proximity to with accommodation but has not been identified in humans.
the MLF. The levator palpebrae subnucleus is a single central nu- The axons of neurons in the visceral cell column accompany
cleus in the caudal third of the nucleus. Axons from the neurons those of the somatic motor column as far as the orbit. In the or-
of this single nucleus divide into right and left bundles to supply bit they part company, and the visceral axons project to the cil-
the two levator palpebrae muscles. Discrete lesions in individual iary ganglion. Postganglionic fibers from the ciliary ganglion in-
subnuclei of the oculomotor nuclear complex have been re- nervate the sphincter pupillae and ciliaris muscles. Lesions in
ported (using magnetic resonance imaging) with isolated unilat- this component of the oculomotor nerve result in a dilated pupil
eral inferior rectus paresis, bilateral inferior rectus paresis and that is unresponsive to light or accommodation.
unilateral superior rectus weakness, and isolated unilateral infe- Lesions of the oculomotor nerve outside the brain stem
rior rectus and contralateral superior rectus weakness. (Figure 9–16A) result in (1) paralysis of the muscles supplied by
Axons of neurons in the somatic motor column course through the nerve, manifested by drooping of the ipsilateral eyelid (ptosis)
the tegmentum of the midbrain, pass near or through the red nu- and deviation of the ipsilateral eye downward and outward by the
cleus, and emerge from the interpeduncular fossa medial to the action of the intact lateral rectus and superior oblique muscles
cerebral peduncle. In their course in the midbrain tegmentum, (supplied by the abducens and trochlear nerves, respectively),
oculomotor nerve fascicles are organized so that fascicles to the in- (2) double vision (diplopia), and (3) paralysis of the sphincter
ferior oblique are most laterally placed, followed from lateral to pupillae and ciliaris muscles, manifested by an ipsilateral dilated
medial by superior rectus, medial rectus, inferior rectus, and pupil- pupil that is unresponsive to light and accommodation.
lary fascicles. The levator palpebrae fascicles lie dorsally close to Lesions at the interpeduncular fossa (Figure 9–16B) involving
those of the medial rectus. Discrete lesions involving one or more the cerebral peduncle and the rootlets of the oculomotor nerve re-
of these fascicles may result in partial oculomotor nerve paresis. sult in (1) deviation of the ipsilateral eye downward and outward,
The oculomotor nerve leaves the brain stem between the su- with drooping of the eyelid, (2) diplopia, (3) ipsilateral loss of
perior cerebellar artery and the posterior cerebral artery. Once it light and accommodation reflexes, (4) dilatation of the ipsilateral
leaves the brain stem, this nerve courses anteriorly in the sub- pupil, and (5) contralateral upper motor neuron paralysis.
arachnoid space until it pierces the dura covering the roof of the Lesions in the mesencephalon involving the red nucleus and
cavernous sinus. In the anterior part of the cavernous sinus, the the rootlets of the oculomotor nerve (Figure 9–16C )
oculomotor nerve divides into superior and inferior divisions. are manifested by (1) deviation of the ipsilateral eye
The superior division innervates the levator palpebrae superioris downward and outward, with drooping of the eyelid,
MORITZ BENEDIKT SYNDROME
Deviation of eye downward

Oculomotor and outward
nucleus Drooping of eyelid
Dilated, nonresponsive pupil
Contralateral tremor
Red nucleus
WEBER SYNDROME
and outward
Drooping of eyelid
Cerebral Dilated, nonresponsive pupil
peduncle Contralateral upper motor
neuron paralysis
Oculomotor
nerve
OCULOMOTOR NERVE PALSY
showing lesions of the oculomotor Deviation of eye downward
and outward
nerve in its intra- and extra-axial Drooping of eyelid
course and their respective clinical Dilated, nonresponsive pupil
manifestations.
142 / CHAPTER 9
(2) diplopia, (3) ipsilateral loss of light and accommodation re- the nucleus fastigii of the cerebellum. The two RiMLF nuclei are
flexes, (4) dilatation of the ipsilateral pupil, and (5) contralateral interconnected. The nucleus projects to ocular motor neurons (cra-
tremor. nial nerves III and IV). Each RiMLF projects simultaneously to
Following lesions in the oculomotor nerve, atypical move- motor neurons that move each eye in the same direction (e.g., infe-
ments of the pupil, lid, or eye can occur due to aberrant nerve rior rectus muscle of one eye and the superior oblique muscle of the
degeneration. This phenomenon is referred to as oculomotor other eye). Projections to motor neurons that innervate elevator
synkinesis. In most of these cases, the oculomotor nerve lesion is (upgaze) muscles are bilateral, with crossing occurring within the
extra-axial. Occasional oculomotor synkinesis has been reported cranial nerve nucleus (cranial nerve III). Projections to motor neu-
in ischemic intra-axial lesions. rons that innervate depressor (downgaze) muscles are ipsilateral.
The relationship of the oculomotor nerve to the posterior The RiMLF also projects to the interstitial nucleus of Cajal.
cerebral and superior cerebellar arteries makes this nerve vulner- (3) Darkschewitsch’s Nucleus —Darkschewitsch’s nucleus lies
able to aneurysms in those vessels. Rupture of these aneurysms is dorsal and lateral to the somatic motor cell column of the oculo-
usually manifested by the sudden onset of headache and signs of motor nerve. It projects to the nuclei of the posterior commis-
oculomotor nerve lesion. sure but does not project to the oculomotor nuclear complex.
It is worth noting that the parasympathetic fibers concerned (4) Nucleus of the Posterior Commissure —This nucleus is
with the pupillary light reflex travel on the superficial aspect of located within the posterior commissure. It has connections with
the oculomotor nerve in its cisternal portion and thus are the pretectal and posterior thalamic nuclei. Lesions involving nuclei
most susceptible to extrinsic compression by extraneural masses of the posterior commissure and crossing fibers from Cajal’s in-
such as posterior communicating artery aneurysms. Conversely, terstitial nuclei produce bilateral eyelid retraction and impairment
in the majority of cases of vascular ischemic disease of the nerve, of vertical eye movement.
such as diabetes mellitus, which affect centrally located fibers, the The accessory oculomotor nuclei are directly or indirectly
pupillary fibers are spared. The blood supply of the oculomotor connected with the oculomotor complex. Cajal’s interstitial nu-
nerve dips deep into the nerve, and thus interruption of the blood cleus also sends fibers to the spinal cord via the MLF.
supply adversely affects deeper fibers and spares the more superfi-
cial ones concerned with the pupillary light reflex. The pupillary D. CENTRAL (PERIAQUEDUCTAL) GRAY
fibers are also of the small unmyelinated type and are relatively
resistant to ischemia. The central gray region of the mesencephalon surrounds the
The sparing of parasympathetic pupillary fibers in ischemic aqueduct of Sylvius and contains scattered neurons, several nu-
disease and their dysfunction in compressive disease are not, how- clei, and some fine myelinated and unmyelinated fibers. The
ever, absolute. In 3 to 5 percent of aneurysms, the pupil may be oculomotor, accessory oculomotor, and trochlear nuclei, as well
spared. Pupil-sparing oculomotor nerve palsy is not, however, as the mesencephalic nucleus of the trigeminal nerve, lie at the
unique to nerve involvement outside the brain stem (in the sub- edge of this region. The dorsal longitudinal fasciculus (fasciculus
arachnoid space or cavernous sinus). These palsies also have been of Schütz) is a periventricular ascending and descending fiber
reported with intra-axial (within the midbrain) lesions. Many, system that courses in the central gray matter. It arises in part
however, are associated with other neurologic signs (e.g., tremor), from the hypothalamus and contains autonomic fibers. It gener-
suggesting the involvement of adjacent structures such as the red ally connects the hypothalamus with the periaqueductal gray
nucleus. Few cases of pupil-sparing oculomotor nerve palsy from and with autonomic nuclei in the pons and medulla. The neuro-
intra-axial lesions have been reported without another associated peptide enkephalin has been identified in the central gray
neurologic sign. Such cases are explained by isolated involvement matter. Stimulation of certain sites within the central gray
of the appropriate nerve fascicles by the ischemic process. matter release enkephalins, which act on serotonergic neu-
rons in the medulla oblongata, which in turn project on primary
c. Accessory oculomotor nuclei. The accessory oculomo- afferent axons (concerned with pain conduction) in the dorsal
tor nuclei include the following nuclei (see Figure 9–12). horn of the spinal cord to produce analgesia. Stimulus-produced
(1) Interstitial Nucleus of Cajal —The interstitial nucleus of analgesia has been achieved by stimulation of ventrolateral regions
Cajal is located rostral to the Edinger-Westphal nucleus and cau- of the central gray matter. In contrast, stimulation of the rostral
dal to the rostral interstitial nucleus of the medial longitudinal and lateral central gray matter facilitates pain sensations.
fasciculus. It contains two subpopulations of neurons. One sub- In addition to its role in central analgesic mechanisms, the
population is related to integration of vertical gaze, and the other central (periaqueductal) gray region has been implicated in vocal-
is concerned with eye-head coordination. The nucleus receives in- ization, control of reproductive behavior, modulation of medullary
puts from burst neurons in the rostral interstitial nucleus of the respiratory centers, aggressive behavior, and vertical gaze. The peri-
medial longitudinal fasciculus and from the vestibular nuclei. It aqueductal gray, along with deep layers of the superior colliculus,
projects fibers (via the posterior commissure) to the ocu- have been shown to be involved in different components of aver-
lar motor nuclei (cranial nerves III and IV) and the con- sive states. Escape behavior and defensive or fear-like behavior are
tralateral interstitial nucleus of Cajal. It also sends fibers elicited by stimulation of these areas. The periaqueductal gray re-
to the reticular formation and both RiMLF. ceives information about urinary bladder filling and thus is in-
(2) Rostral Interstitial Nucleus of the Medial Longitudinal volved in the central process of micturition. Through connections
Fasciculus—The RiMLF is located dorsomedial to the red nu- to the hypothalamus and rostral medulla, the periaqueductal gray
cleus, rostral to the oculomotor nucleus, and ventral to the peri- has been implicated in the process of penile erection. Afferents to
aqueductal gray matter. Synonyms include the nucleus of the pre- this region arise from the hypothalamus, the amygdala, the brain
rubral field and the nucleus of the field of Forel. The nucleus stem reticular formation, the locus ceruleus, and the spinal cord.
contains burst neurons that fire with both upward and downward Immunoreactivity to a variety of neuropeptides has been demon-
eye movements. The nucleus receives inputs from the frontal eye strated in periaqueductal neurons; these neuropeptides include
fields; raphe nucleus interpositus, which gates activity of burst neu- enkephalin, substance P, cholecystokinin, neurotensin, serotonin,
rons; nucleus of the posterior commissure; superior colliculus; and dynorphin, and somatostatin.
LIGHT REFLEX
LIGHT REFLEX Optic nerve lesion =
Loss of both direct and
Stimulation of the retina by light sets off a reflex with the follow- consensual light reflexes
ing afferent and efferent pathways (Figure 9–17).
Consensual Direct
Retina
Afferent Pathway
From the retina the impulse travels via the optic nerve and optic
tract to the pretectal area. After synapsing on neurons of the pre- Oculomotor
tectal area, the impulse travels via the posterior commissure to nerves
both Edinger-Westphal nuclei in the oculomotor complex. Lesion
Efferent Pathway Oculomotor

nucleus
From the Edinger-Westphal nucleus, parasympathetic pregan- Optic
glionic fibers travel with the somatic motor component of the nerve
oculomotor nerve as far as the orbit. In the orbit, the parasympa-
thetic fibers project on neurons in the ciliary ganglion. Postgan-
glionic fibers arise from the ciliary ganglion (short ciliary nerves)
and innervate the sphincter pupillae and ciliaris muscles. Pretectal
Thus, when light is thrown on one retina, both pupils respond nucleus
by constricting. The response of the ipsilateral pupil is the
direct light reflex, whereas that of the contralateral pupil
is the consensual light reflex. A consensual light reflex Figure 9–18. Schematic diagram showing the effects of op-
is possible because of the projection of the pretectal area to both tic nerve lesions on the direct and consensual pupillary light
oculomotor nuclei. reflexes.
Lesions of the optic nerve (Figure 9–18) abolish both direct
and consensual light reflexes in response to light stimulation of
the ipsilateral retina. Lesions of the oculomotor nerve (Figure The Marcus Gunn phenomenon is a paradoxical dilatation of
9–19) abolish the direct light reflex but not the consensual both pupils that occurs when light is shone in the symptomatic
light reflex in response to light stimulation of the ipsilateral eye (optic nerve lesion) after having been shone in the normal
retina. eye. When light is shone in the normal eye, both pupils constrict
(direct and consensual light reflexes). When light is then swung
to the symptomatic eye, less light reaches the oculomotor nucleus
LIGHT REFLEX
Lesion of oculomotor
nerve = Loss of direct
light reflex only
Consensual Direct
Retina
Oculomotor
nerves
Optic nerve Ciliary
ganglion Lesion
Oculomotor Oculomotor
nerve nucleus
Optic
nerve
Oculomotor
nucleus
(Edinger-Westphal)
Pretectal
nucleus
Pretectal
nucleus
Figure 9–19. Schematic diagram showing the effects of oculo-
Figure 9–17. Schematic diagram showing the afferent and motor nerve lesions on the direct and consensual pupillary light
efferent pathways of the pupillary light reflex. reflexes.
144 / CHAPTER 9
because of the optic nerve lesion (optic neuropathy). The oculo- Normally, 90 percent of parasympathetic nerves in the ciliary gan-
motor nucleus senses the less intense light and shuts off the glion innervate the ciliary body and the remaining 10 percent in-
parasympathetic response, resulting in paradoxical pupillary di- nervate the iris sphincter. When the ciliary ganglion is damaged,
latation (Figure 9–20). the pupil becomes dilated and unresponsive to light or accommo-
Adie’s pupil, or tonic pupil, is characterized by a widely dilated dation. During recovery reinnervation takes place in a random
pupil and a sluggish, prolonged pupillary contraction in reaction fashion. As a result, 90 percent of the parasympathetic fibers that
to light. When it is constricted, the pupil takes a long time to di- previously innervated the pupil now innervate the ciliary body.
late. The affected pupil is larger than the normal pupil, but in When light is shone in the eye, 90 percent of the parasympathetic
darkness it may be smaller, since the normal pupil is free to dilate instruction to constrict the pupil is dissipated in the ciliary body,
widely. Adie’s pupil shows a more definite response to accommo- leaving only 10 percent for pupillary constriction.
dation. It results from pathology in the ciliary ganglion within the
orbit. The etiology of Adie’s pupil is unknown, but believed to be ACCOMMODATION-CONVERGENCE REFLEX
due, in part, to redirection of regenerating parasympathetic fibers.
The accommodation-convergence reflex involves the following
processes:
1. The assumption of a convex shape by the lens is secondary to
contraction of the ciliary muscle, which causes relaxation of
the suspensory ligament. This is a process of accommodation
of the lens, which thickens to keep the image in sharp focus.
2. Contraction of both medial recti muscles for convergence
Light to eye with normal optic nerve brings the eyes into alignment.
Pupils constrict bilaterally 3. Pupillary constriction occurs as an aid in regulating the depth
of focus for sharper images.
The accommodation-convergence reflex occurs when the eyes
converge voluntarily to look at a nearby object or make a reflex
response to an approaching object.
The pathway of the accommodation-convergence reflex has
not been well delineated. It is believed, however, that afferent
impulses from the retina reach the occipital cortex and that the
Light to eye with optic nerve lesion efferent pathway from the occipital cortex reaches the oculomo-
Pupils dilate because fewer impulses are reaching the tor complex after synapsing in the pretectal nucleus and/or supe-
pretectal nucleus
rior colliculus. In the oculomotor complex, Perlia’s nucleus has
been assumed to play a role in convergence (Figure 9–21). The
pathway for the accommodation-convergence reflex is thus dif-
ferent from that of the light reflex. This is supported clinically
by a condition known as the Argyll Robertson pupil, in
which the light reflex is lost while the accommodation-
convergence reflex persists. The site of the lesion in this
condition has not been established with certainty, but its etiol-
Ciliary
ganglion
ogy is known to be syphilis of the nervous system.
Optic nerve MESENCEPHALIC RETICULAR FORMATION

lesion
The mesencephalic reticular formation is a continuation
of the pontine reticular nuclei and merges rostrally with
Optic the zona incerta. The major output from the mesen-
nerve cephalic reticular formation ascends to the diencephalon and
cerebral cortex and is involved in wakefulness and sleep.
Oculomotor nucleus The reticular nuclei of the mesencephalon and other brain
(Edinger-Westphal) stem areas are discussed in the chapter on reticular formation,
Oculomotor
nerve
wakefulness, and sleep.
Pretectal VERTICAL GAZE

ucleus
Whereas control of lateral gaze is a function of the pons, the ros-
tral midbrain at the mesencephalic-diencephalic junction is crit-
ical in the mediation of vertical gaze.
The following structures are important for vertical eye move-
ments:
Figure 9–20. Schematic diagram showing response to light 1. Motor neurons in the oculomotor (cranial nerve III) and
stimulation of the Marcus Gunn pupil. trochlear (cranial nerve IV) nuclei that supply ocular muscles
Ciliary muscle Paralysis of both upward and downward gaze by both

saccadic and vestibular means usually implies involvement of
the interstitial nucleus of Cajal or the posterior commissure
Ciliary ganglion singly or together.
Optic nerve
5. Nucleus of the posterior commissure. The nucleus of the pos-
Oculomotor nerve terior commissure has an important role (not fully explored
Optic tract Edinger-Westphal yet) in vertical eye movements as well as in lid movement.
Lateral
nucleus/Nucleus 6. The medial longitudinal fasciculus. The medial longitudinal
of Perlia fasciculus carries inputs from vestibular nuclei to oculomo-
geniculate
body tor nuclear complex, trochlear nuclear complex, and the in-
Pretectal
area terstitial nucleus of Cajal. These fibers carry signals impor-
Optic radiation tant for vertical vestibular eye movements and, to a lesser
extent, vertical gaze-holding commands.
Visual
cortex
CONTROL OF SACCADIC EYE MOVEMENT
Figure 9–21. Schematic diagram showing the afferent and
efferent pathways of the accommodation-convergence reflex. Commands for saccadic eye movements are initiated from the
cerebral cortex (Figure 9–22). The frontal eye field (area 8 in the
frontal lobe), the angular gyrus (area 39), and the adjacent area 19
of the parieto-occipital cortices project to the superior colliculus.
involved in vertical eye movements: superior rectus, inferior The cortical areas of ocular motility are interconnected. The su-
rectus, inferior oblique (cranial nerve III), and superior oblique perior colliculus in turn projects to the brain stem pulse genera-
(cranial nerve IV). tors in the pons and midbrain. The pulse generators also receive
cortical input directly from the frontal eye fields. The pulse gen-
2. RiMLF. This nucleus constitutes the neural substrate for ver-
erator for horizontal saccades is in the PPRF. The pulse generator
tical eye movements. It contains burst neurons that fire on
for vertical saccades is in the mesencephalic RiMLF. Thus, there
upward and downward gaze. Although the RiMLF is the key
are two pathways concerned with saccadic movements: (1) an an-
substrate for vertical eye movements, vertical burst neurons
terior pathway from the frontal eye fields directly and in-
also reside in the mesencephalic reticular formation.
directly (via the superior colliculus) to the brain stem
Bilateral lesions in the RiMLF abolish all vertical
centers for saccadic movements (PPRF for horizontal
(up and down) eye movements. Unilateral lesions result
saccades and the mesencephalic RiMLF for vertical saccades), and
in defect in downward gaze. The difference in outcome be-
(2) a posterior pathway from the parieto-occipital cortex to the
tween bilateral and unilateral lesions is consistent with bilat-
superior colliculus and then to the brain stem centers for saccadic
eral projections of the nucleus to elevator motor neurons and
ipsilateral projections to the depressor motor neurons.
3. Interstitial nucleus of Cajal (INC). The INC is the neural in-
tegrator for vertical gaze. Bilateral lesions in the nucleus result CEREBRAL CORTEX
in limitations in the range of vertical gaze and in gaze holding.
Because of the projections of the INC to ocular motor
neurons (cranial nerves III and IV) and to the opposite INC
Frontal eye fields Parieto-occipital
via the posterior commissure, a lesion in one INC becomes
in effect a bilateral lesion.
Reflex eye movements in response to head turning (ocu-
locephalic response) are mediated by vestibular originating Superior colliculus
fibers destined to the oculomotor and trochlear nuclear com-
plexes via the medial longitudinal fasciculus with relays in
the interstitial nucleus of Cajal. Lesions in the interstitial nu-
cleus of Cajal are thus associated with abolition of the oculo- BRAIN STEM PULSE GENERATOR
cephalic response.
4. Posterior commissure. The posterior commissure contains
crossing nerve fibers intermixed with the nucleus of the pos- Pons Mesencephalon
terior commissure (NPC). The fibers in the posterior com-
missure are: (a) projections from the INC to the contra-
lateral ocular motor nuclear complex (cranial nerves III and
IV) and the contralateral interstitial nucleus of Cajal, PPRF Interstitial nucleus MLF
(b) projections from the NPC to the contralateral INC and
the RiMLF. Lesions of the posterior commissure result in
impairment of vertical gaze holding and restrict all vertical
eye movements, but especially upward movements. The im- Horizontal saccades Vertical saccades
pairment of vertical gaze holding is explained by involvement
of axons of INC. The restriction of vertical eye movements Figure 9-22. Schematic diagram showing cortical and subcor-
is attributed to involvement of the nucleus of the posterior tical control of saccadic eye movements. MLF, medial longitudi-
commissure. nal fasciculus; PPRF, paramedian pontine reticular formation.
146 / CHAPTER 9
movements. The anterior pathway generates intentional saccades; etal region. The pathogenesis of the pursuit deficits and pathways
the posterior pathway generates reflexive saccades. Each pathway involved in smooth pursuit eye movements are not completely un-
can compensate partially for the other. derstood. Specific lesions in the temporo-occipito-parietal cortex
that are associated with smooth pursuit deficits in humans corre-
SMOOTH PURSUIT EYE MOVEMENTS spond to Brodmann areas 19, 37, and 39. Lesions in the frontal
eye field also have been associated with deficits in smooth pursuit.
Each hemisphere has been shown to mediate smooth pursuit eye The corticofugal pathway for smooth pursuit movements
movements to the ipsilateral side. The cortical areas in- remains controversial. Two pathways have been described. The
volved in smooth pursuit are not as well delineated as are first courses from the temporo-occipito-parietal cortex through
those involved in saccadic eye movements but probably the posterior limb of the internal capsule to the dorsolateral pon-
include the posterior parietal cortex or the temporo-occipito-pari- tine nucleus. The second courses from the frontal eye field to the
BLOOD SUPPLY
Superior Trochlear nerve

cerebellar
artery Inferior colliculus
Trochlear nucleus
Spinothalamic tract
Medial longitudinal
fasciculus
Variable
blood supply Medial lemniscus
Substantia nigra
Paramedian
branches
Brachium
of basilar artery
conjunctivum
Cerebral peduncle
A Inferior colliculus
Superior Superior colliculus

cerebellar
artery Periaqueductal
gray
Spinothalamic tract
Posterior Oculomotor
cerebral nucleus
artery
Medial lemniscus
Red nucleus
Substantia nigra
Tip of the Cerebral peduncle

basilar artery Oculomotor
B Superior colliculus
Pretectal area
Posterior
cerebral Red nucleus
artery
Cerebral peduncle
Paramedian
branches of
basilar artery showing vascular territories of the
Oculomotor nerve midbrain at three caudal-rostral
C Pretectal area levels.
dorsolateral pontine nucleus and the nucleus reticularis tegmenti Anisocoria (Greek anisos, “unequal, uneven”; kore, “pupil”).
pontis. Pursuit pathways in the brain stem and cerebellum are Inequality in the diameters of the pupils.
less well defined, although the dorsolateral pontine nucleus and Aqueduct of Sylvius (cerebral aqueduct) (Latin aqua, “water”;
the cerebellar flocculus are important in the monkey. Cerebral ductus, “canal”). The narrow passage in the midbrain linking
hemisphere lesions impair ocular pursuit ipsilaterally or bilater- the third and fourth ventricles. Described by Jacques Dubois
ally, whereas posterior fossa lesions impair ocular pursuit contra- (Sylvius) in 1555.
laterally or ipsilaterally. This variability probably reflects the in- Argyll-Robertson pupil. A pupil that reacts to accommodation
volvement of a presumed pursuit pathway that crosses from the but not to light. Described by Argyll Robertson, a Scottish oph-
pontine nuclei to the cerebellum and then consists of a unilateral thalmologist, in 1869. Syphilis is the classical etiology, but dia-
projection from the cerebellum to the vestibular nuclei. betes and lesions in the midbrain can cause this phenomenon.
Brachium conjunctivum (Latin, Greek brachion, “arm”; con-
BLOOD SUPPLY junctiva, “connecting”). An armlike bundle of fibers that con-
Compared with the vascular supply of the pons, the midbrain vas- nects the cerebellum and midbrain.
culature is complex (Figure 9–23). The mesencephalon (mid- Colliculus (Latin, a “small elevation”). The inferior and supe-
brain) receives its blood supply from the basilar artery via parame- rior colliculi are small elevations in the dorsal surface of the
dian as well as superior cerebellar and posterior cerebral branches. midbrain.
Collier’s sign. Bilateral lid retraction seen in the pretectal syndrome.
Inferior Colliculus Level (Figure 9–23A) Corpora quadrigemina (Latin corpus, “body”; quadrigeminus,
“fourfold”). Four bodies in the dorsal aspect of the midbrain,
At the level of the inferior colliculus (lower midbrain), the para-
consisting of two inferior colliculi and two superior colliculi.
median branches supply the medial region of the mesencephalon,
including the MLF, the paramedian reticular nuclei, and the Darkschewitsch’s nucleus. One of the accessory oculomotor nu-
brachium conjunctivum. The superior cerebellar artery supplies clei. Named after Liverij Osipovich Darkschewitsch, a Russian
the lateral region of the midbrain, including the inferior colliculus, anatomist.
the rootlets of the trochlear nerve, the spinal and medial lemnis- Dentate nucleus (Latin dentatus, “toothlike”). A nucleus in
cus, and the lateral part of the cerebral peduncle. A wedge between the cerebellum that is serrated like a tooth.
these two regions, which includes the trochlear nucleus, the cere- Diplopia (Greek diploos, “double”; ops, “eye”). Double vision.
bral peduncle, and the medial part of the medial lemnis- Dorsal longitudinal fasciculus (fasciculus of Schütz). A peri-
cus, has a variable and inconstant blood supply. ventricular ascending and descending fiber system that connects
the hypothalamus with the periaqueductal gray matter and with
Superior Colliculus Level (Figure 9–23B) autonomic nuclei in the pons and medulla oblongata.
At the level of the superior colliculus (middle midbrain), the Edinger-Westphal nucleus. The parasympathetic component of
mesencephalon is divided into three zones of blood supply. The the oculomotor nuclear complex. Described by Ludwig Edinger,
medial zone, which includes the third cranial nerve nuclear com- a German anatomist and neurologist, in 1885 and by Carl Fried-
plex, receives blood from the tip of the basilar artery. The tectum reich Otto Westphal, a German psychiatrist, neurologist, and
(dorsal zone) is supplied by the superior cerebellar artery. The anatomist, 2 years later.
rest of the midbrain is supplied by the posterior cerebral artery. Emboliform (Greek embolos, “plug”). The emboliform nucleus
This zone includes the spinal and medial lemnisci, the substantia in the cerebellum “plugs” the dentate nucleus.
nigra, the cerebral peduncle, the red nucleus, and the third cra- Globose (Latin globus, “a ball, sphere-shaped”). The globose
nial nerve rootlets. nucleus in the cerebellum is spherical in shape.
Habenula (Latin habena, “small strap or bridle rein”). The
Pretectal Level (Figure 9–23C) habenular nuclei in the caudal diencephalon near the pineal
At the level of the upper midbrain (the pretectal level), the me- gland form part of the epithalamus. Early anatomists considered
dial zone, including the medial part of the red nucleus, and the pineal gland the abode of the soul; it was likened to a driver
rootlets of the oculomotor nerve receive blood from paramedian who directs the operations of the mind via the habenula, or reins.
branches of the basilar artery. The rest of the midbrain receives Huntington’s chorea (Greek choreia, “dance”). A progressive
blood from the posterior cerebral artery. neurodegenerative disorder inherited as an autosomal dominant
trait. The disease was imported to America from Suffolk in the
TERMINOLOGY United Kingdom by the emigrant wife of an Englishman in 1630.
Her father was choreic, and the groom’s father disapproved of the
Adduction (Latin adducere, “to draw toward”). The process match because of the bride’s father’s illness. The disorder is named
of drawing toward the median plane. after George Sumner Huntington, a general practitioner who de-
Adie’s pupil (tonic pupil, Holmes-Adie syndrome). A condi- scribed it in 1872. Characterized by the ceaseless occurrence of a
tion in which the pupil exhibits sluggish prolonged constriction wide variety of rapid, complex, jerky movements performed in-
to light and, when it is constricted, takes a long time to dilate. voluntarily and resembling a dance.
The phenomenon results from pathology in the ciliary gan- Intorsion (Latin in, “toward”; torsio, “twisting”). Inward ro-
glion. Described by James Ware in 1812, by Piltz in 1899, and tation of eye.
by others before William John Adie, an Australian neurologist, Koerber-Salus-Elschnig syndrome. A syndrome of vertical gaze
described it in 1931. palsy, anisocoria, light-near dissociation, conversion retraction
Akinesia (Greek a, “negative”; kinesis, “motion”). Poverty or nystagmus, lid retraction, impaired convergence, skewed eye de-
absence of movement. viation, papilledema, and lid flutter associated most commonly
148 / CHAPTER 9
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Mesencephalon (Midbrain): 10
Clinical Correlates
Mesencephalic Vascular Syndromes Walleyed Syndrome

Syndrome of Weber Vertical One-and-a-Half Syndrome
Syndrome of Benedikt Locked-in Syndrome
Claude’s Syndrome Top of the Basilar Syndrome
Nothnagel’s Syndrome Peduncular Hallucinosis Syndrome
Plus-Minus Lid Syndrome Akinetic Mutism
Parinaud’s Syndrome Decerebrate Rigidity
KEY CONCEPTS
The syndrome of Weber consists of oculomotor nerve The vertical one-and-a-half syndrome consists of bilateral
paralysis ipsilateral to the midbrain lesion and contralat- impairment of downgaze and monocular paralysis of eye
eral hemiplegia. elevation. A variant syndrome consists of bilateral impair-
ment of upgaze and monocular downgaze paralysis.
The syndrome of Benedikt consists of oculomotor nerve
paralysis ipsilateral to the midbrain lesion and contralat- The locked-in syndrome consists of mute quadriplegia,
eral tremor. Contralateral hemianesthesia may occur. preservations of consciousness, and communication by
ocular movement and blinking.
Claude’s syndrome consists of oculomotor nerve paralysis
ipsilateral to the midbrain lesion and contralateral ataxia The top of the basilar syndrome consists of a variety of vi-
and tremor. sual defects, abnormalities of eye movements, pupillary
abnormalities, and behavioral disturbances. The pedun-
Nothnagel’s syndrome is variably described as consisting
cular hallucinosis syndrome consists of hallucinations
of bilateral oculomotor nerve paralysis, ipsi- or contralat-
and somnolence.
eral gait ataxia, and vertical gaze palsy.
Akinetic mutism characterized by complete immobility
Parinaud’s syndrome consists of upgaze palsy, pupillary
except in the eyes occurs with lesions in the midbrain
abnormalities, lid retraction, and convergence retraction
reticular formation.
nystagmus on upward gaze.
Decerebrate rigidity is associated with midbrain lesions
The walleyed syndrome consists of exotropic gaze and
caudal to the red nucleus, between it and the vestibular
an absence of ocular adduction. This syndrome is also
nuclei.
known as the walleyed bilateral internuclear ophthalmo-
plegia (WEBINO) syndrome.
MESENCEPHALIC VASCULAR SYNDROMES ritory, followed by the posterior cerebral artery territory and the
territory intermediate between the two. Involvement of the terri-
Midbrain infarcts have not been studied extensively. There have tory of the superior cerebellar artery is rare.
been only a few reports of single cases, well described clinically Patients with middle midbrain infarcts have a localizing clin-
and by magnetic resonance imaging (MRI), of isolated midbrain ical picture that is linked to involvement of the third nerve or
infarcts (Table 10–1). its nucleus. Paramedian infarcts are associated with the nuclear
The most commonly affected region is the middle midbrain, syndrome of the oculomotor nerve, whereas more lateral infarcts
and the most frequently involved territory is the paramedian ter- are associated with fascicular involvement of the third nerve in
150
MESENCEPHALON (MIDBRAIN): CLINICAL CORRELATES / 151
Table 10–1. Midbrain Vascular Syndromes
Syndrome Ipsilateral Contralateral Lesion site
Weber’s Oculomotor palsy Hemiparesis CN III, CP

Benedikt Oculomotor palsy Tremor hemi-anesthesia CN III, RN ML, ST
Claude’s Oculomotor palsy Tremor and ataxia CN III, RN, BC
Nothnagel’s Oculomotor palsy and ataxia Oculomotor palsy ataxia CN III, BC
Plus-minus lid syndrome Ptosis Lid retraction CN III fascicles to the
levator palpebrae
muscle. Nucleus of
posterior commissure
Parinaud’s Upward gaze paralysis Pretectal region
Pupillary abnormalities
Large pupil
Light-near dissociation
Covergence retraction
nystagmus on upgaze
Lid retraction (Collier’s sign)
Walleyed Internuclear ophthalmoplegia Internuclear ophthalmoplegia MLF, bilateral
(MLF syndrome) (MLF syndrome)
Vertical one-and-a-half Downgaze palsy Downgaze palsy Efferents of RiMLF, CBF
Monocular elevation palsy
Locked-in Mute quadriplegia Ventral mesencephalon
Peduncular hallucinosis Hallucinations, somnolence Tegmentum, CP
NOTE: CN, cranial nerve; CP, cerebral peduncle; RN, red nucleus; BC, brachium conjunctivum; ML, medial lemniscus; ST, spinothalamic tract; MLF,
medial longitudinal fasciculus; RiMLF, rostral interstitial nucleus of the medial longitudinal fasciculus; CBF, corticobulbar fibers.
isolation or with contralateral hemiparesis (syndrome of Weber) hemianesthesia has been described by some researchers and is at-
or hemiataxia (Claude’s syndrome). tributed to involvement of the medial lemniscus and spinotha-
Patients with rostral or caudal midbrain infarcts have a less lo- lamic tract. This syndrome was first described by a Viennese
calizing neurologic picture except for vertical gaze impairment in physician, Moritz Benedikt, in 1889.
those with dorsal rostral midbrain infarcts. Ipsilateral trochlear The tremor in this syndrome has been called rubral tremor on
nerve palsy, Horner’s syndrome, and contralateral ataxia point to the basis of damage to the red nucleus or the superior cerebellar
the territory of the superior cerebellar artery. Hand-foot-mouth peduncle. The tremor is usually of low frequency and may have
hyperesthesia is due to involvement of the medial lemniscus and resting, postural, and kinetic components. The kinetic component
the ventral ascending tract of the trigeminal nerve. may be explained by the involvement of the superior cerebellar pe-
duncle or the red nucleus. The resting and postural components
are due to the involvement of dopaminergic nigrostriatal fibers
Syndrome of Weber that arise from the pars compacta of the substantia nigra and run
In the syndrome of Weber the patient presents with signs of ipsi- ventral to the red nucleus and through field H of Forel (prerubral)
lateral oculomotor nerve paralysis and contralateral upper motor on their way to the hypothalamus and striatum. This component
neuron paralysis that includes the lower face. The vascu- of the tremor responds well to treatment with levodopa.
lar lesion, usually an infarct, affects rootlets of the oculo-
motor nerve and the underlying cerebral peduncle (Figure Claude’s Syndrome
10–1). This syndrome was described by Adolph-Marie Gubler, Described by the French psychiatrist and neurologist Henry
a French physician, about 4 years before Sir Herman David Claude in 1912, this syndrome is very rare. Claude’s original case
Weber, a German-English physician, described the syndrome in had midbrain infarction that involved the medial half of
1863, and 17 years before Ernst Victor von Leyden, a German the red nucleus, the adjacent decussating fibers of supe-
physician, described a similar syndrome in 1875. The syndrome rior cerebellar peduncle, and oculomotor nerve fascicles.
is therefore referred to by some as the Gubler-Weber syndrome, Patients present with ipsilateral oculomotor nerve palsy and con-
Leyden paralysis, and Leyden syndrome. Other synonyms in- tralateral tremor and ataxia. Oculomotor nerve palsy is partial in
clude the cerebral peduncle syndrome, hemiplegia alternans su- most patients. The medial rectus is most commonly involved,
perior peduncularis, and syndrome of the cerebral peduncle. followed in order of frequency by the levator palpebrae, superior
rectus, inferior oblique, and inferior rectus. The pupil is spared
Syndrome of Benedikt in the majority of patients. Although the tremor and ataxia are
generally attributed to a lesion in the red nucleus, it has recently
In the syndrome of Benedikt the patient presents with signs of been shown that the main pathology is in the superior cerebellar
ipsilateral oculomotor nerve paralysis and contralateral tremor. peduncle, just below and medial to the red nucleus, and that the
The vascular lesion affects rootlets of the oculomotor nerve red nucleus contributes little to the syndrome. Infarction in the
within the tegmentum of the mesencephalon and the territory of the anteromedial branches of the posterior cerebral
underlying red nucleus (Figure 10–1). Contralateral artery is the cause of the syndrome in the majority of patients.
152 / CHAPTER 10
MORITZ BENEDIKT SYNDROME

Oculomotor and outward
nucleus Drooping of eyelid
Dilated, nonresponsive pupil
Contralateral tremor
Red nucleus
C
WEBER SYNDROME
and outward
Drooping of eyelid
Cerebral B Dilated, nonresponsive pupil
peduncle Contralateral upper motor
neuron paralysis
A
Oculomotor
nerve
OCULOMOTOR NERVE PALSY
Figure 10–1. Schematic dia-
gram showing lesions of the oculo-
and outward
Drooping of eyelid motor nerve in its intra- and extra-
Dilated, nonresponsive pupil axial course and their respective
clinical manifestations.
Nothnagel’s Syndrome (Collier’s sign), and convergence retraction nystagmus on up-

ward gaze. This syndrome was described in 1883 by Parinaud,
Nothnagel’s syndrome has been variably described by different who vaguely speculated about the lesion site. Definitive localiza-
authors. In 1879, Nothnagel, an Austrian physician, described a tion of the lesion in the pretectal area resulted from experimental
patient with bilateral asymmetric oculomotor palsies of varying and human observations made between 1969 and 1974 by
degree and gait ataxia. Subsequently, the syndrome was Bender, who coined the term pretectal syndrome.
variously described in patients with oculomotor nerve
palsy and ipsilateral or contralateral ataxia and patients
with oculomotor nerve palsy and vertical gaze palsy. The lesion Walleyed Syndrome
in the original report involved the superior and inferior colliculi.
The walleyed syndrome is also known as the walleyed
Subsequent reports described pathology in the oculomotor nerve
bilateral internuclear ophthalmoplegia (WEBINO) syn-
fascicles and the brachium conjunctivum. The syndrome may be
drome. The lesion is bilateral and involves the rostral
regarded as a variant of the dorsal midbrain (Parinaud’s) syn-
medial longitudinal fasciculus. This syndrome is characterized
drome or as Benedikt syndrome with added vertical gaze palsy.
by lateral deviation of both eyes (exotropic gaze) and the absence
of ocular adduction.
Plus-Minus Lid Syndrome
Described by Gaymard and colleagues in 1992, this syndrome Vertical One-and-a-Half Syndrome
consists of unilateral ptosis and contralateral lid retraction due to The vertical one-and-a-half syndrome is characterized by bilat-
a small lesion in the rostral midbrain involving the nu- eral impairment of downgaze (the one) and monocular
cleus of the posterior commissure and oculomotor fasci- paralysis of elevation (the half ). The lesion usually con-
cles to the ipsilateral levator palpebrae muscle as they sists of bilateral infarcts in the mesencephalic-diencephalic
emerge from the central caudal subnucleus. Ipsilateral ptosis is region that involve efferent tracts of the rostral interstitial nucleus
explained on interruption of oculomotor fascicles to the levator of the medial longitudinal fasciculus (RiMLF) bilaterally and pre-
palpebrae. Lid retraction is explained on overactivation of the motor fibers to the contralateral superior rectus subnucleus and
contralateral levator palpebrae muscle due to loss of inhibitory the ipsilateral inferior oblique subnucleus before or after decussa-
pathways for lid retraction from the nucleus of the posterior tion in the posterior commissure. A variant of this syndrome con-
commissure to the central caudal subnucleus. sists of bilateral impairment of upgaze (the one) with monocular
downgaze palsy (the half ). The vertical one-and-a-half syndrome
Parinaud’s Syndrome was described by Deleu, Buisseret, and Ebinger in 1989.
Parinaud’s syndrome is also known as the sylvian aqueduct syn- Locked-in Syndrome
drome, the dorsal midbrain syndrome, Koerber-Salus-Elschnig
syndrome, the pineal syndrome, and the syndrome of the poste- The locked-in syndrome is also known as the bilateral pyramidal
rior commissure. The lesion is in the pretectal region. Patients system syndrome. It is characterized by mute quadriplegia,
with this syndrome present with upward gaze paralysis, pupillary preservation of consciousness, and communication by vertical
abnormalities (large pupil, light-near dissociation), lid retraction (not lateral) ocular movements and blinking. In most patients
MESENCEPHALON (MIDBRAIN): CLINICAL CORRELATES / 153
the lesion is bilateral in the ventral half of the pons at or DECEREBRATE RIGIDITY
rostral to the level of the abducens nuclei; in some pa-
tients the lesion may be bilateral in the ventral mes- Decerebrate rigidity in humans results from lesions of the brain
encephalon or both internal capsules. The term locked-in syn- stem caudal to the red nucleus and rostral to the vestibular nu-
drome was proposed by Plum and Posner in 1987. This clei. The body is forced backward with the head bent
syndrome is also known as pseudocoma, the de-efferented state, extremely dorsally. The shoulders are internally rotated,
the ventral pontine or brain stem syndrome, cerebromedullary the elbows are extended, and the distal parts of the
disconnection, pontopseudocoma, the pontine disconnection upper limbs are hyperpronated with finger extension at the
syndrome—and the Monte Cristo syndrome in reference to metacarpophalangeal joints and flexion at the interphalangeal
Alexandre Dumas’s novel The Count of Monte Cristo, in which joints. The hips and knees are extended; the feet and toes are
the elderly Noirtier communicated only by eye blinks. plantar flexed. This syndrome is associated with severe head
trauma and compression of the brain stem by herniation.
Top of the Basilar Syndrome
In the top of the basilar syndrome the lesion is not limited to the
mesencephalon but also involves other structures (the thalamus TERMINOLOGY
and portions of the temporal and occipital cortices). The Balint’s syndrome. Also known as Balint-Holmes syndrome,
conglomerate signs and symptoms of this syndrome ocular apraxia, optic ataxia, psychic paralysis of visual fixation,
include (1) visual defects such as hemianopia, cortical and cortical paralysis of visual fixation. A rare syndrome result-
blindness (loss of vision with intact pupillary light reflexes), and ing from bilateral parieto-occipital disease and characterized by
Balint’s syndrome (optic ataxia) caused by involvement of the an inability to direct the eyes to a certain point in the visual field
occipital, parietal, and temporal cortices, (2) abnormalities of eye despite intact eye movements and vision. Discovered by Rudolph
movements, including vertical gaze abnormalities, lid retraction Balint, a Hungarian neurologist, in 1909.
(Collier’s sign), and convergence disorder, (3) pupillary abnor-
malities, including light-near dissociation and a small reactive or Claude’s syndrome. Described by a French psychiatrist and
large fixed pupil, (4) behavioral disturbances (somnolence, mem- neurologist, Henri Claude, in 1912.
ory defects, agitation, hallucination), and (5) motor and sensory Collier’s sign. Bilateral lid retraction seen in the pretectal
deficits. The usual etiology of this syndrome is occlusion of the syndrome.
rostral basilar artery. Horner’s syndrome. Drooping of the eyelid (ptosis), constric-
tion of the pupil (miosis), retraction of the eyeball (enophthal-
Peduncular Hallucinosis Syndrome mos), and loss of sweating on the face (anhidrosis) constitute a
syndrome described by Johann Friedrich Horner, a Swiss oph-
The peduncular hallucinosis syndrome is characterized by non- thalmologist, in 1869. The syndrome is caused by interruption
threatening hallucinations, often formed nonstereotypically, col- of descending sympathetic fibers. Also known as Bernard-
ored, and vivid, that usually occur in somnolent patients with Horner syndrome and oculosympathetic palsy. The syndrome
presumed tegmental and cerebral peduncle lesions. The symp- was described in animals by François du Petit in 1727. Claude
toms probably arise from thalamic or occipitotemporal lesions Bernard in France in 1862 and E. S. Hare in Great Britain in 1838
rather than from the midbrain. This condition was first de- gave precise accounts of the syndrome before Horner did.
scribed by Jean Jacques Lhermitte, a French neurologist, in 1922 Koerber-Salus-Elschnig syndrome. A syndrome of vertical
in a 75-year-old woman with midbrain infarct whose hallucina- gaze palsy, anisocoria (unequal pupil sizes), light-near dissocia-
tions consisted of animals and people sharing the room with her. tion, conversion retraction nystagmus, lid retraction, impaired
The name was suggested by Ludo Van Bogaert, a Belgian neurol- convergence, skewed eye deviation, papilledema, and lid flutter
ogist, in 1924. associated most commonly with pineal tumors or disorders of
the pretectal region. Also known as Parinaud’s syndrome, the
AKINETIC MUTISM sylvian aqueduct syndrome, and the syndrome of the posterior
commissure. The best of the original descriptions was that of
Various levels of unconsciousness occur in patients with Salus in 1910.
lesions of the mesencephalic reticular formation. Evi- Nothnagel’s syndrome. Described by Carl Wilhelm Hermann
dence from experimental work points to a tonic role of Nothnagel, an Austrian internist, neurologist, and pathologist,
the mesencephalic reticular formation in cortical excitability and in 1879.
the maintenance of awareness. Bilateral limited lesions of the Optic ataxia. A rare syndrome resulting from bilateral parieto-
mesencephalic reticular formation have been associated with aki- occipital disease and characterized by inability to direct the eyes
netic mutism (Cairns syndrome), a clinical condition character- to a certain point in the visual field despite intact eye movements
ized by absolute mutism and complete immobility except for the and vision. Also known as Balint’s syndrome, Balint-Holmes
eyes, which are kept open and move in all directions. The patient syndrome, and ocular apraxia.
appears awake and maintains a sleep-wake cycle, but no commu-
nication with the patient through either painful or auditory Parinaud’s syndrome. Described by Henri Parinaud, a French
stimuli can be established. The condition was first reported by an neuro-ophthalmologist, in 1883.
Australian neurosurgeon, Sir Hugh Cairns, in 1941. This condi- Syndrome of Benedikt. Described in a 4-year-old patient by
tion may result from injury to the mesencephalic reticular for- Moritz Benedikt, an Austrian physician, in 1889.
mation caused by transtentorial brain herniation with edema, Syndrome of Weber. Named after Sir Herman David Weber,
hemorrhage, or occlusion of branches of the basilar artery. The a German-English physician who described the syndrome in
condition is also known as persistent vegetative state. 1863.
154 / CHAPTER 10
SUGGESTED READINGS Gaymard B et al: Plus-minus lid syndrome. J Neurol Neurosurg Psychiatry
1992; 55:846–848.
Balint R: Seelenlahmung des “Schauens,” optische Ataxia, raumliche storung Keane JR: The pretectal syndrome: 206 patients. Neurology 1990; 40:684–690.
der Aufmerskameit. Monatsschr Psychiatr Neurol 1909; 25:51–81. Liu GT et al: Midbrain syndromes of Benedikt, Claude, and Nothnagel:
Benedikt M: Tremblement avec paralysie croisée du moteur oculaire commun. Setting the record straight. Neurology 1992; 42:1820–1822.
Bull Soc Med Hop Paris 1889; 3:547–548. Mehler MF: The neuro-ophthalmologic spectrum of the rostral basilar artery
Bogousslavsky J et al: Pure midbrain infarction: Clinical syndromes, MRI, and syndrome. Arch Neurol 1988; 45:966–971.
etiologic patterns. Neurology 1994; 44:2032–2040. Nothnagel H: Topische diagnostik der Gehirnkrankheiten. Berlin, Hischwalden,
Breen LA et al: Pupil-sparing oculomotor nerve palsy due to midbrain infarc- 1879:220.
tion. Arch Neurol 1991; 48:105–106. Parinaud H: Paralysie des mouvements associés des yeux. Arch Neurol (Paris)
Cairns H et al: Akinetic mutism with an epidermoid cyst of the 3rd ventricle. 1883; 5:145–172.
Brain 1941; 64:273–290. Plum F, Posner JB: The Diagnosis of Stupor and Coma. Philadelphia, Davis, 1987.
Claude H: Syndrome pedunculaire de la region du noyau rouge. Rev Neurol Pryse-Phillips W: Companion to Clinical Neurology. Boston, Little, Brown, 1995.
(Paris) 1912; 23:311–313. Ranalli PJ et al: Palsy of upward and downward saccadic, pursuit, and vestibu-
Claude H, Loyez M: Ramollissement du noyau rouge. Rev Neurol (Paris) lar movements with a unilateral midbrain lesion: Pathophysiologic cor-
1912; 24:49–51. relation. Neurology 1988; 38:114–122.
Deleu D et al: Vertical one-and-a-half syndrome: Supranuclear downgaze Salus R: Acquired retraction movements of the globe. Arch Augenheilk 1910;
paralysis with monocular elevation palsy. Arch Neurol 1989; 46:1361– 68:61–67.
1363. Seo SW et al: Localization of Claude’s syndrome. Neurology 2001; 57:2304–
Felice KJ et al: “Rubral” gait ataxia. Neurology 1990; 40:1004–1005. 2307.
Galetta SL et al: Unilateral ptosis and contralateral eyelid retraction from a tha- Weber HD: A contribution to the pathology of the crura cerebri. Med Chir
lamic-midbrain infarction. J Clin Neuroophthalmol 1993; 13:221–224. Trans 1863; 46:121–139.
Diencephalon 11
Gross Topography Internal Capsule

Divisions of Diencephalon Subthalamus
Epithalamus
Thalamus (Dorsal Thalamus) and Metathalamus
KEY CONCEPTS
The term diencephalon includes the following structures: The ventral posterior lateral nucleus links the somatosen-
epithalamus, thalamus (including the metathalamus), sory (medial lemniscus and spinothalamic) neural system
hypothalamus, and subthalamus. from the contralateral half of the body with the somato-
sensory cortex.
Based on their rostrocaudal and mediolateral location,
thalamic nuclei are divided into the following groups: an- The ventral posterior medial nucleus links the somatosen-
terior, medial, lateral, intralaminar and reticular, midline, sory neural system from the contralateral face (tri-
and posterior. geminothalamic) and taste system with the somatosen-
sory cortex.
The anterior group of thalamic nuclei have reciprocal
connections with the mamillary bodies and cingulate The intralaminar, reticular, and midline nuclei belong to
gyrus. They belong to the modality-specific and limbic the nonspecific system of thalamic nuclei. They are con-
group of thalamic nuclei. cerned with arousal, motor control, and the awareness of
sensory experiences.
The medial group of thalamic nuclei have a reciprocal re-
lationship with the prefrontal cortex. They belong to the The medial geniculate nucleus is a relay station in the au-
multimodal associative group of thalamic nuclei and ditory pathway. It belongs to the modality-specific and
play a role in affective behavior, memory, and the integra- sensory groups of thalamic nuclei.
tion of somatic visceral activities.
The lateral geniculate nucleus is a relay station in the
The pulvinar and lateral posterior nuclei form a single nu- visual pathway. It belongs to the modality-specific and
clear complex based on their anatomic connections and sensory groups of nuclei.
functions. The pulvinar–lateral posterior complex links
The posterior thalamic nucleus belongs to the multimodal
subcortical visual areas with the association cortical visual
associative group of thalamic nuclei. It is a convergence
areas. The pulvinar–lateral posterior complex belongs to
center for multimodal sensory modalities.
the multimodal associative group of thalamic nuclei.
Based on their neural connectivity, thalamic nuclei are
The ventral anterior nucleus links the basal ganglia and
grouped into the following categories: modality-specific,
the cerebral cortex.It belongs to the modality-specific and
multimodal associative, nonspecific, and reticular.
motor groups of thalamic nuclei.
Based on their function, thalamic nuclei are grouped into
The ventral lateral nucleus links the cerebellum with the
the following categories: motor, sensory, and limbic.
cerebral cortex. It belongs to the modality-specific and
motor groups of thalamic nuclei.
155
156 / CHAPTER 11
(continued from previous page) Vascular lesions in the thalamus are associated with a
characteristic pain syndrome, the thalamic syndrome.
Vascular lesions in the posterior limb of the internal cap-
Lesions of the subthalamic nucleus or of the subthalamo-
sule are associated with contralateral hemiplegia and
pallidal pathways are associated with contralateral
hemisensory loss. Lesions that involve the visual and au-
hemiballismus.
ditory radiations are in addition associated with con-
tralateral visual loss and hearing deficit. Lesions that in- The H fields of Forel contain pallidal and cerebellar effer-
volve the genu are associated with cranial nerve signs. ents to the thalamus.
The thalamus receives its blood supply from four parent

vessels: basilar, posterior cerebral, posterior communicat-
ing, and internal carotid.
GROSS TOPOGRAPHY first three subdivisions will be discussed in this chapter. The fourth
(Figures 11–1, 11–2, and A5-17) subdivision, the hypothalamus, will be discussed in Chapter 19.
The diencephalon, or “in-between brain,” is completely sur-

rounded by the cerebral hemispheres except at its ventral surface. Epithalamus
It is limited posteriorly by the posterior commissure and anteriorly
by the lamina terminalis and the foramen of Monro. The posterior The epithalamus occupies a position dorsal to the thalamus and
limb of the internal capsule limits the diencephalon laterally. includes the following structures (Figure 11–1).
Medially, the diencephalon forms the lateral wall of the third ven-
tricle. The dorsal surface forms the floor of the lateral ventricle and A. STRIA MEDULLARIS THALAMI
is marked medially by a band of nerve fibers, the stria medullaris This band of nerve fibers courses dorsomedial to the thalamus
thalami. The ventral surface contains hypothalamic structures. A and connects the septal (medial olfactory) area, located under-
groove extending between the foramen of Monro and the aque- neath the rostral end of the corpus callosum in the frontal lobe,
duct of Sylvius (the hypothalamic sulcus) divides the dienceph- with the habenular nuclei.
alon into a dorsal portion, the thalamus, and a ventral portion, the
hypothalamus. The two thalami are connected across the midline
B. HABENULAR NUCLEI
in about 70 percent of humans through the interthalamic adhe-
sion (massa intermedia). The diencephalon develops from the cau- These nuclei are located in the caudal diencephalon; one is on
dal vesicle of the embryologic prosencephalon. each side, dorsomedial to the thalamus. They receive the stria
medullaris and project via the habenulo-interpeduncular tract
DIVISIONS OF DIENCEPHALON (fasciculus retroflexus of Meynert) to the interpeduncular nu-
cleus of the midbrain. The two habenular nuclei are connected
The diencephalon is divided into four major subdivisions. These by the habenular commissure. The habenular nuclei, part of a
are (1) the epithalamus, (2) the thalamus and metathala- neural network that includes the limbic and olfactory systems,
mus, (3) the subthalamus, and (4) the hypothalamus. The are concerned with mechanisms of emotion and behavior.
Fornix Massa
s intermedia Thalamus
Lateral ventricle Stria medullaris thalami
Corpus callosum Epithalamus

Habenula
Foramen Pineal
of Monro
Posterior
Hypothalamus commissure
Lamina terminalis Hypothalamic sulcus

Figure 11–1. Schematic diagram showing the subdivisions of the diencephalon as seen in a midsagittal
view.
DIENCEPHALON / 157
Lateral ventricle Third ventricle Corpus callosum
Fornix
Thalamus Stria medullaris thalami
Internal medullary lamina
Massa intermedia
Mamillothalamic
tract Subthalamus
Internal capsule
Hypothalamic Globus pallidus

sulcus
Fornix
Optic tract Third ventricle Hypothalamus
Figure 11–2. Schematic diagram showing the subdivisions of the diencephalon as seen in a
composite coronal view.
C. PINEAL GLAND The thalamus is the largest component of the diencephalon,

This endocrine gland is located just rostral to the superior colli- with a rostrocaudal dimension in humans of about 30 mm, height
culi in the roof of the third ventricle. The functions of the pineal of about 20 mm, width of about 20 mm, and an estimated
gland are not well understood. It may have roles in gonadal func- 10 million neurons in each hemisphere. It is subdivided into the
tion and circadian rhythm. It secretes the biogenic amines sero- following major nuclear groups (Figure 11–3) on the basis of
tonin, norepinephrine, and melatonin and contains several hypo- their rostrocaudal and mediolateral location within the thalamus:
thalamic peptides including thyrotropin-releasing hormone 1. Anterior
(TRH), leuteinizing hormone–releasing hormone (LHRH), and 2. Medial
somatostatin–release inhibitory factor (SRIF). It synthesizes mela-
tonin from serotonin in a rhythmic fashion that fluctuates with 3. Lateral
the daily cycle of light. The pineal gland usually calcifies after the 4. Intralaminar and reticular
age of 16 years. This fact is used in the detection of midline shifts 5. Midline
in skull x-rays. In normal skull x-rays, pineal calcifications are 6. Posterior
seen in the midline. Shifts of pineal calcification away from the
midline suggest the presence of space-occupying lesions displac- The thalamus is traversed by a band of myelinated fibers, the
ing the pineal. Such a lesion could be blood in the subdural or internal medullary lamina, which runs along the rostrocaudal
epidural space, a hematoma within the brain, or a brain tumor. extent of the thalamus. The internal medullary lamina separates
Pineal gland tumors (pinealomas) depress gonadal function and the medial from the lateral group of nuclei. Rostrally and cau-
delay the onset of puberty. In contrast, lesions that destroy the dally, the internal medullary lamina splits to enclose the anterior
pineal gland may be associated with precocious onset of puberty, and intralaminar nuclear groups, respectively. The internal me-
suggesting that the pineal gland exerts an inhibitory influence on dullary lamina contains intrathalamic fibers connecting the dif-
gonadal function. Tumors in the region of the pineal gland usu- ferent nuclei of the thalamus with each other. Another medul-
ally interfere with vertical gaze. This loss of vertical gaze, known lated band, the external medullary lamina, forms the lateral
as Parinaud’s syndrome, results from pressure of the pineal lesion boundary of the thalamus medial to the internal capsule. Be-
on the pretectal area and/or the posterior commissure. tween the external medullary lamina and the internal capsule is
the reticular nucleus of the thalamus. The external medullary
Thalamus (Dorsal Thalamus) and Metathalamus lamina contains nerve fibers leaving or entering the thalamus on
their way to or from the adjacent capsule.
The term thalamus derives from a Greek word that means “inner Literature on the thalamus in general, and on thalamic
chamber.” Use of the terms optic thalamus and chamber of vision surgery in particular, is difficult to read because different nomen-
relates to the tracing, in the second century A.D., of optic nerve clatures are in use. Most available nomenclatures are derived
fibers to the thalamus by Galen. The prefix optic was dropped from studies in primates. The different nomenclatures are based
when it was discovered that sensory modalities other than vision either on the cytoarchitectonic definition of nuclei or on their
are also processed in the thalamus. subcortical afferents. Human thalamic nomenclature is based
158 / CHAPTER 11
Anterior group lary bodies) and the cerebral cortex (cingulate gyrus). The ante-
rior group also receives significant input from the hippocampal
formation of the cerebral cortex (subiculum and presubiculum)
Medial group via the fornix.
External The reciprocal fibers between the anterior thalamic nuclear
medullary group and the mamillary bodies travel via the mamillothalamic
amina tract (tract of Vicq d’Azyr). The projections from the mamillary
bodies to the anterior group of thalamic nuclei is topographically
Lateral organized such that the medial mamillary nucleus projects to the
group ipsilateral principal anterior nucleus, whereas the lateral mamil-
lary nucleus projects to both anterodorsal nuclei. The reciprocal
Internal connections between the anterior nuclear group and the cingu-
medullary late gyrus accompany the anterior limb of the internal capsule.
lamina The projection from the anterior thalamic group to the cingulate
gyrus is topographically organized such that the medial part of
Reticular the principal anterior nucleus projects to rostral parts of the cin-
nucleus
gulate gyrus, whereas the lateral part of the principal nucleus and
the anterodorsal nucleus project to caudal parts of the cingulate
Internal gyrus. The anterior nuclear group of the thalamus is part of the
Intralaminar capsule
group limbic system, which is concerned with emotional behavior and
memory mechanisms. Discrete damage to the mamillothalamic
Figure 11–3. Schematic diagram showing the major nuclear tract has been associated with deficits in a specific type of mem-
groups of the thalamus. ory, episodic long-term memory, with relative sparing of short-
term memory and intellectual capacities.
B. MEDIAL NUCLEAR GROUP
entirely on cytoarchitectonic subdivisions and on transfer of Of the medial nuclear group, the dorsomedial nucleus is the
knowledge by analogy from monkey to human. Problems, how- most highly developed in humans. In histologic sections stained
ever, have arisen when trying to transfer the detailed knowledge for cells, three divisions of the dorsomedial nucleus are recog-
from the monkey to the human brain. nized: a dorsomedial magnocellular division located rostrally, a
dorsolateral parvicellular division located caudally, and a para-
A. ANTERIOR NUCLEAR GROUP laminar division adjacent to the internal medullary lamina. The
The anterior tubercle of the thalamus (dorsal surface of the most dorsomedial nucleus develops in parallel with and is reciprocally
rostral part of the thalamus) is formed by the anterior nuclear connected with the prefrontal cortex (areas 9, 10, 11,
group. In humans, the anterior nuclear group of tha- and 12), via the anterior thalamic peduncle, and the
lamic nuclei consists of two nuclei: principal anterior frontal eye fields (area 8) (Figure 11–5). It also receives
and anterodorsal. The principal anterior nucleus of hu- inputs from the temporal neocortex (via the inferior thalamic pe-
mans corresponds to the anteromedial and anteroventral nuclei duncle), amygdaloid nucleus and substantia nigra pars reticulata,
of other species. The anterior group of thalamic nuclei has recip- and adjacent thalamic nuclei, particularly the lateral and intra-
rocal connections (Figure 11–4) with the hypothalamus (mamil- laminar groups. The dorsomedial nucleus belongs to a neural

showing the reciprocal connec-
tions among the anterior nucleus
Mamillothalamic tract Mamillary Anterior thalamic Cingulate gyrus of the thalamus, mamillary body,
(of Vicq dÕAzyr) body nucleus and cingulate gyrus.
DIENCEPHALON / 159
Amygdala Temporal neocortex C. LATERAL NUCLEAR GROUP

The lateral nuclear group of the thalamus is subdivided into two
Pre
cor groups, dorsal and ventral.
1. Dorsal Subgroup. This subgroup includes, from rostral to
caudal, the lateral dorsal, lateral posterior, and pulvinar nuclei.
The lateral dorsal nucleus, although anatomically part of the
dorsal tier of the lateral group of thalamic nuclei, is functionally
part of the anterior group of thalamic nuclei, with which it col-
lectively forms the limbic thalamus. Similar to the anterior group
of thalamic nuclei, the lateral dorsal nucleus receives inputs from
the hippocampus (via the fornix) and an uncertain input from
the mamillary bodies and projects to the cingulate gyrus. In
histologic sections stained for myelin, the lateral dorsal nucleus
is characterized by a distinct capsule of myelinated fibers sur-
rounding it.
The borderline between the lateral posterior nucleus and the
pulvinar nucleus is vague, and the term pulvinar–lateral posterior
complex has been used to refer to this nuclear complex.
Caudate nucleus The pulvinar–lateral posterior complex has reciprocal con-
nections caudally with the lateral geniculate body and rostrally
THALAMIC NUCLEI
with the association areas of the parietal, temporal, and occipital
Lateral cortices (Figure 11–6). It also receives inputs from the pretectal
Intralaminar
Dorsomedial area and superior colliculus. The pulvinar is thus a relay station
between subcortical visual centers and their respective associa-
tion cortices in the temporal, parietal, and occipital lobes. The
pulvinar has a role in selective visual attention. There is evidence
that the pulvinar nucleus plays a role in speech mechanisms.
Stimulation of the pulvinar nucleus of the dominant hemisphere
MESENCEPHALON
SUPERIOR
COLLICULUS
Substantia nigra
Figure 11–5. Schematic diagram showing the major afferent

and efferent connections of the dorsomedial nucleus of the
Internal
thalamus.
capsule
system concerned with affective behavior, decision making and

judgment, memory, and the integration of somatic and visceral THALAMIC
activity. Bilateral lesions of the dorsomedial nucleus result in a NUCLEI
syndrome of lost physical self-activation, manifested by apathy, Pulvinar
indifference, and poor motivation. The reciprocal connections
between the prefrontal cortex and the dorsomedial nucleus can Lateral
be interrupted surgically to relieve severe anxiety states and other geniculate
psychiatric disorders. This operation, known as prefrontal lobot-
omy (ablation of prefrontal cortex) or prefrontal leukotomy (sev-
erance of the prefrontal-dorsomedial nucleus pathway), is rarely
Optic tract Tectum
practiced nowadays, having been replaced largely by medical
treatment that achieves the same result without undesirable side Figure 11–6. Schematic diagram showing the major afferent
effects. and efferent connections of the pulvinar.
160 / CHAPTER 11
has produced anomia (nominal aphasia). The pulvinar nucleus Ventral Cerebral cortex
also has been shown to play a role in pain mechanisms. anterior (areas 6,8)
Lesions in the pulvinar nucleus have been effective in nucleus
the treatment of intractable pain. Experimental studies
have demonstrated connections between the pulvinar nucleus Internal
capsule
and several cortical and subcortical areas concerned with pain
mechanisms.
The pulvinar–lateral posterior complex and the dorsomedial
nucleus are known collectively as multimodal association tha-
lamic nuclei. They all have the following in common:
1. They do not receive a direct input from the long ascending
tracts.
2. Their input is mainly from other thalamic nuclei.
3. They project mainly to the association areas of the cortex.
2. Ventral Subgroup. This subgroup includes the ventral ante- Intralaminar
rior, ventral lateral, and ventral posterior nuclei. The neural con- nucleus
nectivity and functions of this subgroup are much better under-
stood than those of the dorsal subgroup. In contrast to the dorsal
subgroup, which belongs to the multimodal association thalamic
nuclei, the ventral subgroup belongs to the modality-specific
thalamic nuclei. These nuclei share the following characteristics:
1. They receive a direct input from the long ascending tracts.
2. They have reciprocal relationships with specific cortical
areas.
3. They degenerate on ablation of the specific cortical area to
which they project.
Globus
a. Ventral anterior nucleus. This is the most rostrally pallidu
placed of the ventral subgroup. It receives fibers from several
sources (Figure 11–7).
Globus pallidus. A major input to the ventral anterior nucleus
is from the internal segment of globus pallidus. Fibers from
the globus pallidus form the ansa and lenticular fasciculi and
reach the nucleus via the thalamic fasciculus. Pallidal
fibers terminate in the lateral portion of the ventral ante-
rior nucleus.
Substantia nigra pars reticulata. Nigral afferents termi-
nate in the medial portion of the nucleus in contrast to the
pallidal afferents, which terminate in its lateral portion. Substantia nigra
Intralaminar thalamic nuclei. pars reticulata
Premotor and prefrontal cortices (areas 6 and 8)
The inputs from globus pallidus and substantia nigra are
GABAergic inhibitory. The inputs from the cerebral cortex
are excitatory.
The major output of the ventral anterior nucleus goes to the
premotor cortices and to wide areas of the prefrontal cortex, in-
cluding the frontal eye fields. It also has reciprocal connections
with the intralaminar nuclei. A projection to the primary motor Figure 11–7. Schematic diagram showing the major connec-
cortex has been described. tions of the ventral anterior nucleus of the thalamus.
Thus the ventral anterior nucleus is a major relay station in
the motor pathways from the basal ganglia to the cerebral cortex.
As such, it is involved in the regulation of movement. The me-
dial (magnocellular) part of the ventral anterior nucleus is con-
cerned with control of voluntary eye, head, and neck move- b. Ventral lateral nucleus. This nucleus is located caudal to
ments. The lateral (parvicellular) part of the nucleus is concerned the ventral anterior nucleus and, similar to the latter, plays a ma-
with control of body and limb movements. Lesions in this nu- jor role in motor integration. The ventral anterior and ventral
cleus and adjacent areas of the thalamus have been placed surgi- lateral nuclei together comprise the motor thalamus. The affer-
cally (thalamotomy) to relieve disorders of movement, especially ent fibers to the ventral lateral nucleus come from the following
parkinsonism. sources (Figure 11–8).
DIENCEPHALON / 161
CEREBRAL CORTEX Thus the ventral lateral nucleus, like the ventral anterior nu-
Ventral cleus, is a major relay station in the motor system link-
lateral
nucleus
ing the cerebellum, the basal ganglia, and the cerebral
cortex. Deep cerebellar nuclei have been shown to pro-
Internal ject exclusively to ventral lateral thalamic nuclei, whereas the
capsule projection from the globus pallidus targets mainly the ventral
anterior nucleus. Physiologic studies have shown that the cere-
bellar and pallidonigral projection zones in the thalamus are sep-
arate; very few cells have been identified that respond to both
cerebellar and pallidonigral stimulation.
As in the case of the ventral anterior nucleus, lesions in the
ventral lateral nucleus have been produced surgically to relieve
disorders of movement manifested by tremor. Physiologic re-
cordings during surgical procedures (thalamotomy) for relief of
Globus parkinsonian tremor have identified four types of neurons in the
pallidu ventral thalamic nuclear group (Table 11–1): (1) cells with activ-
ity related to somatosensory stimulation (sensory cells), (2) cells
with activity related to active movement (voluntary cells), (3) cells
with activity related to both somatosensory stimulation and ac-
tive movement (combined cells), and (4) cells with activity
related to neither somatosensory stimulation nor active move-
ment (no-response cells). Combined voluntary and no-response
cells are located in the region of the thalamus, where a lesion will
stop tremor, and anterior to the region, where sensory cells were
found. These findings suggest that thalamic cells unresponsive to
somatosensory stimulation (voluntary and no-response cells) and
Brachium conjunctivum those responsive to somatosensory stimulation (combined cells)
are involved in the mechanism of parkinsonian tremor. Activity
in sensory cells lags behind tremor, while activity of combined
cells leads the tremor.
c. Ventral posterior nucleus. This nucleus is located in the
caudal part of the thalamus. It receives the long ascending tracts
conveying sensory modalities (including taste) from the con-
tralateral half of the body and face. These tracts (Figure
CEREBELLUM
11–9) include the medial lemniscus, trigeminal lemnis-
Figure 11–8. Schematic diagram showing the major afferent cus (secondary trigeminal tracts), and spinothalamic tract.
and efferent connections of the nucleus ventralis lateralis of the Vestibular information is relayed to the cortex via the
thalamus. ventral posterior as well as the intralaminar and poste-
rior group of thalamic nuclei.
The ventral posterior nucleus is made up of two parts: the
ventral posterior medial (VPM ) nucleus, which receives the tri-
geminal lemniscus and taste fibers, and the ventral posterior lat-
Deep cerebellar nuclei. The dentatothalamic system consti- eral (VPL) nucleus, which receives the medial lemniscus and
tutes the major input to the ventral lateral nucleus. As de- spinothalamic tracts. Both nuclei also receive input from the pri-
tailed in Chapter 15, this fiber system originates in the deep mary somatosensory cortex. A visceral nociceptive input to the
cerebellar nuclei (mainly dentate), leaves the cerebellum via VPL has been described. The VPL nucleus is divided into two sub-
the superior cerebellar peduncle, and decussates in the mes- nuclei: pars oralis (VPLo) and pars caudalis (VPLc ). Pars oralis is
encephalon. Some fibers synapse in the red nucleus, while functionally a part of the ventral lateral nucleus (motor function)
others bypass it to reach the thalamus.
Globus pallidus (internal segment). Although the pallidotha-
lamic fiber system projects primarily on ventral anterior neu-
rons, some fibers reach the anterior (oral) portion of the ven- Table 11–1. Motor Thalamus Cell Population
tral lateral nucleus.
Primary motor cortex. There is a reciprocal relationship be- Activation
tween the primary motor cortex (area 4) and the ventral lat- Cell type
eral nucleus. Active movement Somatosensory
stimulation
The efferent fibers of the ventral lateral nucleus go primarily
to the primary motor cortex in the precentral gyrus. Other corti- Voluntary cellsa
cal targets include nonprimary somatosensory areas in the pari- Sensory cells
etal cortex (areas 5 and 7) and the premotor and supplementary Combined cellsb
motor cortices. The parietal cortical targets play a role in decod- No-response cell
ing sensory stimuli that provide spatial information for targeted a
Cells involved in parkinsonian tremor.
b
movements. Site of tremor-relieving lesion.
162 / CHAPTER 11
Leg area 1. Afferent connections (Figure 11–10). Fibers projecting

Arm area Internal on the intralaminar nuclei come from the following sources.
capsule (1) Reticular formation of the brain stem. This constitutes
Internal
the major input to the intralaminar nuclei.
capsule (2) Cerebellum. The dentatorubrothalamic system projects
Face area on the ventral lateral nucleus of the thalamus. Collaterals of this
system project on the intralaminar nuclei.
(3) Spinothalamic and trigeminal lemniscus. Afferent fibers
from the ascending pain pathways project largely on the ventral
posterior nucleus but also on the intralaminar nuclei.
Ventral CEREBRAL
posterior posterior CORTEX
lateral medial
nucleus nucleus Secondary
trigeminal
tract
Medial
lemniscus
Taste
fibers
Spinothalamic
tract DIENCEPHALON
Figure 11–9. Schematic diagram showing the major afferent Caudate

nucleus
and efferent connections of the ventral posterior lateral and ven-
tral posterior medial nuclei of the thalamus.
Putamen
Globus
pallidus
and like VL receives input from the cerebellum and projects to
the primary motor cortex. Intralaminar
The output from both nuclei is to the primary somatosensory nucleus
cortex (SI) in the postcentral gyrus (areas 1, 2, and 3). The pro-
jection to the cortex is somatotopically organized in such a way
that fibers from the ventral posterior medial nucleus project to
the face area, while different parts of the ventral posterior lateral
nucleus project to corresponding areas of body representation in
the cortex. A cortical projection from the part of the ventral pos-
terior medial nucleus that receives taste fibers to the parietal
operculum (area 43) has been demonstrated.
A group of cells located ventrally between the ventral posterior CEREBELLUM
lateral and ventral posterior medial nuclei comprises the ventral
posterior inferior (VPI ) nucleus. Cells in this nucleus provide the
major thalamic projection to somatosensory area II (SII). Reticular
The ventral posterior lateral and ventral posterior medial nu- formation MID-MEDULLA
clei are collectively referred to as the ventrobasal complex.
D. INTRALAMINAR, MIDLINE, AND RETICULAR NUCLEI Trigeminal
The intralaminar nuclei, as their name suggests, are enclosed nucleus
Spinothalamic tract
within the internal medullary lamina in the caudal thalamus.
The reticular nuclei occupy a position between the external
medullary lamina and the internal capsule (Figure 11–3).
1. Intralaminar Nuclei. The intralaminar nuclei include sev- SPINAL CORD
eral nuclei, divided into caudal and rostral groups. The caudal
group includes the centromedian and parafascicular nuclei,
which are the most important functionally in humans. The ros-
tral group includes the paracentral, centrolateral, and centrome- Figure 11–10. Schematic diagram showing the major affer-
dial nuclei. The intralaminar nuclei have the following afferent ent and efferent connections of the intralaminar nuclei of the
and efferent connections. thalamus.
DIENCEPHALON / 163
(4) Globus pallidus. Pallidothalamic fibers project mainly on nisms, and by virtue of the input from ascending pain-mediating
the ventral anterior nucleus. Collaterals of this projection reach pathways, they are also involved in the awareness of painful sen-
the intralaminar nuclei. sory experience. The awareness of sensory experience in the in-
(5) Cerebral cortex. Cortical fibers arise primarily from the tralaminar nuclei is poorly localized and has an emotional quality,
motor and premotor areas. Fibers originating in the motor cor- in contrast to cortical awareness, which is well localized.
tex (area 4) terminate on neurons in the centromedian, paracen-
tral, and centrolateral nuclei. Those originating from the premo- E. METATHALAMUS
tor cortex (area 6) terminate on the parafascicular and The term metathalamus refers to two thalamic nuclei, the medial
centrolateral nuclei. In contrast to other tha-lamic nuclei, the geniculate and lateral geniculate.
connections between the intralaminar nuclei and cerebral cortex
1. Medial Geniculate Nucleus. This is a relay thalamic nucleus
are not reciprocal.
in the auditory system. It receives fibers from the lateral
(6) Other Afferent Connections. Retrograde transport stud-
lemniscus directly or, more frequently, after a synapse in
ies of horseradish peroxidase have identified afferent connec-
the inferior colliculus. These auditory fibers reach the
tions to the intralaminar nuclei from the vestibular nuclei, peri-
medial geniculate body via the brachium of the inferior colliculus
aqueductal gray matter, superior colliculus, pretectum, and the
(inferior quadrigeminal brachium). The medial geniculate nu-
locus ceruleus.
cleus also receives feedback fibers from the primary auditory cor-
2. Efferent Connections. The intralaminar nuclei project to tex in the temporal lobe. The efferent outflow from the medial
the following structures. geniculate nucleus forms the auditory radiation of the internal
(1) Other thalamic nuclei. The intralaminar nuclei influence capsule (sublenticular part) to the primary auditory cortex in the
cortical activity through other thalamic nuclei. There are no di- temporal lobe (areas 41 and 42). Small hemorrhagic infarctions
rect cortical connections for the intralaminar nuclei. One excep- in the medial geniculate nucleus are associated with auditory illu-
tion has been demonstrated, with both the horseradish peroxi- sions such as hyperacusis and palinacusis and complete extinction
dase technique and autoradiography showing a direct projection of the contralateral ear input. The medial geniculate may have
from one of the intralaminar nuclei (centrolateral) to the pri- roles in spectral analysis of sound, sound pattern recognition, au-
mary visual cortex (area 17). The significance of this finding is ditory memory, and localization of sound in space, in addition to
twofold. First, it shows that intralaminar nuclei, contrary to pre- matching auditory information with other modalities.
vious concepts, do project directly to cortical areas. Second, it 2. Lateral Geniculate Nucleus. This is a relay thalamic nucleus
explains the reported response of area 17 neurons to nonvisual in the visual system. It receives fibers from the optic tract con-
stimuli (e.g., pinprick or sound); such responses would be medi- veying impulses from both retinae. The lateral geniculate nu-
ated through the intralaminar nuclei. cleus is laminated, and the inflow from each retina pro-
(2) The striatum (caudate and putamen). The striatal projects on different laminae (ipsilateral retina to laminae
jection is topographically organized such that the centromedian II, III, and V; contralateral retina to laminae I, IV, and
nucleus projects to the putamen and the parafascicular nucleus VI). Feedback fibers also reach the nucleus from the primary
to the caudate nucleus. visual cortex (area 17) in the occipital lobes. The efferent outflow
from the lateral geniculate nucleus forms the optic radiation of
2. Midline Nuclei. Consist of numerous cell groups, poorly de- the internal capsule (retrolenticular part) to the primary visual
veloped in humans, located in the medial border of the thalamus cortex in the occipital lobe. Some of the efferent outflow projects
along the banks of the third ventricle. They include the paraven- to the pulvinar nucleus and to the secondary visual cortex (areas
tral, central, and reunien nuclei. Their input includes projections 18 and 19). Thalamic nuclei and their cortical targets are illus-
from the hypothalamus, brain stem nuclei, amygdala, and para- trated in Figure 11–11.
hippocampal gyrus. Their output is to the limbic cortex and ven-
tral striatum. They have a role in emotion, memory, and auto-
nomic function. F. POSTERIOR THALAMIC NUCLEAR GROUP
The intralaminar and midline nuclei comprise the nonspecific This group embraces the caudal pole of the ventral posterior
thalamic nuclear group. group of thalamic nuclei medial to the pulvinar nucleus and
extends caudally to merge with the medial geniculate
3. Reticular Nuclei. The reticular nucleus is a continuation of
body and the gray matter medial to it. It receives inputs
the reticular formation of the brain stem into the diencephalon.
from all somatic ascending tracts (medial lemniscus and
It receives inputs from the cerebral cortex and other thalamic nu-
spinothalamic), as well as from the auditory pathways and possi-
clei. The former are collaterals of corticothalamic projections,
bly the visual pathways. Neurons in this part of the thalamus are
and the latter are collaterals of thalamocortical projections. The
multimodal and respond to a variety of stimuli. The outflow
reticular nucleus projects to other thalamic nuclei. The in-
from the posterior group projects to the association cortices in
hibitory neurotransmitter in this projection is gamma-aminobu-
the parietal, temporal, and occipital lobes. The posterior nuclear
tyric acid (GABA). The reticular nucleus is unique among thala-
group is thus a convergence center for varied sensory modalities.
mic nuclei in that its axons do not leave the thalamus. Based on
It lacks the modal and spatial specificity of the classic ascending
its connections, the reticular nucleus plays a role in integrating
sensory systems but allows for interaction among the divergent
and gating activities of thalamic nuclei.
sensory systems that project on it. Unlike the specific sensory
Thus the intralaminar nuclei and reticular nucleus collectively
thalamic nuclei, the posterior group does not receive reciprocal
receive fibers from several sources, motor and sensory, and project
feedback connections from the cerebral cortex.
diffusely to the cerebral cortex (through other thalamic
nuclei). Their multisource inputs and diffuse cortical
projections enable them to play a role in the cortical G. NOMENCLATURE
arousal response. The intralaminar nuclei, by virtue of their basal There are several nomenclature systems for thalamic nuclei based
ganglia connections, are also involved in motor control mecha- on shared features of fiber connectivity and function. Two such
164 / CHAPTER 11
Figure 11–11. Schematic diagram of thalamic nuclei and their cortical targets. A, anterior nucleus; DM, dorso-
medial nucleus; IML, internal medullary lamina; LP, lateral posterior nucleus; Pul, pulvinar nucleus; MG, medial genicu-
late nucleus; LG, lateral geniculate nucleus;VP, ventral posterior nucleus;VL, ventral lateral nucleus,VA, ventral anterior
nucleus; CC, corpus callosum.
nomenclature systems are used commonly. The first nomencla- by inputs from the brain stem reticular formation. These nuclei
ture system groups thalamic nuclei into three general categories: include the intralaminar, midline, and reticular nuclei.
(1) modality-specific, (2) multimodal associative, and Low-frequency stimulation of the modality-specific thalamic
(3) nonspecific and reticular. The modality-specific nuclei results in a characteristic cortical response known as the
group of nuclei shares the following features in com- augmenting response. This response consists of a primary excita-
mon: (1) they receive direct inputs from long ascending tracts tory postsynaptic potential (EPSP) followed by augmentation of
concerned with somatosensory, visual, and auditory information the amplitude and latency of the primary EPSP recorded from
(ventral posterior lateral and medial, lateral geniculate, medial the specific cortical area to which the modality-specific nucleus
geniculate) or else process information derived from the basal projects.
ganglia (ventral anterior, ventral lateral), the cerebellum (ventral Stimulation of the nonspecific nuclear group, on the other
lateral), or the limbic system (anterior, lateral dorsal); (2) they hand, gives rise to the characteristic recruiting response in the
have reciprocal connections with well-defined cortical areas (pri- cortex. This is a bilateral generalized cortical response (in con-
mary somatosensory, auditory, and visual areas, premotor and trast to the localized augmenting response) characterized by a
primary motor areas, cingulate gyrus); and (3) they undergo de- predominantly surface-negative EPSP that increases in ampli-
generation on ablation of the specific cortical area to which they tude and, with continued stimulation, will wax and wane.
project. The other nomenclature system groups thalamic nu-
The multimodal associative group, in contrast, receives no di- clei into the following categories: (1) motor, (2) sensory,
rect inputs from long ascending tracts and projects to association (3) limbic, (4) associative, and (5) nonspecific and retic-
cortical areas in the frontal, parietal, and temporal lobes. These ular. The motor group receives motor inputs from the basal gan-
nuclei include the dorsomedial nucleus and the pulvinar–lateral glia (ventral anterior, ventral lateral) or the cerebellum (ventral
posterior nuclear complex. lateral) and projects to the premotor and primary motor cortices.
The nonspecific and reticular group of nuclei are character- The sensory group receives inputs from ascending somatosen-
ized by diffuse and widespread indirect cortical projections and sory (ventral posterior lateral and medial), auditory (medial
DIENCEPHALON / 165
geniculate), and visual (lateral geniculate) systems. The limbic CEREBRAL

group is related to limbic structures (mamillary bodies, hip- CORTEX
+
pocampus, cingulate gyrus). The associative and nonspecific and
reticular groups correspond to the same groupings in the other
nomenclature system. Table 11–2 combines the two nomencla- Reticular
ture systems. nucleus
H. NEUROTRANSMITTERS AND NEUROPEPTIDES
+ +
The following neurotransmitters have been identified in the thal-
amus: (1) GABA is the inhibitory neurotransmitter in terminals
from the globus pallidus, in local circuit neurons, and in projec- +
– + THALAMUS
tion neurons of the reticular nucleus and lateral geniculate nu-
cleus; and (2) glutamate and aspartate are the excitatory neuro-
–
transmitters in corticothalamic and cerebellar terminals and in + +
Local circuit
thalamocortical projection neurons. Several neuropeptides have neuron
been identified in terminals of long ascending tracts. They in- Projection
clude substance P, somatostatin, neuropeptide Y, en-kephalin, neuron
and cholecystokinin.
I. NEURONAL CIRCUITRY
SUBCORTEX
Thalamic nuclei contain two types of neurons. The predominant
type is the principal (projection) neuron, whose axon projects on
extrathalamic targets. The other neuron is the local-circuit inter- Figure 11–12. Schematic diagram showing neuronal circuitry
neuron. Inputs to thalamic nuclei from subcortical and cortical within the thalamus.
sites facilitate both the projection and local-circuit neurons, the
neurotransmitter being glutamate or aspartate. An exception to
this is the subcortical input from the basal ganglia, which is in-
hibitory GABAergic. The local-circuit neuron, in turn, inhibits Internal Capsule (Figure 11–13)
the projection neuron. The neurotransmitter is GABA. Thus af-
ferent inputs to the thalamus influence projection (thalamocorti- The internal capsule is a broad, compact band of nerve fibers
cal) neurons via two pathways: a direct excitatory pathway and that are continuous rostrally with the corona radiata and cau-
an indirect (via the local-circuit neuron) inhibitory pathway dally with the cerebral peduncles. It contains afferent and effer-
(Figure 11–12). The local-circuit neuron thus modulates activity ent nerve fibers passing to and from the brain stem to the cere-
of the projection neuron. Projection neurons send their axons to bral cortex. In axial sections of the cerebral hemispheres, the
the extrathalamic targets (cerebral cortex, striatum). Neurons in internal capsule is bent with a lateral concavity to fit the
the reticular nucleus act like local-circuit neurons. They are facil- wedge-shaped lentiform nucleus. It is divided into an anterior
itated by collaterals of corticothalamic and thalamocortical limb, genu, posterior limb, retrolenticular part, and sublenticu-
projections, and they, in turn, inhibit projection neurons by lar part.
GABAergic transmission (Figure 11–12). The anterior limb is sandwiched between the head of the cau-
date nucleus medially and the lentiform nucleus (putamen and
globus pallidus) laterally. It contains frontopontine, thalamocor-
tical, and corticothalamic bundles; the latter two bundles recip-
Table 11–2. Thalamus Nuclear Groups rocally connect the dorsomedial and anterior thalamic nuclei
with the prefrontal cortex and cingulate gyrus, respectively.
Modality- Multimodal Nonspecific Some investigators add the caudatoputamenal interconnections
specific associative and reticular to components of the anterior limb.
Motor The genu of the internal capsule contains corticobulbar and
Ventral anterior X corticoreticulobulbar fibers that terminate on cranial nerve nu-
Ventral lateral X clei of the brain stem. Evidence obtained from stimulation of the
Sensory internal capsule during stereotaxic surgery and from vascular le-
Ventral posterior X sions of the internal capsule suggests, however, that corticobul-
Lateral geniculate X bar fibers are located in the posterior third of the posterior limb
Medial geniculate X rather than in the genu.
Limbic The posterior limb is bounded medially by the thalamus and
Anterior X laterally by the lentiform nucleus. It contains corticospinal and
Lateral dorsal X corticorubral fibers, as well as fibers that reciprocally connect the
Associative lateral group of thalamic nuclei (ventral anterior, ventral lateral,
Dorsomedial X ventral posterior, and pulvinar) with the cerebral cortex. The
Pulvinar X corticospinal bundle is somatotopically organized in such a way
Posterior X that the fibers to the upper extremity are located more anteriorly,
Reticular/nonspecific followed by fibers to the trunk and the lower extremity. Recent
Reticular X data suggest that the corticospinal fiber bundle is largely con-
Intralaminar X fined to the caudal half of the posterior limb. The thalamocorti-
Midline nuclei X cal projections from the ventral anterior nucleus to premotor
166 / CHAPTER 11
GENU ANTERIOR LIMB
Corticobulbar fibers Frontopontine fibers

Corticoreticulobulbar fibers Caudate Thalamocortical fibers
Corticothalamic fibers
Caudatoputamenal fibers
Putamen
Thalamus Globus pallidus
POSTERIOR LIMB SUBLENTICULAR PART
Corticospinal fibers Auditory radiation

Corticorubral fibers Corticopontine
Corticothalamic fibers Visual radiation
Thalamocortical fibers
Medial Lateral RETROLENTICULAR PART

geniculate geniculate
Visual radiation Figure 11–13. Schematic dia-
Corticotectal gram showing component parts of
Corticonigral
Corticotegmental the internal capsule and the fiber
bundles within each component.
cortex (area 6), from ventral lateral nucleus to the precentral different authors use different terminology to refer to the same
gyrus (area 4), from the ventral posterior nucleus to the postcen- vessel, accounts of blood supply of the thalamus may be confus-
tral gyrus (areas 1, 2, and 3), and from the pulvinar to temporal ing. Table 11–3 is a summary of blood supply of the thalamus
and visual cortices are segregated in the internal capsule, with the and clinical manifestations of thalamic infarcts.
cortical projection from ventral anterior nucleus most rostral fol-
lowed by those from ventral lateral nucleus, ventral posterior nu- B. BLOOD SUPPLY OF INTERNAL CAPSULE (Figure 11–14)
cleus, and pulvinar nucleus. Small focal capsular lesions may se- The anterior limb of the internal capsule is supplied by the stri-
lectively involve one of these thalamocortical projections. ate branches of the anterior and middle cerebral arteries. The
The retrolenticular part of the internal capsule contains corti- genu is supplied by striate branches of the middle cerebral and
cotectal, corticonigral, and corticotegmental fibers, as well as internal carotid arteries. The bulk of the posterior limb is sup-
part of the visual radiation. The sublenticular part of the internal plied by striate branches of the middle cerebral artery. The ante-
capsule contains corticopontine fibers, the auditory radiation, rior choroidal artery provides supply to the caudal portion of the
and part of the visual radiation. posterior limb.
Because of the crowding of corticothalamic and thalamocor-
tical fibers in the internal capsule, lesions in the capsule produce C. FUNCTIONS
more widespread clinical signs than similar lesions elsewhere in The function of the thalamus is to integrate sensory and motor
the neuraxis. Vascular lesions in the posterior limb of the internal activities. In addition, it has roles to play in arousal and con-
capsule are associated with contralateral hemiplegia and sciousness, as well as in affective behavior and memory. In a
hemisensory loss. Lesions in the most posterior region will, in sense, it is the gateway to the cortex.
addition, be associated with contralateral visual loss (hemianop- The thalamus plays a central role in sensory integration. All
sia) and hearing deficit (hemihypacusis). Lesions involv- somatic and special senses, except olfaction, pass through the
ing the genu of the internal capsule will be associated thalamus before reaching the cerebral cortex. Sensory activity
with cranial nerve signs. within the thalamus is channeled in one of three routes.
The first route is through the modality-specific sensory relay
nuclei (medial geniculate, lateral geniculate, and ventral poste-
A. BLOOD SUPPLY OF THALAMUS rior). Sensations relayed in the modality-specific sensory relay
Blood supply of the thalamus is derived from four parent vessels: nuclei have direct access to the respective sensory cortical areas.
basilar root of the posterior cerebral, posterior cerebral, posterior They are strictly organized with regard to topographic and
communicating, and internal carotid. The basilar root of the modal specificities and are discriminative and well localized.
posterior cerebral artery, via paramedian branches, sup- The second route is through the nonspecific nuclei. With its
plies the medial thalamic territory. The posterior cere- many sources of input and diffuse projections to the cortex, this
bral artery, via its geniculothalamic branch, supplies the route serves the low extreme of the modality-specificity gradient.
posterolateral thalamic territory. The posterior communicating The third route is through the posterior nuclear group. This
artery, via the tuberotha-lamic branch, supplies the anterolateral route receives from multiple sensory sources and projects to the
thalamic territory. The internal carotid artery, via its anterior association cortical areas. It plays an intermediate role between
choroidal branch, supplies the lateral thalamic territory. Because the modality-specific and nonspecific routes described above.
Table 11–3. Blood Supply of Thalamus
Thalamic territory Blood supply Synonyms Parent BV Structures supplied Clinical manifestations
of thalamic infarcts
(Concomitant PCA infarction)

Posterolateral Geniculothalamic Posterolateral Posterior VPL,VPM, MG, Complete: Pansensory loss (clinical hallmark)
Thalamogeniculate cerebral pulvinar, CM, (Pure hemisensory loss)
artery (PCA) DM, PL, ret, Pf, (Dejerine- Dysthesia
LG (primary Roussy Hemiparesis
sensory nuclei) syndrome) Visual field defect
Choreiform movements
Hemispatial neglect (with associated PCA infarct)
Partial: ↓ Pain and touch in part of body (face, arm, leg)
Occasional dysarthria
Visual field defect
No hemiparesis
Visual perceptual defect (with associated
PCA infarct)
Anterolateral Tuberothalamic Polar Posterior VA,VL, DM, AV Facial paresis for emotional movements
Anterior communicating Hemiparesis
internal optic Visual field defect (PCA infarct)
Premamillary Sensory loss rarely
pedicle Severe neuropsychological impairment
(L) Speech, intellect, language, memory
167
(R) Visuospatial
Medial Paramedian Posteromedial Basilar root CM, Pf, DM Drowsiness
Deep interpeduncular of PCA (bilateral or Vertical gaze paresis
profunda unilateral), CP, Memory, attention, intellect defects
Posterior internal VL, AV,VPL,VPM Hemiparesis occasionally
optic No sensory deficit
Thalamoperforating
Lateral Anterior choroidal — Internal IC (posterior limb), Hemiparesis
carotid GP, amygdala, optic tract, Sensory loss for pain and touch
lateral thalamus Dysarthria
(LG,VPL, pul, ret), Visual field defect, occasionally
medial temporal lobe Neuropsychological defect,
(L) memory, (R) visuospatial
Pure motor hemiparesis
Posterior Posterior choroidal — PCA LG, pul, DL, Homonymous quadrantaposia
DM, AV, Hemisensory dysfunction (hemihypesthesia)
hippocampus Neuropsychological disturbances
rostral midbrain (memory, transcortical aphasia)
Hemiparesis
Choreoathetosis
NOTE: AV, anterior ventral; BV, blood vessel; CM, centromedian; CP, cerebral peduncle; DM, dorsomedial; GP, globus pallidus; IC, internal capsule; LG, lateral geniculate; MG, medial geniculate; PCA,
posterior cerebral artery; PL, posterior lateral; Pf, parafascicular; pul, pulvinar; ret, reticular;VA, ventral anterior;VL, ventral lateral;VPL, ventral posterior lateral;VPM, ventral posterior medial; L, left;
R, right.
168 / CHAPTER 11
cortex can be activated directly by cholinergic, serotonergic, nor-

adrenergic, and histaminergic arousal systems that originate in
brain stem, basal forebrain, or hypothalamus and do not pass
through the thalamus.
The connections of the medial thalamus with the prefrontal
cortex reflect its role in affective behavior and executive function.
Ablation of the prefrontal cortex or its connections with the dor-
somedial nucleus causes changes in personality characterized by
lack of drive, flat affect, indifference to pain, and defects in deci-
sion making and judgment.
The connections of the anterior thalamic nuclei with the
hypothalamus and cingulate gyrus enable them to play a role in
memory, visceral function, and emotional behavior.
Damage to several and distinct areas of the thalamus (anterior
thalamic nucleus, mamillothalamic tract, dorsomedial nucleus,
intralaminar nuclei, and midline nuclei) contribute to memory
deficits (amnesia).
Discrete damage to the mamillothalamic tract has been asso-
ciated with deficits in a specific type of memory, episodic long-
term memory, with relative sparing of short-term memory and
intellectual capacity.
Figure 11–14. Schematic diagram of internal capsule showing
sources of blood supply. Cd, caudate nucleus; Put, putamen nu- D. ROLE OF THALAMUS IN PAIN
cleus; GP, globus pallidus nucleus; Th, thalamus; MCA, middle The thalamus receives and processes all nociceptive information
cerebral artery; ACA, anterior cerebral artery. destined to reach the cortex. The thalamus has a role in percep-
tion of pain and in the pathophysiology of central pain and
other types of chronic pain. Nociceptive information reaches
Some sensory modalities are perceived at the thalamic level the thalamus via the spinothalamic tracts (lateral and anterior)
and are not affected by ablation of the sensory cortex. Following and the trigeminothalamic pathways. Some nociceptive input
sensory cortical lesions, all sensory modalities are lost, but soon to the thalamus is mediated via other spinal pathways and from
pain, thermal sense, and crude touch return. The sense of pain the brain stem, but their role and importance in pain has not
that returns is the aching, burning type of pain that is carried by been established. The regions of the thalamus involved in pain
C-fibers. It is this type of pain that is believed to terminate in the and where responses to noxious stimuli are recorded include the
thalamus, whereas the pricking, well-localized pain carried by VPL, VPM, VPI, centrolateral (CL), parafascicular (PF), and the
the A-fibers terminates in the sensory cortex and is lost with its dorsomedial (DM) nuclei. Most of the thalamic nuclei that re-
ablation. In patients with intractable pain, placement of ceive nociceptive input have projections to cortical areas impli-
a surgical lesion in the ventral posterior or intralaminar cated in pain. Ventral posterior lateral and medial nuclei project
nuclei (centromedian) may provide relief. Vascular le- to somatosensory cortex (SI), ventral posterior inferior nucleus
sions of the thalamus result in a characteristic clinical syndrome projects to the secondary somatosensory cortex (SII), and the
known as the thalamic syndrome. Following an initial period of dorsomedial nucleus to the anterior cingulate cortex. Most of the
loss of all sensations contralateral to the thalamic lesion, pain, neurons in VPL and VPM are relay neurons for tactile informa-
thermal sense, and some crude touch return. However, the tion. Ten percent of neurons are nociceptive neurons of the wide
threshold of stimulation that elicits these sensations is elevated, dynamic range (WDR) type that discharge maximally to noxious
and the sensations are exaggerated and unpleasant when per- mechanical and noxious heat stimuli. VPI neurons are of the
ceived. The syndrome is usually associated with a marked affec- wide dynamic range type as well as nociceptive-specific (NS)
tive response attributed to the intact dorsomedial nucleus, usu- type. They tend to have larger receptive fields than those of VPL
ally unaffected by the vascular lesion. and VPM. The intralaminar nuclei (CL, Pf ) and the dorsome-
The role of the thalamus in motor control is evident from the dial nucleus (DM) mediate, in particular, the affective motiva-
input it receives from the cerebellum, basal ganglia, and motor tional aspect of pain as well as central pain.
areas of the cortex. Based on striatothalamic, thalamostriate, and
thalamocortical connections, it has been suggested that the thal- Subthalamus
amus may be a place for interaction between the input and out-
put systems of the basal ganglia. It is proposed that the informa- The subthalamus is a mass of gray and white substance in the
tion processed by the basal ganglia and directed to the cerebral caudal diencephalon. It is bordered medially by the hypothala-
cortex through the thalamus could be reaching the basal ganglia mus, laterally by the internal capsule, dorsally by the thalamus,
again via the striatum (thalamostriate connections) and thus and ventrally by the internal capsule. The subthalamus consists
influencing its overall organization. A tremorogenic center has of three main structures; these are the subthalamic nucleus, the
been postulated for the ventral lateral nucleus. Lesions have been fields of Forel, and the zona incerta.
placed in the ventral lateral nucleus to relieve abnormal move-
ment resulting from cerebellar and basal ganglia disorders. A. SUBTHALAMIC NUCLEUS (Figure 11–15)
The thalamus, as part of the ascending reticular activating The subthalamic nucleus (of Luys) is a biconvex gray mass that
system, has a central role in the conscious state and attention. replaces the substantia nigra in caudal diencephalic levels. The
The role of the thalamus as essential for arousal and wakefulness subthalamic nucleus receives a massive GABAergic (inhibitory)
has been challenged, in part by the recognition that the cerebral input from the external segment of globus pallidus and a glu-
DIENCEPHALON / 169
CEREBRAL
CORTEX
Fornix Thalamus
Lateral Corpus Cingulate Caudate
ventricle callosum gyrus nucleus
Reticular
nucleus
Interthalamic
Internal capsule
adhesion
Thalamic
fasciculus
Putamen
Zona incerta
Globus pallidus
Lenticular
fasciculus
Subthalamic
Subthalamic fasciculus
nucleus
Mamillary
Third body Supramamillary Prerubral Temporal
ventricle (hypothalamus) commissure field lobe
Figure 11–15. Schematic diagram of the subthalamic region showing its component parts and
the major afferent and efferent connections of the subthalamic nucleus.
tamatergic (excitatory) input from the cerebral cortex (areas 4 reach their respective thalamic nuclei. The fields of Forel are
and 6). The input from the globus pallidus travels in the sub- named after August Forel, the Swiss psychiatrist, neurologist,
thalamic fasciculus, whereas the input from the cerebral cortex and anatomist who is best remembered for his anatomic studies
travels in the internal capsule. Other inputs include those from on the basal ganglia and subthalamic region. The H is from the
the thalamus (primarily from the intralaminar nuclei) and the German word Haube, meaning “a cap” or “hood.”
brain stem reticular formation. The two subthalamic nuclei
communicate via the supramamillary commissure. Projections C. ZONA INCERTA
to the subthalamic nucleus are arranged in distinct sensorimotor, The zona incerta (Figure 11–15) is the rostral continuation of the
associative, and limbic territories similar to those reported for mesencephalic reticular formation that extends laterally into
other basal ganglionic nuclei. The output from the subthalamic the reticular nucleus of the thalamus. It is sandwiched between
nucleus is to both segments of the globus pallidus and to the the lenticular fasciculus and the thalamic fasciculus. The zona
substantia nigra pars reticulata. The neurotransmitter in both incerta has been implicated in a variety of functions, including
these projections is glutamate (excitatory). It has been shown locomotion, eye movements, sociosexual behavior, feeding and
that the projections to the external and internal segments of the drinking, arousal, and attention, and in aspects of visual, noci-
globus pallidus arise from different subthalamic neurons. ceptive, and somatosensory processing. The precise role of the
Interruption of the subthalamopallidal pathways or the sub- zona incerta in many of these functions is not certain. The diver-
thalamic nucleus is responsible for the involuntary violent hy- sity of functions ascribed to zona incerta reflects its widespread
perkinesia of the contralateral upper and lower extremi- connectivity. Reciprocal connections have been described in
ties known as hemiballismus. Facial and neck muscles different species to almost all parts of the neuraxis, including
may be involved. the neocortex, thalamus, brain stem, basal ganglia, cerebellum,
hypothalamus, basal forebrain, and spinal cord. Chronic, high-
B. FIELDS OF FOREL (Figure 11–16) frequency, deep-brain stimulation of the zona incerta in humans
This term refers to fiber bundles containing pallidal and cerebel- and non-human primates has been shown to suppress limb
lar efferents to the thalamus. Pallidothalamic fibers follow one of tremor. GABAergic neurons in the zona incerta have been shown
two routes. Some traverse the internal capsule and gather dorsal to pause immediately prior to onset of and during saccades, sug-
to the subthalamic nucleus as the lenticular fasciculus gesting an inhibitory role of these neurons on saccadic eye move-
(H2 field of Forel); others make a loop around the inter- ments. These neurons have been shown to project to deep layers
nal capsule as the ansa lenticularis. Both groups of fibers of the superior colliculus and the nucleus of Darkschewitsch,
join the dentatothalamic fibers in the prerubral field (H field of which are important in controlling saccades. The zona incerta has
Forel) and then join the thalamic fasciculus (H1 field of Forel) to also been shown to project to the pretectal area. The incertopre-
170 / CHAPTER 11
Figure 11–16. Schematic diagram of the fields of Forel.
tectal pathway is believed to play a role in the guidance of tectally Hypothalamus (Greek hypo, “under, below”; thalamos, “in-
initiated saccades by somatosensory stimuli. The zona incerta has ner chamber”). The region of the diencephalon below the thal-
been shown to receive collaterals from corticothalamic fibers and amus.
to send GABAergic projections to thalamic relay neurons. Luys, Jules Bernard (1828–1895). French clinical neurologist
who described the subthalamic nucleus (nucleus of Luys).
TERMINOLOGY Mamillary bodies (Latin diminutive of mamma, “breast, nip-
ple”). A pair of small round swellings on the ventral surface of
Diencephalon (Greek dia, “between”; enkephalos, “brain”). the hypothalamus mimicking the mammas.
The part of the central nervous system between the two hemi- Massa intermedia. Bridge of gray matter that connects the thal-
spheres. It includes the epithalamus, thalamus (including the ami of the two sides across the third ventricle; also called in-
metathalamus), subthalamus, and hypothalamus. The dien- terthalamic adhesion.
cephalon is the posterior of the two brain vesicles formed from Metathalamus (Greek meta, “after”; thalamos, “inner cham-
the prosencephalon of the developing embryo. ber”). The metathalamus includes the lateral and medial genicu-
Epithalamus (Greek epi, “upon”; thalamos, “inner cham- late bodies.
ber”). Part of the diencephalon dorsal to the thalamus. It in- Meynert, Theodor Hermann (1833–1892). Austrian psychia-
cludes the stria medullaris thalami, habenular nucleus, and pineal trist and neurologist. Described the habenulointerpeduncular
gland. tract in 1867.
Forel, August Henri (1848–1931). Swiss neuropsychiatrist Palinacusis. (Greek palin, “backward” or “again”; curis,
who described the fiber bundles of the subthalamus (H fields of “hearing, sound”). Auditory perseveration. The pathologic
Forel). continuance or recurrence of an auditory sensation after the
Galen, Claudius (A.D. 130–200). Hellinistic physician who stimulus is gone.
practiced mainly in Rome and Pergamon. He was the leading Parinaud, Henri (1844–1905). French ophthalmologist. De-
medical authority of the Christian world for 1400 years. The scribed the Parinaud syndrome in 1883. Wrote extensively about
great cerebral vein is named after him. ocular movements, having had access to the large numbers of
Geniculate (Latin geniculare, “to bend the knee”). Abruptly Charcot patients at the Salpêtrière hospital in Paris. He is re-
bent, as in lateral and medial geniculate nuclei of the thalamus. garded as the father of neuro-ophthalmology.
Genu (Latin “knee”). A kneelike structure. The genu of the cor- Pineal gland (Latin pinea, “a pine cone”). A small midline or-
pus callosum. gan shaped like a pine cone.
Habenula (Latin diminutive of habena, “a small strap or Pulvinar (Latin pulvinar, “a cushioned reclining seat”). The
rein”). The habenular nuclei are part of the epithalamus. pulvinar nucleus is located in the posterior pole of the thalamus
Hemiballismus (Greek hemi, “half ”; ballismos, “jumping overhanging the superior colliculus and geniculate bodies.
about”). Violent flinging involuntary movements of one side of Subthalamus (Latin sub, “under”; Greek thalamos, “inner
the body due to a lesion in the contralateral subthalamic nucleus. chamber”). Region of the diencephalon beneath the thalamus.
Hypacusis (Greek hypo, “under, below”; akousis, “hearing”). Thalamus (Greek thalamos, “inner chamber”). Also meant “a
Decreased hearing. bridal couch,” so the pulvinar nucleus is its cushion or pillow.
Hyperacusis. Abnormal perception of sound as being loud. Part of the diencephalon on each side of the third ventricle and
DIENCEPHALON / 171
above the hypothalamic sulcus. Galen made up the word thala- Ilinsky IA et al: Quantitative evaluation of crossed and uncrossed projections
mus, and Willis was the first to use the term in its modern sense. from basal ganglia and cerebellum to the cat thalamus. Neuroscience
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Diencephalon: Clinical Correlates 12
Clinical Correlates of Thalamic Anatomy Memory Deficits

Thalamic Infarcts Thalamus and Arousal
Posterolateral Thalamic Territory The Cheiro-Oral Syndrome
Anterolateral Thalamic Territory The Alien Hand Syndrome
Medial Thalamic Territory Thalamic Acalculia
Lateral Thalamic Territory Language Deficits
Posterior Thalamic Territory Clinical Correlates of Subthalamic Anatomy
Thalamic Pain Syndromes Hemiballismus
KEY CONCEPTS
Posterolateral (thalamogeniculate) thalamic territory le- lamic pain, proprioceptive and exteroceptive sensations,
sions are characterized by pansensory loss associated and abnormalities in somatosensory evoked potentials.
with thalamic pain, the Dejerine-Roussy syndrome.
Encoding memory defects, severe distractibility, and ver-
Anterolateral (tuberothalamic) thalamic territory lesions bal memory disturbances have been described in tha-
are characterized by neuropsychological impairment. lamic lesions.
Medial (paramedian) thalamic territory lesions are char- The thalamus is one (indirect) of two mechanisms for
acterized by alteration in state of consciousness. Akinetic cortical activation. The other (direct) mechanism is via
mutism and the Kleine-Levin syndrome occur with lesions cholinergic, serotonergic, noradrenergic, and histaminer-
in this thalamic territory. gic nonthalamic systems.
Lateral (anterior choroidal) thalamic territory lesions are Language deficits occur with dominant thalamic lesions
characterized by hemiparesis and dysarthria. and are transient.
Posterior (posterior choroidal) thalamic territory lesions A violent dyskinesia (hemiballismus) occurs with lesions
are characterized by hemisensory dysfunction and visual in the subthalamic nucleus or its connections with globus
field defects. pallidus.
Four types of thalamic pain syndromes have been de-
scribed based on the presence or absence of each of tha-
CLINICAL CORRELATES nuclear boundaries, and (3) simultaneous involvement of neigh-

OF THALAMIC ANATOMY boring areas such as the midbrain in paramedian thalamic vascu-
lar lesions, the internal capsule in lateral thalamic vascular lesions,
A multiplicity of neurologic signs and symptoms has been re- and the subthalamus in posterior thalamic vascular lesions.
ported in disorders of the thalamus. These reflect (1) the anatomic The conglomerate of signs and symptoms associated with tha-
and functional heterogeneity of the thalamus, (2) simultaneous lamic lesions includes the following: sensory disturbances, thalamic
involvement of several nuclei even by discrete vascular lesions due pain, hemiparesis, dyskinesias, disturbances of consciousness, mem-
to the fact that arterial vascular territories in the thalamus cross ory disturbances, affective disturbances, and disorders of language.
172
DIENCEPHALON: CLINICAL CORRELATES / 173
Correlation of signs and symptoms with affected thalamic ter- An athetoid posture of the contralateral hand (thalamic hand)
ritory is best with vascular lesions (infarcts) of the thalamus (Table may appear 2 or more weeks following lesions in this territory.
12–1). Clinicoanatomic correlation in patients with occlusion of The hand is flexed and pronated at the wrist and metacarpopha-
thalamic arteries has been greatly facilitated by neuro-imaging langeal joints and extended at the interphalangeal joints. The fin-
methods (computed tomography and magnetic resonance imag- gers may be abducted. The thumb is either abducted or pushed
ing). The different vascular territories of the thalamus and associ- against the palm. The conglomerate of signs and symptoms asso-
ated neurologic signs and symptoms are outlined in the next sec- ciated with posterolateral thalamic territory infarcts comprises
tions. Most thalamic infarcts are reported in the posterolateral the thalamic syndrome of Dejerine and Roussy. In this syndrome,
and the medial thalamic territories supplied by the geniculotha- severe, persistent, paroxysmal, and often intolerable pain (tha-
lamic and paramedian arteries, respectively. Only a few cases are lamic pain) resistant to analgesic medications occurs at the time
reported in the anterolateral and posterior territories supplied by of injury or following a period of transient hemiparesis, hemi-
the tuberothalamic and posterior choroidal arteries, respectively. ataxia, choreiform movements, and hemisensory loss. Cutaneous
stimuli trigger paroxysmal exacerbations of the pain that outlast
THALAMIC INFARCTS the stimulus. Because the perception of “epicritic” pain (from a
pinprick) is reduced on the painful areas, this symptom is known
Posterolateral Thalamic Territory (Figure 12–1) as anesthesia dolorosa, or painful anesthesia. The syndrome is
named after Joseph-Jules Dejerine, a French neurologist, and his
Infarcts in this thalamic territory are due to occlusion of the assistant, Gustave Roussy, a Swiss-French neuropathologist, who
geniculothalamic (thalamogeniculate, posterolateral) artery, a described the “thalamic syndrome” in 1906 in six patients with a
branch of the posterior cerebral artery. Thalamic struc- vascular thalamic lesion who presented with a characteristic clus-
tures involved by the infarct are the primary sensory ter of symptoms: hemihypoesthesia, intractable pain, slight tran-
thalamic nuclei, which include the ventral posterior lat- sient hemiparesis, hemiataxia, and choreoathetotic movements.
eral, ventral posterior medial, medial geniculate, pulvinar, and The etiology of the thalamic pain syndrome is not clear but may
centromedian nuclei. Other nuclei that are inconsistently involved be the result of alterations in frequencies and patterns of inputs
include the dorsomedial, posterior lateral, reticular, parafascicu- to the thalamus, qualities of injured neurons, or changes in qual-
lar, and lateral geniculate nuclei. The clinical hallmark of postero- ity of output to the cortex.
lateral thalamic territory infarcts is a pansensory loss contralateral
to the lesion, paresthesia, and thalamic pain. In addition, one or Anterolateral Thalamic Territory
more of the following may occur: transient hemiparesis, homony-
mous hemianopsia, hemiataxia, tremor, choreiform movements, Infarcts in the anterolateral territory of the thalamus are usually
and spatial neglect, all contralateral to the lesion in the thalamus. secondary to occlusion of the tuberothalamic branch of the pos-
Figure 12–1. T2-weighted axial magnetic resonance image

(MRI) showing an infarct (arrow) in the posterolateral thalamic
territory.
Table 12–1. Blood Supply of Thalamus
Thalamic territory Blood supply Synonyms Parent BV Structures supplied Clinical manifestations
of thalamic infarcts
(Concomitant PCA infarction)

Posterolateral Geniculothalamic Posterolateral Posterior VPL,VPM, MG, Complete: Pansensory loss (clinical hallmark)
Thalamogeniculate cerebral pulvinar, CM, (Pure hemisensory loss)
artery (PCA) DM, PL, ret, Pf, (Dejerine- Dysthesia
LG (primary Roussy Hemiparesis
sensory nuclei) syndrome) Visual field defect
Choreiform movements
Hemispatial neglect (with associated PCA infarct)
Partial: ↓ Pain and touch in part of body (face, arm, leg)
Occasional dysarthria
Visual field defect
No hemiparesis
Visual perceptual defect (with associated
PCA infarct)
Anterolateral Tuberothalamic Polar Posterior VA,VL, DM, AV Facial paresis for emotional movements
Anterior communicating Hemiparesis
internal optic artery Visual field defect (PCA infarct)
Premamillary Sensory loss rarely
pedicle Severe neuropsychological impairment
(L) Speech, intellect, language, memory
174
(R) Visuospatial
Medial Paramedian Posteromedial Basilar root CM, Pf, DM Drowsiness
Deep interpeduncular of PCA (bilateral or Vertical gaze paresis
profunda unilateral), CP, Memory, attention, intellect defects
Posterior internal VL, AV,VPL,VPM Hemiparesis occasionally
optic No sensory deficit
Thalamoperforating
Lateral Anterior choroidal — Internal IC (posterior limb), Hemiparesis
carotid GP, amygdala, optic tract, Sensory loss for pain and touch
artery lateral thalamus Dysarthria
(LG,VPL, pul, ret), Visual field defect, occasionally
medial temporal lobe Neuropsychological defect,
(L) memory, (R) visuospatial
Pure motor hemiparesis
Posterior Posterior choroidal — PCA LG, pul, DL, Homonymous quadrantaposia
DM, AV, Hemisensory dysfunction (hemihypesthesia)
hippocampus Neuropsychological disturbances
rostral midbrain (memory, transcortical aphasia)
Hemiparesis
Choreoathetosis
NOTE: AV, anterior ventral; BV, blood vessel; CM, centromedian; CP, cerebral peduncle; DM, dorsomedial; GP, globus pallidus; IC, internal capsule; LG, lateral geniculate; MG, medial geniculate; PCA,
posterior cerebral artery; PL, posterior lateral; Pf, parafascicular; pul, pulvinar; ret, reticular;VA, ventral anterior;VL, ventral lateral;VPL, ventral posterior lateral;VPM, ventral posterior medial; L, left;
R, right.
terior communicating artery. Synonyms for this branch include frontal lobe damage has been reported in medial thalamic terri-
the polar, anterior internal optic, and the premamillary pedicle. tory infarcts.
Thalamic nuclei involved in the infarct include the ventral ante- Two syndromes have also been reported in medial thalamic ter-
rior, ventral lateral, dorsomedial, and anterior. The clinical man- ritory infarcts: akinetic mutism and the Kleine-Levin syndrome.
ifestations include contralateral hemiparesis, visual field In akinetic mutism (persistent vegetative state), patients appear
defects, facial paresis with emotional stimulation, and awake and maintain a sleep-wake cycle but are unable to com-
rarely, hemisensory loss. Severe, usually transient neuro- municate in any way. In addition to thalamic infarcts, akinetic
psychological impairments predominate in lesions in this thalamic mutism has been reported to occur with lesions in the basal gan-
territory. Abulia, lack of spontaneity and initiative, and reduced glia, anterior cingulate gyrus, and pons. The Kleine-Levin syn-
quantity of speech are the predominant findings. Other impair- drome (hypersomnia-bulimia syndrome) is characterized by re-
ments consist of defects in intellect, language, and memory in current periods (lasting 1 to 2 weeks every 3 to 6 months) in
left-sided lesions and visuospatial deficits in right-sided lesions. adolescent males of excessive somnolence, hyperphagia (compul-
sive eating), hypersexual behavior (sexual disinhibition), and im-
Medial Thalamic Territory (Figure 12–2) paired recent memory, and eventually ending with recovery. A
confusional state, hallucinosis, irritability, or a schizophreniform
Infarcts in the medial territory of the thalamus are associated state may occur around the time of the attacks. The syndrome was
with occlusion of the paramedian branches of the basilar first reported by Antimoff in 1898 but more fully by Willi Kleine
root of the posterior cerebral artery. These branches in- in 1925 in German and by Max Levin 4 years later in English.
clude the posteromedial, deep interpeduncular profunda,
posterior internal optic, and thalamoperforating. The thalamic Lateral Thalamic Territory (Figure 12–3)
nuclei involved include the intralaminar (centromedian, parafas-
cicular) and dorsomedial, either unilaterally or bilaterally. The Infarcts in the lateral territory of the thalamus are associated with
paramedian territory of the midbrain is often involved by the occlusion of the anterior choroidal branch of the internal carotid
lesion. The following nuclei are inconsistently involved: the ven- artery. Structures involved in the lesion include the posterior
tral lateral, anterior, and ventral posterior. The hallmark of the limb of the internal capsule, lateral thalamic nuclei (lat-
clinical picture is drowsiness. In addition, there are abnormalities eral geniculate, ventral posterior lateral, pulvinar, reticu-
in recent memory, attention, intellect, vertical gaze, and occa- lar), and medial temporal lobe. The clinical hallmarks of
sionally, mild hemiparesis or hemiataxia. No sensory deficits are the infarct are contralateral hemiparesis and dysarthria. Lesions
as a rule associated with lesions in this territory. Utilization be- in the lateral thalamic territory may manifest with only pure
havior (instrumentally correct but highly exaggerated response motor hemiparesis. Other clinical manifestations include hemi-
to environmental cues and objects) that is characteristic of sensory loss of pain and touch, occasional visual field defects,
Figure 12–2. T2-weighted axial MRI showing an infarct

(arrow) in the medial thalamic territory.
176 / CHAPTER 12
Figure 12–3. Proton density MRI showing an infarct (arrow)

in the lateral thalamic territory.
and neuropsychological defects. The latter consist of memory ceptive sensations are lost and somatosensory evoked potentials
defects in left-sided lesions and visuospatial defects in right-sided are absent. In type III, central pain as well as proprioceptive and
lesions. exteroceptive sensations are present, whereas somatosensory
evoked potentials are reduced in amplitude. In type IV (pure al-
Posterior Thalamic Territory (Figure 12–4) getic), central pain is present, proprioceptive and exteroceptive
sensations are unimpaired, and somatosensory evoked potentials
Infarcts in the posterior thalamic territory are associated with oc- are normal.
clusion of the posterior choroidal branch of the posterior cerebral
artery. Thalamic nuclei involved include the lateral genic-
ulate, pulvinar, and dorsolateral nuclei. The following Memory Deficits
structures are inconsistently involved in the lesion: dor-
somedial and anterior thalamic nuclei, hippocampus, Discrete lesions of the thalamus can cause severe and lasting
and rostral midbrain. Clinical manifestations include contra- memory deficits. Although it remains uncertain which
lateral homonymous quadrantanopsia and hemihypesthesia, as thalamic structures are critical for memory, evidence
well as neuropsychological deficits, including memory defects from human and animal research suggests that one or
and transcortical aphasia. Inconsistent signs include contralateral more of the following structures are important: anterior
hemiparesis and choreoathetosis. nuclei, midline and intralaminar nuclei, dorsomedial nucleus,
and mamillothalamic tract. There are three distinct behavioral
Thalamic Pain Syndromes and anatomic types of memory impairment associated with di-
encephalic lesions: (1) Severe encoding defects are associated with
Four types of pain syndromes have been described in association lesions in the mamillary bodies, mamillothalamic tracts, midline
with thalamic lesions (Table 12–2). The four types are differenti- thalamic nuclei, and the dorsomedial nucleus. Performance of
ated from each other on the basis of the presence or absence in such patients never approximates normal memory. (2) A milder
each of central (thalamic) pain, proprioceptive sensations form of memory deficit characterized by severe distractibility
(vibration, touch, joint), exteroceptive sensations (pain occurs in lesions of the intralaminar and medial thalamic nuclei.
and temperature), and abnormalities in somatosensory (3) Disturbances in verbal memory (retrieval, registration, and
evoked potentials. retention) occur in lesions of the left thalamus that include the
In type I (analgetic type), central pain is absent, both proprio- ventrolateral and intralaminar nuclei and the mamillothalamic
ceptive and exteroceptive sensations are lost, and no somato- tract. Memory disturbances, which may be transient or perma-
sensory evoked potentials are elicitable. In type II, both central nent, are most common with bilateral thalamic lesions but do
pain and exteroceptive sensations are present, whereas proprio- occur with unilateral lesions of either side.
Figure 12–4. T2-weighted MRI showing an infarct (arrow) in

the posterior thalamic territory.
Thalamus and Arousal two areas is contiguous not only in the primary somatosensory
cortex but also elsewhere in the neuraxis.
The essential role of the thalamus as the sole mechanism for
cortical arousal has been challenged. It is now acknowledged that
cortical activation is mediated by two mechanisms: (1) an in- The Alien Hand Syndrome
direct mechanism, via the thalamus, comprised of the ascend-
ing reticular activating system (ARAS), and (2) a direct The alien hand syndrome is defined as unwilled, uncontrollable
mechanism (nonthalamic), via cholinergic, serotonergic, movements of an upper limb together with failure to recognize
noradrenergic, and histaminergic arousal systems that ownership of a limb in the absence of visual cues. The syndrome
originate in the brain stem, basal forebrain, or hypothalamus and was first described by Goldstein in 1908. Most cases are associ-
do not pass through the thalamus. ated with lesions in the corpus callosum and mesial frontal area,
alone or in combination. The condition has also been reported
in infarcts involving the posterolateral and anterolateral thalamic
The Cheiro-Oral Syndrome territories (supplied by the geniculothalamic and tuberothalamic
This syndrome consists of sensory disturbances confined to one arteries, respectively). The lesion usually involves the ventral pos-
hand and to the ipsilateral mouth region. It is associated with fo- terior, ventral lateral, and dorsomedial nuclei.
cal lesions in the ventral posterior thalamic nucleus. A similar
syndrome has been reported with lesions in the somatosensory Thalamic Acalculia
cortex, border of the posterior limb of the internal capsule and
corona radiata, midbrain, and pons. The involvement of the hand Infarctions in the left anterolateral thalamic territory supplied
and mouth areas suggests that the sensory representation of these by the tuberothalamic artery have been reported to produce
Table 12–2. Thalamic Pain Syndromes Subtypes
Type Central pain Vibration, touch, joint Pain, temperature Somatosensory evoked potentials
I (analgetic) Absent Lost Lost Absent

II Present Lost Present Absent
III Present Present Present Reduced
IV (pure algetic) Present Present Present Normal
178 / CHAPTER 12
acalculia. The lesion usually involves the ventral lateral and dor- tion, hemorrhage, or tumor, or that may stimulate tissue, as in
somedial thalamic nuclei. epilepsy.
Levin, Max. American neuropsychiatrist of Latvian origin. In
Language Deficits 1929, he described a case of Kleine-Levin syndrome 4 years after
Kleine described his cases. In 1936, he summarized the features
Dominant hemisphere thalamic lesions may cause a transient of seven cases as a new syndrome of periodic somnolence and
deficit in language. Three types have been described: (1) medial, morbid hunger.
(2) anterolateral, and (3) lateral. In the medial type, in-
volving the dorsomedial and centromedian nuclei (me- Paresthesia (Greek para, “beside, near, beyond”; aisthesis,
dial thalamic territory), the language deficit is character- “perception”). Distorted sensation, tingling, “pins and needles.”
ized by anomia and attentionally induced language impairment. Proprioceptor (Latin proprius, “one’s own”; receptor, “re-
Lesions in this area are associated with memory and attention ceiver”). Sensory endings in muscles, tendons, and joints that
deficits. In the anterolateral type, the lesion involves ventral an- provide information about movement and position of body parts.
terior and anterior ventral nuclei (anterolateral thalamic terri- Syndrome (Greek syndromos, “a running together, combin-
tory). This type is associated with an aphasic syndrome resem- ing”). A group of co-occurring symptoms and signs that charac-
bling transcortical aphasia. In the third type, the lesion involves terize a disease.
the lateral thalamic territory. The language deficit in this type is
characterized by mild anomia. Several authors have suggested
that thalamic language disturbances are due to cortical hypoper-
fusion and hypometabolism. SUGGESTED READINGS
Beric A: Central pain: “New” syndromes and their evaluation. Muscle Nerve
CLINICAL CORRELATES 1993; 16:1017–1024.
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imaging correlation. J Clin Neuroophthalmol 1985; 5:217–223.
Hemiballismus Bjornstad B et al: Paroxysmal sleep as a presenting symptom of bilateral para-
Lesions in the subthalamic nucleus or in the pallidosub- median thalamic infarction. Mayo Clin Proc 2003; 78:347–349.
thalamic system are associated with violent, involuntary, Bogousslavsky J et al: Thalamic infarcts: Clinical syndromes, etiology, and prog-
flinging, ballistic movements of the contralateral half of nosis. Neurology 1988; 38:837–848.
the body. The abnormal movement involves primarily the ex- Bogousslavsky J et al: Loss of psychic self-activation with bithalamic infarc-
tremities; the head and neck also may be involved. tion: Neurobehavioral, CT, MRI, and SPECT correlates. Acta Neurol
Scand 1991; 83:309–316.
Brandt T et al: Posterior cerebral artery territory infarcts: Clinical features,
TERMINOLOGY infarct topography, causes and outcome. Cerebrovasc Dis 2000; 10:
170–182.
Abulia (Greek a, “without”; boulé, “will”). A state in which Caplan LR: “Top of the basilar” syndrome. Neurology 1980; 30:72–79.
the patient manifests lack of initiative and spontaneity with pre-
Castaigne P et al: Paramedian thalamic and midbrain infarcts: Clinical and
served consciousness. neuropathological study. Ann Neurol 1981; 10:127–148.
Aphasia (Greek a, “without”; phasis, “speech”). Defect in Engelborghs S et al: Functional anatomy, vascularisation and pathology of the
communication by language. human thalamus. Acta Neurol Belg 1998; 98:252–265.
Ataxia (Greek a, “without”; taxis, “order”). Loss of muscle co- Eslinger PJ et al: “Frontal lobe” utilization behavior associated with parame-
ordination with irregularity of movement. dian thalamic infarction. Neurology 1991; 41:450–452.
Contralateral (Latin contra, “opposite”; lateris, “of a side”). Gentilini M et al: Bilateral paramedian thalamic artery infarcts: Report of
Of the other side of the body. eight cases. J Neurol Neurosurg Psychiatry 1987; 50:900–909.
Dysarthria (Greek dys, “difficult”; arthroun, “to articulate”). Graff-Radford NR et al: Nonhemorrhagic thalamic infarction. Brain 1985; 108:
485–516.
Difficulty in speaking.
Guberman A, Stuss D: The syndrome of bilateral paramedian thalamic infarc-
Exteroceptor (Latin exterus, “external”; receptor, “receiver”). tion. Neurology 1983; 33:540–545.
Sensory receptor that serves to acquaint the individual with the
Isono O et al: Cheiro-oral topography of sensory disturbances due to lesions of
external environment. Includes pain and temperature receptors. thalamocortical projections. Neurology 1993; 43:51–55.
Hemianopsia (Greek hemi, “half ”; an, “negative”; opsis, Kinney HC et al: Neuropathological findings in the brain of Karen Ann
“vision”). Defect of half the field of vision. Quinlan: The role of the thalamus in the persistent vegetative state.
Hemiballismus (Greek hemi, “half ”; ballismos, “jumping N Engl J Med 1994; 330:1469–1475.
about”). Violent flinging movement of one side of the body due Marey-Lopez J et al: Posterior alien hand syndrome after a right thalamic infarct.
to a lesion in the contralateral subthalamic nucleus. J Neurol Neurosurg Psychiatry 2002; 73:447–449.
Infarction (Latin infarcire, “to stuff into”). Vascular occlusion Mauguiere F, Desmedt JE: Thalamic pain syndrome of Dejerine-Roussy: Dif-
ferentiation of four subtypes assisted by somatosensory evoked potentials
leading to death of tissue. data. Arch Neurol 1988; 45:1312–1320.
Kleine, Willi. German neuropsychiatrist who, in 1925, reported Mendez MF et al: Thalamic acalculia. J Neuropsychiatry Clin Neurosci 2003;
five cases of periodic somnolence and morbid hunger attributed 15:115–116.
to hypothalamic lesion. The syndrome had been previously de- Mennemeier M et al: Contributions of the left intralaminar and medial tha-
scribed in 1898 by Antimoff. lamic nuclei to memory. Arch Neurol 1992; 49:1050–1058.
Lesion (Latin laesum, “hurt or wounded”). The term is ap- Miwa H et al: Thalamic tremor: Case reports and implications of the tremor-
plied to an abnormality that may destroy tissue, as in infarc- generating mechanism. Neurology 1996; 46:75–79.
Mori E et al: Left thalamic infarction and disturbances of verbal memory: A Roitberg BZ et al: Bilateral paramedian thalamic infarct in the presence
clinicoanatomical study with a new method of computed tomographic of an unpaired thalamic perforating artery. Acta Neurochir 2002; 144:
stereotaxic lesion localization. Ann Neurol 1986; 20:671–676. 301–304.
Nea JP, Bogousslavsky J: The syndrome of posterior choroidal artery territory Szczudlik A et al: Vascular thalamic syndromes—clinical and topographic
infarction. Ann Neurol 1996; 39:779–788. analysis. Neur Neurochir Pol 1996; 30(Suppl 2):55–63.
Reilly M et al: Bilateral paramedian thalamic infarction: A distinct but poorly Wallesch CW et al: Neuropsychological deficits associated with small unilat-
recognized stroke syndrome. Q J Med 1992; 29:63–70. eral thalamic lesions. Brain 1983; 106:141–152.
The Basal Ganglia 13
Definitions and Nomenclature Corticostriatothalamocortical Loops

Neuronal Population, Synaptic Relations, Split Pathways
and Internal Organization Basal Ganglia Function
Neostriatum (Striatum) Motor Function
Globus Pallidus and Substantia Nigra Pars Reticulata Gating Function
Neostriatal Input Cognitive Function
Neostriatal Output Emotion and Motivation Function
Pallidal and Nigral Inputs Spatial Neglect
Pallidal and Nigral Outputs Complementarity of Basal Ganglia and
Subthalamic Nucleus Cerebellum in Motor Function
Ventral (Limbic) Striatum Blood Supply
KEY CONCEPTS
The terms corpus striatum, striatum, dorsal striatum, Corticostriatothalamocortical connections are organized
neostriatum, ventral striatum, pallidum, paleostriatum, into five parallel and segregated loops and/or three split
and lentiform nucleus refer to well-defined components circuits.
of the basal ganglia as summarized in Table 13–1.
The role of the basal ganglia in motor control includes
The striatum receive inputs from the cerebral cortex (major the preparation for and execution of cortically initiated
source) and subcortical structures (substantia nigra com- movement.
pacta, thalamus, raphe nuclei, locus ceruleus, and exter-
The basal ganglia subserve roles in cognitive function,
nal segment of globus pallidus).
emotion, and motivation.
The striatum projects to the output nuclei (globus pallidus
Blood supply of the basal ganglia is derived from lenticu-
internus and substantia nigra reticulata) via two path-
lostriate branches of the middle and anterior cerebral
ways; direct and indirect.
arteries and the anterior choroidal branch of the internal
The striatum is the principal receptive structure and the carotid artery.
globus pallidus is the principal output structure of the
basal ganglia.
Lesions of subthalamic nucleus result in ballism,and stim-
ulation relieves the symptoms of Parkinsonism.
The neural control of movement is the product of interactions such as occurs in stroke, lesions in the basal ganglia or cerebel-
within and among a number of cortical and subcortical neural lum result in incoordinated and disorganized movement, such as
structures (Figure 13–1). Among the various subcortical struc- occurs in Parkinsonism and Huntington’s chorea. Recent experi-
tures, three are of particular significance. They are the basal gan- mental studies and clinical observations have focused on a new
glia, cerebellum, and the dopaminergic mesencephalic system. role for the basal ganglia in nonmotor functions, including cog-
Whereas lesions in the motor cortex result in loss of movement, nition and behavior.
180
THE BASAL GANGLIA / 181
CEREBRAL
CORTEX
2 6 1 6 3
THALAMUS
CEREBELLUM BASAL GANGLIA
4 1 5
7 7
DOPAMINERGIC DOPAMINERGIC
SYSTEM SYSTEM
SPINAL
CORD
Figure 13–1. Simplified schematic diagram of major cortical and subcortical neural structures in-
volved in movement: 1, corticospinal tract; 2, cerebrocerebellar pathways; 3, corticostriate pathways;
4, dentatothalamic pathways; 5, striatothalamic pathways; 6, thalamocortical pathways; and 7, dopamin-
ergic pathways.
DEFINITIONS AND NOMENCLATURE NEURONAL POPULATION, SYNAPTIC

The basal ganglia are a group of interconnected nuclei involved in RELATIONS, AND INTERNAL ORGANIZATION
motor and nonmotor functions. Anatomically, the term refers to Neostriatum (Striatum)
the following nuclei: caudate, putamen, globus pallidus, nucleus
accumbens septi, and olfactory tubercle, all of which are topo- The terms neostriatum and striatum refer to the caudate nu-
graphically located in the “basement” of the brain (Figure 13–2). cleus and putamen. Both nuclei are of telencephalic origin.
Functionally, the substantia nigra and subthalamic nucleus are in- During ontogenesis, the caudate nucleus follows the curvature
cluded within the basal ganglia. The anatomic network of basal of the telencephalic vesicle and thus becomes a C-shaped struc-
ganglia was not outlined with precision until the 20th century. ture with an expanded rostral extremity, the head, which tapers
Galen used the term “buttocks” to refer to cellular masses (cau- down in size to form a body and a tail. The head of the caudate
date nuclei) protruding into the lateral ventricles. Prior to 1786, nucleus bears a characteristic relationship to the anterior horn
the basal ganglia were lumped with the thalamus in the “striated of the lateral ventricle (Figure 13–2). This part of the caudate
body”. A major step in its definition was made when the thalamus characteristically bulges into the lateral ventricle. In degenera-
was separated from the striated body by the French anatomist tive central nervous diseases involving the caudate nucleus,
Felix Vicq d’Azir in 1786. The term basal ganglia was first intro- such as Huntington’s chorea, described by the American gen-
duced in the English language by Ferrier in 1876. The distinction eral practitioner George Huntington in 1872, the characteristic
between striatum and pallidum was made at the beginning of the bulge of the caudate nucleus into the lateral ventricle is lost.
20th century, and the importance of the corticostriatal connec- While the head and body of the caudate nucleus maintain a re-
tions were recognized in the late 1960s. As revealed by magnetic lationship to the lateral wall of the anterior horn and body of
resonance imaging (MRI), basal ganglia volume is significantly the lateral ventricle, respectively, the tail of the caudate occu-
larger on the right side, irrespective of handedness and gender. pies a position in the roof of the inferior horn of the lateral
The term corpus striatum refers to the caudate, putamen, and ventricle (Figure 13–3). The tail of the caudate is very small in
globus pallidus. The terms striatum, dorsal striatum, and neostria- humans.
tum refer to the caudate and putamen. The terms pal- The putamen is located lateral to the globus pallidus and
lidum and paleostriatum refer to globus pallidus. The puta- medial to the external capsule (Figure 13–2). It is separated
men and globus pallidus together compose the lentiform from the caudate nucleus by the internal capsule, except ros-
nucleus. The term ventral striatum refers to the ventral parts of trally, where the head of the caudate and the putamen are con-
caudate and putamen, the nucleus accumbens septi, and the stri- tinuous around the anterior limb of the internal capsule (Figure
atal part of the olfactory tubercle (Table 13–1). The term extra- 13– 4).
pyramidal system, coined in 1912 by British neurologist Kinnier Neostriatal neurons are of two types: aspiny and spiny. Aspiny
Wilson, refers to the basal ganglia and an array of brain stem nu- neurons (4 percent) are intrinsic neurons (interneurons). They
clei (red nucleus, subthalamic nucleus, substantia nigra, reticular are divided into four types: large cholinergic, small GABAergic
formation) to which they are connected. This conglomerate of and parvalbumin-containing (largest population), somatostatin
neural structures plays an important role in motor control. and neuropeptide Y–containing, and calretinin immunoreactive
182 / CHAPTER 13
Internal capsule Internal pallidal lamina

A
Thalamus
Caudate
Nucleus
External
pallidal lamina
Putamen
Cerebellum
Globus Pallidus
Caudate
Internal nucleus
capsule (head)
Putamen
Globus
External pallidus
capsule
Nucleus
accumbens
septi
Figure 13–2. Parasagittal A and coronal B sections of the brain showing the anatomic components of the basal ganglia.
neurons. In addition, immunocytochemical studies demonstrate Spiny neurons, the neostriatal projection (principal) neu-
the presence of intrinsic dopaminergic interneurons in the stria- rons, constitute the great majority (96 percent) of neostriatal
tum. They are few in number in the normal striatum but in- neurons. They contain GABA, taurine, and a number of neu-
crease in number when the dopaminergic input to the striatum ropeptides, including substance P, enkephalin, neurotensin,
is interrupted, as in Parkinson’s disease. dynorphin, and cholecystokinin. Spiny neurons are silent at rest
Table 13–1. Basal Ganglia Nomenclature
Corpus striatum Striatum, dorsal striatum, Ventral striatum Pallidum, Lentiform nucleus
neostriatum paleostriatum
Caudate
Putamen
Globus pallidus
Nucleus accumbens
Olfactory tubercle
and discharge when stimulated by cortical or other inputs. and exert feedback control on dopaminergic transmission. In
Spiny projection neurons and the large cholinergic aspiny in- Parkinson’s disease, D1 receptors are reduced, while D2 receptors
terneurons are lost in Huntington’s chorea. are significantly increased. Colocalization of D1 and D2 recep-
Molecular biology techniques have identified at least six dopa- tors has been reported in virtually all striatal neurons.
mine receptor isoforms grouped into two subfamilies (D1-like Axons from the cerebral cortex terminate on distal spines of
and D2-like). D1 and D2 receptors are found in the striatum. D2 projection neurons. Axons from substantia nigra, thalamus, and
receptors mediate the antipsychotic effects of neuroleptic drugs intrastriatal sites (interneurons and other spiny neurons) termi-
Lateral Caudate
ventricle nucleus
(anterior (head)
horn)
Putamen
Caudate
nucleus
(tail)
Lateral
ventricle
(inferior,
temporal
horn)
Figure 13–3. Axial section of the brain showing the head and tail of the caudate nucleus, and their relationships to the ante-
rior and inferior (temporal) horns of the lateral ventricle.
184 / CHAPTER 13
Internal capsule Caudate

(anterior nucleus
limb) (head)
External Putamen
capsule
Figure 13–4. Coronal section of the brain showing continuity of the putamen with the head of the caudate around the
anterior limb of the internal capsule.
nate on dendritic shafts and cell bodies of projection neurons for acetylcholine esterase and is interspersed between strongly
(Figure 13–5). This pattern of termination allows cortical input staining areas, the matrix compartment. Besides differences in
to be modulated or inhibited by the other inputs to the projec- acetylcholine esterase reactivity, the two compartments differ in
tion neurons. their input, output, neurotransmitters, neuromodulators, sources
The adult neostriatum is made up of two compartments: The of dopaminergic input, and distribution of dopaminergic recep-
patches (striosomes) compartment contains cells that stain weakly tor subtypes (Table 13–2).
Local input External input
Cholinergic
interneurons Sp
D
Medium spiny Cerebral

neurons cortex
Substantia Figure 13–5. Schematic diagram of striatal medium

S nigra spiny projection neuron showing the different patterns
of termination of cortical, nigral, thalamic, and intrastri-
atal neurons on dendrites and soma. S, soma; D, dendrite;
Sp, dendritic spine. (Modified from Trends in Neurosci-
Thalamus ence 13:259–265, 1990, figure 3, with permission
from Elsevier Science Ltd.)
Table 13–2. Characteristics of Striosome and Matrix Compartments
Striosomes Matrix
Acetylcholinesterase staining Light Heavy

Cell development Early Late
Input Medial frontal cortex, limbic cortex, substantia Sensorimotor cortex, supplementary motor cortex,
nigra pars compacta, ventral substantia association cortex, limbic cortex, intralaminar
nigra pars reticulata thalamic nuclei, ventral tegmental area, dorsal
substantia nigra pars compacta
Output Substantia nigra pars compacta Substantia nigra pars reticulata, globus pallidus
Neurotransmitter GABA GABA
Neuromodulators Neurotensin, dynorphin, substance P Somatostatin, enkephalin, substance P
Dopamine receptor D1 D2
NOTE: GABA, gamma-aminobutyric acid.
Globus Pallidus and Substantia ganized into three distinct striatal territories: (1) sensorimotor
Nigra Pars Reticulata (post-commissural putamen), (2) associative (caudate and pre-
commissured putamen), and (3) limbic (nucleus accumbens).
The globus pallidus is a wedge-shaped nuclear mass located be- The sensorimotor territory receives its inputs from sensory and
tween the putamen and internal capsule. A lamina of fibers (ex- motor cortical areas. The associative territory receives fibers from
ternal pallidal lamina) separates the globus pallidus from the the association cortices. The limbic territory receives input from
putamen. Another lamina (internal pallidal lamina) divides the limbic and paralimbic cortical areas. The cingulate cortex pro-
globus pallidus into a larger lateral (outer) and a smaller medial jects to both the sensorimotor and limbic striatum. It thus serves
(inner) segment (Figure 13–2A). The entopeduncular nucleus of to modulate motor responses based on limbic information.
nonprimate mammals is part of the medial pallidal segment in Corticostriate pathways are also somatotopically organized
primate mammals. such that cortical association areas project to the caudate nu-
The substantia nigra pars reticulata occupies the ventral zone cleus, whereas sensorimotor cortical areas preferentially project
of the substantia nigra and contains iron compounds. to the putamen. Corticoputamenal projections are further orga-
Morphologically and chemically, the globus pallidus and the nized in that the cortical arm, leg, and face areas project to corre-
substantia nigra pars reticulata are similar. The latter is consid- sponding areas within the putamen. The somatotopic organiza-
ered the part of the globus pallidus containing head and neck tion of corticostriate projection is replicated throughout the
representation, whereas the internal segment of globus pallidus basal ganglia. The excitatory neurotransmitter of corticostriate
has arm and leg representation. projections is glutamate.
Most neurons in the globus pallidus and substantia nigra pars
reticulata are large multipolar projection neurons. Interneurons B. MESENCEPHALOSTRIATE PROJECTIONS
are infrequent. All pallidal and nigral neurons use GABA as the The principal mesencephalostriate projection originates from
inhibitory neurotransmitter. Pallidal and nigral neurons are dopamine-containing cells of the substantia nigra pars com-
about 100 times less numerous than spiny striatal neurons, thus pacta. Dopamine has a net excitatory effect on D1 striatal neu-
providing convergence of input from the striatum to the pal- rons that project to the internal segment of globus pallidus and
lidum. About 90 percent of the input to pallidal and nigral neu- substantia nigra pars reticulata and a net inhibitory effect on D2
rons originates from the striatum. striatal neurons that project to the external segment of globus
pallidus (Figure 13–7). Collaterals from nigrostriate projections
Subthalamic Nucleus have recently been traced to globus pallidus and subthalamic
Subthalamic nucleus neurons are cytologically homogenous, use
glutamate as their neurotransmitter, have only few spines, and
are intermediate in their dendritic arborization between those of
striatal and pallidal neurons. CEREBRAL CORTEX
Neostriatal Input 2
3 1
A. CORTICOSTRIATE PROJECTIONS THALAMUS
Projections from the cerebral cortex to the striatum are both direct 4
and indirect. Direct corticostriate projections reach the neostria-
tum via the internal and external capsules and via the subcallosal STRIATUM
fasciculus. The indirect pathways include the corticothalamostri-
ate pathway, collaterals of the cortico-olivary pathway, and collat- PONS
erals of the corticopontine pathway (Figure 13–6).
The corticostriate projection comprises the most massive stri-
atal afferents. Almost all cortical areas contribute to this OLIVE
projection. Cortical areas interconnected via corticocor-
tical fibers tend to share common zones of termination Figure 13–6. Schematic diagram of the direct (1) and indirect
in the neostriatum. Corticostriatal fibers are topographically or- (2, 3, 4) corticostriate projections.
186 / CHAPTER 13
Striatum ternal segment of globus pallidus. Figure 13–8 is a schema of the

SNr major inputs to the neostriatum. The main target of striatal af-
DA + GABA −
D1 GPi ferents is the GABAergic medium-size spiny projection neuron.
Substantia
Although less massively innervated, the aspiny interneurons also
Nigra Pars
DA − GABA − receive direct cortical, thalamic, and nigral inputs.
Compacta D2 GPe
Neostriatal Output
Figure 13–7. Schematic diagram of nigrostriatal pathway
The neostriatum projects to the substantia nigra pars reticulata,
showing the facilitatory action () of dopamine on striatal neu-
both segments of the globus pallidus, and the ventral pallidum.
rons that project to substantia nigra pars reticulata and internal
There is also a small projection from the neostriatum to the sub-
segment of globus pallidus, and the inhibitory action () of stantia nigra pars compacta.
dopamine on striatal neurons that project to the external seg- The neostriatal projections to the different target areas, al-
ment of globus pallidus. D1, dopamine 1 class receptor neuron; though containing one neurotransmitter (GABA), have different
D2, dopamine 2 class receptor neuron; DA, dopamine; GABA, neuropeptides (Table 13–3).
gamma-aminobutyric acid; GPe, external segment of globus pal- The striatal output to the globus pallidus and the
lidus; GPi, internal segment of globus pallidus; SNr, substantia substantia nigra pars reticulata is organized into direct
nigra pars reticulata. (Modified from J Child Neurol 9:249–260, and indirect projections (Figure 13–9). The direct pro-
1994, figure 1, with permission from Decker Periodicals.) jection is from the neostriatum to the internal segment of the
globus pallidus and the substantia nigra pars reticulata (output nu-
clei). The indirect projection is from the neostriatum to the exter-
nal segment of the globus pallidus and via the subthalamic nu-
nucleus. These collaterals provide the anatomic basis for nigral cleus to the internal segment of the globus pallidus and the
dopaminergic neurons to directly affect the pallidum and sub- substantia nigra pars reticulata. The two pathways have opposing
thalamic nucleus. effects on the output nuclei and their thalamic targets. Activa-
In addition to the substantia nigra, the following mesen- tion of the direct pathway leads to a net disinhibitory (facilita-
cephalic dopaminergic nuclear groups project to the striatum: tory) effect on the thalamus and an increase in motor behavior.
the ventral tegmental area of Tasi (area A-10) and the retrorubral Activation of the indirect pathway leads to increased inhibition of
nucleus (substantia nigra pars dorsalis, area A-8). the thalamus and decreased motor activity. Enhanced activity of
the indirect pathway may be responsible for the poverty of move-
C. THALAMOSTRIATE PROJECTIONS ment (hypokinesia) of some basal ganglia disorders (Parkinson’s
Thalamostriate projections are the second most prominent affer- disease), whereas reduced activity in the direct pathway may result
ents to the striatum. The centromedian nucleus projects mainly in excessive activity (hyperkinesia) of some basal ganglia disorders
to the sensorimotor striatal territory, while the parafascicular nu- (Huntington’s chorea).
cleus projects to the associative and limbic striatal territories. The concept of separate direct and indirect pathways has
Other thalamic sources of input to the striatum include ventral been challenged by the following recent findings: (1) direct pro-
anterior, ventral lateral, and posterior thalamic nuclei. Thala- jections from the external pallidal segment to the output nuclei
mostriate projections from ventral anterior and ventral lateral and to the striatum, (2) subthalamic nucleus projections to the
nuclei overlap extensively with corticostriate projections from striatum, external pallidal segment, and substantia nigra pars
frontal motor cortical areas. Thalamostriate fibers are believed to compacta, (3) abundant collateralization of striatal axons termi-
be excitatory. The neurotransmitter is glutamate. nating in several target nuclei, and (4) interconnection of striatal
neurons giving rise to the direct and indirect pathways and the
D. OTHER PROJECTIONS convergence of both pathways at single output neurons. The in-
Other projections to the neostriatum include those from the raphe direct pathway is functionally immature in childhood, whereas
nuclei (serotonergic), the locus ceruleus (noradrenergic), and ex- the direct pathway is functionally mature in childhood.
CEREBRAL CORTEX
Sensorimotor Association Limbic
Glu Glu Glu
NEOSTRIATUM
Sensorimotor Association Limbic
Glu DA DA Glu Glu DA
THALAMUS THALAMUS
Centromedian, ventral Parafascicular nucleus
lateral, ventral medial,
posterior nuclei Figure 13–8. Schematic diagram of major sources of input to
MESENCEPHALON
the sensorimotor, association, and limbic zones of the neostria-
Dopaminergic system
tum. Glu, glutamine; DA, dopamine.
Table 13–3. Neurotransmitters and Neuromodulators GABA

Involved in Striatal Output Neostriatum Indirect
To GPi To Gpe To SNr To SNc GPe
GABA Direct GABA

Substance P GABA
Enkephalin −
− −
Dynorphin
Subthalamic
Neurotensin +
SNr GPi Nucleus
NOTE: Gpi, internal segment of globus pallidus; Gpe, external segment
of globus pallidus; SNr, substantia nigra pars reticulata; SNc, substan- Pallidum
tia nigra pars compacta; GABA, gamma-aminobutyric acid. + +
Glutamate
Figure 13–9. Schematic diagram of the direct and indirect

Pallidal and Nigral Inputs striatopallidal pathways. GABA, gamma-aminobutyric acid; GPe,
external segment of globus pallidus; GPi, internal segment of
A. STRIATOPALLIDAL AND STRIATONIGRAL PROJECTIONS globus pallidus; SNr, substantia nigra pars reticulata; , facilita-
The input to both segments of the globus pallidus is primarily tory pathway; , inhibitory pathway.
from the putamen and the subthalamic nucleus, whereas the in-
put to the substantia nigra pars reticulata is primarily from the
caudate and the subthalamic nucleus. The input from the neo-
striatum is GABAergic (inhibitory). The input from the subtha- to reach the target thalamic nuclei. The target thalamic nuclei
lamic nucleus is glutamatergic (excitatory). are the ventral anterior, ventral lateral, dorsomedial, and in-
tralaminar nuclei. The neurotransmitter is GABA. Pallidal out-
B. OTHER PROJECTIONS put thus inhibits the excitatory thalamocortical loop. The palli-
Other, less significant pallidal afferents include those from dopa- dothalamic and nigrothalamic projections constitute the link
minergic and serotonergic neurons of the brain stem. between the neostriatum and the cerebral cortex.
The intralaminar nuclei (centromedian and parafascicular)
Pallidal and Nigral Outputs (Figure 13–10) are crucial elements in the striatothalamocortical circuitry. The
centromedian nucleus forms a nodal point in sensorimotor, and
A. MAJOR OUTPUT the parafascicular nucleus an important relay in the associative-
The major output from the internal segment of the globus pal- limbic components of the circuit.
lidus and the substantia nigra pars reticulata (output B. MINOR OUTPUT
nuclei) is to the thalamus. Pallidothalamic fibers follow
one of two routes. Some traverse the internal capsule Minor outputs from the internal segment of the globus pallidus
and gather dorsal to the subthalamic nucleus as the lenticular and the substantia nigra pars reticulata go to the following areas.
fasciculus (H2 field of Forel, after the Swiss neuropsychiatrist 1. Nucleus Tegmenti Pedunculopontis. This projection serves
August Henri Forel, who described these bundles); others pass to link the basal ganglia with the spinal cord via the reticulo-
around the internal capsule (ansa lenticularis). Both groups of spinal tract. The projection to the nucleus tegmenti pedunculo-
fibers gather together to form the prerubral field (H field of pontis assumes particular significance because of the multiple
Forel) and then join the thalamic fasciculus (H1 field of Forel) connections and functions of this nucleus, the best known being
Cortex
Thalamus
Limbic System
Subthalamus
Major Output
Side Track
Output
GPe
Superior SNr GPi Habenular
Figure 13–10. Schematic diagram of the efferent con- Colliculus Nucleus
nections of internal segment of globus pallidus and sub- Minor
stantia nigra pars reticulata. GPe, external segment of Output N. Tegmenti
globus pallidus; GPi, internal segment of globus pallidus; Pedunculopontis
Reticular
SNr, substantia nigra pars reticulata. (From J Child Neurol Inferior Olive
Formation
9:249–260, 1994, figure 2, with permission from Decker
Spinal Cord
Periodicals.)
188 / CHAPTER 13
motor function (mesencephalic locomotor center), arousal, and Nigrosubthalamic Projection. This dopaminergic pathway
sleep. Others include motivation, attention, and learning. originates from the substantia nigra pars compacta and the
2. Habenular Nucleus. Via this connection, the basal ganglia are ventral tegmental area as collateral branches from the nigro-
linked with the limbic system. striatal pathway.
3. Superior Colliculus. Through this pathway, the basal gan- Reticulosubthalamic Projection. The dorsal nucleus of the
glia are linked (via the tectospinal tract) to the spinal cord and raphe is the main source of this serotonergic projection.
(via the tectoreticular tract) to brain stem nuclei related to head The major outflow from the subthalamic nucleus is to both
and eye movements. segments of globus pallidus and to the substantia nigra pars
reticulata. Subthalamic nucleus lesions or lesions interrupting
C. SIDE TRACK OUTPUT the subthalamic–pallidal connection are responsible for
This output reciprocally relates the external segment of the globus the violent hyperkinesia of ballism. The subthalamic nu-
pallidus with the subthalamic nucleus. The neurotransmitter is cleus has been a favorable site for deep brain stimulation
GABA. in treatment of Parkinson’s disease. Information flow through
The inputs and outputs of the basal ganglia are schematically the striatum and the subthalamic nucleus is different. Cortical
summarized in Figure 13–11. input to the subthalamic nucleus is from the frontal lobe,
The basal ganglia and its related neural systems may be viewed whereas the striatum receives from virtually all cortical areas. The
as composed of (1) a core and (2) regulators of the core. The core output from the striatum is GABAergic (inhibitory) and slow,
is composed of the striatum and its pallidal and nigral targets. The whereas subthalamic nucleus output is glutamatergic (excitatory)
regulators of the core fall into two categories: (1) regulators of the and fast. Subthalamic projection to the output nuclei interacts
striatum and (2) pallidonigral regulators (Figure 13–12). with many output neurons, whereas striatal projection is focused
on a single neuron. The pathway through the subthalamic nu-
cleus thus provides a fast, divergent excitation, whereas the path-
Subthalamic Nucleus (Figure 13–13) way through the striatum provides focused inhibition of the out-
Like the striatum, the subthalamic nucleus is divided into senso- put nuclei. These two pathways provide the anatomic basis for
rimotor, associative, and limbic territories. It receives inputs from the model of focused inhibition and surround excitation of out-
the following sources: put nuclei.
Corticosubthalamic Projection. Although the striatum is
the main site of cortical input, the subthalamic nucleus re- Ventral (Limbic) Striatum
ceives excitatory glutamatergic projections primarily from the Currently, the term ventral striatum refers to the following nu-
primary motor area, with minor contributions from pre- clei: nucleus accumbens septi, striate-like deep portions of the
frontal, premotor, and supplementary motor cortices. They olfactory tubercle and ventral parts of the caudate nucleus, and
are somatotopically and topographically organized, similar to the putamen (Table 13–1). The ventral striatum receives fibers
the corticostriate projections. from the following sources: hippocampus, amygdala, entorhinal
Pallidosubthalamic Projection. A massive GABAergic pro- and perirhinal cortices (areas 28 and 35), anterior cingulate
jection from the external segment of globus pallidus to the subcortex (area 24), medial orbitofrontal cortex, and widespread
thalamic nucleus plays an important role in the indirect path- sources within the temporal lobe. Dopaminergic input to the
way that links input and output nuclei of the basal ganglia. ventral striatum is substantial. The output from the ventral stria-
Thalamosubthalamic Projection. Centromedian and parafas- tum is to the ventral pallidum. As is evident from its connec-
cicular nuclei comprise the major sources of this projection. tions, the ventral striatum is related to the limbic system. The
Cerebral cortex
+
Figure 13–11. Simplified schematic
+ Mesencephalic
Thalamus DA
dopaminergic system
summary diagram of afferent and effer-
NA Striatum
Ser
ent connections of the basal ganglia
Locus ceruleus showing that the striatum is the major
Raphe nuclei
receiving area, whereas the internal seg-
+
GPe ment of globus pallidus and substantia
+ − nigra pars reticulata constitute the major
− − −
Superior colliculus output nuclei. , facilitation; , inhibi-
SNr + GPi Subthalamic N. + tion; DA, dopamine; Ser, serotonin; NA,
+ noradrenaline; GPe, external segment of
Pallidum
Pedunculopontine N. globus pallidus; GPi, internal segment of
− − Habenula
globus pallidus; SNr, substantia nigra
− − − − pars reticulata; VA, ventral anterior nu-
− Pedunculopontine N.
VA VL VA cleus; VL, ventrolateral nucleus; CM, cen-
Prefrontal Thalamus
tromedian nucleus; DM, dorsomedial nu-
limbic DM CM Motor cleus. (Modified from J Child Neurol
cortex + + Premotor 9:249–260, 1994, figure 3, with per-
Cortex
mission from Decker Periodicals.)
CORTEX
Input
REGULATORS REGULATORS
CORE
Dopaminergic System
Centromedian Nucleus Striatum
Parafascicular Nucleus
Pallidonigral Subthalamic Nucleus

Targets Lateral Globus Pallidus
Figure 13–12. Schematic diagram showing the or-

ganization of the basal ganglia–associated neural sys- THALAMUS
tem into a core made up of the striatum and its palli-
donigral targets, and regulators acting either on the
striatum or pallidonigral components of the core. Output
ventral striatum has been the focus of various studies suggesting ventral), and thalamus before returning to the major cortical
that the nucleus accumbens septi plays a prominent role in me- area(s) from which each circuit originated. According to this
diating reward and motivation, with potential involvement in model, cortical areas that are targets of output from a channel are
drug addiction and mental disorders such as schizophrenia and the cortical areas from which the major input to the channel
Tourette syndrome. originated. Injury to a circuit results in selective disturbance in
motor, cognitive, or emotional behavior.
Corticostriatothalamocortical Loops
Corticostriatothalamocortical connections are organized in five A. MOTOR LOOP PATHWAY
parallel and largely segregated loops (circuits): motor, oculomotor, The motor loop pathway is centered on the putamen and its
dorsolateral prefrontal, lateral orbitofrontal, and limbic (Figure connections (Figure 13–14A). The putamen of primates receives
13–14). Their names reflect the major cortical area(s) of somatotopically organized (arm, leg, face) inputs from the pri-
origin and/or function of each. Information flow in each mary motor, primary sensory, somatosensory association, pre-
circuit passes from its cortical area of origin to the stria- motor, and supplementary motor cortices. Within each of these
tum (caudate, putamen, or ventral striatum), pallidum (dorsal or anatomic subchannels, further levels of functional organization
CORTEX
Frontal Lobe
Glu
GLOBUS PALLIDUS
THALAMUS GABA
Centromedian and Glu SUBTHALAMIC External
parafascicular NUCLEUS Glu
nuclei Internal
Glu
DA
Ser
Glu
SUBSTANTIA
NIGRA DORSAL NUCLEUS
OF RAPHE
Compacta
Reticulata
Figure 13–13. Schematic diagram of the input and output of the subthalamic nucleus. Glu, gluta-
matergic pathway; DA, dopaminergic pathway; Ser, serotonergic pathway; GABA, GABAergic pathway.
190 / CHAPTER 13
Cerebral Cortex Cerebral Cortex

MC, SC, SSA, PM, SMA FEF, SEF, DLPC, PPC
Putamen Caudate Nucleus
GPi, SNr STh GPe SNr GPi STh GPe
Pedunculopontine
Nucleus SC
Thalamus Thalamus
VLo, VA(pc, mc), CM VA(pc, mc), DMpm
A B
Cerebral Cortex
Cerebral Cortex LOFC
DLPC, PPC
Caudate Nucleus
Caudate Nucleus
GPi, SNr STh GPe

GPi, SNr STh GPe
Thalamus
Thalamus VAmc, DMmc
VApc, DMpc
C D
Cerebral Cortex
ACC, MOFC
Ventral Striatum
Ventral Pallidum
DMmc
Figure 13–14. Schematic diagrams showing the anatomic substrates of the motor loop A,
oculomotor loop B, dorsolateral prefrontal loop C, lateral orbitofrontal loop D, and the limbic
loop E. MC, primary motor cortex (area 4); SC, primary sensory cortex (areas 3, 1, and 2); SSA, so-
matosensory association cortex (area 5); PM, premotor cortex; SMA, supplementary motor area;
GPi, internal segment of globus pallidus; SNr, substantia nigra pars reticulata; STh, subthalamic
nucleus; GPe, external segment of globus pallidus; VLo, ventrolateral nucleus of thalamus, pars
oralis; VApc, ventral anterior nucleus of thalamus, pars parvicellularis; VAmc, ventral anterior nu-
cleus of thalamus, pars magnocellularis; CM, centromedian nucleus of thalamus; FEF, frontal eye
field (area 8); SEF, supplementary eye field; DLPC, dorsolateral prefrontal cortex (areas 9 and 10);
PPC, posterior parietal cortex; DMpm, dorsomedial nucleus of thalamus, pars multiformis; SC,
superior colliculus; LOFC, lateral orbitofrontal cortex; DMmc, dorsomedial nucleus of thalamus,
pars magnocellularis; ACC, anterior cingulate cortex; MOFC, medial orbitofrontal cortex. (From
J Child Neurology 9:352–361, 1994, figures 2 to 6, with permission from Decker Periodicals.)
exist pertaining to such behavioral variables as target location, by thalamocortical projections to the supplementary motor, pre-
limb kinematics, and muscle pattern. The putamen projects to motor, and primary motor cortices.
both segments of the globus pallidus and to the substantia nigra An offshoot from the pallidothalamic component of the mo-
pars reticulata. The internal pallidal segment projects to ventral tor loop is a projection from the internal segment of the globus
lateral, ventral anterior, and centromedian nuclei of the thala- pallidus to the pedunculopontine nucleus.
mus, whereas the substantia nigra pars reticulata projects to the A side loop in this motor pathway passes from the putamen
ventral anterior thalamic nucleus. The motor loop is completed to the external segment of the globus pallidus and from there to
the subthalamic nucleus and back to the internal segment of the Cerebral cortex
globus pallidus.
B. OCULOMOTOR LOOP PATHWAY GI
The oculomotor loop pathway (Figure 13–14B) is centered on +

the caudate nucleus. Cortical sources of input to the caudate nu- Striatum
cleus include the frontal eye field, supplementary eye field, dor-
solateral prefrontal cortex, and posterior parietal cortex. The GABA
caudate, in turn, projects to the internal segment of the globus −
Substance P
pallidus and the substantia nigra pars reticulata. The thalamic
GPi, SNR
targets of the oculomotor loop include the ventral anterior and
dorsomedial nuclei. The oculomotor loop is completed by tha-
lamocortical projections to frontal eye field and supplementary GABA
eye field. −
C. DORSOLATERAL PREFRONTAL LOOP PATHWAY Thalamus
The dorsolateral prefrontal loop pathway (Figure 13–14C) is Figure 13–15. Schematic diagram showing the anatomic sub-
also centered on the caudate nucleus. Corticostriate input to this strates of the direct striatopallidal pathway. Gl, glutamate; GABA,
pathway originates from the dorsolateral prefrontal cortex and gamma-aminobutyric acid; GPi, internal segment of globus pal-
posterior parietal cortex. The caudate nucleus projects to the in- lidus; SNR, substantia nigra pars reticulata; , facilitation; , inhi-
ternal segment of the globus pallidus and the substantia nigra bition. (Modified from J Child Neurol 9:352–361, 1994, figure 7,
pars reticulata. The thalamic targets of this pathway are the ven-
with permission from Decker Periodicals.)
tral anterior and dorsomedial nuclei. The loop is completed by
thalamic projections to the dorsolateral prefrontal cortex.
D. LATERAL ORBITOFRONTAL PREFRONTAL LOOP PATHWAY bic. Within each of these circuits, there are both closed and open
loops (Figures 13–17). The novel feature of the open and closed
The lateral orbitofrontal prefrontal loop pathway (Figure 13– loops (split circuitry) model is that in each split circuit the en-
14D) is similarly centered on the caudate nucleus. The cortico- gaged striatal area can influence, via its open loop, a cortical field
striate projection originates from the lateral orbitofrontal cortex. that does not project to it. Thus, it allows for the coexistence of
The caudate nucleus projects to the internal segment of the different symptoms and signs (motor, cognitive, and emotional)
globus pallidus and the substantia nigra pars reticulata. The tha- as a result of a lesion in only one of the circuits. Interaction be-
lamic targets of this pathway are the dorsomedial and ventral an- tween split circuits can occur at two levels, the cerebral cortex and
terior nuclei. The loop is completed by thalamic projections to the substantia nigra.
the lateral orbitofrontal cortex.
E. LIMBIC LOOP PATHWAY BASAL GANGLIA FUNCTION
The limbic loop pathway (Figure 13–14E) is centered on the
ventral striatum. Corticostriate projections originate from the The basal ganglia have long been considered central in the con-
anterior cingulate cortex, medial orbitofrontal cortex, and wide- trol of movement. It is now widely accepted that they also play a
spread areas in the temporal lobe. The ventral striatum projects role in nonmotor behavior, including cognition and emotion.
to ventral pallidum. The thalamic target of this pathway is the
dorsomedial nucleus. The loop is completed by thalamic projec- Motor Function
tions to anterior cingulate and medial orbitofrontal cortices. A
role for the limbic circuit in the genesis of schizophrenia has The basal ganglia play a role in the automatic execution of learned
been proposed. motor plan and in the preparation for movement. Studies that
Each of the five circuits has a direct and an indirect pathway
from the striatum to the output nuclei (internal segment of the
+
globus pallidus and substantia nigra pars reticulata). The direct Cerebral cortex
pathway contains GABA and substance P and directly connects GI
the striatum with the output nuclei (Figure 13–15). The indirect +
pathway (Figure 13–16) connects the striatum with the output Striatum
nuclei via relays in the external segment of globus pallidus and Thalamus GABA
+ − ENK
the subthalamic nucleus. Activation of the direct pathway tends
GPe
to disinhibit thalamocortical target neurons. Activation of the
indirect system has a net effect of increasing the inhibition of − GABA
GPi + GI
thalamocortical target neurons. SNr STh
Figure 13–16. Schematic diagram showing the anatomic sub-

Split Pathways strates of the direct striatopallidal pathway. Gl, glutamate; GABA,
The preceding five circuits (loops) are characterized by parallel, gamma-aminobutyric acid; ENK, enkephalin; GPe, external seg-
segregated, and closed connections, in which little, if any, inter- ment of globus pallidus; GPi, internal segment of globus pallidus;
communication takes place. An alternate model has been pro- SNr, substantia nigra pars reticulata; STh, subthalamic nucleus; ,
posed that allows for cross-communication between circuits. In this facilitation; , inhibition. (Modified from J Child Neurol 9:352–
model, three circuits are proposed: motor, associative, and lim- 361, 1994, figure 8, with permission from Decker Periodicals.)
192 / CHAPTER 13
Cortex Motor Association Cerebral Cortex
1
Command
Striatum Motor 2 3 Thalamus

striatum SNc Striatum
Damping Information +
Updating Others
Pallidum GPi SNr 4

Transmission of
Integrated Information
Thalamus VA DM
GP 5
SNr
Closed loop Open loop
Figure 13–17. Schematic diagram of split motor circuit show- Figure 13–18. Schematic diagram of information flow in the
ing the closed loop and the open loop of the circuit. (Modified basal ganglia (1) Command from cortex initiates action in stria-
from Neuroscience 63:363–379, 1994, figure 3, with permis- tum. (2) Nigral input from SNc to striatum provides continuous
sion from Elsevier Science Ltd.) damping of static so that cortical command will be focused.
(3) Input from the thalamus and other sites updates and informs
striatum of activity in other systems. (4) Striatum has an integra-
time neuronal discharge in relation to onset of stimulus-triggered tor role and feeds its results to GP and SNr. (5) GP and SNr influ-
movement suggest that activity within the basal ganglia is initi- ence (facilitate or inhibit) activity of thalamus and other targets
ated at cortical levels. In the cortically initiated movement, infor- (superior colliculus, reticular formation, etc). SNc, substantia nigra
mation flow from the cortex to the basal ganglia (Figure 13–18) pars compacta; GP, globus pallidus; SNr substantia nigra pars
begins with a command from the cortex to the striatum that ini- reticulata. (Modified from J Child Neurol 9:352–361, 1994, fig-
tiates action of striatal neurons. The nigral input to the striatum ure 9 with permission from Decker Periodicals.)
provides a continuous damping effect so that cortical commands
will be focused. The input from the thalamus and other
sites informs and updates the striatum of the activity in
other systems concerned with movement. The striatum external sensory cues in Parkinson’s disease and the sensory trick
integrates and feeds information to the globus pallidus and the in dystonia support such a role. According to the gating hy-
substantia nigra pars reticulata. These in turn influence activity of pothesis, in normal subjects, dopamine (inhibitory) and cortical
the thalamus and other targets (i.e., superior colliculus, reticular sensorimotor (excitatory) inputs to the striatum are in physio-
formation). According to Marsden, the basal ganglia are respon- logic balance. The inhibitory output of the pallidum thus regu-
sible for the automatic execution of a learned motor plan. As a lates sensorimotor access. In Parkinson’s disease, the loss of
motor skill is learned, the basal ganglia take over the role of auto- dopamine (inhibitory) will allow cortical facilitation a free hand
matically executing the learned strategy. When basal ganglia are to stimulate the inhibitory basal ganglia output. This limits ac-
damaged, the individual must revert to a slower, less automatic, cess of sensory information to the motor system and decreases
and less accurate cortical mechanism for motor behavior. motor activity (hypokinesia). In Huntington’s chorea, loss of
Other roles for the basal ganglia in motor control include the basal ganglia neurons results in a decrease in inhibitory output of
preparation for movement. During both the preparation and the basal ganglia, with a resulting increase in access of sensory in-
execution of movement, separate populations of neurons within formation to the motor system and increased activity.
the motor loop discharge selectively in relation to either target
location in space, direction of limb movement, or muscle pat- Cognitive Function
tern. Similarly, in the oculomotor loop, populations of neurons
have been described that discharge in relation to visual fixation, In addition to their role in motor control, the basal ganglia sub-
saccadic eye movement, or passive visual stimuli. A subset of cau- serve cognitive function. Lesions of the dorsolateral prefrontal
date neurons has been shown to participate in the reward-based circuit (loop) result in cognitive deficits and deficits on
control of visual attention. tasks that require spatial memory. The basal ganglia play
The recognition that basal ganglia neurons respond to stimuli a role in retrieval of episodic and semantic information
colored by memory or significance indicates that this region of for explicit memory and in implicit tasks that require
the brain is concerned with higher-order motor control. A role the initiation or modification of central motor programs.
for the basal ganglia in Tourette syndrome, a chronic tic disorder Lesions in the dorsolateral prefrontal circuit in humans
described by the French neuropsychiatrist George Gilles de la have been linked to cognitive disturbances in schizophrenia,
Tourette in 1885, has been proposed. A hypothetical model for Huntington’s chorea, and Parkinson’s disease. Lesions in the lat-
basal ganglia reorganization in tic disorders and Tourette syn- eral orbitofrontal circuit have been linked to obsessive-compul-
drome has also been proposed. sive behavior.
Gating Function Emotion and Motivation Function

Several lines of evidence support a role of the basal ganglia in The limbic loop plays a role in emotional and motivational
gating of sensory information for motor control. The benefit of processes. A role for the limbic loop in schizophrenia and depres-
INPUT OUTPUT
CEREBRAL CORTEX
PERIPHERY Unmodified Information Repository
Information Computation
Cortico-
n
Inf mplex
atio
spinal
orm
Tract
Co
BASAL GANGLIA
Context Encoders
CEREBELLUM
Pattern Generator
Figure 13–19. Simplified schematic diagram showing Executor
varied types of information received by the cerebral cor-
tex, and the complementarity of basal ganglia and cere- SPINAL CORD
bellar roles in motor function.
sion has also been proposed. Decrease in size of the basal ganglia and gating of action. The cerebellum, in contrast, functions as
has been reported in bipolar disorders. pattern generator and executor. According to this concept, the
cerebral cortex, which receives diverse sensory information from
Spatial Neglect the periphery via the different ascending tracts, as well as com-
plex information already processed within the basal ganglia and
Various studies have implicated the putamen (and to a lesser cerebellum, serves two functions: a repository function to receive
extent, the caudate) in spatial neglect with right-sided basal gan- this diverse information, compute it, and share it with the basal
glia lesions. Both nuclei are directly connected with the superior ganglia and cerebellum and an executive function to implement
temporal gyrus, which plays a central role in spatial neglect. the action emanating from its collective computation process.
COMPLEMENTARITY OF BASAL GANGLIA BLOOD SUPPLY (Table 13–4)

AND CEREBELLUM IN MOTOR FUNCTION
The basal ganglia receive their blood supply from perforating
Review of basal ganglia and cerebellar structure, connectivity, and (lenticulostriate) branches of the middle and anterior cerebral ar-
organization reveals many features in common. Both are compo- teries and the anterior choroidal branch of the internal carotid
nents of the motor system, both influence cerebral cortical activ- artery. The caudate and putamen nuclei (the striatum) are sup-
ity via the thalamus, both are linked with the cerebral cortex via plied mainly by the lateral striate branches of the middle
recurrent loops, both have internal (local) circuitry that modulates cerebral artery. Rostromedial parts of the head of the
loop activity, and both receive modulating inputs that influence caudate nucleus receive blood supply from the medial
their activities (climbing fibers in the cerebellum and dopaminer- striate artery (of Huebner), a branch of the anterior cerebral
gic input in the basal ganglia). artery. The tail of the caudate nucleus and caudal part of the
The emerging concept (Figure 13–19) of the complementar- putamen receive branches of the anterior choroidal artery. Most
ity of basal ganglia and cerebellum in motor function suggests of the globus pallidus is supplied by the anterior choroidal
that the basal ganglia function as context encoders, providing to branch of the internal carotid artery. The lateral (outer) segment
the cerebral cortex information that could be useful in planning of the globus pallidus receives blood supply also from the lateral
striate branch of the middle cerebral artery.
Table 13–4. Blood Supply of Basal Ganglia TERMINOLOGY

Middle Anterior Internal Ballism (Greek ballismos, “jumping”). Violent involuntary
cerebral, cerebral, carotid, movement due to a lesion in the subthalamic nucleus.
lateral striate medial striate anterior Caudate nucleus (Latin, “having a tail”). The caudate nucleus
branch branch choroidal is so named because it has a long extension or tail.
Caudate nucleus Chorea (Latin from Greek choros, “a dance”). Disorder of the
Head X X neostriatum causing irregular, involuntary movements of the
Body X limbs or face. Formerly called St. Vitus dance.
Tail X Corpus striatum (Latin corpus, “body”; striatus, “striped”).
Putamen Gray matter comprising caudate, putamen, and globus pallidus
Rostral X with striped appearance produced by myelinated fibers travers-
Caudal X ing the gray matter.
Globus pallidus Extrapyramidal system. Vague term introduced but not defined
Lateral X X by the British neurologist Kinnier Wilson. Currently used to re-
Medial X
fer to the basal ganglia and their connections.
194 / CHAPTER 13
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Pallidum (Latin pallidus, “pale”). The paler part of the basal Nauta HJW, Cole M: Efferent projections of the subthalamic nucleus: An
ganglia comprises the globus pallidus. autoradiographic study in monkey and cat. J Comp Neurol 1978;
180:1–16.
Putamen (Latin, “shell”). Lateral part of the lentiform nucleus.
O’Connor WT: Functional neuroanatomy of basal ganglia as studied by
Striatum (Latin striatus, “striped”). The caudate and puta- dual-probe microdialysis. Nucl Med Biol 1998; 25:743–746.
men, so named because of their striped appearance in sections. Parent A: Extrinsic connections of the basal ganglia. Trends Neurosci 1990;
Substantia nigra (Latin, “black substance”). Group of neu- 13:254–258.
rons between the cerebral peduncle and midbrain tegmentum. Penney JB, Young AB: GABA as the pallidothalamic neurotransmitter:
So named because of their melanin-containing neurons. Implications for basal ganglia function. Brain Res 1981; 207:195–199.
Vicq d’Azir, Felix (1748–1794). French physician to queen Prensa L et al: Dopaminergic innervation of human basal ganglia. J Chem
Neuroanat 2000; 20:207–213.
Marie Antoinette. Among his many contributions are his de-
Rolls E: Neurophysiology and cognitive functions of the striatum. Rev Neurol
scriptions of the insula (before Reil), the substantia nigra, and 1994; 150:648–660.
the mamillothalamic tract (tract of Vicq d’ Azir). Sadikot AF et al: The center median and parafascicular thalamic nuclei project
respectively to the sensorimotor and associative-limbic striatal territories
in the squirrel monkey. Brain Res 1990; 510:161–165.
SUGGESTED READINGS Schneider JS et al: Deficits in orofacial sensorimotor function in Parkinson’s
disease. Ann Neurol 1986; 19:275–282.
Afifi AK: Basal ganglia: Functional anatomy and physiology. Part I. J Child Segawa M: Development of the nigrostriatal dopamine neuron and the path-
Neurol 1994; 9:249–260. ways in the basal ganglia. Brain Dev 2000; 22(Suppl):S1–S4.
Afifi AK: Basal ganglia: Functional anatomy and physiology. Part II. J Child Selemon LD, Goldman-Rakic PS: Common cortical and subcortical targets of
Neurol 1994; 9:352–361. the dorsolateral prefrontal and posterior parietal cortices in the rhesus
Afifi AK, Uc EY: Cortical–subcortical circuitry for movement, cognition and monkey: Evidence for a distributed neural network subserving spatially
behavior. In CE Coffey, RA Brumback (eds): Textbook of Pediatric guided behavior. J Neurosci 1988; 8:4049–4068.
Neuropsychiatry. Washington, American Psychiatric Press, 1998:65–100. Selemon LD, Goldman-Rakic PS: Longitudinal topography and interdigita-
Albin RL et al: The functional anatomy of basal ganglia disorders. Trends tions of corticostriatal projections in the rhesus monkey. J Neurosci
Neurosci 1989; 12:366–375. 1985; 5:776–794.
Alexander GE et al: Basal ganglia–thalamocortical circuits: Parallel substrates Smith AD, Bolam JP: The neural network of the basal ganglia as revealed by
for motor, oculomotor, “prefrontal” and “limbic” functions. Prog Brain the study of synaptic connections of identified neurones. Trends Neurosci
Res 1990; 85:119–146. 1990; 13:259–265.
Butters N et al: Specificity of the memory deficits associated with basal ganglia Staines WA et al: Neurotransmitters contained in the efferents of the striatum.
dysfunction. Rev Neurol 1994; 150:580–587. Brain Res 1980; 194:391–402.
Carpenter MB et al: Connections of the subthalamic nucleus in the monkey. Steckler T et al: The pedunculopontine tegmental nucleus: A role in cognitive
Brain Res 1981; 224:1–29. processes? Brain Res Rev 1994; 19:298–318.
Cossette M, Levesque M, Parent A: Extrastriatal dopaminergic innervation of Stoetter B et al: Functional neuroanatomy of Tourette syndrome: Limbic-
human basal ganglia. Neurosci Res 1999; 34(Suppl):51–54. motor interactions studied with FDG PET. Adv Neurol 1992; 58:213–
Flaherty AW, Graybiel AM: Anatomy of basal ganglia. In Marsden CD, 226.
Fahn S (eds): Movement Disorders. Boston, Butterworth-Heinemann, Yelnik J: Functional anatomy of the basal ganglia. Movement Dis 2002; 17
1994:3–27. Suppl 3:S15–S21.
Basal Ganglia: Clinical Correlates 14
Hyperkinetic Disorders Tic Disorder

Chorea Tourette Syndrome
Athetosis Hypokinetic Disorders
Ballism Parkinsonism
Dystonia
KEY CONCEPTS
Movement disorders associated with basal ganglia lesions Tourette syndrome is a conglomerate of signs and symp-
are of two categories: hyper- and hypokinetic or akinetic. toms that includes motor and vocal tics and behavioral
abnormalities (attention, compulsiveness, etc.).
There are two varieties of chorea: benign reversible
Sydenham’s chorea and malignant progressive Hunting- Parkinson’s disease is characterized by tremor, rigidity, and
ton’s chorea. akinesia or hypokinesia.
Athetosis frequently accompanies chorea (choreoathetosis) Depletion of dopaminergic neurons in the substantia
and involves predominantly distal parts of extremities. nigra and, secondarily, dopamine stores in the striatum
are the pathologic landmarks of Parkinson’s disease.
Ballism, a violent flinging movement of extremities con-
tralateral to a lesion in the subthalamic nucleus.
Dystonia may be focal (writer’s cramp), regional (torticol-
lis), or generalized.
Diseases of the basal ganglia are associated with abnormal invol- taneous thought, and emotional response) has been described in
untary movements that typically occur at rest and disappear in association with discrete lesions in the caudate nucleus.
sleep. They are generally divided into two categories: hyper- The genetic basis of many movement disorders is being in-
kinetic, characterized by excessive involuntary movement and creasingly recognized. Familiarity with such disorders is impor-
hypokinetic, characterized by slow movement (bradyki- tant in making accurate diagnoses and in family counseling.
nesia) or absence or difficulty in initiating movement
(akinesia). The hyperkinetic variety is seen in such disor-
ders as chorea, athetosis, ballism, dystonia, tremor, and tics. The HYPERKINETIC DISORDERS
hypokinetic variety is seen largely in Parkinson’s disease. Despite Chorea
voluminous literature on basal ganglia, clinicoanatomic correla-
tions are not available for all basal ganglia disorders. However, Chorea is a disorder of movement characterized by sudden, fre-
the following anatomic loci for pathology are agreed on: sub- quent, involuntary, purposeless, and quick jerks of the trunk, ex-
stantia nigra in Parkinson’s disease, caudate nucleus in chorea, tremities, and head associated with facial grimaces. The term
and subthalamic nucleus in ballism. Discrete lesions in the cau- chorea is derived from the Greek word choreia, for “dance.” The
date nucleus are more likely to cause behavioral and cognitive lesion producing chorea is believed to be in the caudate nucleus
manifestations, whereas similar lesions in the putamen are more (Figure 14–1), although the pathology is often diffuse and mul-
likely to be associated with motor manifestations. These observa- tiple involving other neural structures.
tions are consistent with known anatomic connections of these At the cellular level, reduced levels of the following neuro-
nuclei. Abulia (a syndrome of apathy and loss of initiative, spon- transmitters and neuropeptides have been reported: gamma-
195
196 / CHAPTER 14
Figure 14–1. Coronal brain section

from a patient with Huntington’s
chorea showing atrophy of the cau-
date nucleus.
aminobutyric acid (GABA), acetylcholine, enkephalin, substance movements of the limbs in this disorder are sudden,
P, dynorphin, and cholecystokinin. Loss of noradrenergic neu- quick, continuous, unusually violent, and flinging in na-
rons in the locus ceruleus also has been reported. Two varieties of ture. The hyperkinesia is usually confined to one side of
chorea are known to occur. These are a benign, reversible variety the body (hemiballismus) contralateral to the lesion in the sub-
(Sydenham’s chorea) occurring in children as a complica- thalamic nucleus.
tion of rheumatic fever and a malignant variety (Hunting-
ton’s chorea) that is a hereditary (autosomal dominant)
disorder linked to a single gene defect on chromosome 4 and
associated with progressive mental and cognitive deterioration.
Appendicular musculature is predominantly involved in the
Sydenham’s variety, whereas truncal musculature is predomi-
nantly involved in the Huntington’s variety. Choreic patients are
often unable to sustain a tight hand grip (milkmaid’s grip) and
cannot maintain a protruded tongue, which tends to dart in and
out irregularly (trombone tongue). Figure 14–2 is a diagram
showing how the striatal lesion in Huntington’s chorea results in
random expression of unwanted movement. A variety of chorea
associated with pregnancy (chorea gravidarum) usually occurs
during the second trimester of pregnancy in patients with a pre-
vious history of Sydenham’s chorea.
Athetosis
Athetosis is a disorder of movement characterized by slow,
writhing, continuous, wormlike movements of the distal parts of
the extremities, chiefly the fingers, which show bizarre Figure 14–2. Schematic diagram showing how the striatal le-
posturing. The term athetosis is derived from the Greek sion in Huntington’s chorea affects the indirect striatopallidal
word athetos, meaning “without position.” The lesion pathway and results in random expression of movement. (1) Loss
producing athetosis is probably in the putamen. Differentiation of matrix neurons projecting to external segment of globus pal-
of athetosis from chorea may at times be difficult because it is lidus (GPe). (2) Disinhibition of GPe. (3) Excess inhibition of sub-
common to see patients with mixed choreoathetosis. thalamic nucleus (STh). (4) Decreased excitation of internal seg-
ment of globus pallidus (GPi) and substantia nigra pars reticulata
(SNr). (5) Less inhibition of thalamus. (6) Random expression of
Ballism unwanted movement. (Modified from Adel K. Afifi: Basal gan-
Ballism is a disorder of movement usually caused by a vascular glia: Functional anatomy and physiology. Part II. J Child Neurol
lesion in the subthalamic nucleus. The term ballism is derived 9:352–361, 1994, figure 12, with permission from Decker
from the Greek word ballismos, meaning “jump or throw.” The Periodicals.)
BASAL GANGLIA: CLINICAL CORRELATES / 197
shrug) or meaningful verbalizations. Tics may be transient (days

to weeks) or chronic (months to years), and they may be a pre-
lude to Tourette syndrome.
Tourette Syndrome
Tourette syndrome is characterized by motor and vocal tics.
Motor tics are sudden, brief involuntary movements involving
muscles in different body parts such as eye blinking and shoul-
der shrugging. Vocal tics consist of gutteral sounds,
grunts, or verbalization of words and phrases. The mo-
tor manifestations are often associated with behavioral
abnormalities such as attention deficits and compulsive ritualis-
tic behaviors.
Previously considered a psychiatric or emotional disorder,
Tourette syndrome is currently believed to have organic etiology.
Morphometric magnetic resonance imaging (MRI) studies in
Tourette syndrome reveal volume reduction in the caudate nu-
cleus and the lenticular nucleus.
Postmortem studies in Tourette syndrome brains, although
limited in number, report a decrease in overall volume of the
striatum coupled with an increase in the number of small neu-
rons and decreased dynorphin in striatopallidal axons. Based on
the motor manifestations of Tourette syndrome (tics), the motor
circuit of the basal ganglia or some subunits of it have been pro-
posed as the primary site of pathology. The associated behavioral
manifestations lend credence to involvement of the limbic basal
ganglia circuit. An inhibitory limbic system drive acting on the
Figure 14–3. Computed tomography scan of brain showing motor cortex and motor striatum (Figure 14–4) has been pro-
a lesion in the caudate nucleus and putamen in a patient with posed as instrumental in the genesis of tics.
dystonia. Tourette syndrome is named after Gilles de la Tourette, a
French physician who described the syndrome in 1885. The first
afflicted sufferer was reportedly the French prince of Condé,
who had to stuff clothes into his mouth to stop himself from
barking (vocal tics) at King Louis XIV.
Dystonia
Dystonia is characterized by a twisting, slow, contorting, invol-
untary movement that is somewhat sustained and often repeti-
tive. The term dystonia is derived from the Greek words
dys and tonos, for “bad tone.” The affected body part may,
with time, develop a fixed abnormal posture. Dystonia
may be focal (involving a single body part such as the
hand), segmental (involving two or more adjacent body parts
such as the neck and arm), or generalized. Writer’s cramp, an in-
voluntary contraction of hand or finger muscles while writing, is
an example of focal dystonia. Torticollis (involuntary turning or
tilting of head) combined with facial dystonia constitutes seg-
mental dystonia. Idiopathic torsion dystonia, a hereditary (auto-
somal dominant) disorder that begins in childhood, is an exam-
ple of generalized dystonia.
No obvious specific pathology has been defined in the basal
ganglia in hereditary idiopathic dystonia. However, discrete le-
sions in the striatum (Figure 14–3) caused by stroke, tumor, or
trauma have been associated with the development of dystonia. Figure 14–4. Schematic diagram depicting the roles of the lim-
bic system drive, cerebral cortex, and subcortical motor centers
in the genesis of tics. In early stages of tics A, the cerebral cortex
Tic Disorder plays the major role in tic generation (thick arrow), while subcor-
Tics are brief, sudden, rapid, and intermittent movements (mo- tical motor centers play a minor role (thin arrow). In late stages of
tor tics) or sounds (vocal tics). Tics may be simple or complex. tics B, both the cortex and subcortical centers are equally capa-
Simple tics are caused by contractions of only one group of mus- ble of generating tics. (From A. E. Lang, et al: “Signing tics”:
cles (e.g., eye blinking) or a single meaningless sound (e.g., “ah”). Insights into the pathophysiology of symptoms in Tourette’s
Complex tics consist of coordinated sequenced movement of syndrome. Ann Neurol 33:212–215, 1993, figures A and B,
more than one group of muscles (e.g., eye blinking and shoulder with permission.)
198 / CHAPTER 14
tently. The lesion thus affects the dopaminergic nigrostriatal

fiber system and depletes the striatal dopamine stores. The dis-
ease thus can be ameliorated by administration of L-dopa. Figure
14–5 is a diagram showing how dopamine depletion contributes
to the poverty of movement and the difficulty in switching to new
behaviors. In addition to the depletion of dopamine, reduction in
concentration of the following neuropeptides occurs: enkephalin,
somatostatin, neurotensin, substance P, and bombesin. Decrease
in angiotensin II binding sites and loss of adrenergic neurons in
the locus ceruleus also have been reported.
Prior to the discovery of the significance of L-dopa in parkin-
sonism, the tremor and rigidity of parkinsonism were treated by
surgical lesions in the globus pallidus or thalamus. The former
was more effective in the relief of rigidity and the latter in the re-
lief of tremor.
Surgical approaches to treatment became less popular follow-
ing the introduction of L-dopa therapy. Based on recent physio-
Figure 14–5. Schematic diagram showing how dopamine de- logic and anatomic data, it is now recognized that hyperactivity
pletion in Parkinson’s disease affects the direct and indirect stri- of the subthalamic nucleus is an important feature of Parkinson’s
atopallidal pathways and movement. A: Slowness and poverty disease. Hyperactivity of the subthalamic nucleus increases the
of movement. (1) Loss of excitatory dopamine (DA) input to stri- excitatory drive onto the internal segment of globus pallidus and
atal neurons projecting to internal segment of globus pallidus substantia nigra pars reticulata, which, in turn, overinhibits the
(GPi) and substantia nigra pars reticulata (SNr). (2) Decreased in- motor projections to the thalamus. Thus, the subthalamic nu-
hibition of GPi and SNr neurons. (3) Decreased disinhibition of cleus and internal segment of globus pallidus have become the
thalamic neurons. (4) Slowness and poverty of movement. B: preferred surgical targets to treat selected drug-refractory pa-
Inhibition of unwanted movement; difficulty switching to new tients. Lesions in these sites (pallidotomy and subthalamic nu-
behavior. (1) Loss of inhibitory DA input to striatal neurons pro- cleotomy) or functional blockade (by deep brain stimulation)
jecting to external segment of globus pallidus (GPe). (2) In- have been increasingly used.
creased inhibition of GPe neurons. (3) Disinhibition of subtha-
lamic nucleus (STh) input to GPi and SNr. (4) Reinforcing TERMINOLOGY
inhibition of unwanted movement. (Modified from Adel K. Afifi:
Basal ganglia: Functional anatomy and physiology. Part II. J Abulia (Greek, “without will”). A state in which the patient
Child Neurol 9:352–361, 1994, figure 11, with permission from manifests lack of initiative and spontaneity with preserved con-
Decker Periodicals.)
sciousness.
Akinesia (Greek a, “negative, without”; kinesis, “move-
ment”). Lack of spontaneous movement as seen in Parkinson’s
disease.
Athetosis (Greek athetos, “without position or place”).
Involuntary movement disorder characterized by irregular, slow,
HYPOKINETIC DISORDERS writhing movements of distal parts of extremities. The condition
was described by William Hammond in 1871.
Parkinsonism
Ballism (Greek ballismos, “jumping, throwing”). Violent fling-
Parkinson’s disease is characterized by tremor, rigidity, and hy- ing movements usually of one side of the body due to a lesion in
pokinesia or akinesia. The tremor of Parkinson’s disease is rhyth- the contralateral subthalamic nucleus.
mic fine tremor recurring at the rate of 3 to 6 cycles per second Bradykinesia (Greek brady, “slow”; kinesis, “movement”).
and is best seen when the extremity is in a fixed posture rather Abnormal slowness of movement as seen in Parkinson’s disease.
than in motion (in contradistinction to cerebellar tremor, Chorea (Latin choros, “a dance”). Irregular involuntary move-
which is seen during movement of an extremity). ments of the limbs or face secondary to striatal lesion. The names
The rigidity is characterized by resistance to passive of four saints (Vitus, Valentine, Modesti, and John) have been
movement of a joint throughout the range of motion (cogwheel associated with chorea over the ages. The most used is St. Vitus’s
rigidity), resulting from an increase in tone of muscles with op- dance.
posing action (agonists and antagonists).
Hypokinesia or akinesia is manifested by a diminution or loss Cogwheel rigidity. The arrhythmic, repetitive alteration of re-
of associated movements (e.g, swinging of upper extremities sistance to passive stretch occurring during passive movement of
when walking), difficulty in initiating movement, and slow a joint; palpable tremor. A sign of basal ganglia disorder.
movement. The hypokinesia often causes difficulties for patients Dystonia. Sustained and patterned muscle contractions of ago-
in getting dressed, feeding, and maintaining personal hygiene. nists and antagonist muscles leading to twisting involuntary
The coexistence of rigidity and hypokinesia in facial muscles movements. The clinical condition was first described by German
accounts for decreased blinking rate and the expressionless mask physician Marcus Walter Schwalbe in 1908.
facies. Huntington’s chorea. Progressive neurodegenerative disorder
The lesion producing Parkinson’s disease is widespread in the inherited as an autosomal dominant trait. The disease was im-
central nervous system but affects the dopaminergic neu- ported to America from Suffolk in the United Kingdom by the
rons in the substantia nigra pars compacta most consis- emigrant wife of an Englishman in 1630. Her father was choreic,
BASAL GANGLIA: CLINICAL CORRELATES / 199
and his father disapproved of the match because of the bride’s fa- tated by writing or typing. When first described by Bell in 1830,
ther’s illness. The disorder is named after George Sumner it was considered a psychiatric disorder.
Huntington, a general practitioner who described the disease.
Hypokinesia. Poverty of willed movement. SUGGESTED READINGS
Milkmaid’s grip. Variability in the isometric force exerted by Bhatia KP, Marsden CD: The behavioral and motor consequences of focal
the wrist and by individual fingers during attempts to grasp an lesions of the basal ganglia in man. Brain 1994; 117:859–876.
object. The sign is present in chorea. Ceballos-Baumann AO et al: Restoration of thalamocortical activity after
posteroventral pallidotomy in Parkinson’s disease. Lancet 1994; 344:814.
Parkinsonism. A chronic progressive degenerative disease char-
Dogali M et al: Stereotactic ventral pallidotomy for Parkinson’s disease.
acterized by tremor, rigidity, and akinesia. It was described ini- Neurology 1995; 45:753–761.
tially by English physician James Parkinson under the rubric
Koller WC: Chorea, hemichorea, hemiballismus, choreoathetosis and related
“shaking palsy” published in 1817. Earlier descriptions were made disorders of movement. Curr Opin Neurol Neurosurg 1991; 4:350–353.
by Galen, Boetius, and others. Lavoie B et al: Immunohistochemical study of the basal ganglia in normal and
Sydenham’s chorea. An acute, benign, and self-limited chorea, a parkinsonian monkeys. Adv Neurol 1992; 58:115–121.
manifestation of rheumatic fever. Named after Thomas Sydenham, Lozano AM et al: Effect of GPi pallidotomy on motor function in Parkinson’s
the English physician who first described the disorder in 1686. disease. Lancet 1995; 346:1387–1388.
Tics. Sudden, brief, repetitive involuntary movements that may Munro-Davis LE et al: The role of the pedunculopontine region in basal-
be suppressed for a period by effort or will. ganglia mechanism of akinesia. Exp Brain Res 1999; 129:511–517.
Obeso JA et al: Pathophysiologic basis of surgery for Parkinson’s disease.
Torticollis (Latin tortere, “to twist”; collis, “neck”). A focal Neurology 2000; 55(Suppl 6):S7–S12.
dystonia causing intermittent or persistent rotation of the neck. Peterson B et al: Reduced basal ganglia volumes in Tourette’s syndrome using
Tourette syndrome. A dominantly inherited syndrome charac- three-dimensional reconstruction techniques from magnetic resonance
terized by motor and vocal tics and a variety of behavioral symp- images. Neurology 1993; 43:941–949.
toms and signs that include attention deficits and obsessive- Rice JE, Thompson PD: Movement disorders II: The hyperkinetic disorders.
compulsive behaviors. The syndrome is named after George- Med J Aust 2001; 174:413–419.
Edmond-Albert-Brutus Gilles de la Tourette, the French neuro- Swedo SE et al: Sydenham’s chorea: Physical and psychological symptoms of
psychiatrist who described the condition in 1885. The first St. Vitus dance. Pediatrics 1993; 91:706–713.
recorded sufferer was the French prince of Condé, who stuffed Wilson SAK: Progressive lenticular degeneration: A familial nervous disease
clothes into his mouth to stop himself from barking at King associated with cirrhosis of the liver. Brain 1912; 34:295–509.
Louis XIV. Yoshida M: The neural mechanism underlying Parkinsonism and dyskinesia:
Differential roles of the putamen and caudate nucleus. Neurosci Res 1991;
Trombone tongue. Repetitive protrusion and replacement of 12:31–40.
the tongue seen characteristically in Huntington’s disease. Young AB, Penney JB: Neurochemical anatomy of movement disorders.
Writer’s cramp. A focal (hand) occupational dystonia precipi- Neurol Clin 1984; 2:417–433.
Cerebellum 15
Gross Features Cerebrocerebellar and Cerebellocerebral Circuitries

Lobes and Subdivisions Neurotransmitters
Somatotopic Representation Cerebellar Physiology
Microscopic Structure Cerebellar Cortex
Cerebellar Cortex Deep Cerebellar Nuclei
Principal (Purkinje) Neuron Cerebellar Function
Intrinsic Neurons Historical Perspective
Cerebellar Glomerulus Motor Functions of the Cerebellum
Cerebellar Input Neocerebellar Signs
Inferior Cerebellar Peduncle Archicerebellar and Paleocerebellar Signs
Middle Cerebellar Peduncle Ocular Motor Signs
Superior Cerebellar Peduncle Cerebellum and Epilepsy
Internal Cerebellar Circuitry Complementarity of Basal Ganglia and Cerebellum
Mossy Fiber Input in Motor Function
Climbing Fiber Input Nonmotor Functions of the Cerebellum
Cerebellar Output The Cerebellum and Autism
Deep Cerebellar Nuclei Sensory Systems and Cerebellum
Dentate Nucleus Arterial Supply
Interposed Nuclei Venous Drainage
Fastigial Nucleus
KEY CONCEPTS
The cerebellum is divided into three imperfectly delin- Deep cerebellar nuclei provide cerebellar output to ex-
eated lobes or zones based on morphology, connectivity, tracerebellar targets. Extracerebellar targets include the
function, or phylogeny. vestibular and reticular nuclei, red nucleus, and thalamus.
The cerebellar cortex has three layers and contains five Signs of cerebellar disorders include asynergia (dyssyner-
cell types (one principal and four intrinsic). gia), dysarthria, adiadochokinesis, dysmetria, tremor, mus-
cular hypotonia, ataxia, and nystagmus.
The major inputs to the cerebellum are from three sources:
spinal cord, vestibular system, and cerebral cortex. Nonmotor roles for the cerebellum in autonomic regula-
tion, behavior, cognition, and learning are being increas-
Within the cerebellum, various inputs are segregated into
ingly documented.
one of three fiber systems.
Blood supply of the cerebellum is provided by three
Cerebellar inputs excite Purkinje cells directly via climbing
arteries from the vertebral–basilar arterial system. They
fibers and indirectly via granule cell axons. Intrinsic cere-
are the posterior inferior cerebellar, anterior inferior cere-
bellar neurons are excited by cerebellar inputs and in turn
bellar, and superior cerebellar.
inhibit Purkinje cells.
200
CEREBELLUM / 201
GROSS FEATURES
The cerebellum, or “small brain,” develops from the embryo-
logic rhombic lip, a zone of cells between the alar and roof plates
at the level of the pontine flexure. Although it develops from a
“sensory” region (the rhombic lip), the cerebellum is concerned
primarily (but not exclusively) with motor function.
The cerebellum is located in the posterior fossa of the skull,
separated from the occipital lobes by a dural fold, the tentorium
cerebelli. It overlies the dorsal surfaces of the pons and medulla
oblongata and contributes to the formation of the roof of the
fourth ventricle.
The cerebellum consists of a midline vermis and two later-
ally placed hemispheres. The parts of the hemispheres adjacent
to the vermis are known as the paravermal or intermediate zones
(Figure 15–1).
The dorsal cerebellar surface is rather flat; the demarcation
of vermis and hemispheres is not evident on this surface (Figure
15–2). The ventral surface is convex with a deep groove (vallecula)
in the midline through which the vermis is apparent (Figure 15–3). Figure 15–1. Schematic diagram of ventral surface of the cere-
The adult human cerebellum weighs approximately 150 g bellum showing its subdivision into vermis, paravermis, and
(10 percent of brain weight) and has a surface area of approxi- hemisphere.
mately 1000 cm2 (40 percent of the cerebral cortex).
The cerebellum is connected to the midbrain, pons, and
medulla oblongata by three pairs of peduncles (Figure 15–4). cortex). Embedded in the white matter core are four pairs of deep
1. The superior cerebellar peduncle (brachium conjunctivum) cerebellar nuclei arranged from lateral to medial (Figure 15–5).
connects the cerebellum with the midbrain. 1. Dentate nucleus
2. The middle cerebellar peduncle (brachium pontis) connects 2. Emboliform nucleus
the pons with the cerebellum. 3. Globose nucleus
3. The inferior cerebellar peduncle (restiform and juxtaresti- 4. Fastigial nucleus
form bodies) connects the medulla with the cerebellum.
The globose and emboliform nuclei are referred to collec-
The contents of each of these peduncles are discussed in the tively as the interposed nucleus. A commonly used mnemonic to
chapters on the mesencephalon (Chapter 9), pons (Chapter 7), recall the deep cerebellar nuclei is “Don’t Eat Greasy Food.”
and medulla oblongata (Chapter 5).
The cerebellum consists of a highly convoluted layer of gray Lobes and Subdivisions (Table 15–1)
matter, the cerebellar cortex, surrounding a core of white matter
that contains the afferent and efferent tracts. The branching pat- The cerebellum is divided anatomically by two transverse fissures
tern of the white matter was referred to by early anatomists as the (anterior and posterolateral or prenodular) into three
arbor vitae (tree of life) (Figure 15–4). Hence the cortical convo- lobes: anterior, posterior, and flocculonodular. The de-
lutions in the cerebellum are referred to as folia (leaves) instead of marcation of the three lobes is best seen in midsagittal
gyri (term used to describe cortical convolutions in the cerebral sections (Figure 15–6). The posterior lobe contains, on its inferior
Figure 15–2. Photograph of dorsal surface of the

cerebellum. (From Gluhbegovic and Williams: The
Human Brain, A Photographic Guide. Harper and Row
Publishers, 1980, courtesy of the authors.)
202 / CHAPTER 15
Hemisphere
Vermis
Tonsil Figure 15–3. Photograph of ventral

surface of the cerebellum. (From
Gluhbegovic and Williams: The Human
Brain, A Photographic Guide. Harper
and Row Publishers, 1980, courtesy of
the authors.)
surface, the cerebellar tonsils (Figure 15–3). In cases of increased The cerebellum is also subdivided into three longitudinal
intracranial pressure such as occurs in brain tumors, intracranial zones, based on the arrangement of projections from the cerebel-
hemorrhage, or severe head trauma, the cerebellar tonsils may lar cortex to deep cerebellar nuclei (Figure 15–1). These are the
herniate through the foramen magnum. This tonsillar herniation midline (vermis) zone, the intermediate (paravermal) zone, and
is a life-threatening neurologic emergency due to compromise of the lateral (hemisphere) zone. The cortex of the vermis projects
vital centers in the brain stem. to the fastigial deep cerebellar nucleus, that of the paravermis to
Cerebral hemisphere
Vermis
Dentate
nucleus
Arbor Superior cerebellar

vitae peduncle
Middle cerebellar
Folium peduncle
Inferior cerebellar peduncle
Fourth ventricle Medulla oblongata
Figure 15–4. Section through the cerebral hemisphere and cerebellum showing the three cerebellar peduncles (superior, middle,
inferior). Shown also are the arbor vitae and folia of the cerebellum.
CEREBELLUM / 203
Figure 15–5. Schematic diagram of unfolded

cerebellum showing the four cerebellar nuclei.
the interposed deep nuclei (emboliform and globose), and that In the anterior lobe, the body appears inverted, with hindlimbs
of the cerebellar hemisphere to the dentate nucleus. The borders represented rostral to the forelimbs and face. In the posterior
that separate each of the transverse and longitudinal lobes and lobe, the body appears noninverted and dually represented on
zones are far from precise. Clear functional subdivisions are thus each side of the midline, with face anteriorly and legs posteriorly
scarcely possible with reference to either the transversely oriented represented. In general, the trunk is represented in the midline,
lobes or the longitudinally oriented zones. and the extremities are represented more laterally in the hemi-
Based on fiber connectivity, however, three functional sub- spheres. Thus, in disorders predominantly affecting the midline
divisions of the cerebellum have been delineated: cerebellum, disturbances of movement will be manifest primar-
ily in trunk musculature and would affect body equilibrium. In
1. The vestibulocerebellum (corresponds best with the floccu-
contrast, in disorders primarily affecting the cerebellar hemi-
lonodular lobe) has reciprocal connections with vestibular
spheres, disturbances of movement will manifest primarily in ex-
and reticular nuclei and plays a role in control of body equi-
tremity movement.
librium and eye movement.
2. The spinocerebellum (corresponds best to the anterior lobe)
has reciprocal connections with the spinal cord and plays a MICROSCOPIC STRUCTURE
role in control of muscle tone as well as axial and limb
movements, such as those used in walking and swimming. Cerebellar Cortex
3. The cerebrocerebellum or pontocerebellum (corresponds The cerebellar cortex is made up of the following three
best to the posterior lobe) has reciprocal connections with layers.
the cerebral cortex and plays a role in planning and initiation
1. Outer molecular layer (about 300 m in thickness)
of movements, as well as the regulation of discrete limb
movements. 2. Middle Purkinje cell layer (about 100 m in thickness)
3. Innermost granule cell layer (about 200 m in thick-
Phylogenetically, the cerebellum is divided into three zones: ness)
The archicerebellum, the oldest zone, corresponds to the floccu-
lonodular lobe. The paleocerebellum, of more recent phylogenetic Five cell types (Table 15–2) are distributed in the different
development than the archicerebellum, corresponds to the anterior cortical layers. Basket and stellate cells are in the molecular layer,
lobe and a small part of the posterior lobe. The neocerebellum, the Purkinje cells are in the Purkinje cell layer, and granule and
most recent phylogenetically, corresponds to the posterior lobe. Golgi cells are in the granule cell layer.
Of these five cell types, the Purkinje cell constitutes the prin-
Somatotopic Representation (Figure 15-7) cipal neuron of the cerebellum, since it is the only cerebellar
neuron that sends its axons outside the cerebellum (projection
Somatotopic representation of body parts in the cerebellum was neuron). All the other cells are intrinsic neurons and establish con-
first described in 1943 by Adrian and later confirmed by others. nections within the cerebellum.
Table 15–1. Cerebellar Lobes and Subdivisions
A Anatomic subdivisions
Transverse plane Anterior lobe Posterior lobe Flocculonodular lobe
Longitudinal plane Vermis Paravermis Hemisphere
B Functional subdivisions Spinocerebellum Cerebrocerebellum Vestibulocerebellum
C Phylogenetic subdivisions Paleocerebellum Neocerebellum Archicerebellum

204 / CHAPTER 15
Figure 15–6. Schematic diagram of

midsagittal view of the cerebellum
and brain stem showing the three
anatomic lobes of the cerebellum.
Principal (Purkinje) Neuron (Table 15-2) arranged at right angles to the long axis of the folium. The den-
dritic tree is made up of a sequence of primary, secondary, and
Described in 1837 by the Bohemian priest and physiologist tertiary branches, with the smaller dendritic branches profusely
Johannes Purkinje, cell bodies of Purkinje cells are arranged in a covered with dendritic spines or gemmules. It is estimated that
single row at the border zone between the molecular and granule each Purkinje cell has over 150,000 spines on its dendritic tree.
cell layers. The cell is flask-shaped when viewed in the transverse Each Purkinje cell has a single axon that courses through the
plane and is narrow and vertical when viewed in longitudinal granule cell layer and deep white matter to project on deep cere-
sections. The Purkinje cell measures approximately 30 to 35 m bellar nuclei. Some Purkinje cell axons (from the vermis) bypass
in transverse diameter. Adjacent Purkinje cells are separated by the deep cerebellar nuclei to reach the lateral vestibular nucleus.
50 m in the transverse plane and by 50 to 100 m in the lon- Recurrent collateral axonal branches arise from Purkinje cell
gitudinal plane. Each Purkinje cell has an elaborate dendritic tree axons and project on adjacent Purkinje cells as well as on basket,
that stretches throughout the extent of the molecular layer and is stellate, and Golgi cells in neighboring or even distant folia. It is
estimated that there are about 15 million Purkinje cells in the
human cerebellum.
Intrinsic Neurons (Table 15–2)

A. BASKET CELL
Basket cells are situated in deeper parts of the molecular layer in
close proximity to Purkinje cells. Dendritic arborizations of bas-
ket cells are disposed in the transverse plane of the folium in a
manner similar to but less elaborate than the Purkinje cells. The
axon courses in the molecular layer in the transverse plane of the
folium just above the cell bodies of Purkinje cells. Each axon
gives rise to several descending branches that surround Purkinje
cell perikarya and initial segments of their axons in the form of a
basket, hence their name. Each basket cell axon covers the terri-
tory of about 10 Purkinje cells. Basket formation, however, skips
the Purkinje cell immediately adjacent to the basket cell and de-
scends on the second Purkinje cell and onward in the row. In ad-
dition, axonal branches extend in the longitudinal plane of the
folium to reach an additional three to six rows of Purkinje cells
on both sides of the main axons. As a result of this, a single bas-
ket cell may reach as many as 200 Purkinje cells. More than one
Figure 15–7. Schematic diagram of unfolded cerebellum basket cell may contribute to a single basket formation around
showing somatotopic representation of body parts in the cere- one Purkinje cell. While the descending branches of basket cell
bellum. H, head; UE, upper extremity; LE, lower extremity; T, trunk. axons establish contact with Purkinje cell perikarya and initial
CEREBELLUM / 205
Table 15–2. Cerebellar Cortex Neurons
Neuron Type Layer Projection Synaptic action
Purkinje Principal (projection) Purkinje Deep cerebellar nuclei Inhibitory

Lateral vestibular nucleus
Other Purkinje cells
Intrinsic neurons
Basket Interneuron Molecular Purkinje cell Inhibitory
Stellate Interneuron Molecular Purkinje cell Inhibitory
Granule Interneuron Granule Purkinje cell Excitatory
Basket cell
Stellate cell
Golgi cell
Golgi Interneuron Granule Granule cell Inhibitory
segments of their axons, ascending branches of basket cell axons rons arborize in either the molecular or the granule cell layer.
ascend in the molecular layer to reach the proximal dendrites of Those which remain in the granule cell layer contribute to the
Purkinje cells. It is estimated that there are about 7 million bas- glomeruli of that layer. Those which reach the molecular layer
ket cells in the human cerebellum. arborize widely and overlap the territories of three Purkinje cells
in both the transverse and longitudinal planes. The Golgi neuron
B. STELLATE CELL dendritic arborization is thus three times that of the Purkinje cell.
Stellate cells are located in the superficial and deeper parts of the Axons of Golgi cells take part in the formation of the glomer-
molecular layer. Axons of stellate cells are also disposed trans- ulus. They are characterized by a dense arborization of short
versely in the folium and terminate on Purkinje cell dendrites. It axonal branches that span the entire granule cell layer. The field
is estimated that there are 12 million stellate cells in the human of axonal arborization approaches that of dendritic arborization.
cerebellum. The axonal arborization of the Golgi neurons is among the most
The basket and stellate cells can be considered as belonging to unique in the brain. The Golgi neuron forms the central point of
the same class. Both receive the same input, and both act on a functional hexagon that includes about 10 Purkinje cells. It is
Purkinje cells. The difference lies in the fact that stellate cells es- estimated that there are 4 million Golgi cells.
tablish contact with the dendrites of Purkinje cells, whereas bas-
ket cells establish contact with dendrites, perikarya, and axons of Cerebellar Glomerulus
Purkinje cells.
In histologic sections of the cerebellar cortex there are islands be-
C. GRANULE CELL tween granule cells that stain lighter than the rest of the granule cell
Granule cells are among the smallest cells in the brain (6 to layer. These are the cerebellar glomeruli (Figure 15–8). They are
9 m) and fill the granule cell layer. Each cell gives rise to about the sites of synaptic contact between the incoming cerebellar fibers
three to five dendrites that establish synaptic contacts with axons (mossy fiber system) and processes of neurons within the granule
in a synaptic zone (the glomerulus) within the granule cell layer. cell layer. The elements that form a cerebellar glomerulus are
Axons of granule cells ascend in the granule cell layer, Purkinje
layer, and molecular layer, where they bifurcate in a T fashion 1. Cerebellar input via the mossy fiber system (origins of this
and run parallel to the surface to form the parallel fiber system. system will be discussed later)
Parallel fibers run horizontally in the molecular layer perpendic- 2. Dendrites of granule cells
ular to the plane of the Purkinje dendrites. Each parallel fiber 3. Axon terminals of Golgi neurons
branch is 1 to 1.5 mm in length; thus the axon of a single gran- 4. Proximal parts of Golgi dendrites
ule cell spans an area of approximately 3 mm. The parallel fibers
establish contact with dendrites of Purkinje cells, Golgi cells, Electron micrographs have shown that the mossy fiber axonal
stellate cells, and basket cells. Generally, a parallel fiber comes in terminal is the central element in the glomerulus (terminal
contact with a Purkinje cell only once or, rarely, twice. The indi- rosettes), around which are clustered dendrites of granule cells
vidual parallel fibers are thus not a strong drive to the Purkinje and axons of Golgi neurons. Both mossy fiber axons and Golgi
neuron. axons act on the dendrites of granule cells. In addition, mossy
A single Purkinje cell, however, can receive up to 100,000 fiber axons project on dendrites of Golgi neurons. The whole
parallel fibers. Although a single parallel fiber is not a strong complex is surrounded by a glial envelope. It is estimated that a
drive to the Purkinje neuron, contact by 100,000 parallel fibers glomerulus contains about 100 to 300 dendritic terminals from
can provide a powerful drive to this neuron. some 20 granule cells.
The total number of granule cells is estimated to be on the or-
der of 2.2 billion. CEREBELLAR INPUT
D. GOLGI TYPE II CELL Containing more than half the neurons in the brain, the cerebel-
Golgi neurons occupy the superficial part of the granule cell lum is one of the busiest neuronal intersections in the brain, re-
layer adjacent to the Purkinje cells. They are large neurons, about ceiving input from and sending signals back to every major part of
the same size as the Purkinje cell bodies. Dendrites of Golgi neu- the central nervous system. Input to the cerebellum originates
206 / CHAPTER 15
Figure 15–8. Schematic diagram of a cerebellar glomeru-

lus showing the different sources of converging fibers.
from a variety of sources. The three major sources of af- an inhibitory effect on Purkinje cell activity. It has been postulated
ferents, however, are the spinal cord, vestibular system, that the input from the locus ceruleus plays a role in the develop-
and cerebral cortex. ment of Purkinje cells. The terminals from the locus ceruleus de-
Inputs from the spinal cord are transmitted to the cerebellum velop prior to Purkinje cell maturation. Destruction of the locus
(Figure 15–9) via the dorsal and ventral spinocerebellar tracts ceruleus results in immature development of Purkinje cells.
and the rostral extension of the dorsal spinocerebellar tract, the In the past few years, a series of investigations has revealed the
cuneocerebellar tract. These tracts provide the cerebellum with existence of a complex network of direct and indirect pathways
information related to the position and condition of muscles, between the hypothalamus and the cerebellum. The projections
tendons, and joints. are bilateral with ipsilateral preponderance. They originate from
Inputs from the vestibular system (Figure 15–10) arise from various hypothalamic nuclei and areas but principally from the
the primary vestibular end organ in the vestibular labyrinth, as lateral, dorsal, and posterior hypothalamic areas and the dorso-
well as from vestibular nuclei (inferior and medial) in the brain medial, ventromedial, supramamillary, lateral mamillary, and
stem. Vestibulocerebellar inputs provide information related to tuberomamillary nuclei. The indirect pathway reaches the cere-
body equilibrium. bellum after relays in a number of brain stem nuclei. Hypo-
Cortical inputs to the cerebellum originate in neocortical as thalamocerebellar fibers terminate in relation to neurons in all
well as paleocortical and archicortical areas. These include pri- layers of the cerebellar cortex. The hypothalamocerebellar net-
mary motor and sensory cortices as well as association and lim- work may provide the neuroanatomic substrate for the auto-
bic cortices. Inputs from neocortical areas (Figure 15–11) reach nomic responses elicited from cerebellar stimulation.
the cerebellum after relays in the pontine nuclei (the vast major- Fiber inputs to the cerebellum from the preceding various
ity) and inferior olive. Inputs from paleocortical and archicorti- sources arrive via three cerebellar peduncles: the inferior (restiform
cal areas establish relays in the reticular nuclei and hypothala- body), the middle (brachium pontis), and the superior (brachium
mus prior to reaching the cerebellum. Corticocerebellar inputs conjunctivum). Figure 15–12 is a composite schematic diagram of
provide information related to the planning and initiation of inputs to the cerebellum.
movement.
Other fiber inputs to the cerebellum include a noradrener-
gic projection from the locus ceruleus (A-6 cell group of pri- Inferior Cerebellar Peduncle
mates), a dopaminergic projection from the ventral tegmental The fiber systems reaching the cerebellum via this peduncle are
area of Tsai in the midbrain (A-10 cell group of primates), and the following:
a serotonergic projection from the raphe nuclei (B-5 and B-6
cell groups of primates) in the brain stem. The input from the 1. Dorsal spinocerebellar tract from the dorsal nucleus of Clarke
locus ceruleus projects on Purkinje cell dendrites and exerts 2. Cuneocerebellar tract from the accessory cuneate nuclei
CEREBELLUM / 207
3. Olivocerebellar tract from the inferior olivary nuclei (major

component)
4. Reticulocerebellar tract from the reticular nuclei of the brain
stem
5. Vestibulocerebellar tract (both primary afferents from the
vestibular end organ and secondary afferents from the vestibu-
lar nuclei)
6. Arcuatocerebellar tract from the arcuate nuclei of the
medulla
7. Trigeminocerebellar tract from the spinal and main sensory Inferior
nuclei of the trigeminal nerve cerebellar
Middle Cerebellar Peduncle

The fiber systems reaching the cerebellum via this route are the
following:
1. Pontocerebellar (corticopontocerebellar) tract from the pon-
tine nuclei (major component)
2. Serotonergic fibers from the raphe nuclei
Figure 15–10. Schematic diagram of vestibular input to the

cerebellum.
Superior Cerebellar Peduncle

The fiber input to the cerebellum via this route includes the
following:
1. Ventral spinocerebellar tract
2. Trigeminocerebellar tract from the mesencephalic trigeminal
nucleus
3. Cerulocerebellar tract from the nucleus ceruleus
4. Tectocerebellar tract from the superior and inferior colliculi
The various inputs to the cerebellum are segregated
within the cerebellum into one of three fiber systems:
climbing, mossy, and a recently described multilayered.
A. CLIMBING FIBER SYSTEM (Figure 15–13)
It is generally believed that the olivocerebellar tract is the major
component of this system. Climbing fibers establish synapses on
dendrites of the principal neuron of the cerebellum (the Purkinje
cell), as well as on dendrites of intrinsic neurons (Golgi, basket,
and stellate) (Table 15–3). The climbing fiber input is known to
Figure 15–9. Schematic diagram of spinocerebellar input. DSCT, exert a powerful excitatory effect on a single Purkinje cell and a
dorsal spinocerebellar tracts; VSCT, ventral spinocerebellar tract; much less powerful effect on intrinsic neurons. The relationship
ACN, accessory cuneate nucleus; CCT, cuneocerebellar tract. of climbing fibers to principal neurons is so intimate that one
208 / CHAPTER 15
of the climbing fiber system elicits a prolonged burst of high-fre-

quency action potentials (complex spike) from the Purkinje cell
capable of overriding any ongoing activity in that cell. Several
lines of evidence suggest that olivocerebellar input via the climb-
ing fiber pathway is powerfully modulated during active move-
ments. Available data suggest that access of sensory signals from
the spinal cord to the cerebellum via the inferior olive (spino-
olivo-cerebellar pathway) and the climbing fiber system is power-
fully gated and is subject to central control. The importance of
the climbing fiber system is evident by the fact that ablation of
Cerebellum the inferior olive (source of climbing fiber pathway) results in
movement disorder similar to the motor deficits that follow direct
damage to the cerebellum. One notable aspect of the olivocere-
bellar projection is its highly ordered topography.
B. MOSSY FIBER SYSTEM
The mossy fiber system includes all afferents to the cerebellum ex-
cept those which contribute to the climbing fibers and the multi-
layered fiber system. Like the climbing fibers, mossy fibers enter
the cerebellum via the core of deep white matter. They then di-
verge into the folia of the cerebellum, where they branch out into
the granule cell layer. Within the granule cell layer, mossy fibers di-
vide into several subbranches of terminal rosettes that occupy the
center of each glomerulus, where they come in contact with den-
drites of granule and Golgi neurons (Figure 15–13 and Table 15–3).
It is estimated that each mossy fiber establishes contact with ap-
proximately 400 granule cell dendrites within a single folium and
that each terminal mossy rosette contacts approximately 20 differ-
Inferior ent granule cells. On the other hand, each granule cell receives
synaptic contacts from four to five different mossy fiber terminals.
The mossy fiber is believed to stimulate the largest number of cells
Figure 15–11. Schematic diagram showing neocortical input to be activated by a single afferent fiber. Thus, in contrast to the
to the cerebellum with relay in the pontine nuclei and inferior climbing fiber input, which is highly specific and sharply focused
olive. MCP, middle cerebellar peduncle (brachium pontis); ICP, in-
on the Purkinje cell, the mossy fiber input is diffuse and complex
(Figure 15–13). In addition to their contribution to the Purkinje
ferior cerebellar peduncle (restiform body).
and granule cells of the cerebellar cortex, both climbing and mossy
fibers send collaterals to the deep cerebellar nuclei (Figure 15–13).
These collaterals are excitatory in nature and help maintain a con-
climbing fiber is restricted to one Purkinje cell and follows the stant background discharge of these deep nuclei.
branches of the Purkinje cell dendrites like a grapevine. The
climbing fiber effect on a Purkinje cell is thus one-to-one, all-or- C. MULTILAYERED FIBER SYSTEM
none excitation. It is estimated that one climbing fiber establishes This recently described fiber system includes afferents to the cere-
1000 to 2000 synaptic contacts with its Purkinje cell. Stimulation bellum from the hypothalamus, as well as the serotonergic input
Figure 15–12. Composite schematic diagram showing

major sources of input to the cerebellum.
CEREBELLUM / 209
Figure 15–13. Schematic diagram comparing the climbing and mossy fiber systems within the
cerebellum.
from the raphe nuclei, the noradrenergic input from the nucleus produce a row of activated Purkinje cells flanked on each side by
locus ceruleus, and the dopaminergic input from the mes- a strip of inhibited Purkinje cells. The inhibited rows of Purkinje
encephalic dopaminergic neurons. Similar to the climbing and cells, by silencing surrounding activity, help the process of neural
mossy fiber systems, the multilayered fiber system projects on sharpening within the activated row of Purkinje cells.
neurons in the cerebellar cortex and the deep cerebellar nuclei. If the activated bundle of parallel fibers becomes wide enough
to span the dendritic field of a Golgi neuron, the Golgi cell is
INTERNAL CEREBELLAR CIRCUITRY then excited and, through its axon in the glomerulus, will inhibit
the granule cell. Thus, a mossy fiber excitatory input to the gran-
(Figures 15–14 and 15–15) ule cell will be transferred into inhibition via one of two mecha-
Mossy Fiber Input nisms (Figure 15–14):
A mossy fiber input excites dendrites of a group of granule cells. 1. Mossy fiber to granule cell dendrite to granule cell axon (par-
The discharge from these granule cells will be transmitted allel fibers) to basket and stellate cells dendrites to basket and
through their axons (parallel fibers), which bifurcate in a T con- stellate cells axons to Purkinje cell body (basket cells axons)
figuration in the molecular layer, coming in contact with den- and dendrites (stellate cells axons)
drites of Purkinje, stellate, basket, and Golgi neurons. If the ex- 2. Mossy fibers to granule cell dendrite to granule cell axon
cited parallel fiber bundle is wide enough to cover the Purkinje (parallel fibers) to Golgi cell dendrites, to Golgi cell axon, to
cell dendritic field, activation will result in a firing of a granule cell dendrites.
single row of Purkinje cells and in the related basket and
stellate cells. The activation of the basket and stellate A third inhibitory mechanism of the mossy fiber system
cells will inhibit a wide zone of Purkinje cells on each side of the (Figure 15–15) is via mossy fiber input to Golgi cell dendrites to
row of activated Purkinje cells. Thus the mossy fiber input will Golgi cell axon and back to granule cell dendrites.
Table 15–3. Climbing and Mossy Fibers
Projection targets
Fiber type
Deep nuclei Purkinje Basket Stellate Granule Golgi
Climbing X X X X X
Mossy X X X
210 / CHAPTER 15
PC Dendritic Field Go Dendritic Field

D + + + + + PF PF
+ + + + D ++ + + + + + ML
S D D D S D D
D D
− D D A −
B B
PCL
− A A D
PC PC PC
−
GO GCL
A A
G
D −
+ +
MF
Figure 15–14. Schematic diagram showing how an excitatory mossy fiber input can be transformed into inhibi-
tion via granule cell axon. MF, mossy fiber; G, granule cell; GO, Golgi cell; B, basket cell; S, stellate cell; PC, Purkinje
cell; ML, molecular layer; PCL, Purkinje cell layer; GCL, granule cell layer; PF, parallel fibers; A, axon; D, dendrite; ,
facilitation; , inhibition.
PF PF
ML
A D PCL
GO
A
G GCL
−
D++D
D + + D

MF MF showing how an excitatory mossy
fiber input can be transformed
into inhibition via Golgi cell axon.
MF, mossy fiber; G, granule cell;
GO, Golgi cell; ML, molecular layer;
PCL, Purkinje cell layer; GCL, gran-
ule cell layer; PF, parallel fibers; A,
axon; D, dendrite; , facilitation; ,
inhibition.
CEREBELLUM / 211
The mossy fiber input has both high divergence and conver- neuron a central role in cerebellar organization. Through its con-
gence ratios. A single mossy fiber has 40 rosettes, each rosette tact with both the mossy fibers in the glomerulus and the climb-
connects with the dendritic terminals of 20 granule cells, and a ing fiber collaterals, the Golgi neuron is able to select what input
single granule cell connects through the parallel fibers with 100 will reach the Purkinje cell at any one time.
to 300 Purkinje cells. This gives a divergence ratio of about
1:100,000 to 1:300,000 from one mossy fiber to Purkinje cells. CEREBELLAR OUTPUT
On the other hand, each Purkinje cell has about 100,000 den-
dritic spines in synaptic contact with parallel fibers (granule The cerebellar output system has two components: intracerebel-
cells) and hence a large ratio of convergence. lar and extracerebellar. The intracerebellar component comprises
the inhibitory projections of Purkinje cells to deep cerebellar nu-
Climbing Fiber Input clei. These projections are somatotopically organized (Figure 15–
17). Purkinje cells in the vermis project to the nucleus fastigii,
Similarly, a climbing fiber input will excite Purkinje cells as well while those in the paravermal and cerebellar hemisphere zones
as stellate, basket, and Golgi neurons. The effect on these differ- project, respectively, to the interposed nucleus (emboliform and
ent cells is similar to that described for the mossy fiber input and globose) and the dentate nucleus. The vast majority of the ex-
helps to focus on the activation of the Purkinje cell amid a zone tracerebellar component comprises the projections of deep cere-
of inhibition induced by basket, stellate, and Golgi neurons. In bellar nuclei to extracerebellar targets. A smaller part of it origi-
contrast to the mossy fiber system, the convergence and diver- nates from a group of Purkinje cells in the vestibulocerebellum
gence factors for the climbing fiber input are small (1:1). whose axons bypass the deep cerebellar nuclei and project on the
Incoming fibers (climbing and mossy) to the cerebellum thus lateral vestibular nucleus in the brain stem. Extracere-
excite Purkinje and granule cells of the cerebellar cortex, as well bellar targets of deep cerebellar nuclei (Figures 15–18 to
as the deep cerebellar nuclei. Purkinje cells are excited directly by 15–20) include the vestibular and reticular nuclei of the
climbing fibers and indirectly (via the granule cell) by mossy brain stem (from the nucleus fastigii), the red nucleus in the mid-
fibers. The excitation of Purkinje cells is modulated by several brain and the inferior olivary nucleus in the medulla (from the in-
feedback circuits (via basket and stellate inhibitory interneurons) terposed nucleus), the thalamus (from the dentate and interposed
that inhibit Purkinje cell activity and suppress transmission of nuclei), and the hypothalamus (from all deep cerebellar nuclei).
impulses from Purkinje cells to deep cerebellar nuclei. The out- Efferents from the cerebellum leave via the inferior and supe-
put of Purkinje cells to the deep cerebellar nuclei is thus a finely rior cerebellar peduncles (Figure 15–21). Cerebellovestibular and
modulated inhibitory signal. The output of the deep cerebellar cerebelloreticular fibers travel via the inferior cerebellar pedun-
nuclei to extracerebellar targets is thus the product of excitatory cle, whereas the cerebellothalamic, cerebellorubral, and cerebello-
input from climbing and mossy fibers and inhibitory projections olivary fibers travel via the superior cerebellar peduncle. The su-
from Purkinje cells (Figure 15–16). perior cerebellar peduncle crosses in the midbrain tegmentum
The mossy fiber pathways conduct faster than the climbing (at the inferior colliculus level) and projects on the contralateral
fiber pathways. However, the ultimate inhibitory potentials pro- red nucleus and ventrolateral nucleus of the thalamus. A small
duced by the mossy fiber system develop slowly so that by the fascicle from this crossed system descends to the inferior olivary
time the climbing fiber input arrives in the cerebellum, the full nucleus. The cerebellum exerts its most important influence on
effect of the mossy fiber inhibitory potentials has not yet devel- the motor and premotor cortices via the ventrolateral nucleus of
oped. This allows the climbing fiber system to act on the back- the thalamus. Electrophysiologic studies show that pyramidal
ground activity of excitation and inhibition initiated by the tract neurons in the motor and premotor cortices receive di-
mossy fiber input. synaptic or trisynaptic excitatory inputs from the dentate and in-
Thus, of all the cells of the cerebellar cortex, only the granule terposed nuclei after relays in the ventrolateral thalamic nucleus.
cell is excitatory; all others, including the Purkinje cells, are in- Other corticofugal neurons in the motor and premotor cortices,
hibitory. Recent studies on the cerebellum have given the Golgi such as those which project to the red nucleus, pontine nuclei,
Inhibitory –
interneurons
+ Purkinje +
neuron
Granule +
cell
+
–
+ Deep cerebellar +
nuclei
Mossy Climbing
Figure 15–16. Schematic diagram of the intrinsic cere- fibers fibers
bellar circuitry. , excitation; , inhibition. Cerebellar output
212 / CHAPTER 15

topographic projections of Purkinje cells of
different cerebellar zones into the respective
deep cerebellar nuclei.
and spinal cord, also receive cerebellar fibers. In addition to the “Lucky Dude Engages Girl From Montana” where L is for lat-
motor and premotor cortices, the cerebellum projects to the eral, D for dentate, E for emboliform, G for globose, F for fastigii,
parietal and temporal association cortices. and M for medial.
DEEP CEREBELLAR NUCLEI Dentate Nucleus

The deep cerebellar nuclei are embedded in the white matter The dentate nucleus is composed of multipolar neurons and re-
core of the cerebellum. There are four pairs of nuclei arranged sembles the inferior olive in configuration. It receives the axons
from lateral to medial as follows: dentate, emboliform, globose, of Purkinje cells located in the lateral part of the cerebellar hemi-
and fastigi (Figure 15–5). A mnemonic used frequently to re- spheres and collaterals of climbing and mossy fibers. The Purkinje
member the lateral to medial order of deep cerebellar nuclei is
Efferents Afferents
Cerebral
Efferents Afferents
cortex
Cerebral
cortex
Thalamus Paravermal
ventrolateral zone
nucleus Purkinje cells
Thalamus Lateral cerebellar

ventrolateral hemisphere Red
nucleus Purkinje cells nucleus
BC Interposed –
nuclei
Dentate – + +
BC nucleus Inferior
+ + olive MF CF
MF CF
Figure 15–18. Schematic diagram showing the afferent and Figure 15–19. Schematic diagram showing the afferent and
efferent connections of the dentate nucleus. , facilitation; , in- efferent connections of the interposed nuclei. , facilitation; ,
hibition; CF, Climbing fiber; MF, mossy fiber; BC, brachium inhibition; CF, climbing fiber; MF, mossy fiber; BC, brachium
conjunctivum. conjunctivum.
CEREBELLUM / 213
(+)
NUCLEUS FASTIGIII
(–) (+)
(+)
(+)
(+) (+)
Figure 15-20. Schematic diagram showing the

afferent and efferent connections of the nucleus
fastigii. , facilitation; , inhibition.
cell input is inhibitory, whereas the inputs from climbing and The interposed nuclei receive afferent fibers from the follow-
mossy fibers are excitatory to the dentate nucleus (Figure 15–18). ing sources (Figure 15–19):
The bulk of axons of the dentate nucleus project via the supe- 1. Axons of Purkinje cells in the paravermal (intermediate)
rior cerebellar peduncle (brachium conjunctivum) to the con- zone of the cerebellum that are inhibitory in function
tralateral ventrolateral nucleus of the thalamus. A relatively small
number of axons project to the intralaminar nuclei of the thala- 2. Collaterals from climbing and mossy fiber systems that are
mus (mainly the central lateral nucleus), to the rostral third of excitatory in function
the red nucleus (origin of rubroolivary tract), and, via the de- Axons of interposed nuclei leave the cerebellum via the supe-
scending limb of the brachium conjunctivum, to the reticu- rior cerebellar peduncle (brachium conjunctivum). The bulk
lotegmental nucleus and inferior olive. projects on neurons in the caudal two-thirds of the red nucleus
The expansion of the dentate nucleus and the lateral cerebellar (the part that gives rise to the rubrospinal tract). A smaller num-
hemisphere in the course of hominid evolution provided the ber of axons project on the ventrolateral nucleus of the thalamus
neural basis for novel cerebellar trajectories and new functions. and, via the descending limb of the brachium conjunctivum, to
The phylogenetically older part of the dentate nucleus (the dorso- the inferior olive.
medial part) maintains connections with the motor cortex via the
motor thalamus (ventrolateral nucleus) and with the spinal cord Fastigial Nucleus
via the red nucleus, in line with the traditionally established role
of the cerebellum in motor control. The phylogenetically newer This nucleus is located in the roof of the fourth ventricle medial
part of the dentate nucleus (the ventrolateral part), in contrast, to the globose nucleus; hence it is called the roof nucleus. It re-
has connections, in addition to the motor cortex, with the pre- ceives afferent fibers from the following sources (Figure 15–20):
frontal cortex, which has expanded in parallel with the dentate 1. Axons of Purkinje cells in the vermis of the cerebellum that
nucleus in the course of hominid evolution. Evidence is accumu- are inhibitory in function
lating in favor of a nonmotor function of the neodentate nucleus. 2. Collaterals of mossy and climbing fiber systems that are
excitatory
Interposed Nuclei
In contrast to efferents from the dentate and the interposed
These nuclei include the emboliform nucleus, located medial to nuclei, efferents of the fastigial nucleus do not travel via the bra-
the hilum of the dentate nucleus, and the globose nucleus, lo- chium conjunctivum. A large number of fastigial efferents cross
cated medial to the emboliform nucleus (Figure 15–5). within the cerebellum and form the uncinate fasciculus. Uncrossed
214 / CHAPTER 15
climbing fibers) and an inhibitory input from the cerebellar cor-

tex (axons of Purkinje cells). In contrast, the output of the deep
cerebellar nuclei is excitatory.
CEREBROCEREBELLAR AND
CEREBELLOCEREBRAL CIRCUITRIES
The cerebral cortex communicates with the cerebellum via a
multitude of pathways, of which the following are well recog-
nized (Figure 15–22):
1. Corticoolivocerebellar via the red nucleus and inferior oli-
vary nucleus
2. Corticopontocerebellar via the pontine nuclei
3. Corticoreticulocerebellar via the reticular nuclei of the brain
stem
The first two pathways convey to the cerebellum precisely
localized and somatotopically organized information. Of these
two, the pathway via the pontine nuclei is quantitatively more
impressive. The pathway via the reticular nuclei is part of a
system with diffuse input and output (reticular formation), in
which information of cortical origin is integrated with informa-
tion from other sources before transmission to the cerebellum.
The cerebellum influences the cerebrum mainly via the den-
tatothalamic system. The cerebellocerebral pathways are modest
in number when compared with the cerebrocerebellar pathways
(approximately 1:3). This is a reflection of the efficiency of the
cerebellar machinery that makes it possible for the cerebellum to
regulate cortically originating signals for movement. Cortico-
Inferior
Olive
cerebellar fibers originate from motor and nonmotor (associative
and limbic) areas of the cerebral cortex. Similarly, cerebellar out-
put fibers target both motor and nonmotor cerebral cortical areas.
NEUROTRANSMITTERS
Figure 15–21. Schematic summary diagram showing the cere- The following neurotransmitters have been identified in the cere-
bellum: gamma-aminobutyric acid (GABA), taurine, glutamate,
bellar output via the superior cerebellar peduncle (SCP) and infe-
aspartate, acetylcholine, norepinephrine, serotonin, and dopamine.
rior cerebellar peduncle (ICP). CBL, cerebellum.
fastigial fibers join the juxtarestiform body. The bulk of fastigial

efferents project on the vestibular nuclei (lateral and inferior)
and several reticular nuclei of the brain stem. Fastigial projec-
tions to vestibular nuclei are bilateral. Fastigioreticular fibers are
mainly crossed. A small number of fastigial efferents course ros-
trally in the brain stem to project on the superior colliculus, nu-
clei of the posterior commissure, and the ventrolateral thalamic
nucleus.
In addition to the efferent projections of the deep cerebellar
nuclei described above, all deep cerebellar nuclei have been
shown to send axon collaterals to the areas of the cerebellar cor-
tex from which they receive fibers; thus the nucleus fastigii sends
axon collaterals to the cerebellar vermis, the interposed nuclei to
the paravermal region, and the dentate nucleus to lateral parts of
the cerebellar hemispheres. Although deep cerebellar nuclei re-
ceive axons of Purkinje cells, their axon collaterals do not project
directly on Purkinje cells but on neuronal elements in the gran-
ule cell layer via the mossy fiber system. The exact cell type in the
granule cell layer that receives these axon collaterals has not been
identified with certainty. Figure 15–22. Schematic diagram of cerebrocerebellar and
Thus all the deep cerebellar nuclei receive a dual input; these cerebellocerebral connections. Heavy arrows denote quantita-
are an excitatory input from extracerebellar sources (mossy and tively significant pathway.
CEREBELLUM / 215
GABA is liberated from axons of Purkinje, basket, and Golgi mately 20 to 40 Hz, granule cells at 50 to 70 Hz, and inhibitory
neurons and exerts an inhibitory effect on target neurons. Taurine interneurons (basket, stellate, and Golgi) at 7 to 30 Hz. This high
is believed to be the inhibitory neurotransmitter of the super- discharge rate of cerebellar neurons is derived from the nature of
ficial stellate cells; taurine levels are high in the molecular layer their synaptic drive.
and drop substantially when stellate cell development is blocked Stimulation of the mossy fiber system or of the parallel fibers
by x-irradiation. Glutamate is believed to be the excitatory neu- (axons of granule cells) elicits in the Purkinje cell a brief excita-
rotransmitter of granule cells; glutamate levels in the granule cell tory postsynaptic potential (EPSP) (simple spike) lasting 5 to
layer drop substantially in the agranular cerebellum of virus- 10 ms, followed by a prolonged inhibitory postsynaptic potential
infected and mutant mice. Glutamate has also been reported to (IPSP). The short EPSP is attributed to the activation of Purkinje
be the excitatory neurotransmitter in climbing and mossy fibers. cell dendrites by the parallel fibers. The IPSP, on the other hand,
Acetylcholine has been reported in granule cells, Golgi cells, and is attributed to the feedforward inhibition of Purkinje cells by
mossy fibers. Glycine, enkephalin, and somatostatin have been stellate and basket cells that are activated simultaneously by the
reported in Golgi cells. Norepinephrine is the inhibitory neuro- beam of parallel fibers (Figure 15–23).
transmitter of the locus ceruleus projection on Purkinje cell den- Stimulation of the climbing fiber system elicits in the
drites. In addition to its presumed role in maturation of Purkinje Purkinje cell an intense and prolonged reaction characterized by
neurons, norepinephrine seems to modulate Purkinje cell re- an initial large spike followed by several small ones. This pattern
sponse to other cerebellar neurotransmitters. Stimulation of the is referred to as a complex spike. This complex EPSP is followed
locus ceruleus enhances sensitivity of Purkinje neurons to both by a prolonged IPSP. The complex spike is explained on the ba-
glutamate and GABA. Serotonin and dopamine are released in sis of more than one mechanism. One mechanism for this com-
terminals of projections from the raphe nuclei and midbrain plex spike in the Purkinje cell is the repetitive discharge emanat-
dopamine neurons, respectively. ing from inferior olive neurons because of axonal collaterals
within the inferior olive. Another mechanism for the complex
response of Purkinje cells lies in the intrinsic property of their
CEREBELLAR PHYSIOLOGY membranes. The IPSP that follows the complex EPSP is attrib-
Cerebellar Cortex uted to simultaneous activation of stellate and basket cells by the
climbing fibers, which in turn inhibit the Purkinje cell by a feed-
Cerebellar neurons are characterized by high rates of resting im- forward pathway. Both mossy and climbing fibers facilitate the
pulse discharge. Purkinje cells discharge at the rate of approxi- Golgi cell, which in turn inhibits the granule cell and can thus
Basket
− + PF + MF
& Granule
Stellate Cell
Cells
+
−
Golgi
Cell −
IPSP +
−
+
EPSP(SS)
Purkinje
Cell
+ CF
EPSP(CS)

showing the mechanism of generation
of excitatory (EPSP) and inhibitory (IPSP)
postsynaptic action potentials in the
Purkinje cell. MF, mossy fiber; CF, climb- Deep Cerebellar
ing fiber; PF, parallel fibers; SS, simple Nuclei
spike; CS, complex spike.
216 / CHAPTER 15
contribute to Purkinje cell inhibition. After their initial activa- C. HUMAN BRAIN INJURIES
tion by the mossy and climbing fiber input, intrinsic neurons Gordon Holmes, in the first quarter of the 20th century, concep-
(basket, stellate, and Golgi) ultimately are inhibited by Purkinje tualized about cerebellar function from observations made on
axon collaterals. The action of the recurrent Purkinje axon collat- patients who received bullet wound injuries to the cerebellum
erals is thus to disinhibit the Purkinje cell. during the first world war. Thus was coined the Holmes triad of
It becomes evident from the preceding that the mossy and asthenia, ataxia, and atonia.
climbing input fibers are excitatory to the granule and Purkinje
cells, whereas the action of all other cells within the cerebellum D. THE ERA OF IMAGING
(except the granule cell) is inhibitory. It is thus not possible for The use of imaging (computerized axial tomography and mag-
cerebellar activity in response to an afferent input to be sustained. netic resonance imaging) in the mid-1970s and 1980s permitted
Several investigators have studied the effects of cerebellar a better correlation of lesions and disturbance of function.
stimulation in humans. The results of such stimulation are simi-
lar to those described above. Motor Functions of the Cerebellum
Deep Cerebellar Nuclei The cerebellum traditionally has been relegated a motor func-
tion. As early as 1822, Flourens showed that the cerebellum was
Like the Purkinje cells, deep nuclei have high rates of impulse
concerned with coordination of movement, and in 1891, Italian
discharge at rest. Also like the Purkinje cells, the deep cerebellar
physiologist Luigi Luciani described the triad of cerebellar signs:
nuclei receive both excitatory and inhibitory inputs, the former
atonia, asthenia (weakness), and astasia (motor incoordination).
arriving via the climbing and mossy fibers and the latter by axons
Later he added a fourth sign, dysmetria.
of Purkinje cells (Figure 15–16). Thus a mossy fiber input, for
Based on studies conducted by Gordon Holmes in the first
example, will cause first a high-frequency burst in the deep cere-
quarter of the 20th century on patients with wound injuries to the
bellar nuclei followed by a lowering of the frequency as a result
cerebellum, the Holmes motor triad of asthenia (easy fatigability),
of inhibition arriving through the slower Purkinje cell loop.
ataxia, and atonia became synonymous with cerebellar disease.
Purkinje cell inhibition is mediated by gamma-aminobutyric acid
Subsequent clinical and experimental studies confirmed a role for
(GABA).
the cerebellum in control and integration of motor activity.
CEREBELLAR FUNCTION Neocerebellar Signs
Historical Perspective The cerebellum is generally thought to integrate motor com-
The cerebellum has puzzled and fascinated anatomists, physiolo- mands and sensory information to help coordinate movement.
gists, and clinicians since its early description by Aristotle and The incoordination of movement noted in diseases of the neo-
Galen. Early observers attributed to it roles as controller of mo- cerebellum is the result of disturbances in speed, range, force, or
tor nerves, seat of memory, director of automatic and involun- timing of movement. These are manifested clinically in
tary visceral movements, and the seat of sexual activity. Fluorens’ the following neocerebellar signs: dyssynergia or asyner-
experiments from 1822 to 1824 showed that the cerebellum was gia, dysarthria, adiadochokinesis, dysmetria, tremor, mus-
concerned with coordination of movement. Fraser in 1880 con- cular hypotonia, ataxia, and nystagmus.
sidered it the seat of sexual appetite. The lack of uniform velocity is responsible for the irregular
and jerky movements of extremities (dyssynergia or asynergia)
A. PHRENOLOGIC ERA of cerebellar disease. Asynergy of muscles of articulation is re-
In phrenologic maps of the brain, the cerebellum was the pri- sponsible for the slow, slurred speech (dysarthria) of cerebellar
mary anatomic locus of amative (sexual) love. The overlying disorders.
occipital pole was the locus of maternal/paternal love. Analysis Proper timing in initiation and termination of movement is
of cerebellar morphology was an important prenuptial check. also essential in the execution of smooth movement. A delay in
Cagey lovers were reported to perform a discrete examination of the initiation of each successive movement will lead to the adiado-
the crania of prospective partners to check on the degree of chokinesis (disturbance in performance of rapid movement us-
prominence of their occipital ridge. Circulated reports at the ing antagonistic muscle groups) of cerebellar disease. A delay in
time described a well-known society physician with a markedly the termination of movement results in dysmetria. Dysmetria
prominent occipital ridge who outlived three wives and required can manifest as overshooting intended target (hypermetria), or
the attention of four mistresses. Another described a Viennese undershooting intended target (hypometria). Thus, adiadocho-
fortune teller, famous for his libidinous desires, whose autopsy kinesis and dysmetria are the result of an error in timing.
revealed a marked degree of cerebellar hypertrophy. It was also Intention (volitional) tremor is due to defective feedback
believed at the time that the cerebellum and external genitalia control from the cerebellum on cortically initiated movement.
were lateralized and reciprocally activating such that an injury to Normally, cerebellar feedback mechanisms control the force and
the left testicle was expected to result in atrophy of the contralat- timing of cortically initiated movement. Failure of these mecha-
eral cerebellar hemisphere. nisms in cerebellar disease results in tremor. The cerebellum is
able to exert its corrective influence on cortically originating
B. EXPERIMENTAL ERA (19TH CENTURY ) movement by virtue of the input it receives from the cerebral
The experimental era of cerebellar function was ushered in by the cortex and periphery. The cerebral cortex informs the cerebellum
studies of Magendie, Cuvier, and Rolando. The experimentalists of intended movement via the cerebrocerebellar pathways de-
described the phrenologist perspective as a collection of absurdi- scribed previously. During movement, the cerebellum receives
ties, incoherence, and gross ignorance. Surgical lesions in cere- also a constant flow of information, both proprioceptive and
bella of experimental animals resulted in various degrees of ipsi- exteroceptive, from peripheral receptors (e.g., muscle spindle,
lateral weakness, disequilibrium, and loss of motor coordination. Golgi tendon organ) concerning movement in progress. The
CEREBELLUM / 217
cerebellum correlates peripheral information on movement in and divergence occur in response to changes in position of a visual
progress with central information on intended movement and target along the far–near axis.
corrects errors of movement accordingly. The cerebellum thus The posterior lobe vermis (oculomotor vermis) and the cau-
serves to optimize cortically originating movement using sensory dal nucleus fastigii to which it projects are necessary for horizon-
information. Based on the cerebellar role in sensory-motor inte- tal saccades and make them fast, accurate, and consistent. In le-
gration, it has been suggested that the cerebellum might be in- sions of the caudal fastigial nucleus, saccades are inaccurate, slow,
volved in generating the prediction of the sensory consequences and abnormally variable in size and speed. The caudal fastigial
of movement. Such a role may explain why we cannot tickle nucleus influences saccadic machinery via its projections to sac-
ourselves. cade-related neurons in the brain stem (excitatory burst neurons,
In addition, the cerebellum may be involved in motor learn- inhibitory burst neurons, omnipause neurons). The interpositus
ing and the initiation of movement. Long-lasting changes in nucleus is related to vertical saccades. Both the caudal fastigial
synaptic efficacy may take place in the cerebellar cortex during nucleus and the floccculus/paraflocculus are necessary for nor-
motor learning, suggesting that the cerebellum may be capable mal smooth pursuit eye movements. The caudal fastigial nucleus
of remembering what was done and thereby adapting its influ- is believed to be important in pursuit initiation and the flocculus
ence on motor neurons in accordance with the outcome of in pursuit maintenance. In addition to playing a role in saccades
movement. Experimental evidence suggests that deep cerebellar and smooth pursuit, the caudal fastigial nucleus and interpositus
nuclei fire simultaneously with pyramidal cortical neurons prior nucleus also influence vergence eye movements.
to movement.
The cerebellum also influences movement via its effects on
the gamma system. The cerebellum normally increases the sensi- Cerebellum and Epilepsy
tivity of muscle spindles to stretch. Cerebellar lesions are associ- Cerebellar stimulation has been shown to have beneficial effects
ated with a depression of gamma motor neuron activity that on both experimentally induced epilepsy and human epilepsy.
leads to erroneous information in the gamma system about the The results are variable, and more study is needed before the role
degree of muscle stretch. The erroneous information conveyed of the cerebellum in the control of epilepsy can be defined clearly.
by the muscle spindle to the alpha motor neuron results in dis-
turbances in discharge of the alpha motor neuron and is mani-
fested by a disturbance in force and timing of movement. Complementarity of Basal Ganglia
The depression of tonic activity of gamma motor neurons in and Cerebellum in Motor Function
cerebellar disease is also the basis of the hypotonia associated
with neocerebellar syndromes. The ataxia of neocerebellar lesions Review of basal ganglia and cerebellar structure, connectivity,
are usually appendicular (unsteady limb movement). The nystag- and organization reveals many features in common. Both are
mus (rhythmic oscillation of eye movements) seen in neocerebel- components of the motor system, influence cerebral cortical ac-
lar lesions is apparent with horizontal ocular movement and re- tivity via the thalamus, are linked with the cerebral cortex via re-
flects dysmetria of eye tracking. current loops, have internal (local) circuitry that modulates
loop activity, receive modulating inputs that influence their ac-
tivities (climbing fibers in the cerebellum and dopaminergic in-
Archicerebellar and Paleocerebellar Signs put in the basal ganglia), have a high convergence ratio of
The archicerebellum and paleocerebellum influence spinal activ- inputs on their principal neurons (spiny neuron in the basal
ity via the vestibulospinal and reticulospinal tracts. Archicerebellar ganglia and Purkinje cell in the cerebellum), and play a role in
signs are usually associated with lesions in the flocculonodular pattern recognition.
lobe and are manifested by truncal ataxia (staggering gait and The emerging concept (Figure 15–24) of the complementar-
unsteady posture while standing) and nystagmus (rhythmic ity of basal ganglia and cerebellar roles in motor function sug-
oscillation of the eyes at rest and/or with ocular movements). gests that the basal ganglia function as detectors of specific con-
Paleocerebellar lesions are rare in humans and usually affect the texts, providing to the cerebral cortex information that could be
anterior lobe. The increase in myotatic and postural reflexes asso- useful in planning and gating of action. The cerebellum, in con-
ciated with the anterior lobe syndrome is due to an increase in trast, functions in programming, execution, and termination of
motor signals to the alpha motor neurons and a simultaneous actions. According to this concept, the cerebral cortex, which re-
decrease in signals to the gamma system. Thus, the rigidity of ceives diverse sensory information from the periphery via the dif-
cerebellar disease is an alpha type of rigidity. In humans, un- ferent ascending tracts as well as complex information already
steadiness of gait (gait ataxia) may be the only manifestation of processed within the basal ganglia and cerebellum, serves two
paleocerebellar lesions. functions: a repository function to receive this diverse informa-
tion, compute it, and share it with the basal ganglia and cerebel-
Ocular Motor Signs lum and an executive function to implement the action emanat-
ing from its collective computation process.
The cerebellum is necessary for the production of both accurate Another complementarity model (Figure 15–25), based on
saccadic and smooth pursuit movements. Evidence is accumulat- the roles of the cerebellum and basal ganglia in both motor and
ing for a role of the cerebellum in vergence eye movements. cognitive functions, suggests that cerebellum, basal ganglia, and
Saccades are the voluntary rapid eye movements that move cerebral cortex are specialized for different types of learning.
our eyes from one visual target to another. The objective of According to this model, the cerebellum is specialized for super-
smooth pursuit eye movements is to reduce the slip of a visual vised (error-based) learning, guided by the error signal encoded
image over the fovea to velocities slow enough to allow clear vi- in the climbing fiber input from the inferior olive. The basal
sion. Vergence is simultaneous movement of both eyes in differ- ganglia are specialized for reinforcement (reward-based) learn-
ent directions. Convergence is movement of both eyes nasally; ing, guided by the reward signals encoded in the dopaminergic
divergence is movement of both eyes temporally. Convergence input from the substantia nigra. The cerebral cortex is specialized
218 / CHAPTER 15
Figure 15–24. Schematic diagram showing the complementarity of the cerebellum and basal ganglia in motor function.
for unsupervised learning guided by the statistical properties of been reported, including cardiovascular and endocrine changes;
the input signal regulated by ascending neuromodulatory inputs. altered respiration, intestinal motility, and bladder tone; reduced
aggressiveness; mood changes; and alerting reactions. These vis-
Nonmotor Functions of the Cerebellum ceral and affective responses were believed to be mediated
through cerebellar connections with brain stem reticular nuclei.
A growing body of data suggest a nontraditional role for Evidence for a complex network of pathways between the hypo-
the cerebellum in the regulation of autonomic function, thalamus and cerebellum suggests an alternate mechanism for
behavior, and cognition. Following cerebellar ablation these responses.
or stimulation, a multitude of visceral and affective responses has The possibility that the cerebellum may be involved in non-
motor function was first suggested by phrenologists in the eigh-
teenth and nineteenth centuries and by later studies dating back
almost half a century. The founder of phrenology, Franz Gall,
Input Output considered the primary function of the cerebellum to be a locus
CEREBRAL of the emotion of love.
CORTEX
Reports of neuropsychological dysfunction in patients with
developmental and acquired cerebellar pathology and neuro-
imaging studies in normal adults have given credence to the pro-
Reward BASAL posed involvement of the cerebellum in “higher-order” nonmotor
Based GANGLIA processes. Psychiatric disorders (schizophrenia, manic depression,
and dementia) have been reported in association with cerebellar
agenesis or hypoplasia by some authors but not by others.
Substantia
Nigra
Damage to the cerebellum has been shown to impair rapid and
accurate mental shifts of attention between and within sensory
modalities. Increased planning and word-retrieval time have
Error-Based
CEREBELLUM been described in patients with cortical cerebellar atrophy; pro-
found deficits in practice-related nonmotoric learning have been
reported in association with right-sided cerebellar infarcts; and
Inferior transient mutism has been reported following posterior fossa
olive craniectomy for cerebellar tumors and following bilateral stereo-
tactic lesions of the dentate nucleus. Mutism and agrammatic,
Figure 15–25. Schematic diagram showing error-based cere- Broca’s aphasia-like speech have also been described with right
bellar and reward-based basal ganglia feedback inputs to the cerebellar infarcts. Data from positron-emission tomography
cerebral cortex. (PET), functional magnetic resonance imaging (fMRI), and sin-
CEREBELLUM / 219
Table 15–4. Functions of Cerebellum
Region Motor function (established) Nonmotor function (proposed)
Archicerebellum Equilibrium and posture Primitive autonomic responses, emotion, affect,

sexuality, affectively important memory
(“limbic” cerebellum)
Neocerebellum Coordination of extremity movement Modulation of thought, planning, strategy
formation, spatial and temporal parameters,
learning, memory, language
gle photon emission computed tomography (SPECT) seem to cerebellar lobe a role in behavior and cognition (Table 15–4).
confirm a role for the cerebellum in nonmotor function. Neo- Thus the archicerebellum may be concerned not only with con-
cerebellar areas are metabolically active during language and cog- trol of equilibrium and posture but also with primitive defense
nitive processes such as the association of verbs to nouns, mental mechanism such as the “fight or flight” response, emotion, affect,
imagery, mental arithmetic, motor ideation, and learning to rec- and sexuality, whereas the neocerebellum may be concerned, in
ognize complicated figures, whereas vermal and paravermal addition to coordination of rapid movement of the extremities,
structures are metabolically active during panic and anxiety with modulation of thought, planning, strategy formation, spa-
states. Developmental dyslexia and autism have been reported in tial and temporal parameters, learning, memory, and language.
developmental cerebellar disorders.
Stimulation of the fastigial nucleus in animals has been re- The Cerebellum and Autism
ported to produce an alerting reaction, grooming response, sav-
age predatory attack, and outbursts of sham rage, suggesting that In 1987, Courchesne and colleagues were the first to report
the fastigial nucleus may serve a modulatory role for emotional hypoplasia of cerebellar vermis and hemispheres in MRI scans
reactions. Following lesions in the cerebellar vermis, aggressive of autistic patients and to suggest that the abnormality may be
monkeys are reported to have become docile, and chronic cere- responsible for the deficits in attention, sensory modulation,
bellar stimulation in humans has been reported to reduce anxi- and motor and behavioral initiation seen in this disorder. In
ety, tension, and aggression. subsequent imaging studies, vermal hypoplasia and hyperpla-
The reported association between cerebellar disorders and sia as well as normal cerebellar morphology have been re-
cognition and behavior does not necessarily imply causality, how- ported. Neuropathologic studies of autistic patients describe
ever. Whether the cognitive and behavioral manifestations re- loss of Purkinje and granule cells in the vermis and hemi-
ported in cerebellar disorders are due to the cerebellar lesion spheres as well as neurons in nucleus fastigii of possible pre-
itself or are secondary to associated cerebral hemisphere dysfunc- natal onset. The cerebellum, however, is not the only site in
tion remains unsettled. The cerebellum and cerebral cortex are the central nervous system to be impaired in autistic disorders.
closely related anatomically and functionally. Other studies have shown reduction in the size of the brain
Based on the available behavioral and cognitive data, a new stem, posterior portion of corpus callosum, parietal lobes,
concept of cerebellar function has evolved that assigns to each amygdala, and hippocampus.
Posterior Inferior
Cerebellar Artery
(PICA)
Anterior Inferior
Cerebellar Artery
(AICA)
Figure 15–26. Photograph of the ventral surfaces of the cerebellum showing the territories of ar-
terial supply.
220 / CHAPTER 15
Superior
Cerebellar
Artery
(SCA)
Posterior
Inferior
Cerebellar
Artery Figure 15–27. Photograph of the
(PICA) dorsal surfaces of the cerebellum show-
ing the territories of arterial supply.
SENSORY SYSTEMS AND CEREBELLUM the size of the infarct with cerebellar, vertebral, or basilar artery
occlusions.
Although the cerebellum is generally regarded as a motor center,
studies suggest that it has a role in sensory mechanisms. The VENOUS DRAINAGE
cerebellum has been shown to receive tactile, visual, and audi-
tory impulses. Furthermore, reciprocal connections have been The cerebellum is drained by three veins: superior, posterior, and
demonstrated between the cerebral and cerebellar tactile, visual, anterior. The superior vein drains the entire superior surface of
and auditory areas. the cerebellum and empties into the great cerebral vein of Galen.
The posterior vein drains the posterior part of the inferior surface
ARTERIAL SUPPLY and empties into the straight or transverse sinus. The anterior
vein, known to neurosurgeons as the petrosal vein, is a constant
The cerebellum is supplied by three long circumferential arteries vein that drains the inferoanterior surface of the cerebellum and
arising from the vertebral basilar system: (1) the posterior inferior empties into the superior or inferior petrosal sinus.
cerebellar artery (PICA), (2) the anterior inferior cerebel-
lar artery (AICA), and (3) the superior cerebellar artery
(SCA). TERMINOLOGY
The posterior inferior cerebellar artery (PICA) arises from the
Archicerebellum (Greek arche, “beginning”). Phylogenetically
rostral end of the vertebral artery and supplies most of the infe-
old part of the cerebellum concerned with equilibrium and
rior surface of the cerebellum (Figure 15–26), including the cere-
posture.
bellar hemispheres, inferior vermis, and the tonsils. It also sup-
plies the choroid plexus of the fourth ventricle and gives collaterals Astasia (Greek a, “without”; stasis, stand). Motor incoordination.
from its medial branch to supply the dorsolateral medulla. Asthenia. (Greek a, “without”; sthenos, “strength”). The as-
The anterior inferior cerebellar artery (AICA) arises from the thenic habitus is a thin, frail person.
caudal third of the basilar artery. Because of its usual small size, it Asynergia (Greek synergia, “cooperation”). Lack of coordina-
supplies a small area of the anterolateral part of the inferior sur- tion among parts. Disturbance of proper association in the con-
face of the cerebellum (Figure 15–26). Proximal branches of the traction of muscles that ensures that the different components of
artery usually supply the lateral portion of the pons, including an act follow in proper sequence and at the proper moment so
the facial, trigeminal, vestibular, and cochlear nuclei, the roots of that the act is executed accurately.
the facial and cochleovestibular cranial nerves, and the spinotha- Ataxia (Greek taxis, “order”). Want of order; lack of coordina-
lamic tract. When there is a large AICA, the ipsilateral PICA is tion, resulting in unsteadiness of movement. The term was used
usually hypoplastic, and the AICA territory then encompasses by Hippocrates and Galen for any morbid state, especially one
the whole anteroinferior aspect of the cerebellum. with disordered or irregular action of any part, such as irregular-
The superior cerebellar artery (SCA) is the most constant in ity of the pulse.
caliber and territory of supply. It arises from the rostral basilar Brachium (Latin “arm”). Denotes a discrete bundle of inter-
artery. The SCA supplies most of the superior surface of the cere- connecting fibers.
bellar hemisphere and vermis (Figure 15–27) as well as the deep
cerebellar nuclei. Along its course, branches of the SCA supply the Cerebellum (Latin “little brain”). The hind brain, located in
lateral tegmentum of the rostral pons, including the superior cere- the posterior fossa.
bellar peduncle, spinothalamic tract, lateral lemniscus, descending Cuvier, Baron de la (1769–1832). French anatomist and natu-
sympathetics, and more dorsally, the root of the trochlear nerve. ralist. He is best known for classification of the animal world in
The three circumferential arteries and their branches are con- his La Règne Animal published in 1817.
nected by numerous free cortical anastomoses that help limit Dentate nucleus (Latin dentatus, “toothed”). Like a tooth.
CEREBELLUM / 221
Dysmetria (Greek dys, “difficult”; metron, “a measure”). Neocerebellum (Greek neos, “new”; Latin cerebellum, “small
Difficulty in accurately controlling (measuring) the range of brain”). Phylogenetically new part of the cerebellum.
movement. Occurrence of errors in judgment of distance when a Nystagmus (Greek nystagmos, “nodding in sleep”). Rhythmic
limb is made to perform a precise movement. involuntary oscillatory movements of the eyes. The term is said
Emboliform nucleus (Greek embolos, “plug”; Latin forma, to have been first used by Plenck. The association of these eye
“form”). Plug-shaped. The emboliform nucleus plugs the open- movements with vertigo was first noted by Purkinje and further
ing of the dentate nucleus. investigated by Flourens.
Fastigial nucleus (Latin fastigium, “apex of a gabled, pointed Paleocerebellum (Greek palaios, “ancient”; Latin cerebellum,
roof ”). The roof nucleus. The nucleus fastigii is located in the “little brain”). Phylogenetically old part of the cerebellum.
pointed roof of the fourth ventricle. Peduncle (Latin pedunculus, “little foot”). Stemlike or stalk-
Fluorens, Marie-Jean-Pierre (1794–1867). French comparative like process by which an anatomic part is joined to the main or-
anatomist who suggested that functions were precisely located in gan. The cerebellar peduncles connect the brain stem with the
many parts of the cerebral cortex. He identified the cerebellum as cerebellum.
concerned with motor coordination, although he wrongly sup- Purkinje, Johannes Evangelista von (1787–1869). Bohemian
posed that this control is exerted contralaterally. He correctly as- priest and professor of physiology at Breslau and Prague.
cribed to the vestibular system a role in vertigo and nystagmus. Described the Purkinje cells in the cerebellum in 1837. Besides
his professional duties, he served as newspaper editor and mem-
Gall, Franz (1758–1829). Viennese physician and anatomist. ber of the Czech parliament. His interest in experimentation led
Founder of the discipline of phrenology, and father of cerebral him to induce seizures in himself by taking camphor. Because of
localization. Described the cervical and lumbar enlargements his ethnicity and his eclectic research, he was known as the
of the spinal cord, differentiated gray from white matter, and “gypsy physiologist.”
described the origins of the optic, oculomotor, trochlear, and
abducens cranial nerves. He is best known, however, for cere- Restiform body (Latin restis, “cord or rope”; forma, “form or
bral localization of function. He isolated 26 brain areas and re- shape”). The inferior cerebellar peduncle has a cordlike appearance
lated them to intellect, sentiments, and mental attribute—most on the dorsolateral surface of the medulla. The restiform body was
of which turned out to be ill-founded. After decades of success, described and named by Humphrey Ridley (1653–1708), an
the discipline of phrenology fell into disrepute when it was English anatomist, in Anatomy of the Brain (London, 1695, p. 78).
claimed as a method for selecting members of parliament among Rolando, Luigi (1773–1831). Italian anatomist. Best known for
others. describing the central sulcus in 1825 (named after him by Leurat
in 1839). Leurat was unaware of the earlier description by Vicq
Globose nucleus (Latin globus, “a ball”). Rounded. The glo- d’Azir. He also is accredited for describing the substantia gelatinosa
bose nucleus is rounded (spherical) in shape. of the spinal cord and ipsilateral motor function of the cerebellum.
Glomerulus (Latin glomero, “to wind into a ball”). Small, Tentorium cerebelli (Latin tentorium, “a tent”). Horizontal
rounded synaptic configuration around mossy fiber rosettes. dural fold between the cerebellum and cerebral hemisphere. The
Golgi, Camillo (1844–1926). Italian anatomist whose staining term was adopted near the end of the 18th century.
method (developed in his kitchen) allowed the full description of Vermis (Latin “a worm”). The midline portion of the cerebel-
neuronal morphology. Described two types of cortical cells in lum. The appearance of its folia bears a resemblance to the seg-
1880. The Golgi neuron of the cerebellum is the type II Golgi mented body of a worm.
neuron. Type I neurons have long axons that terminate at a dis-
tance. He was the first to describe dendrites and shared the
Nobel prize for 1906 with Ramon y Cajal, with whom his rela- SUGGESTED READINGS
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terest in spinal cord tracts and their connections. As consultant Amarenco P: The spectrum of cerebellar infarctions. Neurology 1991; 41:973–
neurologist to the British army during World War One, he and 979.
Sir Percy Sargent, his neurosurgical colleague, treated hundreds Appollonio IM et al: Memory in patients with cerebellar degeneration.
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Luciani, Luigi (1840–1919). Italian physiologist. Pioneer in R16.
cerebellar physiology. He made many important contributions Brodal P, Bjaalie JG: Salient anatomic features of the cortico-ponto-cerebellar
to the physiology of the nervous system, including the cerebellar pathway. Prog Br Res 1997; 114:227–249.
triad of atonia, asthenia, and astasia as well as cortical pathogen- Brown-Gould B: The organization of afferents to the cerebellar cortex in the
esis of epilepsy. He is best known for two monographs: the physi- cat: Projections from the deep cerebellar nuclei. J Comp Neurol 1979;
ology of starvation in man and the physiology and pathology of 184:27–42.
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Magendie, Francois (1783–1855). French physiologist. Cody FWJ, Richardson HC: Mossy and climbing fiber projections of trigeminal
inputs to the cerebellar cortex in the cat. Brain Res 1978; 153:352–356.
Credited with introducing the methods of experimental physiol-
Courchesne E et al: Abnormal neuroanatomy in a nonretarded person with
ogy into pharmacology and pathology. With Sir Charles Bell, he autism: Unusual findings with magnetic resonance imaging. Arch Neurol
developed the Bell-Magendie law (anterior spinal roots being 1987; 44:335–341.
motor and posterior spinal roots sensory). He described the CSF Courville J, Faraco-Cantin F: On the origin of the climbing fibers of the cere-
in 1827, and the foramen of Magendie in the roof of the fourth bellum: An experimental study in the cat with an autoradiographic trac-
ventricle in 1842. ing method. Neuroscience 1978; 3:797–809.
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Cerebellum: Clinical Correlates 16
Clinical Manifestations Anterior Inferior Cerebellar Artery (AICA) Syndrome

Cerebellar Syndromes Posterior Inferior Cerebellar Artery (PICA) Syndrome
Experimental Animals Developmental Syndromes
Humans Chiari Malformation
Vascular Syndromes Dandy-Walker Malformation
Superior Cerebellar Artery (SCA) Syndrome Cerebellar Hypoplasia
KEY CONCEPTS
Signs of cerebellar disease are ipsilateral to the side of the kinesia, intention tremor, muscular hypotonia, dysarthria,
cerebellar lesion. and nystagmus.
Lesions of the vermis are manifest by abnormalities in Three vascular cerebellar syndromes are well defined:
trunk movements, whereas lesions of the cerebellar hemi- superior cerebellar artery (SCA) syndrome, anterior infe-
spheres are manifested by abnormalities of movement in rior cerebellar artery (AICA) syndrome, and posterior infe-
the extremities. rior cerebellar artery syndrome (PICA). The SCA and PICA
syndromes are more frequently encountered than the
Midline cerebellar syndrome is manifested by unsteadi-
AICA syndrome.
ness of gait and nystagmus.
Lateral (hemispheral, neocerebellar) syndrome is mani-
fested by ataxia, dysmetria, dyssynergia, dysdiadocho-
Early descriptions of cerebellar clinical symptoms and signs came CLINICAL MANIFESTATIONS
from studies of patients with heredofamilial (e.g., Friedreich’s
ataxia) and demyelinating (e.g., multiple sclerosis) disorders, both Clinical cerebellar disorders are associated with a variety of etiolo-
of which involve, in addition to the cerebellum, many extra- gies: congenital malformations, hereditary, metabolic, infectious,
cerebellar areas in the brain stem and spinal cord. In the first quar- toxic, vascular, demyelinating, and neoplastic. Cerebellar disorders
ter of the 20th century, Gordon Holmes established the triad of share the following clinical characteristics:
cerebellar signs of asthenia (fatigability), ataxia (incoordination, 1. Ipsilateral signs
unsteadiness), and atonia (decreased muscle tone). He derived his 2. Abnormalities in limb movements (appendicular ataxia)
triad from observation of patients with cerebellar injuries during associated with lateral cerebellar hemisphere lesions
World War I. Attempts at anatomicoclinical correlations of cere-
bellar signs utilizing patients with cerebellar strokes were not re- 3. Abnormalities in trunk movements (truncal ataxia)
warding. Localizing signs could not be elicited in unconscious associated with midline vermis lesions
stroke patients and were present in less than half the conscious pa- 4. Lesions in deep cerebellar nuclei or the superior cere-
tients. The introduction in the mid-1970s of computed tomogra- bellar peduncle producing more severe signs than
phy (CT) scans and in the 1980s of magnetic resonance imaging lesions in the cerebellar cortex
(MRI) and magnetic resonance arteriography (MRA), coupled 5. Signs of cerebellar disease tending to improve with time, es-
with better definition of cerebellar vascular territories, permitted a pecially when the lesion occurs in childhood and the under-
more accurate anatomicoclinical correlation in cerebellar disorders. lying disease is nonprogressive
223
224 / CHAPTER 16
CEREBELLAR SYNDROMES Adiadochokinesia (dysdiadochokinesia): Inability to perform

rapid successive movements such as tapping one hand on the
The classically described archicerebellar, paleocerebellar, and neo- other in an alternating supination and pronation sequence.
cerebellar syndromes in experimental animals following ablation Intention tremor: Terminal tremor as the moving limb ap-
of the respective lobes of the cerebellum are not ordinarily ob- proaches its target.
served in humans. Instead, in humans, two cerebellar syndromes
Muscular hypotonia: Decrease in muscular tone and in the
are clearly delineated: midline (archicerebellar and paleocerebel-
resistance to passive stretching of muscles.
lar) and lateral cerebellar hemisphere (neocerebellar).
Dysarthria: Slurred, hesitating type of speech.
Nystagmus: Nystagmus is frequently observed in cerebellar
Experimental Animals hemisphere lesions with the fast component to the side of the
cerebellar lesion.
A. ARCHICEREBELLAR SYNDROME
The archicerebellum (flocculonodular lobe) is related to the C. PANCEREBELLAR SYNDROME
vestibular system. It receives fibers from the vestibular nuclei and
nerve and projects to the vestibular and reticular nuclei, which in This syndrome is a combination of the preceding two syndromes
turn project to the spinal cord (via the vestibulospinal and retic- and is characterized by bilateral signs of cerebellar dysfunction
ulospinal tracts) and ocular motor system (via the medial longi- involving the trunk, limbs, and eyes.
tudinal fasciculus). The function of this system is the control of The cerebellum is well known for its ability to compensate
body equilibrium and eye movements. Ablation of the flocculo- for its deficits. The compensation is especially marked in chil-
nodular lobe in experimental animals produces nystagmus and dren. The mechanisms underlying this ability to compensate are
disturbances in body equilibrium (truncal ataxia). not known. The assumption of lost cerebellar functions by other
noncerebellar structures or by remaining parts of the cerebellum
B. PALEOCEREBELLAR SYNDROME are two explanations for this compensation.
The paleocerebellum is functionally related to the spinal cord
and is concerned with posture, muscle tone, and gait. Ablation VASCULAR SYNDROMES
of the paleocerebellum in animals produces decerebrate rigidity
and an increase in myotatic and postural reflexes. Superior Cerebellar Artery (SCA)
Syndrome (Figure 16–1)
C. NEOCEREBELLAR SYNDROME
This is the most frequently encountered vascular syndrome of
The neocerebellum is functionally related to the cerebral cortex the cerebellum. Clinical signs include ipsilateral dysmetria, limb
and plays a role in planning and initiation of movement as well ataxia, and Horner’s syndrome, contralateral pain and thermal
as the regulation of discrete limb movements. sensory loss, and contralateral trochlear nerve palsy. Horner’s
syndrome, the pain and thermal sensory deficits, and trochlear
Humans nerve palsy are due to involvement of the brain stem tegmen-
tum. Dysarthria is common and is characteristic of rostral cere-
A. MIDLINE SYNDROME bellar lesions, whereas vertigo is not as common in SCA infarcts
A picture corresponding to the archicerebellar (flocculonodular
lobe) syndrome is often seen in children with a special
type of tumor, the medulloblastoma. This tumor almost
always arises in the most posterior part of the vermis and
is manifested by unsteadiness of gait and nystagmus.
The paleocerebellar syndrome as described in experimental
animals is usually not encountered in humans. However, some
patients with atrophy of the cerebellum demonstrate unsteadi-
ness of gait and increased myotatic reflexes in the lower limbs. It
is believed that in such patients the anterior lobe is affected pri-
marily by the atrophy.
B. CEREBELLAR HEMISPHERE SYNDROME
Lesions of the cerebellar hemispheres (neocerebellum) produce
the following manifestations:
Ataxia: A drunken, unsteady gait.
Dysmetria: Inability to estimate the range of voluntary
movement. In attempting to touch the tip of the finger
to the tip of the nose, a patient will overshoot the finger
past the nose to the cheek or ear.
Decomposition of movement (dyssynergia): Jerky and
tremulous voluntary movements. In attempting to touch the
nose with the finger or to move the heel over the shin, the pa- Figure 16–1. T1-weighted parasagittal MR image showing a
tient’s movements are uneven and jerky throughout the range cerebellar infarct (arrow) in the distribution of the superior cere-
of motion. bellar artery (SCA).
CEREBELLUM: CLINICAL CORRELATES / 225
and is more characteristic of the posterior inferior cerebellar Clinical manifestations of occlusion of the lateral branch of
artery (PICA) syndrome. Isolated dysarthria (without other cere- the PICA are unknown, since reported cases have been chance
bellar signs) has been reported in occlusion of the medial branch autopsy findings with no available clinical information.
of the superior cerebellar artery with an infarct limited to the
paravermal area. Prognosis for recovery in SCA syndrome is usu-
ally good. DEVELOPMENTAL SYNDROMES
Chiari Malformation (Figure 16–3)
Anterior Inferior Cerebellar
Artery (AICA) Syndrome The Chiari malformation was first described by Cleland in 1883.
Chiari provided detailed neuropathologic descriptions in 1891
Occlusion of the anterior inferior cerebellar artery (AICA) is and 1896, and he proposed a classification system that is still
uncommon, and often is misdiagnosed as the lateral medullary used. Three types of Chiari malformation are recognized.
syndrome (PICA syndrome). It is characterized by ipsilateral dys- Type I. In this type, the inferior pole of the cerebellar hemi-
metria, vestibular signs, Horner’s syndrome, facial sensory im- spheres protrude through the foramen magnum. Most pa-
pairment, contralateral pain and thermal sensory loss in the tients are asymptomatic, and the malformation is often found
limbs, and at times, dysphagia. Other signs seen in this syndrome incidentally on MRI. Occasionally, patients present with
and unusual in the lateral medullary syndrome include ipsilateral headache, usually associated with occipital and neck pain and
severe facial motor palsy, deafness, lateral gaze palsy, and multi- exacerbated by coughing and straining. Hydromyelia or sy-
modal sensory impairment over the face due to involvement of ringomyelia may be associated with Chiari malformation.
facial, cochleovestibular, abducens, and trigeminal nerves and/or
nuclei, respectively. AICA occlusion also can be manifest by Type II. In this type, in addition to the protrusion of the cere-
purely cerebellar signs. bellum, the medulla oblongata protrudes through the fora-
men magnum, resulting in kinking of the cervical medullary
junction. Part of the fourth ventricle is also displaced caudally.
Posterior Inferior Cerebellar Artery (PICA) The foramina of Magendie and Luschka are occluded. The
Syndrome (Figure 16–2) malformation is frequently associated with hydromyelia or sy-
ringomyelia, hydrocephalus, and meningomyelocele. Type II
This syndrome is as frequent as the superior cerebellar artery Chiari malformation is frequently referred to as the Arnold-
(SCA) syndrome. Clinical features of the syndrome are described Chiari malformation. The term was coined in 1907 by two
in the chapter on clinical correlates of the medulla oblongata students of Arnold based on Arnold’s description of the mal-
(Chapter 6). formation in 1895. Patients with type II malformation are
Occlusion of the medial branch of the PICA may be clinically symptomatic. They present with dysphonia, respiratory stri-
silent or may present with one of the following three patterns: dor, swallowing difficulties, and other symptoms.
(1) isolated vertigo often misdiagnosed as inner ear disease Type III. This malformation has features of types I and II as
(labyrinthitis), (2) vertigo, ipsilateral axial lateropulsion (invol- well as herniation of the entire cerebellum into a high cervical
untary tendency to go to one side while in motion), and dys- meningocele. Hydrocephalus is a constant finding.
metria or unsteadiness, or (3) classic lateral medullary syndrome
when the medulla is also involved in the lesion.
Dandy-Walker Malformation (Figure 16–4)
This malformation is characterized by a triad of (1) complete or
partial agenesis of the cerebellar vermis, (2) cystic dilation of the
fourth ventricle, and (3) an enlarged posterior fossa with upward
displacement of the tentorium, torcula, and transverse sinus.
Hydrocephalus is frequently present. Mental retardation is also
common. The malformation was first described by Dandy and
Blackfan in 1914 and reviewed by Taggart and Walker in 1942.
The term Dandy-Walker malformation was coined by Benda in
1954. The malformation had been described in 1887 by Sutton
and possibly by Virchow in 1863. Patients present with hydro-
cephalus. Mental retardation is frequent.
Cerebellar Hypoplasia
Cerebellar hypoplasia refers to incomplete development of the
cerebellum. On imaging, the cerebellum appears small, the cere-
bellar sulci and fissures are prominent, and the subarachnoid cere-
bellar cistern (cisterna magna) and fourth ventricle are markedly
enlarged. Cerebellar hypoplasia may occur alone or associated
with malformations elsewhere in the brain. The malformation
Figure 16–2. T1-weighted parasagittal MR image showing a may be sporadic, familial, or associated with chromosomal anom-
cerebellar infarct (arrow) in the distribution of the posterior infe- alies or metabolic disorders. Patients may be asymptomatic or may
rior cerebellar artery (PICA). present with hypotonia and other cerebellar signs.
226 / CHAPTER 16
Figure 16–3. Midsagittal MRI of brain showing cerebellar herniation through the foramen magnum
(Chiari malformation) and associated spinal cord syrinx.
TERMINOLOGY Ataxia (Greek taxis, “order”). Want of order, lack of coordina-

tion, resulting in unsteadiness of movement. The term was used
Arnold, Julius (1835–1915). German physician who described by Hippocrates and Galen for any morbid state, especially one
type II Chiari malformation in 1895. He also described superior with disordered or irregular action of any part, such as irregular-
laryngeal neuralgia. His father, Friedrich Arnold (1803–1890) ity of the pulse.
described the frontopontine tract and made precise differentiation
between the frontal, parietal, occipital, and temporosphenoidal Chiari, Hans (1851–1916). Austrian pathologist. Described
lobes. type I Chiari malformation in 1891 and 1896.
CEREBELLUM: CLINICAL CORRELATES / 227
Figure 16–4. Axial MRI of the brain showing Dandy-Walker malformation.
Dandy, Walter Edward (1886–1946). American neurosurgeon Nystagmus (Greek nystagmos, “nodding in sleep”). Rhythmic
and student of Cushing, with whom he did not get along. De- involuntary oscillatory movements of the eyes. The term is said
scribed the Dandy-Walker malformation in 1914. to have been first used by Planck. The association of these eye
Dysarthria (Greek dys, “difficult”; arthroun, “to articulate” ). movements with vertigo was first noted by Purkinje and further
The indistinct pronunciation of words usually resulting from investigated by Flourens.
disturbances in the muscular control of the speech mechanism.
Dysdiadochokinesia (Greek dys, “difficult”; diadochos, “suc- SUGGESTED READINGS
ceeding”; kinesis, “motion”). Impairment of the ability to per-
Amarenco P: The spectrum of cerebellar infarctions. Neurology 1991; 41:
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and supination of the arm.
Amarenco P et al: Infarction in the anterior rostral cerebellum (the territory of
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ment. Occurrence of errors in judgment of distance when a limb Amarenco P et al: Paravermal infarct and isolated cerebellar dysarthria. Ann
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Disturbance of muscular coordination between contraction and
Barth A et al: The clinical and topographic spectrum of cerebellar infarcts: A
relaxation of muscles that normally act together in a group to clinical–magnetic resonance imaging correlation study. Ann Neurol
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Friedreich’s ataxia. Progressive hereditary degenerative central Chaves CJ et al: Cerebellar infarcts. Curr Neurol 1994; 14:143–177.
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terior column, lateral corticospinal, and spinocerebellar tract Pediatr Neurol 2002; 9:320–334.
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Cerebral Cortex 17
Types of Cortex Primary Visual Cortex (V1)

Isocortex (Neocortex or Homogenetic Cortex) Primary (Unimodal) Visual Association Areas
Allocortex (Paleocortex, Archicortex, or Heterogenetic Primary Auditory Cortex
Cortex) Primary (Unimodal) Auditory Association Cortex
Mesocortex (Periallocortex, Periarchicortex) Primary Gustatory Cortex
Microscopic Structure Primary Olfactory Cortex
Cell Types Primary Vestibular Cortex
Principal (Projection) Neurons Cortical Motor Areas
Interneurons Primary Motor Area (MI)
Layers Supplementary Motor Area (MII)
Input to Cerebral Cortex Premotor Area
Thalamocortical Input Cortical Eye Fields
Extrathalamic Modulatory Input Cortical Language Areas
Association Fiber System Wernicke’s Area
Commissural Fiber System Broca’s Area
Output of Cerebral Cortex The Arcuate Fasciculus
Corticospinal Pathway Sequence of Cortical Activities during Language
Aberrant Pyramidal Tract Processing
Corticoreticular Pathway The Right Hemisphere and Language
Corticobulbar Pathway Cortical Localization of Music
Corticopontine Pathway Other Cortical Areas
Corticothalamic Pathway Prefrontal Cortex
Corticohypothalamic Pathway Major Association Cortex
Corticostriate Pathway The Insula (Island of Reil)
Other Corticofugal Pathways Cortical Electrophysiology
Intracortical Circuitry Evoked Potentials
Cortical Cytoarchitectonic Areas Somatosensory, Visual, and Auditory Evoked
Cortical Sensory Areas Responses
Primary Somesthetic (General Sensory, Somatosensory) Electroencephalography
Area (SI) Blood Supply
Secondary Somesthetic Area (SII) Arterial Supply
Supplementary Sensory Area (SSA) Venous Drainage
Primary (Unimodal)Somatosensory (Somesthetic)
Association Areas
228
CEREBRAL CORTEX / 229
KEY CONCEPTS
The cerebral cortex receives fibers from internal and exter- Three motor areas have been defined: primary motor,
nal sources. Internal sources include the cortex of the supplementary motor, and premotor.
same hemisphere via association fiber bundles and the
The cerebral areas most important for saccadic control
contralateral hemisphere via commissural fibers. External
are the posterior parietal cortex, frontal eye field, supple-
sources of input include the thalamus and nonthalamic
mentary eye field, and the dorsolateral prefrontal cortex.
subcortical sources.
Cortical areas for smooth pursuit movement include the
Corticofugal fiber system includes the corticospinal, corti-
posterior parietal cortex or the temporooccipitoparietal
coreticular, corticobulbar, corticopontine, corticothalamic,
region.
corticohypothalamic, corticostriate, and others.
Two cortical areas traditionally have been associated
Based on thickness of cortex, width of the different cortical
with language function: Wernicke’s and Broca’s areas in
layers, cell types within each layer, and nerve fiber lamina-
the left hemisphere.
tion patterns, the cerebral cortex has been divided into be-
tween 20 and 200 cytoarchitectonic areas.The most widely The prefrontal cortex plays a role in executive function,
used classification is that of Brodmann, which contains emotion, and social behavior.
52 areas numbered in the order in which they were studied.
The major association cortex is interconnected with all
There are six primary sensory cortical areas: somesthetic, the sensory cortical areas and thus functions in higher-
visual, auditory, gustatory, olfactory, and vestibular. order, complex, multisensory perception.
The primary (unimodal) somatosensory association areas
are concerned with the perception of shape,size,and texture
and the identification of objects by contact (stereognosis).
The cerebral cortex is the layer of gray matter capping the white in higher mammals, and comprises 90% of the cerebral cortex in
matter core of the cerebral hemispheres. Its thickness varies from humans.
1.5 to 4.5 mm, with an average thickness of 2.5 mm. The cerebral Isocortex in which the six layers are clearly evident (such as the
cortex is thickest in the primary motor area (4.5 mm thick) and primary sensory cortex) is termed homotypical cortex. Isocortex
thinnest in the primary visual cortex (1.5 mm thick). The cortex in which some of the six layers are obscured (such as the motor
is irregularly convoluted, forming gyri separated by sulci or fis- cortex and visual cortex) is termed heterotypical cortex. The vi-
sures. The outer layer of the human cerebral cortex is around sual cortex is also known as granular cortex or koniocortex (from
0.2 m2, but only one-third of this area is exposed to the surface, the Greek konis, meaning “dust”). The motor cortex, in contrast,
the rest being buried in sulci or incorporated in the insula. The is known as agranular cortex because of the predominance of
number of neurons in the cerebral cortex is estimated at between large pyramidal neurons.
10 and 20 billion. Morphometric studies of the cerebral cortex in
males and females demonstrate no gender-based differences in Allocortex (Paleocortex, Archicortex,
cortical thickness. On the other hand they show neuronal density or Heterogenetic Cortex)
to be higher in the male with a reciprocal increase in neuropil and
neuronal processes in the female. A relatively small area of the The allocortex is three layered and phylogenetically older. It is sub-
cerebral cortex in humans is specialized for receiving sensory in- divided into paleocortex (rostral insular cortex, piriform cortex, and
put from the eyes, ears, and skin and for projecting motor output primary olfactory cortex) and archicortex (hippocampal formation).
down the pyramidal tract to bring about movement. More than
80 percent of the cortex in humans serves an association function Mesocortex (Periallocortex, Periarchicortex)
specially related to integrative and cognitive activities such as lan- This type of cortex is found in much of the cingulate gyrus, en-
guage, calculation, planning, and abstract reasoning. torhinal, parahippocampal, and orbital cortices and is intermedi-
ate in histology between the isocortex and allocortex. The terms
TYPES OF CORTEX periallocortex and periarchicortex are used to refer to this cortex to
denote its transitional nature between neocortex and allocortex.
On the basis of phylogenetic development and microscopic struc-
ture, the following three types of cortices are recognized.
MICROSCOPIC STRUCTURE
Isocortex (Neocortex or Homogenetic Cortex) Cell Types (Figure 17–1)
This cortex is six layered and of recent phylogenetic develop- Attempts to make a comprehensive inventory of types of cortical
ment. It is characteristic of mammalian species, increases in size neurons started with Ramon y Cajal in 1911 and have continued
230 / CHAPTER 17
Dendrites
D
Apical HORIZONTAL
dendrites
Axon
Basal
dendrite
Dendrites
Dendrites
Recurrent
axon collateral
Axon
Axon
Axon Axon Axon
Horizontal
axon collateral
FUSIFORM
Dendrites
C
PYRAMIDAL STELLATE MARTINOTTI

A B E
Figure 17–1. Schematic diagram of the various types of cortical neurons.
until today. The neurons of the cerebral cortex are of two func- are the recurrent axon collaterals (RACs), which project back on
tional categories: (1) principal (projection) neurons and (2) interneurons in more superficial layers, and the horizontal axon col-
neurons. The principal neurons provide corticocortical and cor- laterals (HACs), which extend horizontally to synapse on neu-
ticosubcortical outputs. Interneurons are concerned with local rons in the vicinity.
information processing. Recent evidence suggests that the two Pyramidal neurons are found in all cortical layers except layer I.
neuronal types are generated in distinct proliferative zones. They vary in size; most are between 10 and 50 m in height.
Principal neurons are derived from neuroepithelium in the ven- The largest are the giant pyramidal cells of Betz, which measure
tricular zone. Interneurons, in contrast, arise from the ganglionic about 100 m in height and are found in layer V of the motor
eminence of the ventral telencephalon, which gives rise also to cortex.
the basal ganglia. The cerebral cortex has its full complement of
neurons (10 to 20 billion) by the 18th week of intrauterine life. B. FUSIFORM, SPINDLE NEURONS (Figure 17–1C)
These are small neurons with elongated perikarya in which the
Principal (Projection) Neurons long axis is oriented perpendicular to the cortical surface. A short
dendrite arises from the lower pole of the perikaryon and ar-
Two types of cortical neurons belong to the principal category. borizes in the vicinity. A longer dendrite arises from the upper
They are the pyramidal neurons and the fusiform neurons. The pole of the perikaryon and extends to more superficial layers.
excitatory neurotransmitter in both is glutamate or aspartate. The axon enters the deep white matter. Fusiform neurons are
Principal neurons constitute more than half of all cortical neurons. found in the deepest cortical laminae.
A. PYRAMIDAL NEURONS (FIGURE 17–1A)
Interneurons
These neurons derive their name from their shape. The apex of
the pyramid is directed toward the cortical surface. Each pyrami- Several types of cortical interneurons are recognized on the basis
dal neuron has an apical dendrite directed toward the surface of of dendritic architecture. They include the stellate neurons, the
the cortex and several horizontally oriented basal dendrites that horizontal cells of Cajal, and the cells of Martinotti.
arise from the base of the pyramid. Branches of all dendrites con-
tain numerous spines that increase the size of the synaptic area. A A. STELLATE OR GRANULE NEURONS (Figure 17–1B)
slender axon leaves the base of the pyramidal neuron and pro- These are small (4 to 8 m) star-shaped neurons with short, ex-
jects on other neurons in the same or contralateral hemisphere or tensively branched, spiny dendrites and short axons. They are
else leaves the cortex to project on subcortical regions. The axon most numerous in lamina IV. Stellate cells are the only type of
gives rise within the cortex to two types of axon collaterals. These excitatory interneurons in the cortex. The neurotransmitter is
glutamate. All other interneurons exert inhibitory influence by Table 17–2. Chronologic Age of Cortical Layers
gamma-aminobutyric acid (GABA).
Layer Order of neuroblast migration
B. HORIZONTAL CELLS OF CAJAL (Figure 17–1D)
These are small fusiform neurons with their long axes directed I Oldest (acellular)
parallel to the cortical surface. A branching dendrite arises from II Fifth wave
each pole of the perikaryon, and an axon arises from one pole. III Fourth wave
The dendrites and axon are oriented parallel to the cortical sur- IV Third wave
face. The horizontal cells of Cajal are found only in lamina I and V Second wave
disappear or are rare after the neonatal period. VI First wave
C. CELLS OF MARTINOTTI (Figure 17–1E)

Giovanni Martinotti in 1890 first described cells whose axons
ascend toward the surface of the cortex. Martinotti neurons are B. LAYER II (EXTERNAL GRANULAR)
multipolar with short branching dendrites and an axon that pro- Layer II consists of a dense packing of small and medium-sized
jects to more superficial layers, giving out horizontal axon collat- pyramidal neurons and interneurons intermingled with axons
erals en route. The Martinotti neurons are found in deeper corti- from other cortical layers of the same and opposite hemispheres
cal laminae. (association and commissural fibers), as well as axons and den-
drites passing through this layer from deeper layers. The dendrites
Layers of pyramidal neurons in this layer project to layer I, while their
The division of the neocortex into layers has been the outcome axons project to deeper layers. This layer of the cortex contributes
of extensive cytoarchitectonic (organization based on studies to the complexity of intracortical circuitry.
of stained cells) and myeloarchitectonic (organization based on C. LAYER III (EXTERNAL PYRAMIDAL)
studies of myelinated fiber preparations) studies. Although sev- Layer III consists of pyramidal neurons that increase in size in
eral such studies are available, the most widely used are the cyto- deeper parts of the layer. The dendrites of neurons in this layer
architectonic classification of Brodmann and the myeloarchitec- extend to layer I, while the axons project to other layers within
tonic classification of the Vogts (Césile and Oskar, wife and the same and contralateral hemisphere (association and commis-
husband). According to these two classifications, the neocortex is sural fibers) or leave the hemisphere as projection fibers to more
divided into six layers (Table 17–1). distant extracortical sites. This layer receives primarily axons of
The six layers of the neocortex are recognizable by about neurons in other cortical areas (association and commissural
the seventh month of intrauterine life. The neurons in the six fibers), as well as axons of neurons in extracortical regions such as
cortical layers develop in waves from the periventricular ger- the thalamus. This layer contains the distinctive stripes of Kaes-
minal matrix. Successive waves of migrating neuroblasts be- Bekhterev.
come situated progressively farther away from the germinal
matrix (inside-out gradient of cortical histogenesis) (Table D. LAYER IV (INTERNAL GRANULAR)
17–2). Interruption of the normal process of migration or its Layer IV consists of pyramidal cells and densely packed small
arrest is associated with cortical gyral malformations such as stellate cells with processes that terminate within the same layer,
agyria, pachygyria, micropolygyria, and heterotopia. Many of either on axons of other stellate cells or on axons of cortical or
these are associated with mental retardation, seizures, and subcortical origin passing through this layer. The cell packing
other neurologic deficits. density in layer IV is the greatest of all cortical layers. Few of the
A. LAYER I (MOLECULAR, PLEXIFORM) larger stellate cells in this layer project their axons to deeper cor-
tical layers. Layer IV is especially well developed in primary sen-
Layer I consists primarily of a dense network of nerve cell sory cortical areas. In the primary visual (striate) cortex, this
processes among which are scattered sparse interneurons (hori- layer is traversed by a dense band of horizontally oriented tha-
zontal cells of Cajal) and neuroglia. The nerve cell processes in lamocortical nerve fibers known as the external band of
this layer comprise projection axons from extracortical sites as Baillarger or the stripe of Gennari. The band of Baillarger was
well as axons and dendrites of neurons in other cortical areas. described by the nineteenth-century French neurologist and psy-
This layer of the cortex is primarily a synaptic area. chiatrist Jean-Gabriel-François Baillarger. The stripe of Gennari
was first described in 1782 by Francesco Gennari, an eighteenth-
century Italian medical student, and independently by Vic d’Azyr
in 1786. Because of the presence of this stripe, the primary visual
Table 17–1. Cortical Layers cortex is known as the striate cortex. The internal granular layer
is the major recipient of thalamocortical fibers from modality-
Layer Cytoarchitectonic Myeloarchitectonic specific sensory relay nuclei (visual radiation, auditory radiation,
name name and primary sensory radiation).
I Molecular Tangential E. LAYER V (INTERNAL PYRAMIDAL)
II External granular Dysfibrous Layer V consists of large and medium-sized pyramidal cells, stel-
III External pyramidal Suprastriatal late cells, and cells of Martinotti. The cell packing density in this
IV Internal granular External Baillarger layer is the lowest of all cortical layers. The largest pyramidal cells
V Internal pyramidal Internal of Baillarger
in the cerebral cortex (cells of Betz) are found in this layer (hence
and interstriatal
VI Multiform Infrastriatal
the name ganglionic layer). Dendrites of neurons in this layer
project to the more superficial layers. Axons project on neurons
232 / CHAPTER 17
in other cortical areas but mainly to subcortical sites (projection INPUT TO CEREBRAL CORTEX
fibers) except the thalamus, which receives fibers from layer VI.
This layer receives axons and dendrites arising in other cortical The input to the cerebral cortex originates in four sites
sites or in subcortical sites. It is also traversed by a dense band of (Figure 17–2):
horizontally oriented fibers; this is the internal band of Baillarger. 1. Thalamus
Fibers originating in thalamic sensory nuclei contribute heavily
to the formation of the lines of Baillarger, especially the outer 2. Extrathalamic modulatory
one in lamina IV. The lines of Baillarger are thus prominent in 3. Cortex of the same hemisphere (association fibers)
primary cortical sensory areas. 4. Cortex of the contralateral hemisphere (commissural fibers)
F. LAYER VI (MULTIFORM)
Layer VI consists of cells of varying shapes and sizes, including Thalamocortical Input
fusiform cells and the cells of Martinotti, which are prominent The input from the thalamus travels via two systems. (1) The
in this layer. Dendrites of smaller cells arborize locally or in adja- modality-specific thalamocortical system originates in modality-
cent layers, while those of large neurons reach the molecular specific thalamic nuclei (e.g., ventral anterior, ventral lateral,
layer. Axons of neurons in this layer project to other cortical lam- ventral posterior) and projects on specific cortical areas (primary
inae or to subcortical regions. motor, premotor, and somesthetic cortex). This fiber system
Layers I, V, and VI are present in all types of cortex (neo- reaches the cortex as an ascending component of the internal
cortex, paleocortex, and archicortex). Layers II, III, and IV, how- capsule. The majority of fibers in this system project on neurons
ever, are present only in neocortex and thus are considered of in lamina IV (Figure 17–3A), with some projecting on neurons
more recent phylogenetic development. In general, layers I to IV in lamina III and lamina VI. (2) The nonspecific thalamocortical
are considered receptive. The somata of the majority of cells that system is related to the reticular system and originates in nonspe-
establish intracortical connections (ipsilaterally and contralater- cific thalamic nuclei (intralaminar, midline, and reticular nuclei).
ally) lie in layers II and III. Layers V and VI are efferent. Neurons In the cortex, fibers of this system project diffusely on all lami-
in lamina V give rise to corticofugal fibers that target subcortical nae (Figure 17–3B) and establish mostly axodendritic types of
areas (brain stem and spinal cord). Neurons in lamina VI give synapses. This fiber system is intimately involved in the arousal
rise to corticofugal fibers to the thalamus. response and wakefulness.
In contrast to the horizontal anatomic lamination, the ver-
tical lamination described by Mountcastle seems to be the
more functionally appropriate. The studies of Lorente de Nó, Extrathalamic Modulatory Input
Mountcastle, Szentágothai, and others have shown that the
functional unit of cortical activity is a column of neurons ori- Until recently, it was commonly assumed that essentially all af-
ented vertically to the surface of the cortex. Each such column ferents to the cortex arose from the thalamus. With the develop-
or module is 300 to 500 m in diameter, with its height the ment of methods to visualize monoaminergic and cholinergic
thickness of the cortex, and contains 4000 neurons, 2000 of processes, it is now clear that there are at least four substantial
which are pyramidal neurons. All neurons in a column are acti- extrathalamic projections to the cortex.
vated selectively by the same peripheral stimulus. There are ap- Monoaminergic and cholinergic pathways reach the cerebral
proximately 3 million such modules in the human neocortex. cortex directly without passing through the thalamus.
Each module sends pyramidal cell axons to other modules
within the same hemisphere or to modules in the other hemi- A. MONOAMINERGIC INPUT
sphere. Of interest is the fact that activation of a module tends 1. Serotonergic Input. The serotonergic input to the cerebral
to inhibit neuronal activity in adjacent modules. The columnar cortex originates from the raphe nuclei in the mesencephalon
organization of the neocortex is established in fetal life, but the and rostral pons and runs in the medial forebrain bundle. It
synaptic connections increase in number in the postnatal period terminates in the same cortical layers that receive the thalamo-
in response to stimulation from the external environment. Lack cortical input (layers III, IV, and VI). Serotonergic fibers project
of external stimuli during a critical period of cortical matura- widely in the cerebral cortex with the visual cortex receiving
tion, usually in the first year of life, will adversely affect normal an especially rich serotonergic innervation. The function of the
cortical development. serotonergic pathway to the cortex is not well understood.
Long association fibers Short association fibers
Thalamocortical projection Commissural fibers

Nonspecific
Specific
Nonspecific thalamic
nucleus
Specific thalamic
nucleus Figure 17–2. Schematic diagram
showing sources of fiber input to
the cerebral cortex.
THALAMOCORTICAL INPUT ASSOCIATION AND

COMMISSURAL INPUT
Specific Nonspecific
II
III
IV
VI
Figure 17–3. Schematic diagram of the termination pattern of the various inputs to cortical
laminae.
Serotonergic pathways elsewhere have been related to a variety of motor control. Dysfunction in this system may be responsible
functions, including pain control, emotion, and sleep. The sero- for psychiatric symptoms noted in Parkinson’s disease.
tonergic input to the cortex is believed to alter cortical neuronal 3. Noradrenergic Input. The noradrenergic input to the cere-
responses to afferent input in response to change in state. They bral cortex originates from cells in the locus ceruleus in the ros-
include inhibition of spontaneous activity, excitation, and volt- tral pons. It projects widely to the cerebral cortex and terminates
age dependent facilitation. in cortical layers that give rise to corticofugal fibers. The nor-
2. Dopaminergic Input. The dopaminergic input to the cere- adrenergic input is implicated in higher-order information pro-
bral cortex originates from dopaminergic neurons in the mes- cessing and the state of arousal. It is believed to enhance the
encephalon (ventral tegmental area of Tsai and substantia nigra selectivity and vigor of cortical responses to sensory stimuli or
pars compacta). It terminates in all areas of the cortex, but espe- other synaptic inputs to the target neurons in the cortex.
cially in the motor, prefrontal, and temporal association areas.
The dopaminergic input to the cortex is believed to play a role in 4. Histaminergic Input. The histaminergic input to the cerebral
orienting behavior. The laminar and regional pattern of termina- cortex originates from the tuberomamillary nucleus in the postero-
tion of this system suggests that it influences activities of cortico- lateral hypothalamus. The function of this system is not known.
cortical rather than thalamocortical circuits and higher-order 5. Cholinergic Input. The cholinergic input to the cerebral
integrative processes than the more analytic aspects of sensory cortex originates from the nucleus basalis of Meynert. This input
processing. In addition, it may influence cortical regulation of terminates in all areas of the cortex. It is the most important
234 / CHAPTER 17
system for cortical arousal and motivation. It has been impli- pal gyrus. The superior longitudinal fasciculus (Figure 17–4A
cated in the genesis of memory deficit in Alzheimer’s disease. and C), located in the lateral part of the hemisphere above the
insula, connects portions of the frontal lobe with parietal, occip-
B. GABAERGIC INPUT ital, and temporal lobes. The arcuate fasciculus (Figure 17–4A)
The GABAergic input to the cerebral cortex originates from cells is the part of the superior longitudinal fasciculus that sweeps
in the septum and the diagonal band of Broca. It terminates pri- around the insula (island of Reil) to connect the speech areas in
marily in the hippocampus. the inferior frontal gyrus (Broca’s area) and superior temporal
gyrus (Wernicke’s area). The inferior longitudinal fasciculus
Association Fiber System (Figure 17–2) (Figure 17–4A and C) is a thin sheet of fibers that runs super-
ficially beneath the lateral and ventral surfaces of the temporal and
The association fibers arise from nearby (short association u-fibers) occipital lobes. This fiber bundle is difficult to demonstrate by
and distant (long association fibers) regions of the same hemi- dissection and to separate from other fiber systems running in its
sphere. They too project diffusely in all laminae but mostly in vicinity. The existence of the inferior longitudinal fasciculus in
laminae I to III (Figure 17–3). humans has been questioned. The only long fiber bundle com-
The long association fiber system (Figure 17–4) includes such mon to both the occipital and temporal lobes in humans is the
bundles as the cingulum, superior longitudinal fasciculus, arcu- optic radiation (geniculostriate pathway). In addition, the two
ate fasciculus, inferior longitudinal fasciculus, occipitofrontal lobes are interconnected by a series of u-fibers (short association
fasciculus, and the uncinate fasciculus. The cingulum (Figure fibers) that connect adjacent regions of occipital and temporal
17–4B and C) is the white matter core of the cingulate gyrus. It cortices. Based on this, it has been proposed that the term inferior
connects the anterior perforated substance and the parahippocam- longitudinal fasciculus be replaced by the term occipitotemporal
Insula (island of Reil) Short association, u-fibers
erior longitudinal fasciculus
Uncinate fasciculus Arcuate fasciculus
A Inferior occipitofrontal fasciculus Inferior longitudinal fasciculus
Corpus callosum
Cingulum
Superior occipitofrontal Cingulum Cingulate gyrus

fasciculus
Superior longitudinal Corpus callosum
fasciculus
Lateral ventricle
Sylvian fissure
Caudate nucleus
Putamen
Globus pallidus Third ventricle
Inferior occipitofrontal Thalamus

fasciculus Figure 17–4. Schematic diagram
Internal capsule
showing the long association fiber
C Lateral ventricle bundles.
projection system. The occipitofrontal fasciculus (Figure 17–4A from lamina VI, corticospinal and corticobulbar fibers from lam-
and C) extends backwards from the frontal lobe, radiating into inae III and V, and corticostriate and corticopontine fibers from
the temporal and occipital lobes. Two subdivisions of the occip- lamina V.
itofrontal fasciculus are recognized. The superior (subcallosal) The association and commissural fiber systems have been de-
bundle (Figure 17–4C) is located deep in the hemisphere, dorso- scribed in the section on input to the cortex. Essentially, they
lateral to the lateral ventricle, sandwiched between the corpus represent intrahemispheric and interhemispheric connections.
callosum, internal capsule, and caudate nucleus. The inferior The corticofugal fiber system includes all fiber tracts
bundle (Figure 17–4C ) is located lateral to the temporal horn of that leave the cerebral cortex to project on various sub-
the lateral ventricle and below the insular cortex and lentiform cortical structures. They include the following pathways.
nucleus. The uncinate fasciculus (Figure 17-4A) is the compo-
nent of the inferior occipitofrontal fasciculus that courses at the
bottom of the sylvian fissure to connect the inferior frontal gyrus Corticospinal Pathway (Figure 17–6)
with the anterior temporal lobe. This corticofugal fiber tract connects the cerebral cortex directly
with motor neurons in the spinal cord and is concerned with
Commissural Fiber System highly skilled volitional movement. It arises from pyramidal
neurons in layer V from wide areas of the cerebral cortex but
The commissural fibers arise from corresponding and noncorre- principally from the somatic motor, premotor, and somatosen-
sponding regions in the contralateral hemisphere, travel via the sory cortices. It contains, on each side, roughly 1 million fibers
corpus callosum and project on neurons in all laminae but of various sizes (9 to 22 m), about 3% of which are large in
mostly laminae I, II, and III (Figure 17–3). size and arise from the giant cells of Betz in layer V of the motor
Studies on the topographic distribution of interhemispheric cortex. The fibers of this system descend in the internal capsule,
projections in the corpus callosum have shown that the genu in- the middle part of the cerebral peduncle, the basis pontis, and
terconnects the prefrontal cortex, the rostral part of the body in- the pyramids before gathering in the spinal cord as the lateral
terconnects the premotor and supplementary motor cortices, the and anterior corticospinal tracts. The former (lateral cortico-
middle part of the body interconnects the primary motor and spinal) constitutes the majority of the descending corticospinal
primary and secondary somatic sensory areas, the caudal part of fibers and decussates in the pyramids (motor decussation); the
the body interconnects the posterior parietal cortex, and the latter (anterior corticospinal) is smaller and crosses at segmental
splenium interconnects temporal and occipital cortices. Other levels in the spinal cord. The classic notion that the corti-
interhemispheric commissural systems include the anterior com- cospinal tract is of particular importance for skilled and deli-
missure, which interconnects the two temporal lobes, and the cate voluntary movement is in essence correct, but it is obvious
hippocampal commissure (commissure of the fornix), which in- that a number of other indirect tracts passing through the brain
terconnects the two hippocampi. stem nuclei, reticular formation, and cerebellum are also in-
volved. The direct corticospinal tract most likely superimposes
OUTPUT OF CEREBRAL CORTEX speed and agility on the motor mechanisms subserved by other
descending indirect pathways. The component of the cortico-
Efferent outflow from the cerebral cortex is grouped into three spinal pathway from the somatosensory cortex terminates on
categories (Figure 17–5). These are (1) the association fiber sys- sensory neurons in the dorsal horn of the spinal cord and is con-
tem, (2) the commissural fiber system, and (3) the corticofugal cerned with somatosensory function possibly related to ongoing
fiber system. The laminar origin of axons of most cortical projec- movement. A fairly large proportion of the sensory component
tions are unique. The short association fibers arise from lamina of the corticospinal pathway originates from area 3a, which ad-
II, the long association fibers from laminae III and V, interhemi- joins the primary motor cortex and receives sensory input from
spheric commissural fibers from lamina III, corticothalamic fibers proprioceptors.
Aberrant Pyramidal Tract

Association fibers
This fiber tract separates from the corticospinal fiber system in
the cerebral peduncle and joins the medial lemniscus in the cau-
dal midbrain extending through the pons to the middle medulla
oblongata, where it becomes undetectable. It is presumed to con-
stitute a part of the corticobulbar tract that supplies cranial nerve
nuclei. It is thus responsible for the reported supranuclear cranial
nerve palsies in lesions of medial lemniscus. Some fibers of the
tract have been traced to the spinal cord. The aberrant pyramidal
Commissural
fibers
tract has been described in the literature under the following
synonyms: accessory fillet fibers (Barnes, 1901), fibre aberrantes
protuberantielles (Dejerine, 1901), fasciculi pontini lateralis
(Marburg, 1927), aberrant pyramidal system (Crosby, 1962),
and fibrae corticotegmentalis (Voogd and Van Hujizen, 1963).
Corticofugal
fiber system Corticoreticular Pathway
Figure 17–5. Schematic diagram of the major groups of cor- This fiber tract arises from most if not all parts of the cerebral
tical output. cortex but primarily from motor, premotor, and somatosensory
236 / CHAPTER 17
Corticobulbar Pathway
CEREBRAL CORTEX
Corticobulbar fibers originate from the face area of the motor
cortex. They project on motor nuclei of the trigeminal, facial,
glossopharyngeal, vagus, accessory, and hypoglossal nerves.
Direct corticobulbar fibers (without intermediate synapses on
reticular neurons) are known to project from the cerebral cortex
to nuclei of trigeminal (CN V), facial (CN VII), and hypoglossal
(CN XII) cranial nerves. Corticobulbar fibers descend in the
genu of the internal capsule and occupy a dorsolateral corner of
the corticospinal segment of the cerebral peduncle, as well as a
small area in the medial part of the base of the cerebral peduncle.
Internal In the pons, corticobulbar fibers are intermixed with the corti-
capsule
cospinal fibers within the basis pontis. Bilateral interruption of
the corticobulbar or corticoreticulobulbar fiber system results in
paresis(weakness) but not paralysis of the muscles supplied by
the corresponding cranial nerve nucleus. This condition is known
Cerebral as pseudobulbar palsy to distinguish it from bulbar palsy, which
peduncle is a condition characterized by complete paralysis of muscles
supplied by a cranial nerve nucleus as a result of a lesion of
the nucleus. The corticobulbar input to nuclei of trigeminal and
hypoglossal cranial nerves is bilateral. As a result, pseudobulbar
MESENCEPHALON palsy results only when corticobulbar inputs to these nuclei from
both hemispheres are interrupted. The corticobulbar input to
the facial nucleus is bilateral to the facial subnucleus that sup-
Basis plies upper facial muscles and is only contralateral to the facial
pontis subnucleus that supplies lower facial muscles. As a result, infarcts
in one hemisphere (as in middle cerebral artery occlusion) are
manifested by contralateral lower facial paralysis and sparing of
upper facial muscles. The relationship between the cerebral cor-
tex and the facial nerve nucleus has been the subject of several
investigations. The classical narrative that dominated knowledge
PONS during the past century stated that the primary motor cortex
(M-1) is the source of corticobulbar inputs to facial nucleus, and
that the facial subnucleus that supplies upper facial muscles re-
ceives inputs from both primary motor cortices, whereas the fa-
cial subnucleus that supplies lower facial muscles receives input
only from the contralateral primary motor cortex. While this
narrative was adequate to explain contralateral lower facial palsy
Pyramid in hemispheric lesions, it did not account for the reported disso-
ciation between voluntary and emotional facial movements,
MEDULLA
emotional facial paralysis (amimia), or the uncontrollable exces-
sive emotionally affiliated facial movements.
Lateral Several lines of research have now revealed that there are
corticospinal
tract
five cortical areas for face representation in human and in non-
human primates. In addition to the well-established primary
Anterior motor cortex (M-1), the following areas have face representa-
corticospinal tion: supplementary motor cortex (M-2), rostral cingulate gyrus
tract (M-3), caudal cingulate gyrus (M-4), and the ventral lateral pre-
SPINAL CORD motor cortex (LPMCV). Of these, the primary motor cortex
(M-1) and the ventral lateral premotor cortex (LPMCV) give rise
Figure 17–6. Schematic diagram of the corticospinal path- to the heaviest projections to the facial nucleus, followed by the
way. supplementary motor cortex (M-2), which sends a moderate
projection, and by the cingulate gyrus (M-3 and M-4), which
sends a light projection. It has been shown that the primary motor
cortex (M-1), the caudal cingulate gyrus (M-4), and the ventral
lateral premotor cortex (LPMCV) innervate primarily the con-
cortices and accompanies the corticospinal fiber system, leaving tralateral lower facial subnucleus (Figure 17–7A), whereas the
it at different levels of the neuraxis to project on reticular neu- supplementary motor cortex (M-2) and the rostral cingulate gyrus
rons in the brain stem. The corticoreticular fibers arising from (M-3) provide innervation to both upper facial subnuclei (Figure
one cerebral hemisphere project roughly equally to both sides of 17–7B). It has been suggested that the different cortical face rep-
the brain stem reticular formation. Many of these fibers ulti- resentations mediate different elements of facial expression and
mately project on cranial nerve nuclei in the brain stem, thus that separate neural systems may mediate voluntary and emo-
forming the corticoreticulobulbar pathway. tional facial movements. Thus, volitional facial paresis is asso-
Figure 17–7. Schematic diagram showing origins of corticobulbar fibers to the contralateral lower facial subnucleus
A, and to both upper facial subnuclei B.
ciated with lesions in the primary motor cortex (M-2) and the
underlying subcortical white matter. The cingulate gyrus (M-3
and M-4) projections, in contrast, subserve emotional expressions
of facial movements. Damage in the anterior cingulate gyrus (M-3)
is associated with blunted emotional expression in upper facial
muscles, suggesting that it controls emotionally related move-
ments of the face. Functional neuroimaging studies have shown
that the orbitofrontal cortex plays a role in emotional processing
of pleasant facial expressions. Enhanced responses in the or-
bitofrontal cortex are associated with recognition of happy faces.
Corticopontine Pathway (Figure 17–8) CEREBRAL

CORTEX
Fibers comprising this pathway arise from all parts of the cere-
bral cortex but primarily from the frontal, parietal, and occipital
lobes. Most fibers, however, arise from the primary motor (pre-
central gyrus) and primary sensory (postcentral gyrus) cortices,
with relatively substantial contribution from the premotor, sup-
plementary motor, and posterior parietal cortices and few from
the temporal and prefrontal cortices. These fibers descend in the
internal capsule and occupy the most medial and lateral parts of
the cerebral peduncle before reaching the basis pontis, where Corticopontine
they project on pontine nuclei. The corticopontine fibers consti- fibers MIDBRAIN
tute by far the largest component of the corticofugal fiber sys-
tem. It is estimated that each corticopontine pathway contains
approximately 19 million fibers. With approximately the same
number of pontine neurons on each side of the basis pontis, the
ratio of corticopontine fibers to pontine neurons becomes 1:1.
Corticopontine fibers terminate in sharply delineated lamellae
extending rostrocaudally. Various cortical regions project to Pontine
separate parts of the pontine nuclei, although considerable over- nuclei
lap takes place between some projection areas. Pontine neurons
CEREBELLUM
that receive corticopontine fibers give rise to the pontocerebellar PONS
pathway discussed in the chapter on the pons (Chapter 7). The
corticopontine pathway is thus one of several pathways that link
Pontocerebellar fibers in
the cerebral cortex with the cerebellum for the coordination and middle cerebellar peduncle
regulation of movement. Lesions of the corticopontine pathway
at its sites of origin in the cortex or along its course will result in Figure 17–8. Schematic diagram of the corticopontine and
incoordinated movement (ataxia) contralateral to the lesion. The pontocerebellar pathways.
238 / CHAPTER 17
ataxia observed in some patients with frontal or temporal lobe include the dorsomedial thalamic nucleus and prefrontal cortex,
pathology is thus explained as an interruption of the corticopon- anterior thalamic nucleus and cingulate cortex, ventrolateral tha-
tine pathway. lamic nucleus and motor cortex, posteroventral thalamic nucleus
and postcentral gyrus, medial geniculate nucleus and auditory
Corticothalamic Pathway cortex, and lateral geniculate nucleus and visual cortex. The cor-
ticothalamic input to the reticular thalamic nucleus, however, is
The corticothalamic pathway arises from cortical areas that re- not reciprocal. The reticular nucleus receives afferents from al-
ceive thalamic projections and thus constitutes a feedback mech- most all cortical areas but does not project back to the cerebral
anism by which the cerebral cortex influences thalamic activity. cortex. The reticular nucleus receives collaterals from all tha-
The thalamocortical relationship is such that a thalamic nucleus lamocortical and all corticothalamic projections. Thus the retic-
that projects to a cortical area receives in turn a projection from ular nucleus is informed of activities passing in both directions
that area. Examples of such reciprocal connections (Figure 17–9) between the thalamus and cerebral cortex.
Corticothalamic fibers descend in various parts of the inter-
nal capsule and enter the thalamus in one bundle known as the
Cingulate thalamic radiation, which also includes the reciprocal thalamo-
gyrus cortical fibers.
VA VL VP
Corticohypothalamic Pathway
A The corticohypothalamic fibers arise from prefrontal cortex, cin-
gulate gyrus, amygdala, olfactory cortex, hippocampus, and
DM septal area.
LG
MEDIAL LG Corticostriate Pathway
CEREBRAL
HEMISPHERE Projections from the cerebral cortex to the striatum are both
direct and indirect. Direct corticostriate projections reach the
neostriatum via the internal and external capsules and via the
subcallosal fasciculus. The indirect pathways include the corti-
cothalamostriate pathway, collaterals of the corticoolivary path-
way, and collaterals of the corticopontine pathway.
Prefrontal Premotor Primary Primary The corticostriate projection comprises the most massive stri-
cortex cortex motor cortex somatosensory atal afferents. Almost all cortical areas contribute to this projec-
cortex tion. Cortical areas interconnected via corticocortical fibers tend
to share common zones of termination in the neostriatum.
Corticostriatal fibers are organized topographically into three
VA VL VP distinct striatal territories: (1) sensorimotor, (2) associative, and
(3) limbic. The sensorimotor territory receives its inputs from
sensory and motor cortical areas. The associative territory re-
ceives fibers from the association cortices. The limbic territory
DM MG receives input from limbic and paralimbic cortical areas.
LATERAL
LG Corticostriate pathways are also organized somatotopically
CEREBRAL such that cortical association areas project to the caudate nu-
HEMISPHERE
cleus, whereas sensorimotor cortical areas preferentially project
to the putamen. Corticoputamenal projections are further orga-
nized in that the cortical arm, leg, and face areas project to corre-
Primary Primary sponding areas within the putamen.
auditory visual
area area Other Corticofugal Pathways
THALAMIC These include cortical projections to several sensory brain stem
A nuclei, such as the nuclei gracilis and cuneatus, trigeminal nuclei,
NUCLEI
and others. Most of these fibers serve a feedback purpose. Cor-
VA
DM ticosubthalamic projections originate from the primary motor and
VL premotor cortical areas. A corticotectal projection has been de-
A=Anterior nucleus scribed arising from the frontal eyefields (area 8 of the frontal cor-
DM=Dorsomedial nucleus VP tex) in addition to that from the occipital cortex. Corticorubral
VA=Ventral anterior nucleus
VL=Ventral lateral nucleus fibers originate from the same cortical areas as the corticospinal
IL tract and terminate on the red nucleus in the midbrain.
VP=Ventral posterior nucleus
IL=Intralaminar nuclei
MG=Medial geniculate INTRACORTICAL CIRCUITRY
LG=Lateral geniculate MG
MG LG
Cortical neurons may have descending, ascending, horizontal, or
Figure 17–9. Schematic diagram of thalamocortical relationships. short axons (Figure 17–1). The descending axons contribute to
the association and the corticofugal fiber systems outlined above. deep cortical layers (cells of Martinotti) and in superficial cortical
The ascending, horizontal, and short axons play important roles layers (horizontal cells of Cajal) contribute to intracortical cir-
in intracortical circuitry. Neurons with ascending axons are the cuitry by vertical and horizontal spread of impulses. Martinotti
cells of Martinotti. The horizontal cells of Cajal have horizontal cells, excited by axon collaterals of pyramidal neurons, in turn
axons. Short axons arborizing in the vicinity of the cell body are excite either a pyramidal neuron or another interneuron. Similarly,
seen in stellate neurons. Pyramidal neurons have horizontal and the horizontally oriented axons of the horizontal cells of Cajal in-
recurrent axon collaterals that terminate at all levels of the cortex fluence the vertically oriented processes of pyramidal neurons or
and contribute significantly to intracortical connections. The axon interneurons. Because of their paucity or absence in the post-
collaterals of pyramidal neurons may project on a stellate cell or neonatal period, the horizontal cells of Cajal play a minimal role
a Martinotti cell that in turn may influence other cortical neu- in intracortical circuitry in the adult.
rons and thus provide for rapid dispersion of activity throughout From the preceding it can be seen that an input to the cortex
a population of neurons. This fact was recognized by Cajal, who is spread both horizontally and vertically via the various intracor-
referred to it as avalanche conduction. A simplified account of tical connections. The complexity of these interconnections is far
intracortical circuitry is illustrated diagrammatically in Figure from clear definition, and is the basis of the complexity of hu-
17–10. A thalamocortical input will excite pyramidal (projection) man brain function.
neurons in layer VI and interneurons (excitatory and inhibitory)
in layer IV (point 1 in Figure 17–10). Inhibitory interneurons in
layer IV inhibit other interneurons in the same layer (point 2 in CORTICAL CYTOARCHITECTONIC AREAS
Figure 17–10). Excitatory interneurons in layer IV excite pyra- Different parts of the cortex vary in relation to the following
midal neurons and inhibitory interneurons in layers II and III parameters:
(point 3 in Figure 17–10). Inhibitory interneurons in layers II
and III inhibit pyramidal neurons in the same layers (point 4 in 1. Thickness of the cortex
Figure 17–10). Pyramidal neurons in layers II and III excite pro- 2. Width of the different layers of the cortex
jection neurons in layers IV and V (point 5 in Figure 17–10). 3. Cell types in each layer
Axon collaterals of projection neurons in layer V excite corti- 4. Cell density in each layer
cothalamic projection neurons in layer VI (point 6 in Figure
5. Nerve fiber lamination
17–10). Axon collaterals of corticothalamic projection neurons
in layer VI project back to the excitatory interneurons in layer IV Based on the preceding variations, different investiga-
(point 7 in Figure 17–10), thus closing the loop. Interneurons in tors have parceled the cortex into from 20 to 200 areas
Intrinsic Cortical Circuitry
Lamina I
Inhibitory Dendrite
neuron
4 –
–
+
Lamina II,III + Excitatory
neuron +
3
2 5 +
Lamina IV +
–
+
+
Lamina V 7
1 Axon
collateral
+ + 6
Lamina VI
Axon
From To To To other
Figure 17–10. Schematic diagram showing thalamus thalamus subcortex cortical
intrinsic cortical circuitry. areas
240 / CHAPTER 17
depending on the criteria used. The classification of the German missing. Review of Brodmann’s 1909 monograph revealed that
histologist Korbinian Brodmann, published in 1909, remains the the missing numbers are in the insula (island of Reil). Areas 13
most widely used. It contains 52 cytoarchitectonic areas numbered and 14 refer to the anteriorly placed two insulae breves, and areas
in the order in which he studied them (Table 17–3). 15 and 16 refer to the posteriorly placed two insulae longes.
Careful counting of the numbers of Brodmann areas in text- More important than the cytoarchitectonic classification is the
book illustrations indicates that numbers 13 through 16 are functional classification of the cortex into several motor and sen-
sory areas. The account that follows will focus on functional areas
of the cortex. Brodmann’s terminology will be used because it is
the most frequently cited. The commonly used classification of
Table 17–3. Brodmann Areas cortical areas into purely sensory and motor is somewhat mis-
leading and inaccurate. There is ample evidence to suggest that
Brodmann Neuroanatomic, functional designation motor responses can be elicited from so-called sensory areas.
Area This has prompted the use of the term sensory motor cortex to
refer to previously designated sensory and motor areas.
1, 2, 3 Postcentral gyrus, primary sensory cortex [intermediate However, for didactic purposes, the motor and sensory areas
(1), caudal (2), and rostral (3) parts] of the cortex will be discussed separately.
4 Precentral gyrus, primary motor cortex
5 Superior parietal lobule caudal to postcentral sulcus
6 Precentral gyrus (including supplementary motor area) CORTICAL SENSORY AREAS
7 Superior parietal lobule caudal to area 5
8 Middle frontal gyrus, rostral to area 6 Sensory function in the cortex is localized mainly in three lobes:
9, 10 Prefrontal cortex (dorsolateral and mesial) parietal, occipital, and temporal. There are six primary sensory
11, 12 Orbital gyri areas in the cortex:
13, 14 Anterior part of the insula (island of Reil) 1. Primary somesthetic (general sensory, somatosen-
15, 16 Posterior part of the insula (island of Reil) sory) area in the postcentral gyrus of the parietal lobe
17 Calcarine gyrus, primary visual (striate) cortex 2. Primary visual area in the calcarine gyrus of the oc-
18 Surrounds area 17, secondary visual association cortex cipital lobe
19 Surrounds area 18, tertiary visual association cortex
20 Inferior temporal gyrus, visual association cortex
3. Primary auditory area in the transverse gyri of Heschl of the
21 Middle temporal gyrus, visual association cortex temporal lobe
22 Superior temporal gyrus, auditory association cortex, 4. Primary gustatory (taste) area in the most ventral part of the
Wernicke’s area postcentral gyrus of the parietal lobe
23 Ventral posterior cingulate gyrus, limbic cortex 5. Primary olfactory (smell) area in the piriform and periamyg-
24 Ventral anterior cingulate gyrus, limbic cortex daloid regions of the temporal lobe
25 Subcallosal area, subgenu area 6. Primary vestibular area in the temporal lobe
26 Retrosplenial area, limbic cortex
27 Presubicular area, limbic cortex Each of these areas receives a specific sensory modality (i.e.,
28 Entorhinal cortex pain, touch, vibration, vision, audition, taste, smell). Sensory
29, 30 Retrosplenial cortex, limbic cortex modalities reaching each of these areas (except olfaction) pass
31 Dorsal posterior cingulate gyrus, limbic cortex through the thalamus (modality-specific thalamic nucleus) prior
32 Dorsal anterior cingulate gyrus and adjacent frontal to reaching the cortex. Each of the preceding sensory areas is des-
area ignated as a primary sensory area. Primary sensory cortices have
33 Rostral cingulate gyrus (pregenu area), limbic cortex restricted receptive fields. Adjacent to the primary somesthetic,
34 Dorsal entorhinal area visual, and auditory areas are secondary sensory areas. The sec-
35 Perirhinal area, parahippocampal gyrus ondary sensory areas are found by recording evoked potentials in
36 Ectorhinal area, lateral to the rhinal sulcus, para- the respective areas following an appropriate peripheral stimulus
hippocampal gyrus
(sound, light, etc.). In general, the secondary sensory areas are
37 Occipitotemporal area, inferolateral part of the
temporal lobe, decoding of visual information
smaller in size than the primary areas, and their ablation is with-
38 Temporal pole, retrieval of proper nouns out effect on the specific sensory modality.
39 Angular gyrus
40 Supramarginal gyrus Primary Somesthetic (General Sensory,
41, 42 Heschl’s gyrus, primary auditory cortex Somatosensory) Area (SI)
43 Frontoparietal (rolandic) operculum, gustatory cortex
44 Pars opercularis of inferior frontal gyrus, Broca’s area This area (Figure 17–11) corresponds to the postcentral gyrus
of speech of the parietal lobe (areas 1, 2, and 3 of Brodmann) and the pos-
45 Pars triangularis of inferior frontal gyrus, Broca’s area terior part of the paracentral lobule. Area 3 is divided into two
of speech parts: 3b on the posterior wall of the central sulcus and 3a in the
46 Middle frontal gyrus, dorsolateral prefrontal area, depth of the sulcus. In 1916, Dusser de Barenne applied strych-
association cortex nine, a central stimulant drug, to the postcentral gyrus of mon-
47 Pars orbitalis of inferior frontal gyrus keys and noted that the animals scratched their skin. Subsequent
48 Retrosubicular area work by Head on World War I soldiers with head injuries and by
49 Parasubiculum the neurosurgeons Cushing and Penfield has added tremendously
51 Prepiriform area to knowledge about the function of this area.
52 Parainsular area, superior bank of superior temporal
Although the primary somesthetic area is concerned basically
gyrus along the posterior margin of the insula
with sensory modalities, it is possible to elicit motor responses
Somesthetic the medial surface of this area. The anal and genital regions are
cortex represented in the most ventral portion of the medial surface just
above the cingulate gyrus. The representation of the face, lips,
3 hand, thumb, and index finger is disproportionately large in com-
2 parison with their relative size in the body. This is a reflection of
1
the functional importance of these parts in sensory function.
Stimulation of the primary somesthetic cortex in conscious
patients elicits sensations of numbness and tingling, a feeling of
electricity, and a feeling of movement without actual movement.
These sensations are referred to the contralateral half of the body,
except when the face area is stimulated. The face and tongue are
represented bilaterally.
Lateral view Ablation of the postcentral gyrus will result, in the immediate
postoperative period, in loss of all modalities of sensation (touch,
pressure, pain, and temperature). Soon, however, pain and tem-
perature sensations will return. It is believed that pain and tem-
perature sensations are determined at the thalamic level, whereas
the source, severity, and quality of such sensations are perceived
in the postcentral gyrus. Thus the effects of postcentral gyrus le-
Somesthetic sions would be (1) complete loss of discriminative touch and pro-
cortex prioception and (2) crude awareness of pain, temperature, and
2 3 light touch.
Neurophysiologic studies of the somesthetic cortex have re-
1 vealed the following information: (1) The functional cortical unit
appears to be associated with a vertical column of cells that is
modality specific. Neurons within a cortical unit are activated by
the same peripheral stimulus and are related to the same periph-
eral receptive field. (2) Area 3b is activated by cutaneous stim-
uli and areas 2 and 3a by proprioceptive impulses, whereas area
1 is activated by either cutaneous or proprioceptive impulses.
(3) Somatosensory neurons responding to joint movement show
Medial view a marked degree of specificity in that they respond to displace-
ment in one direction. (4) Fast- and slow-adapting neuronal pools
have been identified in response to hair displacement or cutaneous
deformation. (5) Fibers mediating cutaneous sensations termi-
nate rostrally, while those mediating proprioceptive sensations
terminate more caudally in the somesthetic area.
Figure 17–11. Schematic diagram of the primary somesthetic
cortex.
Secondary Somesthetic Area (SII)
A secondary somesthetic area has been described in humans and
following its stimulation. The primary somesthetic area receives primates. It is located on the most inferior aspect of the post-
nerve fibers from the ventral posterolateral and ventral postero-
medial nuclei of the thalamus. These fibers convey general sensory
(touch, pain, and temperature) as well as proprioceptive sensory
modalities (position, vibration, and two-point discrimination). Thigh Arm
In addition to thalamic afferents, the primary somesthetic
cortex receives commissural fibers through the corpus callosum Leg Hand
from the contralateral primary somesthetic cortex and short as-
sociation fibers from the adjacent primary motor cortex. Efferents Face
Foot
from the primary somesthetic cortex project to the motor cortex,
the opposite primary somesthetic cortex, and the association so-
Tongue
matosensory cortex (areas 5 and 7) in the posterior parietal cor-
Corpus
tex. The primary and secondary somesthetic areas are recipro- callosum Pharynx
cally interconnected. In addition, projection fibers descend within
the internal capsule to the ventral posterior nuclei of the thala-
mus, posterior column nuclei of the medulla oblongata, and dor-
sal horn of the spinal cord. The contralateral half of the body is
represented in a precise but disproportionate manner (sensory
homunculus) in each of the three areas (1, 2, and 3) of the som-
esthetic cortex (Figure 17–12). The pharynx, tongue, and jaw
are represented in the most ventral portion of the lateral surface MEDIAL LATERAL
of the somesthetic area, followed in ascending order by the face,
hand, arm, trunk, and thigh. The leg and foot are represented on Figure 17–12. Schematic diagram of the sensory homunculus.
242 / CHAPTER 17
central gyrus and in the superior bank and depth of the lateral stimuli, which is essential for coordination of eyes and hands in
sulcus (parietal operculum). Body representation in this area is visually guided movements.
bilateral, with contralateral predominance, and is the reverse of Bilateral lesions in the primary somatosensory association
that in the primary area so that the two face areas are adjacent areas in humans are associated with inability to move the hand
to each other. toward an object that is clearly seen (optic ataxia). Such patients
The secondary sensory area contains neurons with receptive are unable to pour water from a bottle into a glass and repeat-
fields that are large, poorly demarcated, overlap extensively, and edly pour the water outside the glass. Unilateral lesions in the
often have bilateral representation. Lesions of the secondary primary somatosensory association areas in the nondominant
somesthetic area and the insula produce asymbolia for pain, hemisphere produce neglect of the contralateral half of the body
suggesting that the secondary somesthetic area is an important and visual space.
cortical locus for the conscious perception of noxious stimuli.
Positron-emission tomographic (PET) studies in human volun- Primary Visual Cortex (V1)
teers subjected to noxious stimuli have demonstrated increased
metabolic activity in the secondary somesthetic area as well as in This area (Figure 17–13) corresponds to the calcarine gyrus on
the postcentral and cingulate gyri. Damage to SII or possibly to the medial surface of the occipital lobe on each side of the cal-
the posterior insula leads to the inability of the patient to identify carine sulcus (area 17 of Brodmann), encompassing parts of the
objects by touch (tactile agnosia, agraphesthesia). The primary lingual gyrus ventrally and cuneus gyrus dorsally. In sections of
and secondary somesthetic areas are reciprocally interconnected. fresh cortex, this area is characterized by the appearance of a
The secondary somesthetic area contains no cells sensitive to prominent band of white matter that can be identified by the
joint movement or joint position. The secondary somesthetic area naked eye and is named the band of Gennari, after the Italian
has been shown to have reciprocal connections with ventral pos- medical student who described it in 1782. The band of Gennari
teromedial and centrolateral nuclei of the thalamus. It also receives represents a thickened external band of Baillarger in layer IV of
inputs from the ipsilateral and contralateral primary somesthetic the cortex. In myelin preparations, the band of Gennari appears
cortices. Efferent connections project to the primary somesthetic as a prominent dark band in the visual cortex, also known as the
and primary motor areas within the same hemisphere. Lesions striate cortex. The term striate refers to the presence in unstained
interrupting connections between the secondary somesthetic area, preparations of the thick white band of Gennari.
posterior parietal cortex, and ventral posteromedial and centro- The primary visual area receives fibers from the lateral genic-
lateral thalamic nuclei have been associated with pseudothalamic ulate nucleus. These fibers originate in the retina, synapse in the
pain syndrome. The pain is spontaneous and characterized as lateral geniculate nucleus, and reach the visual cortex via the op-
burning or icelike and is associated with impairment of pain and tic (geniculocalcarine) radiation. Each visual cortex receives fibers
temperature appreciation. from the ipsilateral half of each retina (Figure 17–14) that con-
vey information about the contralateral half of the visual field.
Supplementary Sensory Area (SSA) Thus lesions of one visual cortex are manifested by loss of vision
in the contralateral half of the visual field (homonymous hemi-
This area was defined originally by Penfield and Jasper with intra- anopsia). The projections from the retina into the visual cortex
operative stimulation studies in humans. The supplementary sen- are organized spatially in such a way that macular fibers occupy
sory area lacks Brodmann’s numeric designation, but it encom- the posterior part of the visual cortex, while peripheral retinal
passes medial area 5 of Brodmann and probably the anterior part fibers occupy the anterior part (Figure 17–15). Fibers originat-
of medial area 7. Neurons in the supplementary sensory area have ing from the superior half of the retina terminate in the superior
large receptive fields, and some neurons are sensitive to pain. part of the visual cortex; those from the inferior half of the retina
Primary (Unimodal) Somatosensory

(Somesthetic) Association Areas Secondary
visual cortex
The primary somatosensory association areas encompass areas
5 and 7 in the superior parietal lobe. They receive their inputs
mainly from the primary somatosensory areas but also have recip- Area 19
rocal connections with the pulvinar nucleus of the thala-
Area 18
mus. Neuronal responses in the primary somatosensory
association areas are complex and involve the integration
of a number of cortical and thalamic inputs. The processing of
multisensory somatosensory inputs in these areas allows for the
perception of shape, size, and texture and the identification of
objects by contact (stereognosis). The primary somatosensory
association areas project to multimodal nonprimary association
areas (areas 39 and 40) in the inferior parietal lobule that receive
inputs from more than one sensory modality and serve inter- Primary
modal integration and multisensory perceptions. visual
Single-cell recordings in area 5 in monkeys suggest that this cortex
area is essential for the proper use of somatosensory information,
for goal-directed voluntary movements, and for the manipula-
tion of objects.
Single-cell recordings in area 7 indicate that this area plays an Figure 17–13. Schematic diagram of the primary and secondary
important role in the integration of visual and somatosensory visual cortices.
Left Right Left Right

Superior
VISUAL FIELD RETINA
Inferior
RETINA
Right
visual
cortex
VISUAL CORTEX
Figure 17–16. Schematic diagram of retinal representation in

the primary visual cortex.
Figure 17–14. Schematic diagram of retinal representation in
the primary visual cortex.
the visual field. The representation of the macula in the visual
cortex is disproportionately large in comparison with its relative
terminate in the inferior part (Figure 17–16). Thus lesions in- size in the retina. This is a reflection of its important function as
volving portions of the visual cortex, such as the inferior cal- the retinal area of keenest vision.
carcine cortex, produce an upper contralateral quadrantanopsia Stimulation of the visual cortex elicits a crude sensation of
in which blindness is limited to the contralateral upper quadrant bright flashes of light; patients with irritative lesions (such as tu-
of the visual field. Similarly, lesions limited to the upper cal- mors) of the visual cortex experience visual hallucinations that
carine cortex produce a lower contralateral quadrantanopsia in consist of bright light. Conversely, lesions that destroy the visual
which blindness is limited to the contralateral lower quadrant of cortex of one hemisphere result in loss of vision in the contralateral
half of the visual field. If the destructive lesion is of vascular origin,
such as occurs in occlusions of the posterior cerebral artery, central
Left Right (macular) vision in the affected visual field is spared. This phe-
nomenon is known clinically as macular sparing and is attributed
Macula
to the collateral arterial supply of the posterior visual cortex (mac-
ular area) from the patent middle cerebral artery.
RETINA
Functional magnetic resonance imaging (fMRI) studies in
blind persons have found increased responsiveness in their pri-
Peripheral mary visual cortex during a verbal memory task without any sen-
sory input. This suggests that, while sighted people devote much
of their cortex to visual processing, the visual cortex in the blind
are recruited for other senses. Elegant neurophysiologic studies
of single neurons in the visual cortex have revealed the following
information:
1. The visual cortex is organized into units that correspond to
specific areas in the retina.
2. These units respond to linear stripe (straight-line) configu-
Right rations.
visual 3. For each unit, a particular orientation of the stimulus is
cortex most effective. Some units respond only to vertically ori-
ented stripes, while others respond only to horizontally ori-
ented stripes. Some units respond at onset of illumination,
while others respond at cessation of illumination.
4. Units are of two varieties, simple and complex. Simple units
Figure 17–15. Schematic diagram of retinal representation in react only to stimuli in corresponding fixed retinal receptive
the primary visual cortex. fields. Complex units are connected to several simple cortical
244 / CHAPTER 17
units. It is presumed that the complex units represent an ad- perception) and movement. The inferotemporal projection is con-
vanced stage in cortical integration. cerned with analysis of form and color. The inferotemporal cortex
5. Units that respond to the same stimulus pattern and orienta- represents highest visual function. Electrical stimulation of area
tion are grouped together in repeating units referred to as 21 evokes lifelike visual hallucinations. Area 37, behind area 21,
columns, similar to those described for the somesthetic cortex. at the occipitotemporal junction contains modules devoted to
Two general varieties of functional columns have been de- recognition of faces. Bilateral lesions in this area result in failure
scribed: ocular dominance and orientation columns. Ocular to recognize familiar faces (prosopagnosia). Color vision is local-
dominance columns are parallel columns arranged perpendic- ized inferiorly in the inferior occipitotemporal cortex (V4). No
ular to the cortical surface and reflect eye preference (right ver- color representation is found in the superior association visual
sus left) of cortical neurons. Alternating ocular dominance cortex. Thus in unilateral inferior association visual cortex lesions
columns are dominated by inputs from the left and right eyes. the patient loses color vision in the contralateral half field (central
Orientation columns comprise a sequence of cells that have hemiachromatopsia). Loss of color vision and face recognition
the same receptive field axis orientation. usually coexist because of the proximity of the areas responsible
6. Visual columns respond poorly, if at all, to diffuse retinal for them. Connections of the association visual cortex to the an-
illumination. gular gyrus (area 39) play a role in recognition of visual stimuli.
Lesions interrupting this connection result in visual agnosia, in-
7. Visual units respond optimally to moving stimuli. ability to recognize objects in the visual field. Bilateral lesions of
8. Most cortical units receive fibers from corresponding recep- the fifth visual area (V5) are associated with a defect in visual mo-
tive fields in both retinas, thus allowing for single-image vi- tion perception (akinetopsia).
sion of corresponding points in the two retinas. Projections from areas 18 and 19 also reach the frontal eye
9. The striate cortex is organized into vertical and horizontal fields (area 8 of Brodmann) in the frontal lobe, as well as the su-
systems. The vertical (columnar) system is concerned with perior colliculus and motor nuclei of extraocular muscles. These
retinal position, line orientation, and ocular dominance. The projections play a key role in conjugate eye movement induced
horizontal system segregates cells of different orders of com- by visual stimuli (visual pursuit).
plexity. Simple cells located in layer IV are driven monocu-
larly, while complex and hypercomplex cells, located in other Primary Auditory Cortex
layers, are driven by impulses from both eyes.
The output from the primary visual cortex follows two path- David Ferrier, a British physician, is credited with localizing the
ways or streams: a dorsal stream to the occipitoparietal cortex primary auditory cortex of monkeys to the superior temporal
(the “where” pathway) and a ventral stream to the occipitotem- gyrus during the latter half of the nineteenth century. This local-
poral cortex (the “what” pathway). Bilateral lesions in the “where” ization was not accepted by his contemporaries. Subsequent stud-
pathway result in the inability to direct the eyes to a certain point ies in animals and humans, however, have confirmed his early
in the visual field despite intact eye movements (Balint-Holmes observations.
syndrome). Bilateral lesions in the “what” pathway result in the The primary auditory cortex (Figure 17–17) corresponds to
inability of patients, with normal visual perception, to compre- the transverse temporal gyri of Heschl (areas 41 and 42 of
hend the meaning of nonverbal visual stimuli (visual agnosia). Brodmann) located in the temporal lobe within the lateral fis-
sure. Recording of primary evoked responses to auditory stimuli
during surgery for epilepsy provides evidence for a restricted
Primary (Unimodal) Visual Association Areas portion of Heschl’s gyrus (its posteromedial part) as the primary
auditory area.
Adjacent to the primary visual area are the primary association vi- The primary auditory cortex receives fibers (auditory radia-
sual areas (extrastriate, prestriate). They include areas 18 and 19 tion) from the medial geniculate nucleus. These fibers reach the
of Brodmann (Figure 17–13) on the lateral and medial aspects of auditory cortex via the sublenticular part of the internal capsule.
the hemisphere. Areas 20, 21, and 37 in the inferior temporal
cortex are also dedicated to visual information processing. The vi-
sual association cortices are concerned with higher-order aspects
of visual processing, as detailed later. Area 18 corresponds to the
second (V2) and area 19 to the third (V3) visual areas. V4, in hu-
mans, is probably located in the inferior occipitotemporal area, in
the region of the lingual or fusiform gyrus. V5 in humans is prob-
ably located in area 19 of Brodmann. V2, like V1, is retinotopi-
cally organized. Visual areas beyond V2 are associated with vary-
ing visual functions. V3 is associated with form, V4 with color,
and V5 with motion. Units in the primary visual association areas
are of the complex or hypercomplex types.
Afferents to areas 18 and 19 are mainly from the primary vi-
sual area (area 17) but include some direct thalamic projections
Lateral fissure
from the lateral geniculate nucleus and pulvinar nucleus. The (widely opened)
primary visual area projects bilaterally and reciprocally to areas
18 and 19. The projections from the pulvinar nucleus constitute Primary
auditory
important extrageniculate links to the visual cortex. cortex
Outputs from areas 18 and 19 project to the posterior parietal
cortex (area 7) and to the inferotemporal cortex (areas 20 and Figure 17–17. Schematic diagram of the primary auditory
21). The projection to area 7 is concerned with stereopsis (depth cortex.
Auditory fibers originate in the peripheral organ of Corti and es- and via the corpus callosum with the prefrontal, premotor, pari-
tablish several synapses in the neuraxis, both homolateral and etal, and cingulate cortices.
contralateral to their side of origin, before reaching the medial
geniculate nucleus of the thalamus. The primary auditory cortex, Primary Gustatory Cortex
therefore, receives fibers originating from both organs of Corti,
predominantly from the contralateral side. Stimulation of the The cortical receptive area for taste is located in the parietal op-
primary auditory cortex produces crude auditory sensations such erculum, ventral to the primary somesthetic area and in close
as buzzing, humming, or knocking. Such sensations are referred proximity to the cortical areas receiving sensory afferents from
to clinically as tinnitus. Lesions of the auditory cortex result in the tongue and pharynx. It corresponds to area 43 of Brodmann.
(1) impairment in sound localization in space and (2) diminu- Irritative lesions in this area in humans have been shown to give
tion of hearing bilaterally but mostly contralaterally. The func- rise to hallucinations of taste, usually preceding the onset of an
tional organization of the auditory cortex is similar to that of the epileptic attack. Such a prodromal symptom preceding an epilep-
somesthetic and visual cortices. Column cells in the auditory tic fit focuses attention on the site of the irritative lesion. Con-
cortex share the same functional properties. Columnar organiza- versely, ablation of this area produces impairment of taste con-
tion is thus based on isofrequency stripes, each stripe responding tralateral to the site of the lesion. The gustatory cortex receives
to a particular tonal frequency. fibers from the posteroventral medial nucleus of the thalamus,
The primary auditory cortex is connected with the primary upon which converge sensory fibers from the face and mouth,
(unimodal) association auditory cortex. Other important connec- including taste fibers. Although crude taste sensations can be
tions include the auditory cortex of the contralateral hemisphere, perceived at the thalamic level, discrimination among different
the primary somesthetic cortex, frontal eye fields, Broca’s area of taste sensations is a cortical function.
speech in the frontal lobe, and the medial geniculate nucleus. Via
its projection to the medial geniculate body in the thalamus, Primary Olfactory Cortex
the primary auditory cortex controls its own input by changing
the excitability of medial geniculate neurons. Responses of some The primary olfactory cortex is located in the tip of the temporal
auditory cortex neurons to sound stimuli depend on whether the lobe and consists of the piriform cortex and the periamygdaloid
type of these sounds was anticipated. A similar anticipatory re- area. The primary olfactory cortex receives fibers from the lateral
sponse to sound stimuli exists in some medial geniculate neurons, olfactory stria and has an intimate relationship with adjacent
suggesting that transmission of information through the auditory cortical regions comprising part of the limbic system. Such rela-
thalamus (medial geniculate nucleus) and on to the auditory cor- tionships, as well as the role of olfaction in emotion and behav-
tex is controlled by behavioral contingencies. ior, are discussed in the chapter on the limbic system (Chapter
Physiologic studies of the primary auditory cortex have re- 21). Adjacent to the primary olfactory cortex is the entorhinal
vealed that it does not play a major role in sound frequency dis- cortex (area 28), which is considered the association or secondary
crimination but rather in the temporal pattern of acoustic stimuli. olfactory cortical area.
Frequency discrimination of sound is a function of subcortical Irritative lesions in the region of the olfactory cortex give rise
acoustic structures. The optimal stimulus that fires auditory corti- to olfactory hallucinations that are usually disagreeable. As in the
cal units seems to be a changing frequency of sound stimuli rather case of taste, such hallucinations frequently precede an epileptic
than a steady-frequency stimulus. fit. Since olfactory hallucinations frequently occur in association
with lesions in the uncus of the temporal lobe (including the
olfactory cortex), they are referred to clinically as uncinate fits.
Primary (Unimodal) Auditory The olfactory system is the only sensory system in which
Association Cortex fibers reach the cortex without passing through the thalamus.
Basic olfactory functions needed for reflex action reside in sub-
Adjacent to the primary auditory cortex is the primary (uni- cortical structures. The discrimination of different odors, how-
modal) auditory association cortex (area 22 of Brodmann). It ever, is a function of the olfactory cortex.
comprises the area adjacent to Heschl’s gyri in the superior tem-
poral gyrus, including the posterior portion of the floor of the Primary Vestibular Cortex
sylvian fissure (the planum temporale). This area is concerned
with the comprehension of spoken sound. Area 22 in the domi- Data are scant about the anatomic location as well as the physio-
nant hemisphere is known as Wernicke’s area. Lesions of this area logic properties of the primary vestibular cortex. Many cortical
are associated with a receptive type of aphasia, a disorder of com- areas have been identified in humans as possibly involved in
munication characterized by the inability of the patient to com- vestibular processing. However, the various methods used pro-
prehend spoken words. The primary auditory association cortex vide variable degrees of accuracy and do not provide precise lo-
in the nondominant (right) hemisphere is specialized for non- calization. Recent studies using cortical stimulation in patients
speech auditory information, such as environmental sounds, mu- undergoing brain surgery for treatment of epilepsy have identi-
sical melodies, and tonal qualities of sound (prosody). Bilateral fied a lateral cortical temporoparietal area (the temporoperisylvian
lesions in the primary auditory association cortices result in the vestibular cortex) from which vestibular symptoms, including
inability to recognize sounds (auditory agnosia) in the presence rotatory sensations, were easily elicited. The area extended above
of normal hearing, alertness, and intelligence. Disconnection of and below the sylvian fissure, mainly inside Brodmann areas 40
the primary auditory association cortex (area 22) from the pri- (supramarginal gyrus), 21 (middle temporal gyrus), and 22 (pri-
mary auditory cortex (areas 41 and 42) results in a condition mary auditory association area in the superior temporal gyrus).
known as pure word deafness, characterized by poor comprehen- It included the parietal operculum. Lesions in this area in hu-
sion of spoken language and poor repetition with intact compre- mans impair perceptual judgments about body orientation and
hension of written language. The auditory association cortex is movement. Such lesions, however, do not impair brain stem
connected via the anterior commissure with the prefrontal cortex vestibular reflexes such as the vestibuloocular reflex.
246 / CHAPTER 17
CORTICAL MOTOR AREAS The motor area receives fibers from the ventrolateral nucleus
of the thalamus, the main projection area of the cerebellum. The
There are three major cerebral cortical areas involved in motor motor area also receives fibers from the somesthetic cortex (areas
control: 1, 2, and 5) and the supplementary motor cortex. The connec-
1. Primary motor area (MI) tions between the primary motor and somesthetic cortices are
reciprocal. The output contributes to the association, commis-
2. Supplementary motor area (MII) sural, and corticofugal fiber systems discussed earlier. The primary
3. Premotor area motor cortex is the site of origin of about 30% to 40% of the
The primary motor area is coextensive with area 4 of fibers in the pyramidal tract. Furthermore, all the large-diameter
Brodmann, and the supplementary motor and premotor axons (approximately 3% of the pyramidal fibers) originate from
areas are coextensive with area 6 of Brodmann. The sup- the giant motor neurons (of Betz) in the primary motor cortex.
plementary motor and premotor areas together represent the non- Most of the neurons contributing fibers to the corticospinal tract
primary motor cortex. The three motor areas differ in their electri- have glutamate or aspartate as their excitatory neurotransmitter.
cal excitability, functional neuronal properties, and connectivity. Ablation of the primary motor cortex results in flaccid (hypo-
They receive inputs from different thalamic nuclei and have differ- tonic) paralysis in the contralateral half of the body associated
ent corticocortical connections and different output projections. with loss of all reflexes. With time, there is recovery of stereo-
typed movement at proximal joints, but the function of distal
Primary Motor Area (MI) muscles concerned with skilled movement remains impaired.
Exaggerated myotatic reflexes and a Babinski sign also appear.
The primary motor area (Figure 17–18) corresponds to the pre- Although the primary motor cortex is not the sole area from
central gyrus (area 4 of Brodmann). On the medial surface of the which movement can be elicited, it is nevertheless characterized
hemisphere, the primary motor area comprises the anterior part by initiating highly skilled movement at a lower threshold of
of the paracentral lobule. The contralateral half of the body is stimulation than the other motor areas. Epileptic patients with a
represented in the primary motor area in a precise but dispropor- lesion in the primary motor cortex frequently manifest a seizure
tionate manner, giving rise to the motor homunculus in the (epileptic) pattern that consists of progression of the epileptic
same way as that described for the primary somesthetic cortex. movement from one part of the body to another in a characteris-
Stimulation of the motor cortex in conscious humans gives tic sequence corresponding to body representation in the motor
rise to discrete and isolated contralateral movement limited to a cortex. Such a phenomenon is known clinically as a Jacksonian
single joint or a single muscle. Bilateral responses are seen in ex- march, after the English neurologist John Hughlings-Jackson.
traocular muscles and muscles of the face, tongue, jaw, larynx, Neurophysiologic studies of motor cortex neurons reveal that ac-
and pharynx. The primary motor cortex thus functions in the tion potentials can be recorded from motor neurons in the cor-
initiation of highly skilled fine movements, such as buttoning tex about 60 to 80 ms before muscle movement. Furthermore,
one’s shirt or sewing. two types of neurons in the motor cortex have been identified.
The representation of bodily regions in the contralateral mo- These are a larger neuron with a phasic pattern of firing and a
tor cortex does not seem to be rigidly fixed. Thus repetitive stim- smaller neuron that fires in a tonic pattern. From experiments on
ulation of the thumb area will produce movement of the thumb, conscious animals performing specific tasks, it has been shown
followed after a while by immobility of the thumb and move- that the frequency of firing is highly correlated with the force ex-
ment at the index finger or even the wrist. This has been inter- erted to perform a specific movement. Motor neurons supplying
preted to mean that in the thumb area of the cortex the motor a given muscle are usually grouped together in a columnar fash-
units controlling the index finger and wrist have a higher thresh- ion. Although some motor neurons can be stimulated from a
old for stimulation than those controlling the thumb. wide area, each has a so-called best point from which it can be
stimulated most easily. Such best points usually are confined to a
cylindric area of cortex about 1 mm in diameter.
Frontal eye field Area 6 Area 4
(area 8)
Supplementary Motor Area (MII)
Middle frontal
The supplementary motor area is located on the medial surface
gyrus of the frontal lobe, anterior to the medial extension of the pri-
mary motor cortex (area 4). It corresponds roughly to the medial
extensions of area 6 of Brodmann. Although the existence of a
motor area in the medial aspect of the frontal cortex rostral to
the precentral leg area of primates has long been known, Penfield
and Welch were the first to call this portion of the cortex the
supplementary motor area in 1949 and 1951. A homunculus has
been defined for the supplementary motor area in which face
and upper limbs are represented rostral to the lower limbs and
trunk. Stimulation in humans gives rise to complex movement
in preparation for the assumption of characteristic postures.
Although simple motor tasks are elicited from stimulation of
the supplementary motor area, the role of this area in simple
motor tasks is much less significant and is likely to be subsidiary
to that of the primary motor area. On the other hand, the sup-
Figure 17–18. Schematic diagram of the primary motor area plementary motor area assumes more significance in executing
(area 4), premotor area (area 6), and the frontal eye field (area 8). simple motor tasks as a compensatory mechanism when the
primary motor area is destroyed. The supplementary motor area The premotor area (Figure 17–18) is located in the frontal
seems crucial in the temporal organization of movement, espe- lobe just anterior to the primary motor area. It corresponds to
cially in sequential performance of multiple movements, and in area 6 of Brodmann. The premotor area is concerned with vol-
motor tasks that demand retrieval of motor memory. Cells were untary motor function dependent on sensory inputs (visual, au-
identified in the supplementary motor area in response to move- ditory, somatosensory). Stimulation of the premotor area elicits a
ments of both proximal and distal extremity muscles, ipsilateral stereotyped gross movement that requires coordination among
and contralateral. Supplementary motor area neurons differ from many muscles, such as turning movements of the head, eyes, and
primary motor area neurons in that only a small percentage (5%) trunk toward the opposite side, elevation of the arm, elbow flex-
of supplementary motor area neurons contribute axons to the ion, and pronation of the hand. The threshold of stimuli that
pyramidal tract and these neurons have insignificant input from elicit responses from this area is higher than that required for the
the periphery and are activated bilaterally. primary motor cortex.
The supplementary motor cortex is connected reciprocally In normal subjects, the premotor area shows increased activ-
with the ipsilateral primary motor (area 4), premotor (area 6), ity when motor routines are run in response to visual, auditory,
and somatosensory (areas 5, 7) cortices and the contralateral sup- or somatosensory cues such as reaching for an object in space,
plementary motor cortex. Subcortical projections to the supple- obeying a spoken command, or identifying an object by manip-
mentary motor area are predominantly from the basal ganglia via ulation. The premotor area exerts influence on movement via the
the thalamus. An input from the cerebellum via the basal ganglia primary motor area or directly through its projections to the
also has been shown to exist. Subcortical projections of the sup- pyramidal and extrapyramidal systems. Approximately 30% of
plementary motor cortex are profuse to parts of the caudate nu- pyramidal fibers originate from the premotor area. The premotor
cleus and putamen and to the ventral anterior, ventral lateral, area is activated when a new motor program is established or
and dorsomedial thalamic nuclei. Approximately 5% of neurons when the motor program is changed on the basis of sensory in-
in the supplementary motor cortex contribute fibers to the corti- formation received, for example, when the subject is exploring
cospinal tract. Available anatomic and physiologic data suggest the environment or objects. Ablation of the premotor cortex in
that the supplementary motor area could be the site where exter- humans may produce a deficit in the execution of skilled, se-
nal inputs and commands are matched with internal needs and quential, and complex movement such as walking. Such a deficit
drives to facilitate formulation (programming) of a strategy of is known clinically as idiomotor apraxia. In such a syndrome, the
voluntary movement. The threshold of stimulation of the sup- patient has difficulty in walking, although there is no voluntary
plementary motor area is higher than that of the primary motor motor paralysis. The grasp reflex attributed to lesions of the pre-
cortex and the responses elicited are ipsilateral or bilateral. motor area in the older literature is now believed to be due to in-
In contrast to the evidence from physiologic studies, few clin- volvement of the supplementary motor cortex.
ical case reports have described persistent effects on motor be- Some neuroscientists consider the separation of the motor
havior of damage to the supplementary motor area. In the acute cortex into primary motor and nonprimary motor areas some-
phase, patients have global reduction in movement (akinesia) what artificial. However, closer consideration of this issue justi-
that is particularly pronounced on the side contralateral to the fies this separation on the basis of the threshold of stimuli that
lesion and a grasp reflex. Lesions in the supplementary motor elicit motor responses (much lower in the primary motor area) as
area of the dominant hemisphere are associated with severe im- well as the type of movement elicited from stimulation (simple
pairment of spontaneous speech with preserved repetition. These from the primary motor area versus coordinated, complex move-
manifestations are mostly transient and resolve within a few ment from the nonprimary areas).
weeks. The lasting disorder of motor behavior reported to occur Although neural activity in relation to each of many aspects
in humans after supplementary motor area lesions has been a of motor control seems to be distributed in multiple cortical areas,
disturbance of alternating movements of the two hands. Other an individual motor area (primary motor, premotor, supplemen-
clinical manifestations, of uncertain etiology, associated with le- tary motor) is used preferentially under specific circumstances
sions in the supplementary motor area include hypertonia, in- requiring a certain variety of motor behavior.
crease in myotatic reflexes, clonus, and the Babinski sign. In clinical situations, however, all areas are more often than
The traditionally defined supplementary motor area includes not involved together in disease processes, be it vascular occlusion
two separate regions: a caudal region (supplementary motor area or hemorrhage leading to stroke or a tumor invading this region
proper) that has reciprocal connections with the primary motor of the cortex. In such situations, the clinical manifestations can
area and projects to the spinal cord and a rostral region (presupple- be classified into those seen immediately after the onset of the
mentary motor area) that receives projections from the prefrontal pathology and those which follow after a few days or weeks. The
and cingulate cortices. Basal ganglia input reaches the caudal re- former consist of loss of all reflexes and hypotonia of affected
gion, whereas cerebellar input reaches the rostral region. Neuronal muscles. Within hours or days, however, stereotyped movement,
responses to visual stimuli prevail in the rostral region, whereas so- particularly in proximal muscles, returns, hypotonia changes to
matosensory responses prevail in the caudal region. The urge to ini- hypertonia and areflexia to hyperactive myotatic reflexes, and a
tiate movement in humans is elicited only from the rostral region. Babinski sign appears. The discrete movements in distal muscles,
however, remain impaired. Such a clinical picture is seen often
Premotor Area following a stroke involving this region of the cortex.
The concept of a premotor cortex was first proposed in 1905 by
Campbell, who called it the intermediate precentral cortex. The Cortical Eye Fields
term premotor cortex was first used by Hines in 1929. The pre-
motor cortex has undergone a strong phylogenetic development. A. SACCADIC EYE MOVEMENTS
Whereas in monkeys the premotor area is equally large as the pri- Saccadic movements are fast eye movements with rapid
mary motor area, in humans the premotor area is about six times refixation of vision from point to point with no interest
larger than the primary motor area. in the points in between. Positron emission tomography
248 / CHAPTER 17
(PET) scans and lesion studies indicate that the cerebral areas arterial occlusion and conjugate deviation of the eyes toward the
most important for saccadic control are: (1) posterior parietal cor- cortical lesion.
tex and (2) frontal premotor cortex. The posterior parietal cortex In humans, conjugate eye deviations occur more frequently
(cortex in the posterior region of the intraparietal sulcus and the after lesions in the right hemisphere than after lesions in the left
adjacent superior parietal lobule) is activated by the primary vi- hemisphere. There is no explanation for this other than that
sual cortex during saccades for which there is a visual goal. it may be related to the neglect syndrome associated more fre-
Three areas in the frontal lobe participate in saccadic process- quently with right hemisphere lesions. Conjugate eye deviations
ing: (1) the frontal eye field (area 8 of Brodmann), (2) the dorso- also have been observed with lesions that spare the frontal eye
lateral prefrontal cortex (area 46 of Brodmann), and (3) the sup- field but that interrupt the connections between the posterior
plementary eye field (anterior part of the supplementary motor parietal and frontal eye fields or their subcortical projections.
area). The frontal and supplementary eye fields are activated dur- 2. Supplementary Eye Field. An oculomotor area in the frontal
ing all types of saccadic movements. The dorsolateral prefrontal cortex, separate from the frontal eye field, was first defined by
cortex is activated during fixation. Schlag in 1985. It is located rostral to the supplementary motor
1. Frontal Eye Field. The frontal eye field (Figure 17–18) is lo- area (MII) on the medial surface of the hemisphere. The supple-
cated in the middle frontal gyrus anterior to or in the anterior mentary eye field receives multiple cortical inputs, in particular
portion of the motor strip. It corresponds to area 8 of Brodmann from the prefrontal cortex and the posterior part of the cerebral
and the immediately adjacent cortex. The frontal eye field trig- hemisphere. The supplementary eye field projects to the frontal
gers intentional (voluntary) saccades to visible targets in the vi- eye field and to subcortical nuclei involved in eye movements
sual environment, to remembered target locations, or to the lo- (superior colliculus and reticular formation). The supplementary
cation where it is predicted that the target will appear. These eye field plays a role in triggering sequences of saccades and in
movements subserve intentional exploration of the visual envi- the control of saccades concerned with complex motor program-
ronment. The frontal eye field receives multiple cortical inputs, ming such as those made during head or body movements (spa-
in particular from the parietooccipital cortex, supplementary eye tiotopic saccades).
field, and the prefrontal cortex (area 46 of Brodmann). The
3. Posterior Parietal Eye Field. The posterior parietal eye field
frontal eye field elicits intentional (voluntary) saccades through
corresponds to areas 39, 40, and 19 of Brodmann. This area trig-
connections to nuclei of extraocular muscles in the brain stem.
gers reflexive, visually guided saccades. It exerts its influence on
The pathway from the frontal eye field to the nuclei of extra-
saccadic eye movements via its connections to the frontal eye
ocular movement is not direct but involves multiple brain stem field or directly to the superior colliculus. Patients with lesions in
reticular nuclei, including the superior colliculus, the interstitial the posterior parietal eye field lose reflexive visually guided sac-
nucleus of the medial longitudinal fasciculus (RiMLF), and the cades but are able to move their eyes in response to command
paramedian pontine reticular formation (PPRF). Irritating le- (intentional saccades).
sions in the frontal eye field, as in an epileptic focus, will deviate
both eyes in a direction contralateral to the irritative lesion B. CORTICAL AREAS PREPARING SACCADES
(Figure 17–19). Conversely, ablation of the frontal eye field will Three cortical areas not involved directly in triggering of saccades
result in deviation of the eyes to the side of ablation (Figure play important roles in planning, integration, and chronologic
17–19) as a result of the unopposed action of the intact frontal ordering of saccades. The prefrontal cortex (area 46 of Brodmann)
eye field. Such a condition is encountered in patients with occlu- plays a role in planning saccades to remembered target locations.
sion of the middle cerebral artery, which supplies the bulk of the The inferior parietal lobule is involved in visuospatial integra-
lateral surface of the hemisphere, including the frontal eye field. tion. Bilateral lesions in this area result in Balint syndrome, named
As a result of the arterial occlusion, infarction (death) of cortical after the Hungarian neurologist Rudolph Balint (optic ataxia,
tissue will ensue. Such patients manifest paralysis of face and ocular apraxia, psychic paralysis of visual fixation), a rare syn-
limbs (upper limbs more than lower) contralateral to the side of drome characterized by the inability to direct the eyes to a cer-
tain point in the visual field despite retention of intact vision and
eye movements. The hippocampus appears to control the tem-
poral working memory required for chronologic order of saccade
sequences.
C. SMOOTH-PURSUIT EYE MOVEMENTS
Smooth-pursuit movements are slow eye movements initiated by
a moving object. The goal of the pursuit system is to produce eye
Ipsilateral conjugate Contralateral conjugate velocity that matches the velocity of the moving object. Unlike
deviation (unopposed deviation
action of intact area 8)
saccades, smooth-pursuit movements cannot occur in
darkness. They require a visual stimulus to occur. Cor-
tical areas involved in smooth pursuit include the tem-
porooccipital region and the frontal eye field. Each of these areas
has direct projections to brain stem neurons that drive pursuit.
The temporooccipital region is driven by input from the primary
visual cortex. Two other cortical areas (the posterior parietal and
the superior temporal cortices) may contribute to smooth pursuit
Ablation of area 8 (right) Stimulation of area 8 (right) indirectly through visual attention. Specific lesions in the tem-
porooccipitoparietal cortex in humans associated with smooth-
Figure 17–19. Schematic diagram of the effects of stimulation pursuit deficits correspond to Brodmann areas 19, 37, and 39.
and lesions in the frontal eye fields on conjugate eye movements. Lesions in the frontal eye field also have been associated with
deficits in smooth pursuit. The corticofugal pathways for smooth- Broca’s Arcuate fasciculus
pursuit movements follow two routes. The first courses from the area
temporooccipitoparietal cortex through the posterior limb of the Wernicke’s
internal capsule to the dorsolateral pontine nucleus in the mid- area
pons. The second courses from the frontal eye field to the dorso-
lateral pontine nucleus and nucleus reticularis tegmenti pontis.
Cortical areas for smooth pursuit also project to the flocculus of
the cerebellum after relays in the dorsolateral pontine nucleus.
The flocculus, in turn, projects on the vestibular nuclei, which
project to cranial nerve nuclei of extraocular movement (CN III,
IV, VI).
Cerebral hemisphere lesions impair ocular pursuit ipsilaterally
or bilaterally, whereas posterior fossa lesions impair ocular pursuit
either contralaterally or ipsilaterally. This variability probably re-
flects involvement of a presumed pursuit pathway that crosses
from the pontine nuclei to the cerebellum and then consists of a
unilateral projection from the cerebellum to vestibular nuclei. Primary auditory area
CORTICAL LANGUAGE AREAS

Language is an arbitrary and abstract way to represent thought Figure 17–20. Schematic diagram showing transmission of
processes by means of sentences and to present concepts or ideas auditory symbols from the primary auditory cortex to Wernicke’s
by means of words. The neural system for language is area for comprehension, and via the arcuate fasciculus, to Broca’s
made up of many components in several areas of the area of speech.
brain. Most components of the language system are lo-
cated in the left hemisphere. The left hemisphere is the domi-
nant hemisphere for language in approximately 95% of humans receptive, posterior, fluent) in which patients have difficulty com-
as determined by functional imaging and cortical stimulation prehending spoken language.
studies. Nearly all right-handers and about two-thirds of left-
handers have such dominance. A disorder in language function
(aphasia or dysphasia) includes disturbances in the ability to Broca’s Area
comprehend (decoding) and/or program (coding) the symbols Broca’s area, named after the French pathologist Pierre Paul Broca
necessary for communication. The cortical area of the left hemi- who defined this area in 1861, comprises the posterior part of
sphere invariably involved in aphasia is a central core surround- the triangular gyrus (Brodmann area 45) and the adjacent oper-
ing the sylvian fissure, which includes Wernicke’s area, the arcuate cular gyrus (Brodmann area 44) in the inferior frontal gyrus of
fasciculus, the angular gyrus, and Broca’s area. This perisylvian the dominant hemisphere (Figure 17–21). Broca’s area receives
core area is surrounded by a larger region in which aphasia oc- inputs from Wernicke’s area via the arcuate fasciculus (Figure
curs less frequently. 17–20). Within Broca’s area, a coordination program for vocal-
Traditionally, a distinction has been made between two major ization is formulated. The elements of the program are transmit-
cortical language areas: (1) Wernicke’s area and (2) Broca’s area.
The two areas are connected via a long association fiber bundle,
the arcuate fasciculus.
Motor speech area Primary motor cortex
(Broca’s area)
Wernicke’s Area
Wernicke’s area, named after the German neurologist Karl
Wernicke, comprises an extensive region that includes the poste-
rior part of the superior temporal gyrus (Brodmann area 22) in-
cluding the planum temporale in the floor of the sylvian fissure,
and the parietooccipitotemporal junction area including the an-
gular gyrus (Brodmann area 39). The latter component is a re-
cent addition to Wernicke’s area not included in the area origi-
nally described by Wernicke. The upper surface of area 22, the
planum temporale, is distinctly longer on the left side (dominant
hemisphere for language) in most people. Wernicke’s area is con-
cerned with the comprehension of language. The superior tem-
poral gyrus component of Wernicke’s area (area 22) is concerned
with comprehension of spoken language, whereas the angular
gyrus (area 39) and adjacent regions are concerned with compre-
hension of written language. Spoken language is perceived in the
primary auditory area (Heschl’s gyrus, areas 41 and 42) in the su-
perior temporal gyrus and transmitted to the adjacently located
Wernicke’s area where it is comprehended (Figure 17–20). Lesions
in Wernicke’s area are associated with a type of aphasia (sensory, Figure 17–21. Schematic diagram of Broca’s area of speech.
250 / CHAPTER 17
ted to the face, tongue, vocal cords, and pharynx areas of the mo- (areas 17, 18, and 19) to the angular gyrus (area 39), which in
tor cortex for execution of speech. Broca’s area is also connected turn arouses the corresponding auditory form of the word in
to the supplementary motor area, which is concerned with the Wernicke’s area (Figure 17–22). From Wernicke’s area, the infor-
initiation of speech. Lesions in Broca’s area are associated with a mation is relayed via the arcuate fasciculus to Broca’s area.
type of aphasia (motor, anterior, expressive, nonfluent) charac-
terized by inability of the patient to express himself or herself by The Right Hemisphere and Language
speech. Such patients are able to comprehend language (intact
Wernicke’s area). Although several areas in the left hemisphere are dominant in the
Electrophysiologic studies and cerebral blood flow studies have reception, programming, and production of language function,
confirmed the role of Broca’s area in speech expression. Records corresponding areas in the right hemisphere are metabolically ac-
made from scalp electrodes placed over Broca’s area have revealed a tive during speech. These areas are believed to be concerned with
slow negative potential of several seconds in duration appearing melodic function of speech (prosody). Lesions in such areas of the
over Broca’s area 1 to 2 s prior to uttering of words. Stimulation of right hemisphere render speech amelodic (aprosodic). Lesions in
Broca’s area in conscious patients may inhibit speech or may result area 44 on the right side, for example, result in a dull monotonic
in utterance of vowel sounds. Studies on cerebral blood flow have speech. Lesions in area 22 on the right side, on the other hand,
shown a marked increase in flow in Broca’s area during speech. may lead to inability of the patient to detect inflection of speech.
Recent data from functional imaging studies of the human Such patients may be unable to differentiate whether a particular
brain reveal that, in addition to a role in language, Broca’s area is remark is intended as a statement of fact or as a question.
also activated during nonlinguistic tasks, such as observation of
finger movement and recognition of manual gestures. CORTICAL LOCALIZATION OF MUSIC
The Arcuate Fasciculus With the allocation of specific functions to each hemisphere, the
question has arisen as to which hemisphere is specialized for mu-
The arcuate fasciculus (Figure 17–20) is a long association fiber sic. In this context, one should separate musical perception from
bundle that links Wernicke’s and Broca’s areas of speech. Damage musical execution by the naive, casual listener and the music
to the arcuate fasciculus is associated with impairment of repeti- professional. Whereas a naive listener perceives music in its over-
tion of spoken language. all melodic contour, the professional perceives music as a relation
between musical elements and symbols (language). With this type
Sequence of Cortical Activities of analysis, it is conceivable that the naive listener perceives mu-
during Language Processing sic in the right hemisphere, whereas the professional perceives
music in the left hemisphere. Musical execution (singing), on the
The sequence of the complex cortical activities during the pro- other hand, seems to be a function of the right hemisphere irre-
duction of language may be summarized as follows: When a word spective of musical knowledge and training.
is heard, the output from the primary auditory area (Heschl’s
gyrus) is conveyed to the adjacent Wernicke’s area, where the OTHER CORTICAL AREAS
word is comprehended (Figure 17–20). If the word is to be spo-
ken, the comprehended pattern is transmitted via the arcuate fas- In addition to the previously discussed cortical areas, the cere-
ciculus from Wernicke’s area to Broca’s area in the inferior frontal bral cortex contains other functionally important areas. These
gyrus (Figure 17–20). If the word is to be read, representations vi- include the multimodal (heteromodal) prefrontal cortex and the
sualized as words or images are conveyed from the visual cortex posterolateral parietal (major association) cortex. Multimodal
cortices are related to more than one sensorimotor modality.
They have undergone major expansion in humans relative to
Angular gyrus animals.
Prefrontal Cortex
The prefrontal cortex (Figure 17–23) comprises the bulk of the
frontal lobe rostral to the premotor cortex (area 6). It includes
Brodmann areas 9, 10, 11, 12, and 46, located on the
medial, lateral and orbital surfaces of the frontal lobe.
Motor responses are as a rule not elicited by stimulation
of this area of the frontal lobe. The prefrontal cortex is well de-
veloped only in primates and especially so in humans. It is be-
lieved to play a role in affective behavior and judgment. Clues
about the functions of the prefrontal cortex have been gained by
studying patients with frontal lobe damage, such as Phineas Gage,
Wernicke’s the New England railroad worker who was struck by a thick iron
area bar that penetrated his prefrontal cortex. Miraculously, he sur-
Visual cortex vived but with a striking change in his personality. Whereas prior
to the injury he was an efficient and capable supervisor, following
the accident he was unfit to perform such work. He became fit-
Figure 17–22. Schematic diagram showing transmission of ful and engaged in profanity. Lesions in the prefrontal cortex lead
output from the primary visual area to the angular gyrus where to impairment in executive functions such as decision making,
the auditory form of the word is elicited from Wernicke’s area. prioritization, and planning. These usually occur in association
Prefrontal Area 6 Area 4 propriate repetition of behavior (speech or motor behavior). Sur-
cortex gical ablation of the prefrontal cortex (prefrontal lobotomy) was
resorted to in the past to treat patients with mental disorders
such as schizophrenia and intractable pain. In the latter group,
the effect of the operation was not to relieve the sensation of pain
but rather to alter the affective reaction (suffering) of the patient
to pain. Such patients continue to feel pain but become indiffer-
ent to it. The ablation of the prefrontal area in patients with
mental illness has been replaced largely by administration of psy-
chopharmacologic drugs. Through its interconnections with as-
sociation cortices of other lobes and with the hypothalamus, me-
dial thalamus, and amygdala, the prefrontal cortex receives
information about all sensory modalities as well as about motiva-
tional and emotional states.
Major Association Cortex

The major association cortex (Figure 17–24) refers to the supra-
Figure 17–23. Schematic diagram of the prefrontal cortex. marginal and angular gyri in the inferior parietal lobule. It cor-
responds to areas 39 and 40 of Brodmann. The major
association cortex in Einstein’s brain was found to be
with alterations in emotion and of social behavior. Such patients 15% wider than in controls, suggesting a role in mathe-
usually neglect their appearance, laugh or cry inappropriately, matical and visual reasoning. The major association cortex is
and have no appreciation of norms of social behavior and con- connected with all the sensory cortical areas and thus functions
duct. They are uninhibited and highly distractible. The prefrontal in higher-order and complex multisensory perception. Its rela-
cortex can be thought of in terms of three divisions: (1) dorso- tion to the speech areas in the temporal and frontal lobes gives it
lateral prefrontal (areas 9, 10, 46), (2) ventromedial (areas 11 and an important role in communication skills. Patients with lesions
12), and (3) superior mesial (mesial 6 and parts of 9 and 32 areas). in the major association cortex of the dominant hemisphere pre-
Damage to the dorsolateral prefrontal area results in impairment sent a conglomerate of manifestations that include receptive and
of working (short-term) memory, allocation of attention, and expressive aphasia, inability to write (agraphia), inability to syn-
speed of processing. Damage to the ventromedial area results in thesize, correlate, and recognize multisensory perceptions (ag-
severe impairment of decision making and emotion. Damage to nosia), left-right confusion, difficulty in recognizing the differ-
the superior mesial area impacts emotion, motivation, and initi- ent fingers (finger agnosia), and inability to calculate (acalculia).
ation of behavior. Bilateral damage tends to produce greater im- These symptoms and signs are grouped together under the term
pairments than does unilateral damage. Patients with prefrontal Gerstmann’s syndrome.
cortex lesion thus exhibit one or more of the following signs: im- Involvement of the major association cortex in the nondomi-
paired decision making, distractibility, emotional lability, social nant hemisphere is usually manifested by disturbances in draw-
disinhibition, impulsiveness, hyperphagia, lack of planning, re- ing (constructional apraxia) and in the awareness of body image.
stricted emotion, deficient empathy, failure to complete tasks, Such patients have difficulty in drawing a square or circle or
and lack of awareness or concern. A characteristic symptom in copying a complex figure. They often are unaware of a body part
humans with prefrontal lobe lesions is perseveration, the inap- and thus neglect to shave half the face or dress half the body.
Primary somesthetic cortex MAJOR ASSOCIATION CORTEX
Supramarginal gyrus
Angular gyrus
Lateral fissure
Superior temporal sulcus

of the major association cortex.
252 / CHAPTER 17
THE INSULA (ISLAND OF REIL) Augmenting responses are recorded following low-frequency
(6–12 cps) stimulation of a specific thalamocortical pathway
Vicq d’Azyr was the first, in 1786, to express interest in the insula. (e.g., from ventrolateral thalamic nucleus). They are characterized
He referred to it as the “convolutions situated between the sylvian by a short latency (monosynaptic pathway), a diphasic, positive-
fissure and the corpus callosum.” In 1809, Reil was the first to de- negative configuration that increases in amplitude and latency
scribe the insula. In humans, the insula is a highly developed during the initial four to six stimuli of the train. The response
structure in the depth of the sylvian fissure, covered by the frontal, to subsequent stimuli remains augmented but waxes and wanes
parietal, and temporal opercula. The sulcus separating the insula in amplitude. This type of response is localized in the primary
from the operculae is referred to by different authors as the peri-
insular sulcus, limiting sulcus, circuminsular sulcus, or insular
sulcus. It is one of the paralimbic structures comprised of meso-
cortex, interposed anatomically and functionally between allocor-
tex and neocortex. A variety of functions have been attributed to
the insula, including olfaction, taste, visceral control, memory, af-
fect, and drive. The insula is shaped like a pyramid. The summit
of the pyramid is the insular apex (referred to by some as insular
pole or limen insula). The insula is traversed by an obliquely di-
rected central insular sulcus which divides the insula into two
zones. The anterior zone is larger and exhibits more gyri than the
posterior zone. The anterior zone exhibits transverse and acces-
sory insular gyri and three short insular gyri (anterior, middle,
and posterior). The transverse and accessory insular gyri form the
insular pole located at the most anterior inferior aspect of the in-
sula. The posterior zone, located caudal to the central insular sul-
cus, is composed of the anterior and posterior long gyri, separated
by the postcentral insular sulcus. The anterior insular zone con- A
nects with the frontal lobe. The posterior zone connects with the
parietal and temporal lobes. Lesion-based analysis has shown that
destruction of the left anterior zone impairs coordination of artic-
ulation and speech production. The insula is surrounded by the
superior longitudinal (arcuate) fasciculus, a long association bun-
dle that interconnects the temporal, parietal, and frontal lobes.
The uncinate fasciculus interconnects the insula with other para-
limbic structures (temporal pole, orbital gyri). The occip-
itofrontal fasciculus, another long association bundle, passes be-
neath the inferior portion of the insular cortex to connect the
frontal, insular, temporal, and occipital regions.
CORTICAL ELECTROPHYSIOLOGY
Evoked Potentials
Evoked potentials represent the electrical responses recorded from
a population of neurons in a particular cortical area following B
stimulation of the input to that area. The most studied of the
evoked potentials is the primary response recorded from the
cortical surface and elicited by a single shock to a major thalamo-
cortical pathway. This response is characterized by a diphasic,
positive-negative wave and is generated primarily by synaptic
currents in cortical neurons.
Evoked potentials elicited by a volley of impulses in thalamo-
cortical pathways are of two varieties, recruiting responses and
augmenting responses.
Recruiting responses are recorded following 6- to 12-cps
(cycles per second) stimulation of a nonspecific thalamocortical
pathway (e.g., from intralaminar nuclei). They are characterized
by a long latency (multisynaptic pathway), a predominantly sur-
face negative response that increases in amplitude to a maximum
by the fourth to the sixth stimulus of a repetitive train. This is
followed by a decrease in amplitude (waxing and waning). Such
a response has a diffuse cortical distribution. This pattern of re- C
sponse is generally attributed to an oscillator network at cortical
as well as thalamic levels in which cortical and thalamic elements Figure 17–25. Electroencephalograms showing the normal
provide both positive and negative feedback. alpha pattern A, slow delta pattern B, and spike potentials C.
cortical area to which the stimulated specific thalamocortical The EEG of unconscious patients is dominated by general-
pathway projects. ized slow frequencies. The EEG in epileptic patients is character-
ized by the presence of spike potentials. Two EEG patterns have
Somatosensory, Visual, and Auditory been associated with sleep. The first is a slow pattern (delta and
Evoked Responses theta) associated with the early phase of sleep. The second is a
fast pattern (beta) associated with a later and deeper stage of
Recording of cortical evoked potentials following somatosensory sleep. This second pattern is associated with rapid eye move-
(skin), visual (flashes or patterns of light), and auditory (sound) ments (REM) and dreaming; hence this stage of sleep has been
stimuli has been used to study pathology along each of these called REM sleep or D-sleep (dreaming).
pathways in humans. The determination of latency and ampli-
tude of the evoked potential frequently can aid in localizing the
site of pathology in the respective pathway. BLOOD SUPPLY
Arterial Supply
ELECTROENCEPHALOGRAPHY
The blood supply to the cerebral cortex is provided by the ante-
Electroencephalography (Figure 17–25) is the recording of spon- rior and middle cerebral arteries (branches of the internal carotid
taneous cortical activity from the surface of the scalp. This pro- artery) and the posterior cerebral artery (branch of the basilar
cedure is used very commonly in the investigation of diseases of artery). The anterior cerebral artery runs through the interhemi-
the brain. Its usefulness is mainly in the diagnoses of epilepsy spheric fissure, giving off five major branches: orbitofrontal,
and localized (focal) brain pathology (e.g., brain tumors). In re- frontopolar, pericallosal, callosomarginal, and paracentral. These
cent years and with the advent of the concept of brain death, the branches supply the medial surface of the frontal and parietal
electroencephalogram (EEG) has been used to confirm a state of lobes as far back as the parietooccipital fissure (Figure 17–26).
electrical brain silence (brain death). In such a condition, elec- All branches cross the convexity of the frontal and parietal lobes
troencephalographic tracings will show no evidence of cortical to supply a strip of marginal cortex on the lateral surface of the
potentials (flat EEG). hemisphere. Occlusion of the anterior cerebral artery results in
The spontaneous rhythmic activity of the cortex is classified paralysis and sensory deficits in the contralateral lower limb due
into four types: to interruption of blood supply to the lower limb area in the me-
1. Alpha rhythm with a range of frequency from 8 to 13 cps. dial surface of the motor and sensory cortices.
This type is most developed over the posterior part of the The middle cerebral artery is a continuation of the main
hemisphere. branch of the internal carotid artery. It courses within the lateral
2. Beta rhythm with a range of frequency faster than 13 cps (sylvian) fissure and divides into a number of branches (frontal,
(17 to 30 cps). This activity can be seen over wide regions of rolandic, temporal, parietal) that supply most of the lateral sur-
the cortex and is especially apparent in records from patients face of the hemisphere (Figure 17–27).
receiving sedative drugs. The posterior cerebral artery constitutes the terminal branch
3. Theta rhythm with a range of frequency from 3 to 7 cps. of the basilar artery. Several branches (temporal, occipital, pari-
etooccipital) supply the medial surfaces of the occipital lobe,
4. Delta rhythm with a range of frequency from 0.5 to 3 cps. temporal lobe, and caudal parietal lobe (Figure 17–26).
The EEG pattern varies in different age groups. The EEG is
dominated by slow activity (theta and delta) in childhood. The Venous Drainage
alpha rhythm increases in amount with the advent of puberty. In
the adult, delta activity and excessive theta activity usually de- Three groups of cerebral veins drain the lateral and inferior sur-
note cerebral abnormality. faces of the cerebral hemisphere: superior, middle, and inferior
Callosomarginal Paracentral Posterior cerebral

branch branch artery
Pericallosal
branch
Frontopolar Parietooccipital
branch branches
Orbitofrontal
branch Occipital branches

gram of the major branches of
the anterior cerebral and posterior
cerebral arteries and the areas they Anterior cerebral Medial striate Temporal branches
supply. artery branch
254 / CHAPTER 17
Frontal Rolandic Parietal branches TERMINOLOGY

branches branch
Acalculia (Greek a, “negative”; Latin calculare, “to reckon” ).
Difficulty in calculating. Usually associated with inability to copy
(acopia). The condition was described and named by Henschen
in 1919.
Agnosia (Greek a, “negative”; gnosis, “knowledge”). Inability
to recognize and interpret sensory information.
Agraphia (Greek a, “negative”; graphein, “to write”). Inability
to express thoughts in writing. The first modern descriptions
were those of Albert Pitres in 1884 and Dejerine in 1891.
Agyria (Greek a, “negative”; gyros, “ring”). A malformation in
which the convolutions of the cerebral cortex are not normally
developed. Also called lissencephaly (smooth brain).
Akinesia (Greek a, “negative”; kinesis, “motion”). Absence or
Middle poverty of movement.
cerebral Temporal Akinetopsia. Cerebral motion blindness, a syndrome in which a
artery branches
patient loses specifically the ability to perceive visual motion as a
Figure 17–27. Schematic diagram of the major branches of result of cortical lesions outside the striate cortex.
the middle cerebral artery and the areas they supply. Allocortex (Greek allos, “other”; Latin cortex, “bark”). Phylo-
genetically old, three-layered cerebral cortex, divided into paleo-
cortex and archicortex.
Aphasia (Greek a, “negative”; phasis, “speech”). Impairment
(Figure 17–28). The superior cerebral group drains the dorso- of language function; inability either to speak (motor aphasia) or
lateral and dorsomedial surfaces of the hemisphere and opens to comprehend (sensory aphasia).
into the superior sagittal sinus. Conventionally, the most promi- Apraxia (Greek a, “negative”; pratto, “to do”). Inability to per-
nent of these veins in the central sulcus is called the superior form complex purposeful movements, although muscles are not
anastomotic vein of Trolard, which connects the superior and paralyzed.
middle groups of veins. Aprosodia (Greek a, “negative”; prosodos, “a solemn proces-
The middle cerebral group runs along the sylvian fissure, sion”). The variation in stress, pitch, and rhythm of speech by
drains the inferolateral surface of the hemisphere, and opens into which different shades of meaning are conveyed; the affective
the cavernous sinus. The inferior cerebral group drains the infe- component of language.
rior surface of the hemisphere and opens into the cavernous and Archicortex (Greek arche, “beginning”; Latin cortex, “bark” ).
transverse sinuses. The anastomic vein of Labbé interconnects Phylogenetically old, three-layered cortex seen in the hippocam-
the middle and inferior groups of cerebral veins. pal formation. A variety of paleocortex or allocortex.
The medial surface of the hemisphere is drained by a num-
ber of veins that open into the superior and inferior sagittal si- Arcuate (Latin arcuatus, “bow-shaped”). Shaped like an arc.
nuses, as well as into the basal vein and the great cerebral vein of The arcuate fasciculus arches around the sylvian fissure to con-
Galen. nect Wernicke’s area in the temporal lobe with Broca’s area in the
frontal lobe.
Asymbolia (Greek a, “negative”; symbolon, “symbol”). Loss
of power to comprehend symbols as words, figures, gestures, and
signs. Asymbolia of pain is the absence of psychic reaction to
Superior Vein of Trolard
cerebral
painful sensations. The term asymbolia for pain was first described
veins by Schilder and Stengel in 1938.
Badal, Jules (1840–1929). French neuroophthalmologist who,
in 1888, published the case of a posteclamptic woman (Valerie)
who developed Gerstmann syndrome.
Baillarger, Jules-Gabriel-François (1809–1890). French psychi-
atrist who described the lines of Baillarger in the cerebral cortex.
Balint syndrome. Also known as Balint-Holmes syndrome, ocular
apraxia, optic ataxia. A rare syndrome resulting from bilateral
parietooccipital disease and characterized by inability to direct the
eyes to a certain point in the visual field despite intact eye move-
Middle ments. Named after Rudolph Balint (1874–1929), a Hungarian
cerebral neurologist.
vein Betz, Vladimir A. (1834–1894). Russian anatomist who de-
scribed the giant pyramidal cells in the motor area of the cerebral
Inferior cerebral veins Vein of Labbé cortex in 1874.
Figure 17–28. Schematic diagram of the superficial system of Bravais, Louis. French physician who described spread of epilep-
venous drainage of the brain. tic seizure (Jacksonian march) in his graduation thesis in 1827.
Broca, Pierre Paul (1824–1880). French pathologist and an- Hemiachromatopsia. Loss of color vision in one-half the visual
thropologist. Broca localized the cortical motor speech area in field.
the inferior frontal gyrus. He also described the diagonal band of Henschen, Solomon Eberhard (1847–1930). Swedish in-
Broca in the anterior perforated substance. He is also credited ternist and neurologist who is credited with describing the stri-
with description of muscular dystrophy before Duchenne. ate and extrastriate cortex in addition to the acalculia. He was
Brodmann, Korbinian (1868–1918). German physicist who one of the physicians who attended Lenin when stricken with
divided the cerebral cortex into 52 areas on the basis of disposi- aphasia.
tion of the cellular (cytoarchitectonics) between 1903 and 1908. Heschl, Richard (1824–1881). Austrian anatomist and patholo-
Campbell, Alfred Walter (1868–1937). Australian neurologist gist who described the anterior transverse temporal gyri (Heschl’s
and psychiatrist. Known for his elegant work on the architec- convolutions), which serve as the primary auditory area.
tonics of the cerebral cortex. He and Brodmann are considered Heterotopia (Greek heteros, “other, different”; topos, “place”).
the fathers of cerebral architectonics. The presence of cortical tissue in an abnormal location during
Cingulum (Latin “a girdle”). A bundle of association fibers development.
within the cingulate gyrus. Heterotypical cortex (Greek heteros, “different”; typos, “pat-
Cortex (Latin “bark”). External gray layer of the cerebrum. tern”). The isocortex (neocortex) in which some of the six layers
are obscured, as in motor cortex and visual cortex.
Cushing, Harvey Williams (1869–1939). American neurosur-
geon, regarded as the father of modern neurosurgery. He trained Holmes, Sir Gordon Morgan (1876–1965). Irish neurologist
with William Osler who taught him about neurology and whose and father of British neurology (along with John Hughlings-
life became the basis for Cushing’s writings and subsequent Jackson). Made significant contributions to sensation (with Head),
Pulitzer Prize. spinal cord injury, cerebellar disease, neuroophthalmology, and
neurological localization. Many of his contributions emanated
Cytoarchitectonic. The design of the cellular characteristics of from observations he made in army field hospitals in northern
the cortex, which varies in different regions of the brain and al- France.
lows mapping of the brain.
Homotypical cortex (Greek homos, “same”; typos, “pattern”).
Dejerine, Joseph-Jules (1849–1917). French neurologist who Association areas of the neocortex all have a similar (same) pat-
contributed significantly to knowledge about the anatomy of the tern six-layered structure. They are thus examples of homotypi-
nervous system, cerebral localization, agraphia, and alexia. cal cortex.
Dysphasia (Greek dys, “difficult”; phasis, “speech”). Difficulty Hughlings-Jackson, John (1835–1911). British neurologist and
in the understanding or expression of language. one of the greatest figures in neurology’s history. Made major
Ferrier, David (1843–1928). Scottish neurophysiologist and contributions, including hierarchical organization of the nervous
neurologist who is credited with localization of the primary au- system, organization of movement, mind–brain relationship,
ditory cortex in the superior temporal gyrus. speech, and epilepsy. He introduced the term uncinate fits in 1899
Fusiform (Latin fusus, “spindle”; forma, “shape”). A cell that and the routine use of the ophthalmoscope.
is widest in the middle and tapering at both ends. Isocortex (Greek isos, “equal”; Latin cortex, “bark”). Six-layered
Gennari, Francesco. Italian physician who, as a medical stu- cerebral cortex.
dent, described the lines of Gennari (outer band of Baillarger) Jacksonian march ( Jacksonian epilepsy, Bravais-Jackson
that characterize lamina IV of the visual cortex. He referred to it epilepsy). The spread of tonic-clonic epileptic activity through
as lineola albidor. contiguous body parts on one side of the body due to spread of
Gerstmann, Josef (1887–1969). Austrian neuropsychiatrist who epileptic activity in the corresponding motor areas of the cortex.
described finger agnosia in 1924 and the full Gerstmann syn- Named after John Hughlings-Jackson (1835–1911), one of the
drome in 1930. Badal’s earlier description of the syndrome, in greatest figures in the history of neurology. Bravais described the
1888, was less complete and was attributed to psychic blindness. same pattern of epileptic spread in his graduation thesis in 1827
but did not elaborate on the etiology.
Gerstmann syndrome. A clinical syndrome characterized by
Koniocortex (Greek konis, “dust”; Latin cortex, “bark”). Areas
right–left disorientation, acalculia, agraphia, and finger agnosia
of cerebral cortex with large number of small neurons.
due to a lesion in the left angular gyrus. Josef Gerstmann, Austrian
neuropsychiatrist, developed the concept of a body image with Lamina (Latin “a thin plate or layer”).
visual, tactile, and somesthetic components in 1924 and con- Lorente de Nó, Rafael. American neurobiologist who described
sidered cortical representation for these in the angular gyrus. columnar organization within the cerebral cortex. In addition,
The syndrome is also known as angular gyrus syndrome and the he is credited with description of the CA1–4 regions of the
Badal-Gerstmann syndrome. Jules Badal’s description of the hippocampus.
syndrome in 1888 was less complete. Martinotti, Giovanni. Italian physician who described the
Gustatory (Latin gustatorius, “pertaining to the sense of taste”). Martinotti neuron in the cerebral cortex.
Head, Sir Henry (1861–1940). English neurologist and neuro- Mesocortex. Intermediate cortex (in histology) between the
physiologist. Among his many contributions is the mapping of isocortex and allocortex. Also known as periallocortex and peri-
dermatomes (Head’s zones), which was the subject of his gradu- archicortex.
ation thesis at Cambridge. He sectioned his own nerves in order Micropolygyria (polymicrogyria) (Greek mikros, “small”;
to delineate the resulting sensory loss. He described the anatomy gyros, “convolutions”). A malformation of the brain character-
and variations of major peripheral nerves and the brachial plexus, ized by the development of numerous small convolutions.
and he localized the site of herpes zoster inflammation to the Myeloarchitectonics. The arrangement of nerve fibers in the
dorsal root ganglia. He also wrote on aphasia and published a cerebral and cerebellar cortex that varies in different regions and
book of poetry. He was afflicted with Parkinson’s disease. allows mapping of the brain.
256 / CHAPTER 17
Neocortex (Greek neos, “new”; Latin cortex, “bark”). The Uncinate (Latin “hook-shaped”) fasciculus. Connects the
most recent phylogenetic development of the cerebral cortex. cortex of the ventral surface of the frontal lobe with that of the
Operculum (Latin opertum, “covered”). The frontal, tempo- temporal pole.
ral, and parietal opercula cover the insular cortex. Uncinate fits. Complex partial seizures in which olfactory hallu-
Optic ataxia. The inability to reach for objects under visual cinations occur as part of the seizure. The term was introduced
guidance. Isolated optic ataxia results from bilateral lesions in the by Hughlings-Jackson in 1899.
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Cerebral Cortex: Clinical Correlates 18
Epileptic Seizures Unilateral (Left) Tactile Anomia

Hemisphere Specialization Left Ear Extinction
Aphasia Prefrontal Lobe Syndrome
Apraxia The Grasp Reflex
Ideomotor Apraxia Forced Collectionism
Ideational Apraxia Alzheimer’s Disease
Visuoconstructive Apraxia Balint’s Syndrome
Alexia (Dyslexia) Gerstmann’s Syndrome
Agnosia Anosognosia (Denial Syndrome, Anton-Babinski
Callosal Syndrome Syndrome)
Visual Effects Anton’s Syndrome
Hemialexia Kluver-Bucy Syndrome
Unilateral (Left) Ideomotor Apraxia Simultanagnosia
Unilateral (Left) Agraphia The Alien Hand (Limb) Syndrome
KEY CONCEPTS
Epileptic seizures are manifestations of synchronized dis- acquired. Two forms of acquired alexia are recognized:
charges of groups of neurons. pure alexia (without agraphia) and alexia with agraphia.
The left hemisphere is specialized or dominant for com- Agnosia pertains to the inability to recognize stimuli that
prehension and expression of language, arithmetic, were recognized formerly. Agnosia is modality specific:
and analytic functions. The right hemisphere is special- visual, auditory, and tactile.
ized or dominant for complex nonverbal perceptual
Callosal syndromes include hemialexia, unilateral (left)
tasks, emotion, and some aspects of visual and spatial
ideomotor apraxia, unilateral (left) agraphia, unilateral
perception.
(left) tactile anomia, and left ear extinction.
Aphasias are classified into two major categories based
Prefrontal lobe syndrome pertains to a conglomerate set of
on whether repetition is intact or not.
signs and symptoms that includes impairments in decision
Apraxia is the inability to perform skilled, learned, pur- making, ability to plan, social judgment, conduct, modula-
poseful motor acts correctly. tion of affect and of emotional response, and creativity.
Alexia pertains to the inability to comprehend written Alzheimer’s disease is the example par excellence of corti-
language (reading disability). It can be developmental or cal dementia.
EPILEPTIC SEIZURES the area of the brain involved. Epileptic seizures are triggered by
synchronized discharges of a group of neurons in the cerebral cor-
Epilepsy is a common clinical condition characterized tex as a result of developmental abnormality, infection, trauma, tu-
by recurrent paroxysmal attacks of motor, sensory, auto- mor, metabolic derangement, or stroke. Epileptic seizures may be
nomic, or psychic symptoms and signs depending on focal or generalized. When generalized, they are usually associated
258
CEREBRAL CORTEX: CLINICAL CORRELATES / 259
with loss of consciousness. The most common generalized seizure APHASIA

type is the tonic-clonic seizure type known as grand mal seizure.
Focal seizures are manifestations of the function of the cortical The term aphasia refers to an acquired disturbance in compre-
area from which epileptic discharges emanate. Epileptic dis- hension, formulation of verbal messages (language), or both. It
charges in the region of the central sulcus may give rise to motor can affect the grammatical structure of sentences (syntax), the
and sensory symptoms. Spreading of the epileptic discharge dictionary of words (contained in language) that denote mean-
along the motor or sensory homunculus produces the so-called ings (lexicon), or the combination of phonemes that results in
Jacksonian seizures or Jacksonian march. In such a patient, a fo- word structure (word morphology).
cal motor seizure may start by shaking of the side of the face con- Aphasia, as a specific impairment of language, should not be
tralateral to the cortical lesion in the precentral gyrus and spread confused with mutism, dysarthria, aphemia, and speech apraxia.
to involve the thumb, hand, arm, and leg in this order in a pat- Mutism is a nonvolitional state in which the patient does not at-
tern consistent with the location of these body parts in tempt to initiate speech. Dysarthria is a speech articulation due
the motor homunculus. A similar pattern of sensory to disturbance in the muscular control of the speech mechanism
march is associated with lesions in the postcentral gyrus. associated with damage to the central or peripheral nervous sys-
An epileptic discharge in the frontal eye field produces attacks tem. Aphemia is a condition in which no articulation occurs due
consisting of contralateral turning of eyes and head (adversive to a central motor deficit. Speech apraxia is an imprecisely de-
seizures). Occipital discharges are associated with visual halluci- fined condition of impaired articulation of speech in which
nations. Discharges in the primary visual cortex produce con- speech is phonetically and prosodically awkward compared to
tralateral flashes of light, whereas discharges in the association vi- dysarthric speech. Aphasia is encountered most frequently in
sual cortex produce well-formed images. Epileptic discharges cortical lesions in the left hemisphere, although it may occur in
from the uncus and adjacent regions of the temporal lobe (unci- subcortical lesions. The cortical area of the left hemisphere in-
nate fits) produce a combination of complex motor and auto- variably involved in aphasia is a central core surrounding the syl-
nomic symptoms (psychomotor seizures). The epileptic attack in vian fissure. The perisylvian core area is surrounded by a larger
such patients consists of a dreamy state, olfactory hallucinations region in which aphasia occurs less frequently.
(usually of “bad” odors), gustatory hallucinations, oral move- The sequence of complex cortical activities during the pro-
ments of chewing, swallowing, or smacking of lips, visual hallu- duction of language may be simplified as follows: When a word
cinations (déjà vu experiences), and possibly aggressive behavior. is heard, the output from the primary auditory area (Heschl’s
Complex acts and movements such as walking and fastening or gyrus) is conveyed to an adjacent cortical area (Wernicke’s area),
unfastening buttons may occur. where the speech sounds are processed into word form and the
word is comprehended (see Figure 17–20). If the word is to be
spoken, the comprehended pattern is transmitted via the arcuate
fasciculus from Wernicke’s area to Broca’s area of speech in the
HEMISPHERE SPECIALIZATION inferior frontal gyrus (see Figure 17–20). If the word is to be
read, the output from the primary visual area in the occipital
The concept of cerebral dominance has undergone significant cortex is transmitted to the angular gyrus, which in turn arouses
modification in recent years, primarily because of studies on pa- the corresponding auditory form of the word in Wernicke’s area
tients with unilateral brain damage. The older concept, intro- (see Figure 17–22).
duced by Gustav Dax and Paul Broca in 1865, which assigned For didactic purposes, aphasia is classified into Broca’s, Wer-
to the left hemisphere a dominant role in higher cerebral func- nicke’s, conduction, transcortical, anomic, and global. The dif-
tion, with the right hemisphere being subordinate to the domi- ferent varieties of aphasia can be classified into those
nant hemisphere, has been replaced by a new concept of hemi- with impaired repetition (Broca’s, Wernicke’s, conduc-
sphere specialization that implies that each hemisphere is in tion, and global aphasias) and those in which repetition
some way dominant for the execution of specific tasks. According is preserved (transcortical and anomic aphasias) (Table 18–1).
to this concept, the left hemisphere is dominant or specialized Broca’s aphasia is also known as nonfluent, anterior, motor, or
for comprehension and expression of language, arithmetic, and expressive aphasia. This type of aphasia is characterized by a dif-
analytic functions, whereas the right hemisphere is specialized ficulty in initiating speech and a decreased and labored language
for complex nonverbal perceptual tasks and for some aspects of output of 10 words or less per minute, during which the patient
visual (e.g., face) and spatial perception. The right side of the utilizes facial grimaces, body posturing, deep breaths, and hand
brain is also dedicated to mapping feelings, bodily sensations gestures to aid output; characteristically, small grammatical
linked to emotions of happiness, anger, and fear. Language is words and the endings of nouns and verbs are omitted, resulting
localized to the left hemisphere in more than 90% of right- in telegraphic speech. The speech output is thus unmelodic and
handed people and two-thirds of left-handers. Thus lesions of dysrhythmic (dysprosody). Despite the preceding limitations in
the left hemisphere are associated with disorders of language verbal output, the speech often conveys considerable informa-
(aphasia or dysphasia), whereas lesions of the right hemisphere tion. These patients are unable to repeat what has been said
are associated with impairment of visuospatial and visuocon- to them. Paraphasias are common and usually involve omission
structive skills. Patients with right hemisphere lesions are more of phonemes or substitution of incorrect phonemes (“ha” for
likely to show such manifestations as constructional apraxia (in- “hall,” “pem” for “pen”). Writing and confrontation naming are
ability to construct or to draw figures and shapes), dressing impaired. Although Broca’s aphasia is usually attributed to a le-
apraxia, denial of the left side of the body (denial that their left sion in Broca’s area of the frontal lobe, recent correlations of
side is part of their body), and hemineglect (visual and spatial aphasic speech with lesions seen on imaging studies have shown
neglect of the left side of their space, including their own body that the lesion is frequently larger than Broca’s area and involves
parts). Idiographic (pictographic) language (Japanese Kanji) the anterior insula, frontal operculum and the underlying white
may be processed by the right hemisphere because of its pictor- matter. Pure damage to Broca’s area (Brodmann areas 44 and 45)
ial features. produces mild transient speech deficit. Since the temporal lobe is
260 / CHAPTER 18
Table 18–1. Aphasias
Type Repetition Fluency Auditory Comprehension Localization
Broca’s X Broca’s area, anterior insula,

frontal operculum, underlying
white matter
Wernicke’s X Posterior and superior temporal
gyrus, planum temporale,
lower parietal cortex
Conduction X X Posterior perisylvian region
Global Massive perisylvian or separate
Broca’s and Wernicke’s areas
Transcortical motor X X Anterior or superior to Broca’s area;
may involve part of Broca’s area
Sensory X X Surrounding Wernicke’s area
Mixed X Border zone, watershed area of
middle and anterior cerebral arteries
Anomic X X X Inferior or anterior temporal
intact in these patients, comprehension of language in aural and Wernicke’s aphasia is named after Karl Wernicke, a German
written forms is usually intact. Most patients with Broca’s apha- neurologist who in 1874 designated the posterior part of the
sia can sing. superior temporal gyrus (area 22) of the left hemisphere as an
Broca’s aphasia occurs often as a result of stroke (infarcts) most area concerned with the understanding of the spoken word.
commonly affecting the middle cerebral artery territory. Such in- Wernicke’s aphasia is also known as Bastian aphasia, after Henry
farcts often involve the motor cortex; thus patients with Broca’s Charlton Bastian, the English neurologist who described it in
aphasia are often hemiplegic with the arm (middle cerebral artery 1869, five years before Wernicke.
territory) more affected than the leg (anterior cerebral artery terri- Conduction aphasia is characterized by fluent paraphasic speech,
tory). Broca’s aphasia is named after Paul Broca, the French intact comprehension, poor naming, and repetition. Classically,
anthropologist-physician who studied the patient Leborgne (nick- patients with conduction aphasia cannot read out loud because
named “Tan” because the only word he could utter was tan) with of paraphasic intervention. Patients with conduction aphasia
aphasia and localized the lesion to the posterior part of the left cannot write to dictation, but write better when copying text
inferior frontal convolutions. Pierre Marie, in 1906, examined and in spontaneous composition. Pathology in these patients is
Leborgne’s brain and found that the lesion was more extensive. usually located in the posterior perisylvian region and interrupts
Wernicke’s aphasia is also known as fluent, posterior, sensory, the output from Wernicke’s area to Broca’s area via the arcuate
or receptive aphasia. In contrast to Broca’s aphasia, the quantity fasciculus.
of output in this type ranges from low normal to supernormal, Global aphasia is a severe form of aphasia in which all the
with an output in most patients of 100 to 150 words per minute. major functions of language (verbal output, comprehension,
Speech is produced with little or no effort, articulation and repetition, naming, reading, and writing) are severely impaired.
phrase length are normal, and the output is melodic. Pauses to Global aphasics retain limited capacity for singing. Global apha-
search for a meaningful word are frequent, and substitution sics are differentiated from patients with mutism in that the for-
without language (paraphasia) is common; this may be substitu- mer make an attempt to speak and communicate with other
tion of a syllable (literal paraphasia) (wellow for yellow), phone- means, whereas the latter do not make such an attempt. Pathol-
mic substitution of a word (kench for wrench) (verbal parapha- ogy is invariably extensive, involving most of the left perisylvian
sia), semantic substitution (knife for fork), or substitution of a area including Broca’s area, Wernicke’s area, the inferior parietal
meaningless nonsense word (neologism). If a word is not readily cortex, and underlying white matter. In rare cases, two separate
available, the patient may attempt to describe it, and the descrip- lesions in Broca’s and Wernicke’s area are found.
tion may necessitate yet another description, resulting in a Transcortical aphasia has been subdivided into motor, sensory,
meaningless output (circumlocution). Very highly paraphasic and mixed types. All are characterized by preserved repetition. In
fluent speech is termed jargon aphasia. Paraphasias also may oc- transcortical motor aphasia, verbal output is nonfluent and com-
cur in Broca’s aphasia, but these are articulatory errors, in con- prehension is intact, but writing and reading are invariably ab-
trast to those in Wernicke’s aphasia, which are true substitutions. normal. Pathology in this type of aphasia is located in the domi-
Despite the fluent nature of speech output in Wernicke’s aphasia, nant frontal lobe in the neighborhood of Broca’s area. It involves
little information is conveyed (empty speech). As in Broca’s the premotor region or a limited part of the inferior frontal gyrus
aphasia, patients with Wernicke’s aphasia are unable to repeat in the left hemisphere. This type of aphasia has been also re-
what is said to them. In contrast to Broca’s aphasia, comprehen- ported with a lesion in the left basal ganglia. In transcortical sen-
sion of both aural and written forms of language is severely im- sory aphasia, speech output is fluent and paraphasic, compre-
paired in Wernicke’s aphasia. As in Broca’s aphasia, naming is im- hension is poor, and there are associated difficulties in reading,
paired. Wernicke’s aphasia is attributed to a lesion in Wernicke’s naming, and writing. Pathology in such cases is usually in the
area in the posterior part of the superior temporal gyrus and ad- border zone between the temporal and parietal lobes in the
jacent areas in posterior temporal (including the planum tempo- neighborhood of Wernicke’s area. Mixed transcortical aphasia,
rale) and lower parietal cortex of the left hemisphere. also known as isolation of the speech area, is characterized by
nonfluent speech output, poor comprehension, and inability to To appreciate the pathophysiology of ideomotor apraxia, it
name, read, or write. Pathology in these patients usually spares should be understood that for a skilled task to be performed, sev-
the perisylvian core region but involves the surrounding border eral events must take place. For example, the command to walk,
zone or watershed area, which is supplied by the most distal trib- if oral, reaches the primary auditory area and is relayed to the left
utaries of the middle cerebral artery. auditory association cortex (Wernicke’s area) for comprehension.
Anomic aphasia, also known as amnestic or nominal aphasia, Wernicke’s area is connected to the ipsilateral premotor area
is characterized primarily by word-finding difficulty. Although (motor association cortex, area 6) via the arcuate fasciculus. The
naming defects are common in almost all aphasic syndromes, motor association area on the left side is connected to the pri-
anomic aphasia refers to an isolated severe impairment of con- mary motor cortex (area 4) on the left side. When the person is
frontation naming without concomitant other speech impair- asked to carry out a command with the left hand, the informa-
ments. This type of aphasia is most commonly encountered with tion is relayed from the left premotor area to the right premotor
lesions in the left inferior or anterior temporal cortex. Different area (via the anterior part of the corpus callosum) and from there
types of naming impairments have been associated with damage to the right primary motor area, which controls movements of
to different cortical areas. Selective noun retrieval deficits have the left side of the body (Figure 18–1). Based on the preceding
been associated with damage to the left inferior and left antero- anatomic connections, three clinical varieties of ideomotor apraxia
lateral temporal cortex. Disproportionate difficulty in verb re- have been recognized: parietal, in which the lesion is in the an-
trieval, on the other hand, has been associated with damage to the teroinferior parietal lobe of the dominant hemisphere; sympa-
left premotor-prefrontal cortex. Within the temporal lobe, lesions thetic, in which the lesion is in the left premotor area; and cal-
in the ventral inferotemporal cortex have been associated with losal, in which the lesion is in the anterior part of the corpus
disproportionate difficulty in naming natural entities (like ani- callosum.
mals), whereas damage in the left temporal pole has been associ-
ated with disproportionate difficulty in naming specific persons.
Crossed aphasia refers to the rare development of aphasia in Ideational Apraxia
right-handed persons, with right (instead of left) hemisphere le- Ideational apraxia is an abnormality in the conception of move-
sion. The aphasic syndrome in crossed aphasia may follow the ment so that the patient may have difficulty sequencing the dif-
classical pattern (Broca, Wernicke, etc) with lesions in the corre- ferent components of a complex motor act. To mail a letter, for
sponding area in the right hemisphere, or be anomalous. In the example, one must seal it, stamp it, and place it in the mailbox.
latter, Broca’s area lesion may present with Wernicke’s aphasia The lesion in ideational apraxia is in the dominant temporo-
and Wernicke’s area lesion with Broca’s aphasia. parietooccipital area.
Subcortical aphasia. Aphasia has been reported in left basal
ganglia and thalamic lesions. Within the basal ganglia, the left
caudate nucleus is especially involved. Within the thalamus, the Visuoconstructive Apraxia
left ventrolateral and anteroventral thalamic nuclei are invariably
involved. Aphasia associated with left basal ganglia lesions is char- Visuoconstructive apraxia, also known as constructional apraxia,
acterized by relatively fluent, paraphasic, and dysarthric speech. is the inability of the individual to put together or articulate
Comprehension and repetition are often impaired. Thalamic component parts to form a single shape or figure, such as assem-
aphasia has the profile of Broca’s or transcortical motor aphasia. bling blocks to form a design or drawing four lines to form a
Pure word deafness, also known as verbal auditory agnosia, is shape. It implies a defect in perceiving spatial relationships
characterized by poor comprehension of spoken language and by among the component parts. Visuoconstructive apraxia was de-
poor repetition with intact comprehension of written language, scribed originally in lesions of the left (dominant) posterior pari-
naming, writing, and spontaneous speech. The lesion in this type etal area. Subsequently, it was shown that this type of apraxia is
of disorder either affects the primary auditory area or disconnects more prevalent and severe in right hemisphere parietal lesions.
this area from Wernicke’s area. This syndrome is “pure” in the
sense that it is not associated with other aphasic symptoms.
Left Right
APRAXIA Corpus callosum
Premotor Premotor
Apraxia is the inability to perform skilled, learned, pur- area area
poseful motor acts correctly despite intact relevant mo-
tor and sensory neural structures, attention, and com- Primary Primary
prehension. The concept of apraxia and the first classification of motor area motor area
apraxia are credited to Hugo Karl Liepmann, the German neu-
rologist. There are several types of apraxia: ideomotor, ideational, Arcuate
a
and visuoconstructive. fasciculus
c
Primary Wernicke’s
Ideomotor Apraxia auditory area area
Ideomotor apraxia is the inability to carry out, on verbal com-
mand, an activity that can be performed perfectly well sponta- Oral
neously. It is implied that this “inability” is not due to compre- command
hension, motor, or sensory defects. Thus a patient with ideomotor
apraxia will not be able to carry out a verbal command to walk, Figure 18–1. Schematic diagram showing the pathways involved
stop, salute, open a door, stick out the tongue, etc. in carrying out a motor skill in response to an oral command.
262 / CHAPTER 18
The term constructional apraxia was suggested by Kleist in 1923 deep lesion in the left occipitotemporal region isolates both oc-
and fully described by Mayer-Gross in 1935. Lord Brain pro- cipital cortices from the left speech area in the angular gyrus.
posed the term apractagnosia. Most commonly, alexia without agraphia occurs as a result of
infarction in the territory of the left posterior cerebral artery that
supplies neural structures involved. Usually, a right homony-
ALEXIA (DYSLEXIA) mous visual field defect is present.
In alexia with agraphia, there is a defect in both reading com-
Alexia (dyslexia) is the inability to comprehend written prehension and writing. The reading disorder is usually verbal
language (reading disability). It may be acquired (ac- (inability to read words). The writing difficulty is usually severe.
quired alexia or dyslexia), as in stroke patients who lose The anatomic substrate of this type of alexia is a lesion in the
the ability to read, or developmental (developmental dyslexia), dominant angular gyrus, hence the name parietal alexia.
in which there is an inability to learn to read normally from The concept of alexia as separate from other language dis-
childhood. Acquired alexia is of two types: pure alexia (alexia orders was developed in 1885 by the German neurologist Ludwig
without agraphia, pure word blindness) and alexia with agraphia Lichtheim. The two types of acquired alexia (without and with
(parietal alexia). agraphia) were introduced by Dejerine in 1891 and 1892.
In pure alexia, the defect in comprehension may manifest as
an inability to read letters (literal alexia) or words (verbal alexia) AGNOSIA
or may be global with a total inability to read either letters or
words (global alexia). The anatomic substrate of pure alexia is Agnosia is the inability of the individual to recognize perceived
usually a lesion in the left primary visual area coupled with an- sensory information. Implied in this definition is an in-
other lesion in the splenium of the corpus callosum (Figure 18–2). tact sensory processing of the input, clear mental state,
The lesion in the left visual area prevents visual stimuli entering and intact naming ability.
the left hemisphere from reaching the left (dominant) angular Agnosia is often modality specific: visual, auditory, and tac-
gyrus, which is necessary for comprehension of written language. tile. Visual agnosias include visual object agnosia (inability to
The lesion in the splenium of the corpus callosum prevents vi- recognize objects presented visually), visual color agnosia (inabil-
sual stimuli entering the intact right visual area from reaching ity to recognize colors), prosopagnosia (i.e., inability to recognize
the left angular gyrus. Writing is normal in this type of alexia, but faces, including one’s own face, cars, types of trees), picture ag-
the patient cannot read what he or she writes. Cases have been de- nosia, and simultanagnosia (inability to recognize the whole,
scribed of pure alexia without a splenial lesion. In such cases, one although parts of the whole are appreciated correctly).
VISUAL VISUAL
FIELDS FIELDS
ANGULAR ANGULAR
GYRUS GYRUS
Relay of visual Relay of visual

information to information to
speech area speech area
is interrupted is interrupted
VISUAL VISUAL
CORTEX CORTEX
Visual Visual Visual

information information information
A not received received B received
Figure 18–2. Schematic diagram showing the neural substrate of the syndrome of pure alexia without agraphia A and of
hemialexia B.
Auditory agnosia is the inability to recognize sounds in the Unilateral (Left) Ideomotor Apraxia
presence of otherwise adequate hearing. It includes auditory verbal
agnosia (inability to recognize spoken language or pure word deaf- In response to verbal commands, patients are unable to carry out
ness), auditory sound agnosia (i.e., inability to recognize nonver- with the left hand some behavior that is readily carried out with
bal sounds such as animal sounds, sound of running water, sound the right hand. The verbal command is adequately received by
of a bell), and sensory amusia (inability to recognize music). the left (dominant) hemisphere but, because of the callosal dis-
Tactile agnosia is the inability to recognize objects by touch. connection, cannot reach the right hemisphere, which controls
It is usually associated with parietal lobe lesions of the contralat- left hand movement (Figure 18–3).
eral hemisphere. Astereognosis is the loss of ability to judge the
form of an object by touch. It includes amorphognosia (im- Unilateral (Left) Agraphia
paired recognition of size and shape of objects), ahylognosia (im- Patients with callosal lesions are unable to write using their left
paired discrimination of quality of objects, such as weight, tex- hand (Figure 18–3).
ture, density), and asymbolia (impaired recognition of the
identity of an object in the absence of amorphognosia and ahylo-
gnosia). Asymbolia is used by some authors to refer to tactile Unilateral (Left) Tactile Anomia
agnosia. Patients with callosal disconnection are unable, with eyes closed,
to name or describe an object placed in the left hand, although
CALLOSAL SYNDROME they readily name the same object in the right hand. The object
placed in the left hand is perceived correctly in the right so-
The disconnection of the right from the left hemisphere by le- matosensory cortex but cannot be identified because of the cal-
sions in the corpus callosum results in the isolation of each hemi- losal lesion that disconnects the right parietal cortex from the left
sphere in such a way that each has its own learning pro- (dominant) hemisphere (Figure 18–3).
cesses and memories that are inaccessible to the other
hemisphere. The following are some of the effects of cal- Left Ear Extinction
losal disconnection. The effects of callosal transection are consid-
erably less in younger children compared with adults because of Patients with callosal lesions show left ear extinction when sounds
the continued reliance in this age group on ipsilateral pathways. are presented simultaneously to both ears (dichotic listening).
Sounds presented to the left ear reach the right temporal cortex
Visual Effects but, because of the callosal disconnection, are not related to the
left temporal cortex (dominant) for comprehension.
Each hemisphere retains its own visual images and memories, but There is evidence to suggest functional specialization of dif-
only the left hemisphere is able to communicate, because of the ferent segments of the corpus callosum. Thus lesions in the pos-
callosal disconnection, what it sees through speech or writing. terior part of the corpus callosum (splenium) are associated with
hemialexia, lesions in the anterior part are associated with left
Hemialexia ideomotor apraxia, and lesions in the middle part are associated
with left-hand agraphia; lesions in the middle and posterior parts
Patients are unable to read material presented in the left hemi- result in left-hand tactile anomia.
field. This occurs when the splenium of the corpus callosum is
involved in the lesion. Such visually presented material reaches PREFRONTAL LOBE SYNDROME
the right occipital cortex but cannot be comprehended because
the splenial lesion interferes with transmission of the visual im- The prefrontal lobe syndrome occurs in association with tumors,
age to the left (dominant) angular gyrus (Figure 18–2). trauma, or degenerative disease in the prefrontal and orbitofrontal
Hand Hand
Premotor
area
Corpus Somatosensory
callosum cortex Corpus
lesion callosum
Motor lesion
area
Speech Speech
area area
A B
Figure 18–3. Schematic diagram illustrating the mechanism of unilateral (left) ideomotor apraxia A and of unilateral (left) tactile
anomia B.
264 / CHAPTER 18
cortices. The syndrome is characterized by a conglomerate of surroundings. The pathologic hallmarks are neurofibrillary tan-
signs and symptoms that include impairments in decision mak- gles and senile plaques. The former are intracellular aggregates of
ing, ability to plan, social judgment, conduct, modula- twisted cytoskeletal filaments and abnormally phosphorylated
tion of affect and of emotional response, and creativity. tau protein. The latter are abnormal neurites surrounding an ag-
Such patients lose spontaneity in motor as well as men- gregated B-amyloid core in the neuropil between nerve cells. The
tal activities. They do not appear to realize that they are neglect- limbic cortex is most affected, the association cortices are heavily
ing themselves and their responsibilities at home and work. affected, the primary sensory areas are minimally affected, and
Affected patients may sit for hours looking at objects in front of the motor cortex is least affected. Within the limbic cortex, the
them or staring out a window. They manifest loss of inhibition in entorhinal cortex (Brodmann area 28) is the most heavily af-
social behavior and are usually euphoric and unconcerned. They fected, thus disconnecting the hippocampus from association ar-
may become incontinent of stools and urine because of the lack of eas of the cortex. In Alzheimer’s disease, about 50% of neurons
spontaneity. Patients with prefrontal lobe syndrome exhibit inap- are lost.
propriate repetitive motor or speech behavior (perseveration) be- Ninety percent of Alzheimer’s disease is sporadic. The familial
cause of their inability to disengage from a behavior that is no cases comprise 10% of cases and are related to abnormal muta-
longer useful. tions in chromosomes 21, 14, and 1. Chromosome 21 mutation
is in the amyloid precursor protein and has been associated with
abnormal quantities of amyloid production. Mutations in chro-
THE GRASP REFLEX mosomes 14 and 1, on the other hand, are associated with protein
Some brain-damaged patients show, in response to tactile stimu- presenilins that are possibly responsible for build up of amyloid.
lation of their hands or to the mere presentation of an object, a Risk factors for Alzheimer’s disease have been associated with
tendency to grasp at the object without any apparent intention chromosome 19, which encodes apolipoprotein, and chromo-
to use it in a purposeful manner. Two types of grasp phenomena some 12, which encodes alpha 2 macroglobulin.
have been described: (1) the grasp reflex and (2) the instinctive
grasp reaction. BALINT’S SYNDROME
The grasp reflex is generally considered an index of frontal
lobe pathology, although the evidence in support of this localiza- This rare syndrome is named after the Hungarian neurologist
tion is not so compelling. The grasp reflex has been reported Rudolph Balint. The syndrome is also known as Balint-Holmes
with pathology in the basal ganglia, temporal lobe, parietal lobe, syndrome, optic ataxia, ocular apraxia, and psychic paralysis of
and parietooccipital region. In the majority of cases, however, visual fixation. It is characterized by a triad of (1) simultanagnosia,
pathology is either in the frontal lobe or in subcortical structures. (2) optic ataxia, and (3) ocular apraxia. Simultanagnosia, also
Unilateral lesions usually result in bilateral grasping. known as visual disorientation, is the inability of the patient to
In contrast, the instinctive grasp reaction (forced groping) is perceive the visual field as a whole. Optic ataxia is the inability to
usually ipsilateral to the focal cerebral lesion and is seen more of- reach for objects under visual guidance. Ocular apraxia is the in-
ten with retrorolandic lesions of the right hemisphere, suggesting ability to direct gaze voluntarily to visual targets. The associated
that it is one of the right hemisphere behavioral syndromes cortical lesion is bilateral parietooccipital junction (Brodmann
caused by disturbances of selective attention. areas 7 and 19).
FORCED COLLECTIONISM GERSTMANN’S SYNDROME

Forced collectionism is a rare prefrontal lobe syndrome charac- This syndrome is named after Josef Gerstmann, an Austrian neuro-
terized by involuntary, irrepressible behavior of searching, col- psychiatrist who described the syndrome in 1930. The syndrome
lecting, and storing that is goal-directed and item-selective. It is also known as the Badal-Gerstmann syndrome and the angular
results from inefficient or loss of frontal lobe inhibition. It is as- gyrus syndrome. Antoine-Jules Badal, a French ophthalmologist,
sociated with bilateral damage to the orbitofrontal and polar pre- had reported some features of the syndrome in 1888. The syn-
frontal cortices. drome consists of the combination of right-left disorientation,
Pathologic patterns of collecting have been observed following acalculia (reduced ability to perform simple calculations), agraphia
frontal lobe injury. They range from a tendency to grasp to the ir- (inability to write), and finger agnosia (inability to recognize
repressible seizure and storage of surrounding objects (hoarding various fingers) due to a lesion in the left angular gyrus. Asym-
behavior). In contrast to forced collectionism, these behaviors are bolia for pain and constructional apraxia are added features in
not planned and not selective. some cases.
ALZHEIMER’S DISEASE ANOSOGNOSIA (DENIAL SYNDROME,

ANTON-BABINSKI SYNDROME)
Alzheimer’s disease is the example par excellence of cortical de-
mentia. It was first described by Alois Alzheimer, the German The term anosognosia was introduced by Josef-François-Felix
psychiatrist, in 1906–1907, based on pathological find- Babinski in 1912 for unawareness of physical deficits or disease.
ings in the brain of a patient (Auguste D) with memory This is seen most often with lesions of the nondominant (right)
impairment. It is characterized by relentlessly progres- parietal lobe, with unawareness of deficits of the left side of the
sive memory loss. Early on in the disease, patients lose recent body. The denial syndrome may include denial that the paretic
memory (telephone numbers, appointments). As the disease limbs belong to the patient. Hemispatial neglect often co-occurs
progresses, remote memory is impaired. In the end stage, mem- with anosognosia. In hemispatial neglect, the contralateral side
ory loss is nearly total. With advance in the disease, patients will of the body and visual space are ignored but can be used if atten-
be unable to recognize their family members or their familiar tion is drawn to them. Hemispatial neglect occurs after damage
to either hemisphere but is typically more common and severe supplementary motor area. The combined callosal and medial
after right parietal lesions. The precise location of the lesion in frontal lesions presumably release the lateral frontal motor sys-
the parietal lobe has not been determined, but most likely is in tem responsible for environmentally driven activity. A sensory
the inferior parietal lobule and the adjacent intraparietal sulcus. alien hand syndrome has also been described in which the right
arm involuntarily attacks the left side of the body, including
ANTON’S SYNDROME choking movement.
Anton’s syndrome traditionally refers to the clinical phenome-

non of denial of blindness (anosognosia for blindness) in a pa- TERMINOLOGY
tient who has suffered acquired cortical blindness. The most
common setting is acute bilateral occipital cortex ischemia sec- Adversive seizures. A variety of seizures in which there is devia-
ondary to posterior circulation insufficiency. Although classically tion of eyes and/or head to one side secondary to a stimulating
a manifestation of cortical blindness, Anton’s syndrome has been lesion in the contralateral frontal eye field region.
reported in patients with blindness from peripheral visual path- Agnosia (Greek a, “negative”; gnosis, “knowledge”). Impairment
way lesions (optic nerve, chiasm). The syndrome is named after of the ability to recognize stimuli that were recognized formerly
Gabriel Anton, an Austrian neurologist who described the syn- despite intact perception, intellect, and language. The term was
drome in 1899. coined by Sigmund Freud in 1891. The lesion is usually in the
posterior parietal region.
KLUVER-BUCY SYNDROME Agraphia (Greek a, “negative”; grapho, “to write”). Inability to
express thoughts in writing due to a cerebral lesion. The first
The Kluver-Bucy syndrome was first described in 1939 in mon- modern descriptions of agraphia are those of Jean Pitres in 1884
keys after bilateral temporal lobectomy. The human counterpart and of Joseph-Jules Dejerine in 1891.
was described by Terzian and Dalle Ore in 1955 after bilateral re- Alzheimer, Alois (1864–1915). German neuropsychiatrist and
moval of the temporal lobes. The syndrome consists of six main pathologist. He described Alzheimer’s disease in a lecture in
elements: (1) blunted affect with apathy, (2) psychic blindness or 1906 and a publication in 1907. The term “Alzheimer’s disease”
visual agnosia with inability to distinguish between friends, rela- was coined in 1910 by Ernst Kraepelin, a German psychiatrist
tives, and strangers, (3) hypermetamorphosis with a marked ten- and co-worker of Alzheimer.
dency to take notice and attend to fine and minute visual stim- Anomia (Greek a, “negative”; onoma, “name”). Inability to
uli, (4) hyperorality, placing all items in the mouth, (5) bulimia name objects or of recognizing and recalling their names.
or unusual dietary habits, and (6) alteration in sexual behavior
(hypersexuality, sexual libertarianism). Anton, Gabriel (1858–1933). Austrian neurologist who de-
scribed visual anosognosia (anosognosia for blindness) in 1899.
The term anosognosia was coined by Babinski in 1912.
SIMULTANAGNOSIA Aphasia (dysphasia) (Greek a, “negative”; phasis, “speech”).
Simultanagnosia is the inability to appreciate more than one as- Language impairment following cortical lesion in the left hemi-
pect of the visual panorama at any single time. Affected patients sphere. Either inability to speak or to comprehend language or
cannot experience a spatially coherent visual field because of an both.
inability to voluntarily control the shifting of attention or to dis- Apraxia (Greek a, “negative”; praxis, “action”). Inability to
engage from a fixed target. Objects in the visual field of affected carry out learned skilled movements on command despite intact
patients appear and disappear erratically. Affected patients fail to motor and sensory systems and good comprehension.
see a match flame held several inches away when their attention Babinski, Josef-François-Felix (1857–1932). French neurologist
is focused on the tip of a cigarette held between their lips. The of Polish descent. Described the “phenomenon of the toes” in
term simultanagnosia was introduced by Wolpert in 1924 to 1896, which became known as the Babinski sign. Coined the
refer to a condition in which the patient is unable to recognize or terms anosognosia, dysdiadochokinesis, and asynergia, among others.
abstract the meaning of the whole (pictures or series of pictures) Bastian, Henry Charlton (1837–1915). English neurologist,
even though the details are appreciated correctly. Simultanagnosia who described Wernicke’s aphasia in 1869, five years before Karl
is frequently a component of Balint’s syndrome. Isolated simul- Wernicke.
tanagnosia is associated with lesions in the unimodal visual asso- Circumlocution. Convoluted, meaningless speech output, pro-
ciation cortex (Brodmann area 19). viding information rather than defining the objects to be com-
municated. Characteristic of Wernicke’s aphasia.
THE ALIEN HAND (LIMB) SYNDROME Dax, Gustav. French physician, who, in 1865, published the ob-
servation of his father, Marc Dax, about left hemisphere domi-
The alien hand (limb) syndrome is characterized by the unwilled nance for language, which was noted, but not published, by his
and uncontrolled actions of an upper limb on either the domi- father in 1836.
nant or nondominant side. The alien hand performs auton-
omous activity that the subject cannot inhibit and then often Déjà vu (French, “already seen”). An illusion in which a new
contrasts with voluntary actions performed by the other hand. situation is incorrectly viewed as a repetition of a previous situa-
Patients often fail to recognize ownership of the limb and state tion. Usually an aura of a temporal lobe seizure.
that the alien hand has a mind of its own. The alien hand syn- Dysphasia (Greek dys, “difficult”; phasis, “speech”). Distur-
drome was first described in 1908 by Goldstein. Two forms of bance in communication involving language.
alien hand exist: (1) an acute, transient condition in the non- Dysprosody (Greek dys, “difficult”; prosodos, “a solemn pro-
dominant hand due to callosal lesion and (2) a chronic condition cession”). Disturbance in stress, pitch, and rhythm of speech. A
resulting from additional medial frontal lesions involving the feature of all types of aphasia, but especially of Broca’s aphasia.
266 / CHAPTER 18
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Hypothalamus 19
Boundaries and Divisions Autonomic Regulation

Preoptic Region Temperature Regulation
Suprachiasmatic (Supraoptic) Region Emotional Behavior
Tuberal Region Feeding Behavior
Mamillary Region Drinking and Thirst
Connections Sleep and Wakefulness
Local Connections Circadian Rhythm
Extrinsic Connections Memory
Functions of the Hypothalamus Sexual Arousal
Control of Posterior Pituitary (Neurohypophysis) Blood Supply
Control of Anterior Pituitary
KEY CONCEPTS
The hypothalamus is divided by the fornix into medial The hypothalamus is involved in a variety of functions that
and lateral zones. include (1) control of water reabsorption in the kidney
through secretion of the antidiuretic hormone (ADH) or va-
The hypothalamus contains the following nuclear group-
sopressin,(2) contraction of uterine smooth muscle and ejec-
ings: preoptic, suprachiasmatic (supraoptic), tuberal, and
tion of milk from the lactating nipple through secretion of
mamillary.
oxytocin, (3) control of anterior pituitary function through
Hypothalamic connections are divided into local (effer- secretion of hypothalamic releasing factors, (4) control of
ent) and extrinsic (afferent and efferent). brain stem and spinal cord autonomic centers related to
cardiovascular, respiratory, and gastrointestinal functions,
Local hypothalamic connections consist of the hypotha-
(5) control of body temperature through thermoreceptors
lamohypophyseal tract and the tuberohypophyseal
that are sensitive to changes in temperature of blood perfus-
(tuberoinfundibular) tract.
ing the hypothalamus,(6) emotional behavior and the “fight
Afferent extrinsic connections include the retinohypo- or flight”reaction,(7) regulation of feeding behavior through
thalamic, fornix, amygdalohypothalamic, thalamohypo- the hypothalamic satiety and feeding centers, (8) regulation
thalamic, medial forebrain bundle, inferior mamillary of drinking and thirst, (9) wakefulness and sleep through the
peduncle, dorsal longitudinal fasciculus (of Schütz), palli- hypothalamic centers for wakefulness and sleep, (10) circa-
dohypothalamic, cerebello-, spino-, and prefrontal hypo- dian rhythm through the connections of the suprachias-
thalamic. matic nucleus,and (11) memory through connections to the
anterior thalamic nucleus and hippocampal formation.
Efferent extrinsic connections include the mamillotha-
lamic, mamillotegmental, fornix, medial forebrain bundle, The blood supply of the hypothalamus is derived from
dorsal longitudinal fasciculus (of Schütz), hypothalamo- perforating branches of the anterior cerebral, anterior
amygdaloid, descending autonomic, hypothalamocere- communicating, posterior communicating, and posterior
bellar and hypothalamo-prefrontal. cerebral arteries.
268
HYPOTHALAMUS / 269
BOUNDARIES AND DIVISIONS The medial preoptic nucleus contains neurons that elaborate
gonadotropic releasing hormone which reaches the anterior pitu-
The hypothalamus is the area of the diencephalon ventral to the itary gland via the tuberoinfundibular tract. It is related to repro-
hypothalamic sulcus (see Figure 11–1). It weighs about 4 g and duction, eating, locomotion, and sexual arousal. The medial pre-
comprises 0.3 to 0.5 percent of brain volume. It is limited ante- optic nucleus is referred to as the sexually dimorphic nucleus. It
riorly by the lamina terminalis and is continuous posteriorly is twice as large in young males compared to females, probably
with the mesencephalon. On its ventral surface, caudal to the because gonadotropin release in males is constant, whereas it is
optic chiasma, the hypothalamus narrows to a small neck, the cyclic in females. The difference in size may also explain the re-
tuber cinereum. The ventral-most portion of the tuber cinereum ported greater sexual arousal to erotic stimuli experienced by
constitutes the median eminence. The median eminence blends men. Functional magnetic resonance imaging (fMRI) studies
into the infundibular stalk, which is continuous with the poste- have shown greater activation in the preoptic region in men
rior lobe of the pituitary gland (hypophysis). In coronal sections, compared to women when viewing erotic films.
the hypothalamus is bordered medially by the third ventricle and
laterally by the subthalamus (see Figure 11–2). The fornix di- Suprachiasmatic (Supraoptic) Region (Figure 19–2)
vides the hypothalamus into medial and lateral regions. The
lateral region contains mainly longitudinally oriented Located above the optic chiasma, this nuclear group contains the
fibers of the medial forebrain bundle (which connects supraoptic, paraventricular, anterior hypothalamic, and supra-
the septal area, hypothalamus, and midbrain tegmen- chiasmatic nuclei. The supraoptic nucleus is located above the
tum), among which are scattered neurons of the lateral hypo- optic tract, whereas the paraventricular nucleus is dorsal to it,
thalamic nucleus. The medial region has a cluster of nuclei orga- lateral to the third ventricle (Figure 19–3). Both nuclei contain
nized into four major groups. In a rostrocaudal orientation magnocellular secretory neurons. Axons of both nuclei course in
(Figure 19–1), these nuclear groups are as follows: the pituitary stalk to reach the posterior lobe of the pituitary (hy-
pothalamoneurohypophyseal system), transporting neurosecre-
1. Preoptic
tory material elaborated in these nuclei and stored in axonal
2. Suprachiasmatic (supraoptic) swellings within the posterior lobe. The neurosecretory material
3. Tuberal consists of vasopressin ADH and oxytocin. There is evidence to
4. Mamillary suggest that the supraoptic nucleus elaborates mainly ADH,
whereas the paraventricular nucleus elaborates mainly oxytocin.
Preoptic Region (Figure 19–2) ADH acts on the distal convoluted tubules of the kidney to in-
crease reabsorption of water. Lesions of the supraoptic nucleus,
The gray matter in the most rostral part of the hypothalamus, the hypothalamoneurohypophyseal system, or the posterior lobe
just caudal to the lamina terminalis, is the preoptic region. The of the pituitary result in excessive excretion of urine (polyuria) of
preoptic region receives many fibers that carry neuromediators, low specific gravity. This condition is known as diabetes in-
such as angiotensin II, sleep-inducing peptides, enkephalin, and sipidus. Another symptom of this condition is excessive intake of
endorphin, among others. It contains medial and lateral preoptic water (polydipsia). Unlike diabetes mellitus, diabetes insipidus is
nuclei and the preoptic periventricular nucleus. not associated with alterations in the sugar content of blood or
Supraoptic Mamillary
region region
Preoptic Tuberal Hypothalamic
region region sulcus
Lamina
terminalis
Optic
chiasm
Figure 19–1. Schematic diagram show-

ing the four regions of the medial hypo- Pituitary Mamillary
thalamus. gland body
270 / CHAPTER 19
Anterior Anterior Paraventricular Dorsomedial Hypothalamic

commissure nucleus nucleus nucleus sulcus
Lamina Posterior
terminalis nucleus
Preoptic
nucleus Mamillary
body
Suprachiasmatic
nucleus
Supraoptic Ventromedial
nucleus nucleus
Optic
chiasm Figure 19–2. Schematic diagram
showing nuclei within each of
Pituitary Arcuate the regions of the medial hypo-
gland nucleus thalamus.
of urine. Production of ADH is controlled by the osmolarity of lation of the anterior part of the hypothalamus in animals results
the blood that bathes the supraoptic nucleus. An increase in in excessive intake of water, suggesting that a center for thirst
blood osmolarity, as occurs in dehydration, increases ADH pro- is located in this region. Tumors in this region in children are
duction, whereas the reverse occurs in states of lowered blood os- associated with refusal of patients to drink despite severe de-
molarity, such as excessive hydration. ADH secretion is increased hydration.
by pain, stress, and such drugs as morphine, nicotine, and barbi- The suprachiasmatic nucleus, poorly developed in humans,
turates; it is decreased by alcohol intake, which explains the in- overlies the optic chiasma. It is involved in regulation of sleep-
crease in urination with alcohol consumption. wake cycle, body temperature, and day-night cycle (circadian
Oxytocin causes contraction of uterine smooth musculature rhythm). It receives bilateral inputs from ganglion cells of the
and promotes milk ejection from the lactating mammary glands retina. It projects to the paraventricular, tuberal, and ventrome-
by stimulating contraction of its myoepithelial cells. Commer- dial nuclei of the hypothalamus. Lesions of the nucleus in exper-
cially produced oxytocin (Pitocin) is used to induce labor. The imental animals will disturb the cyclic variations of a number of
function of oxytocin in males is not yet known. bodily functions (e.g., temperature cycle, sleep-wake cycle, circa-
The anterior nucleus merges with the preoptic region. Stimu- dian changes of hormones).
Tuberal Region (Figure 19–2)

Third ventricle
This is the widest region of the hypothalamus and the one in
which the division of the hypothalamus into medial and lateral
Paraventricular
nucleus areas by the fornix is best illustrated. It extends from the in-
fundibulum anteriorly to the mamillary body posteriorly. The
tuberal region contains the ventromedial hypothalamic, dorso-
Optic tract
medial hypothalamic, and arcuate (infundibular) nuclei.
Supraoptic
The ventromedial nucleus, a poorly delineated area of small
nucleus neurons, is concerned with satiety. Bilateral lesions in the ventro-
medial nucleus in animals produce a voracious appetite, obesity,
and savage behavior. Lesions in the lateral hypothalamus at this
level produce loss of appetite. Thus a center for satiety is believed
to be associated with the ventromedial nucleus and a feeding
center with the lateral hypothalamus.
The dorsomedial nucleus is a poorly delineated mass of small
Hypothalamo- neurons dorsal to the ventromedial nucleus. The arcuate nucleus
neurohypophyseal
tract
consists of small neurons located ventral to the third ventricle
near the infundibular recess. The arcuate nucleus contains dopa-
mine, which controls prolactin and growth hormone secretions.
Posterior (neuro)
hypophysis In addition, neurons of the arcuate nucleus stain positively for
adrenocorticotropic hormone (ACTH), beta-lipotropic pituitary
Figure 19–3. Schematic diagram showing the hypothalamo- hormone (-LPH), and beta-endorphin (-END). These sub-
neurohypophyseal system. stances are transmitted to the anterior pituitary via the tubero-
HYPOTHALAMUS / 271
infundibular tract and the hypophyseal portal system. The arcu- pophysis. Interruption of this tract results in diabetes insipidus,
ate nucleus is believed to play a role in emotional behavior and a condition characterized by excessive urine excretion (poly-
endocrine function. The arcuate nucleus is a major target in the uria) of low specific gravity and excessive intake of water (poly-
hypothalamus for leptin action to suppress food intake. Both dipsia) without alterations in the glucose content of blood or
food promoting (orexinergic) and food inhibiting (anorexiner- urine.
gic) neurons exist in the arcuate nucleus and are targets for lep-
tin action. The arcuate orexinergic neurons are the neuropep- B. THE TUBEROHYPOPHYSEAL (TUBEROINFUNDIBULAR) TRACT
tide Y neurons. This tract arises from the small parvicellular neurons of the arcu-
ate and periventricular nuclei and terminates on capillaries in the
Mamillary Region (Figure 19–2) median eminence and infundibular stem. Fibers in this tract trans-
mit hypothalamic releasing factors (hypophysiotropic agents) to
The most caudal region of the hypothalamus is the mamillary re- the anterior lobe of the pituitary gland via the hypophyseal por-
gion; it contains mamillary and posterior hypothalamic nuclei. tal system. Hypophysiotropic agents stimulate or inhibit secre-
The mamillary nuclei (bodies) are two spherical masses protrud- tion of anterior lobe of the pituitary hormones.
ing from the ventral surface of the hypothalamus caudal to the
tuber cinereum and rostral to the interpeduncular fossa and the Extrinsic Connections
anterior perforated substance. Each mamillary body contains
two nuclei, medial and lateral. The medial nucleus is especially A. AFFERENT EXTRINSIC CONNECTIONS
well developed in man. It is the main target of the fornix and the The following hypothalamic extrinsic inputs have been reported:
source of the mamillothalamic tract.
The posterior hypothalamic nucleus is a mass of large neu- 1. Retinohypothalamic tract. Fibers from ganglion cells of the
rons located dorsal to the mamillary bodies. It is the main source retina project bilaterally to the suprachiasmatic nuclei of the
of descending hypothalamic fibers to the brain stem. hypothalamus via the optic nerve and optic chiasma.
They reach the nucleus as direct fibers from the optic
A. LATERAL REGION chiasm or as collaterals from retinogeniculate fibers. This
The lateral region of the hypothalamus lies lateral to the fornix tract transmits light periodicity information to the suprachi-
and mamillothalamic tract. It contains the medial forebrain bun- asmatic nucleus, which plays a role in the circadian rhythm.
dle and the lateral hypothalamic nucleus. The medial forebrain 2. Fornix. The fornix comprises the major input to the hypo-
bundle connects the hypothalamus with the septal area rostrally thalamus. Arising from the hippocampal formation and
and brain stem reticular formation caudally. The lateral hypo- subiculum, the fornix follows a C-shaped course underneath
thalamus is specifically responsible for feeding. Orexin (hypocre- the corpus callosum as far forward as the interventricular
tin) peptide containing neurons are exclusively located in the lateral foramen of Monro, where it disappears in the substance of
hypothalamic region. Central administration of hypocretin-1 the diencephalon to reach the mamillary bodies. Although
stimulates food intake. Hypocretin neurons in the lateral region the major component of the fornix comes from the hip-
send a dense projection to the hypothalamic arcuate nucleus. pocampal formation and subiculum, it also carries fibers
Hypocretin inhibits anorexinergic and excites orexinergic arcu- from the septal area to the mamillary bodies. Its major target
ate neurons. Hypocretin neurons also project to the paraventric- within the mamillary body is the medial nucleus.
ular and ventromedial hypothalamic nuclei, structures known to 3. Amygdalohypothalamic tract. Inputs to the hypothalamus from
integrate feeding. The orexin/hypocretin system is also the major the amygdala follow two pathways. One is via the phylogenet-
excitatory neuromodulatory system that controls activities of ically older stria terminalis, which links the amygdala with the
monoaminergic and cholinergic systems to control vigilance preoptic, anterior hypothalamic, ventromedial, and arcuate
states. Destruction of orexin/hypocretin neurons is associated nuclei of the hypothalamus. The other is via the phylogeneti-
with the sleep disorder of narcolepsy. cally more recent ventral amygdalofugal fiber system, which
links the amygdala with the lateral hypothalamic nucleus.
CONNECTIONS (Figure 19–3) 4. Thalamohypothalamic fibers. These fibers run from dorsome-
dial and midline thalamic nuclei to the lateral and posterior
The hypothalamus has extensive connections reflecting its hypothalamus and are sparse. Fibers from the anterior tha-
roles in endocrine, autonomic, and somatic integration. lamic nuclei reach the mamillary bodies via the mamillo-
thalamic tract and provide a feedback mechanism to the
Local Connections mamillary bodies.
The hypothalamus influences pituitary function via two 5. Medial forebrain bundle. This fiber bundle runs in the lateral
pathways: the hypothalamohypophyseal (supraoptic- hypothalamus. It conveys to the hypothalamus inputs from a
hypophyseal) tract and the tuberohypophyseal (tubero- variety of sources, including the basal forebrain (olfactory
infundibular) tract. cortex, septal area, nucleus accumbens septi), amygdala, pre-
motor frontal cortex, brain stem reticular formation, and
A. THE HYPOTHALAMOHYPOPHYSEAL (SUPRAOPTIC-HYPOPHYSEAL) spinal cord.
TRACT (Figure 19–3) 6. Inferior mamillary peduncle. This fiber bundle links the dor-
This tract arises from the large magnocellular neurons of the sal and ventral tegmental nuclei of the midbrain with the
supraoptic and paraventricular nuclei of the hypothalamus and mamillary body. It also contains indirect inputs from ascend-
terminates in the posterior lobe of the pituitary gland (neuro- ing sensory pathways.
hypophysis). Axons in this tract transport vasopressin (ADH) 7. Dorsal longitudinal fasciculus of Schütz. Afferent fibers in this
from the supraoptic nucleus and oxytocin from the paraventric- fasciculus link the periaqueductal (central) gray matter of the
ular nucleus to the fenestrated capillary bed in the neurohy- midbrain with the hypothalamus.
272 / CHAPTER 19
8. Pallidohypothalamic fibers. This fiber bundle originates from HYPOTHALAMUS

the lentiform nucleus and projects on neurons in the ventro- Paraventricular nucleus, lateral and posterior regions
medial hypothalamic nucleus.
9. Cerebellohypothalamic fibers. This fiber bundle originates
from all deep cerebellar nuclei and relates the cerebellum to BRAIN STEM
autonomic function. Dorsal motor nucleus of vagus
10. Other inputs. Other afferents to the hypothalamus from the Nucleus ambiguus
brain stem include those from the raphe nuclei (serotoniner- Nucleus solitarius
gic), locus ceruleus (noradrenergic), and nucleus solitarius. SPINAL CORD
These fibers enter the hypothalamus via the medial forebrain Autonomic centers
bundle. Input from the spinal cord reaches the hypothala- Thoracic
mus via the reticular formation of the brain stem. Sacral
11. Prefrontal-hypothalamic fibers. Reciprocal connections be- Figure 19–4. Schematic diagram showing descending auto-
tween the hypothalamus and prefrontal cortex have been nomic projections of the hypothalamus.
demonstrated. Prefrontal-hypothalamic fibers originate pri-
marily from the orbital and medial prefrontal areas and ter-
minate primarily in the posterior hypothalamus, with some
terminations in the tuberal and anterior hypothalamus. The 8. Hypothalamocerebellar fibers. In the past few years, a series of
origin of prefrontal-hypothalamic fibers from limbic pre- investigations has revealed the existence of a complex network
frontal cortex and their targets in the hypothalamus suggest of direct and indirect pathways between the hypothalamus
that they are important links for autonomic response to and cerebellum. The projections are bilateral with ipsilateral
emotion. preponderance. They originate from various hypothalamic
nuclei and areas but principally from the lateral and poste-
B. EFFERENT EXTRINSIC CONNECTIONS rior hypothalamic areas. The direct pathway reaches the
The hypothalamus sends fibers to most areas from which it re- cerebellum via the superior cerebellar peduncle. The indirect
ceives inputs. The following hypothalamic extrinsic efferent con- pathway reaches the cerebellum after relays in a number of
nections have been reported: brain stem nuclei. The hypothalamocerebellar pathway may
provide the neuroanatomic substrate for the autonomic re-
1. Mamillothalamic tract (tract of Vicq d’Azyr) (see sponses elicited from cerebellar stimulation.
Figure 11–4). This is a two-way fiber system connect-
ing the mamillary bodies with the anterior thalamic 9. Hypothalamothalamic fibers: This fiber system connects the
nucleus. preoptic hypothalamic area with the dorsomedial thalamic
nucleus.
2. Mamillotegmental tract. Fibers from the mamillary bodies
10. Hypothalamoprefrontal fibers: These fibers originate princi-
course caudally to terminate on dorsal and ventral tegmental
pally from the posterior hypothalamus with some contribu-
nuclei and secondarily on autonomic cranial (dorsal motor
tions from the anterior and tuberal hypothalamus. In contrast
nucleus of vagus, nucleus solitarius, nucleus ambiguus) and
to the prefrontal hypothalamic connection which originates
spinal nuclei (intermediolateral cell column).
selectively from limbic prefrontal cortex, the hypothalamus
3. Fornix. Reciprocal fibers travel in the fornix from the mamil- prefrontal projection is widespread to all sectors of the pre-
lary body to the hippocampal formation. frontal cortex.
4. Medial forebrain bundle. This bundle conveys impulses from Table 19–1 is a summary of the afferent and efferent connec-
the lateral hypothalamus rostrally to the septal nuclei and tions of the hypothalamus.
caudally to tegmental nuclei and periaqueductal (central)
gray of the midbrain.
FUNCTIONS OF THE HYPOTHALAMUS
5. Dorsal longitudinal fasciculus of Schütz. Fibers in this fascicu-
lus link the medial hypothalamus with the periaqueductal The functions of the hypothalamus, mediated through its varied
gray matter of the midbrain, the accessory oculomotor nu- and complex connections, involve several important
clei, and salivary nuclei. bodily activities. The following is a listing of some of the
6. Hypothalamoamygdaloid fibers. These fibers travel via the most important and best known.
stria terminalis and ventral amygdalofugal fiber system and
provide feedback information to the amygdaloid nucleus. Control of Posterior Pituitary (Neurohypophysis)
7. Descending autonomic fibers (Figure 19–4). Axons of neurons This is served through the hypothalamoneurohypophyseal sys-
in the paraventricular nucleus, the lateral hypothalamic area, tem discussed earlier. Approximately 100,000 unmyelinated fibers
and the posterior hypothalamus project into autonomic cra- extend from the supraoptic and paraventricular nuclei of the hypo-
nial nerve nuclei in the brain stem (dorsal motor nucleus of thalamus to the fenestrated capillary bed of the neurohy-
the vagus, nucleus ambiguus, nucleus solitarius) and auto- pophysis. These fibers convey two peptide hormones: vaso-
nomic spinal cord nuclei in the intermediolateral cell column pressin (ADH) and oxytocin. Vasopressin promotes reabsorption
and the sacral autonomic cell column. Via these connections, of water from the kidney. In lesions of the neurohypophysis,
the hypothalamus exerts control over central autonomic urine output of low specific gravity reaches 10 to 15 liters per
processes related to blood pressure, heart rate, temperature day, a condition known as diabetes insipidus. Oxytocin stimulates
regulation, and digestion. Many of these fibers are compo- contraction of smooth muscles of the uterus and promotes ejec-
nents of the dorsal longitudinal fasciculus of Schütz. tion of milk from the lactating mammary gland.
HYPOTHALAMUS / 273
Table 19–1. Connections of the Hypothalamus
Pathway Afferent Efferent Origin Termination
Hypothalamohypophyseal tract X Supraoptic and paraventricular nuclei Neurohypophysis

Tuberohypophyseal tract X Arcuate and periventricular nuclei Median eminence and infundibular
stalk
Retinohypothalamic tract X Ganglion cells of retina Suprachiasmatic nucleus
Fornix X Hippocampal formation, subiculum Mamillary body
X Mamillary body Hippocampal formation
Stria terminalis X Amygdaloid nucleus Preoptic and arcuate nuclei
X Preoptic and arcuate nuclei Amygdaloid nucleus
Ventral amygdalofugal tract X Amygdaloid nucleus Lateral hypothalamic nucleus
X Lateral hypothalamic nucleus Amygdaloid nucleus
Thalamohypothalamic X Dorsomedial and midline thalamic nuclei Lateral and posterior hypothalamus
Medial forebrain bundle X Basal forebrain, amygdala, premotor Lateral hypothalamus
frontal cortex, brain stem reticular
formation (raphe nuclei, locus
ceruleus, nucleus solitarius),
spinal cord
X Lateral hypothalamus Septal nuclei, tegmental nuclei,
and periaqueductal gray matter
of midbrain
Inferior mamillary peduncle X Tegmental nuclei of midbrain, Mamillary body
ascending sensory pathways
Dorsal longitudinal fasciculus X Periaqueductal gray matter of midbrain Medial hypothalamus
(of Schütz)
X Medial hypothalamus Periaqueductal gray matter
of midbrain
Pallidohyphothalamic X Lentiform nucleus Ventromedial hypothalamic nucleus
Cerebellohypothalamic fibers X Deep nuclei of cerebellum Lateral and posterior hypothalamus
Hypothalamocerebellar fibers X Lateral and posterior hypothalamus Deep cerebellar nuclei and cerebellar
cortex
Mamillothalamic tract X Mamillary body Anterior thalamic nucleus
Mamillotegmental tract X Mamillary body Tegmental nuclei of midbrain
Descending autonomic fibers X Paraventricular nucleus, lateral Autonomic cranial nerve and
hypothalamic area, posterior spinal cord nuclei
hypothalamus
Prefrontal-hypothalamic X Orbitofrontal cortex Posterior hypothalamus
Medial prefrontal cortex Tuberal hypothalamus
Anterior hypothalamus
Hypothalamic-prefrontal X Posterior hypothalamus Prefrontal cortex (wide spread)
Tuberal hypothalamus
Anterior hypothalamus
Control of Anterior Pituitary and luteinizing hormones (LH) from the basophils; growth hor-
mone–releasing factor (GHRF), which influences growth hor-
Several trophic factors (hypophysiotropins, hypothalamic releas- mone (somatostatin, GH) secretion from the acidophils;
ing factors) are produced in the hypothalamus and influence melanocyte-stimulating hormone–releasing factor (MSHRF),
production of hormones in the anterior pituitary. Trophic factors which influences melanocyte-stimulating hormone (MSH) pro-
are released into capillaries of the median eminence, from which duction; prolactin-inhibiting factor (PIF), which inhibits pro-
they reach the anterior pituitary via the hypophyseal portal cir- duction of prolactin from the acidophils; somatic inhibiting–re-
culation. In the anterior lobe, trophic factors act on the appro- leasing factor (SIRF), also known as somatostatin (SS); growth
priate chromophil cell to release or inhibit the appropriate hormone–inhibiting factor (GHIF) or somatotropin release–in-
trophic hormone. The anterior pituitary trophic hormones then hibiting factor (SRIF), which inhibits release of GH and thy-
act on the appropriate target gland. The serum hormone level of rotropin (TSH); and melanocyte-stimulating hormone release–
the target gland has a feedback effect on hypothalamic trophic inhibiting factor (MIF), which inhibits the release of MSH.
factors. The known hypothalamic trophic factors include corti- Secretion of GHRF and GHIF is stimulated by dopamine,
cotropin-releasing factor (CRF), which influences production of norepinephrine, and serotonin. The PIF is dopamine.
ACTH and beta-lipotropin (precursor of ACTH and of endor-
phins) by the pituitary basophils; thyrotropin-releasing factor Autonomic Regulation
(TRF), which influences secretion of thyroid-stimulating hor-
mone (TSH) from the basophils; gonadotropin-releasing factor The hypothalamus is known to control brain stem and spinal
(GnRF), which influences production of follicle-stimulating (FSH) cord autonomic centers. Stimulation or ablation of the hypothal-
274 / CHAPTER 19
amus influences cardiovascular, respiratory, and gastrointestinal also project to ventromedial and paraventricular nuclei of the
functions. Autonomic influences are mediated via the dorsal lon- hypothalamus, structures known to integrate feeding.
gitudinal fasciculus (of Schütz) and the mamillotegmental tract.
Although definite delineation within the hypothalamus of sym- Drinking and Thirst
pathetic and parasympathetic centers is not feasible, it is gener-
ally held that the rostral and medial hypothalamus is concerned In addition to the control of body water by ADH, stimulation of
with parasympathetic control, whereas the caudal and lateral hy- the lateral and anterior regions of the hypothalamus elicits
pothalamus is concerned with sympathetic control mechanisms. drinking behavior that persists despite overhydration. Lesions of
Stimulation of the rostral and medial hypothalamus (preoptic the same area abolish thirst.
and supraoptic areas) results in parasympathetic activation, char-
acterized by a slowing of heart rate, decrease in blood pressure, Sleep and Wakefulness
vasodilatation, pupillary constriction, increased sweating, and in-
creased motility and secretions of the alimentary tract. In contrast, The hypothalamus is believed to play a role in the daily sleep-
stimulation of the posterior and lateral hypothalamus (particu- wakefulness cycle. A sleep center is proposed to be in the anterior
larly the posterior) results in sympathetic activation, characterized part of the hypothalamus and a waking center in the posterior
by an increase in heart rate and blood pressure, vasoconstriction, part. The orexin/hypocretin system in the lateral hypothalamus
pupillary dilatation, piloerection, decreased motility and secre- is the major excitatory neuromodulatory system that controls
tion of the alimentary tract, bladder inhibition, and heightened activities of monoaminergic (dopamine, norepinephrine, sero-
somatic reactions of shivering and running. tonin, histamine) and cholinergic systems that control vigilance
states. Lesions in the orexin/hypocretin system are associated
with a state of irresistible sleep (narcolepsy).
Temperature Regulation
Some regions of the hypothalamus contain thermal receptors Circadian Rhythm
that are sensitive to changes in the temperature of blood perfus-
ing these regions. Anterior regions of the hypothalamus are sen- Through the connections of the suprachiasmatic nucleus with
sitive to a rise in blood temperature and trigger mechanisms for the retina and brain regions related to circadian rhythm, the hy-
heat dissipation, which include sweating and cutaneous vascular pothalamus plays an important role as an internal clock regulat-
dilatation in humans. Bilateral damage to this region, through ing cyclic variations of a number of bodily functions such as
surgery or by tumors or vascular lesions, results in elevation of temperature cycle, sleep-wake cycle, and hormonal cyclic varia-
body temperature (hyperthermia). In contrast, the posterior hy- tions. The suprachiasmatic nucleus serves the function of an en-
pothalamic region is sensitive to the lowering of blood tempera- dogenous pacemaker. It regulates secretion of melatonin by the
ture and triggers the mechanisms for heat conservation, which in- pineal gland. Disruption of release of melatonin is partially re-
clude cessation of sweating, shivering, and vascular constriction. sponsible for the phenomenon of jet lag.
Bilateral damage to this region results in poikilothermia, in which
body temperature fluctuates with environmental temperature. Memory
Through its connections with the hippocampal formation and
Emotional Behavior anterior thalamic nucleus, the mamillary body of the hypothala-
The hypothalamus is a major component of the central auto- mus plays a role in memory.
nomic nervous system and as such plays a role in emotional be-
havior. Lesions of the ventromedial hypothalamic nuclei in ani- Sexual Arousal
mals are associated with a rage reaction, characterized by hissing, Several brain areas have been shown by fMRI to be associated
snarling, biting, piloerection, arching of the back, and pupillary with sexual arousal in humans. These include the anterior cingu-
dilatation. In contrast, stimulation of lateral regions of the ante- late, medial prefrontal, orbitofrontal, insular and occipitotempo-
rior hypothalamus elicits a flight response. Stimulation of some ral cortices, as well as the amygdala, ventral striatum, thalamus,
hypothalamic regions elicits a pleasurable response. Stimulation and hypothalamus. All of these areas have reciprocal connections
of other regions produces unpleasant responses. The role of the with the hypothalamus. fMRI activation during sexual arousal is
hypothalamus in behavior and emotion is intimately related to similar in all areas except the preoptic region of the hypothala-
that of the limbic system. The connection between limbic pre- mus where activation is significantly greater in males. This gen-
frontal cortex and posterior hypothalamus is an important link der difference in activation of the hypothalamus has been corre-
for autonomic response to emotion. lated with the greater sexual arousal generally experienced by
men in response to erotic stimuli, and with the larger volume of
Feeding Behavior the medial preoptic nucleus (the sexually dimorphic nucleus) in
young males compared to young females. Lesions in the medial
As detailed earlier, bilateral lesions in the ventromedial nucleus preoptic area have deleterious effect on copulation in males,
elicit hyperphagia (excessive feeding), whereas similar lesions in while electrical stimulation of this area has facilitatory effect on
the lateral hypothalamic nucleus produce loss of hunger, suggest- this biological function.
ing the presence of a satiety center and feeding center, respec-
tively, in these regions. The lateral hypothalamus has recently
been found to contain orexin/hypocretin peptide containing BLOOD SUPPLY
neurons. Central administration of orexin/hypocretin stimulates
food intake. Orexin/hypocretin neurons in the lateral hypothala- The preoptic and supraoptic regions, as well as the ros-
mus inhibit anorexinergic and excite orexinergic neurons in the tral part of the lateral hypothalamus, are supplied by
arcuate nucleus of the hypothalamus. Orexin/hypocretin neurons perforating branches from the anterior communicating
HYPOTHALAMUS / 275
and anterior cerebral (A-1 segment) arteries. The tuberal and Polyuria (Greek polys, “many”; ouron, “urine”). The passage
mamillary regions, as well as the middle and posterior parts of of a very large volume of urine, characteristic of diabetes.
the lateral hypothalamus, are supplied by perforating branches Satiety (Latin satis, “sufficient”; ety, “state or condition of ”).
from the posterior communicating and posterior cerebral (P-1 Sufficiency or satisfaction or gratification of thirst or appetite.
segment) arteries. Vicq d’Azyr, Felix (1748–1794). French anatomist and physi-
cian to Queen Marie Antoinette who described the mamillothal-
TERMINOLOGY amic tract (tract of Vicq d’Azyr) in 1781, although his observa-
tion was not published until 1805.
Arcuate (Latin arcuatus, “bow-shaped”). The arcuate nucleus
of the hypothalamus has an arcuate shape in coronal sections.
Diabetes insipidus (Greek diabetes, “a syphon”). A condition SUGGESTED READINGS
of excessive production of urine from deficiency of the antidi-
Braak H, Braak E: The hypothalamus of the human adult: Chiasmatic region.
uretic hormone. The condition was distinguished from diabetes Anat Embryol 1987; 175:315–330.
mellitus by Thomas Willis, the English physician in 1674. The
Dietrichs E et al: Hypothalamocerebellar and cerebellohypothalamic projec-
relation of the condition to lesions in the neurohypophysis is at- tion circuits for regulating nonsomatic cerebellar activity? Histol
tributed to the German physiologist Alfred Frank. Histopathol 1994; 9:603–614.
Diabetes mellitus (Greek diabetes, “a syphon”; Latin melli- Hatton GL: Emerging concepts of structure-function dynamics in adult brain:
tus, “honey sweet”). A disorder of carbohydrate metabolism The hypothalamo-neurohypophyseal system. Prog Neurobiol 1990;
with high levels of glucose in blood and urine. Thomas Willis in 34:337–504.
1674 differentiated sweet urine (diabetes mellitus) from clear, in- Holstege G: Some anatomical observations on the projections from the hypo-
sipid urine (diabetes insipidus). thalamus to brain stem and spinal cord: An HRP and autoradiographic
Fornix (Latin “arch”). The fornix is an archlike cerebral struc- tracing study in the cat. J Comp Neurol 1987; 260:98–126.
ture that connects the hippocampal formation with the mamil- Hungs M, Mignot E: Hypocretin/orexin, sleep and narcolepsy. Bioessays 2001;
lary body. The fornix was noted by Galen and described by 23:397–408.
Andreas Vesalius, the sixteenth-century Belgian anatomist. Karama S et al: Areas of brain activation in males and females during viewing
Thomas Willis introduced the name fornix cerebri. of erotic film excerpts. Hum Brain Mapping 2002; 16:1–13.
Hypocretin. A hypothalamic neuropeptide discovered in 1998. Kordon C: Neural mechanisms involved in pituitary control. Neurochem Int
1985; 7:917–925.
Like orexin, it increases food intake. The name hypocretin de-
rives from its hypothalamic origin and its similarity to the gut Meister B, Hakansson ML: Leptin receptors in hypothalamus and circumven-
tricular organ. Clin Expt Pharmac Physiol 2001; 28:610–617.
hormone secretin.
Nauta WJH, Haymaker W: Hypothalamic nuclei and fiber connections. In
Hypophysis (Greek hypo, “under”; phyein, “to grow”). Haymaker W et al (eds): The Hypothalamus. Springfield, IL, Charles C
Anything growing under or beneath. The hypophysis (pituitary Thomas, 1969:136.
gland) is under the brain. Nishino S: The hypocretin/orexin system in health and disease. Biol Psychiatry
Infundibulum (Latin “funnel”). Andreas Vesalius, the Belgian 2003; 54:87–95.
anatomist, used this term to describe the attachment of the pitu- Pickard GE, Silverman AJ: Direct retinal projections to the hypothalamus, pir-
itary gland to the brain. iform cortex, and accessory optic nuclei in the golden hamster as
Orexin (Greek, orexis, “appetite”). A hypothalamic neuropep- demonstrated by a sensitive anterograde horseradish peroxidase tech-
tide discovered in 1998. Central administration of orexin po- nique. J Comp Neurol 1981; 196:155–172.
tently increases food intake. Rafols JA et al: A Golgi study of the monkey paraventricular nucleus:
Neuronal types, afferent and efferent fibers. J Comp Neurol 1987;
Pituitary (Latin pituita, “phlegm or mucus”). Pituitary gland. 257:595–613.
Jacob Berengarius, the Italian anatomist and surgeon, noted the
Remple-Clower NL, Barbas H: Topographic organization of connections be-
presence of the pituitary gland in 1524. Andreas Vesalius, the tween the hypothalamus and prefrontal cortex in the rhesus monkey.
Belgian anatomist, called it “glandula pituitam cerebri excipiens” J Comp Neurol 1998; 398:393–419.
and thought that the gland secreted mucus into the nose, an Saper CB et al: Direct hypothalamo-autonomic connections. Brain Res 1976:
opinion held until the seventeenth century. 117:305–312.
Poikilothermia (Greek poikilos, “varied”; therme, “heat”). Swaab DF et al: Structural and functional sex differences in the human hypo-
Variation of body temperature with environmental temperature. thalamus. Horm Behav 2001; 40:93–98.
Polydipsia (Greek polys, “many”; dipsa, “thirst”). Chronic ex- Swanson LW: The neuroanatomy revolution of the 1970s and the hypothala-
cessive thirst as in diabetes insipidus and mellitus. mus. Brain Res Bull 1999; 50:397.
ch20_6082_Afifi_MGH 12/13/04 12:05 PM Page 276
Hypothalamus: Clinical Correlates 20
Disorders of Water Balance Fröhlich Syndrome (Babinski-Fröhlich Syndrome,

Diabetes Insipidus Dystrophia-Adiposogenitalis)
Syndrome of Inappropriate Secretion of ADH (SIADH) Disorders of Emotional Behavior
Disorders of Thermoregulation Disorders of Sleep
Hypothermia Kleine-Levin Syndrome
Hyperthermia Disorders of Memory
Poikilothermia
Disorders of Caloric Balance
Diencephalic Syndrome of Infancy (Russell Syndrome,
Batten-Russell-Collier Disease)
KEY CONCEPTS
A number of clinical signs and symptoms have been asso- are related to posterior hypothalamic pathology, whereas
ciated with lesions of the hypothalamus. They are related sustained hyperthermia is related to pathology in the
to disorders of water balance, temperature regulation, anterior hypothalamus.
caloric balance, alertness and sleep, memory, and emo-
Disturbances in hypothalamic caloric balance are associ-
tional behavior.
ated with two syndromes: emaciation (diencephalic syn-
Two syndromes are related to disorders of water balance: drome) and obesity (Fröhlich syndrome). The former is
diabetes insipidus and the syndrome of inappropriate related to pathology in the anterior hypothalamus or
antidiuretic hormone (ADH) secretion (SIADH). The lesion its connections; the latter is related to pathology in the
in the former is in the supraoptic and paraventricular nu- ventromedial nucleus.
clei or the supraopticohypophyseal tract. The lesion in
Disturbances in sleep are associated with hypersomno-
SIADH involves hypothalamic osmoreceptors in the region
lence (posterior hypothalamus), insomnia (anterior hypo-
of the supraoptic and paraventricular nuclei.
thalamus), and the Kleine-Levin syndrome.
Disturbances in hypothalamic thermoregulation may re-
Disturbances in episodic memory are associated with
sult in hypothermia, hyperthermia, or poikilothermia re-
lesions in the mamillary body or fornix.
lated to pathology in different regions of the hypothala-
mus. In general, chronic hypothermia and poikilothermia
276
HYPOTHALAMUS: CLINICAL CORRELATES / 277
A large number of clinical signs and symptoms have been tromedial hypothalamus. A reverse Shapiro syndrome has been
reported in association with hypothalamic dysfunction. described, characterized by periodic hyperthermia and agenesis
They include disturbances in (1) water balance, (2) ther- of the corpus callosum.
moregulation, (3) caloric balance, (4) emotional behavior, (5) sleep,
and (6) memory. Poikilothermia
Fluctuations in body temperature with changes in environmental
DISORDERS OF WATER BALANCE temperature are associated with bilateral posterior hypothalamic
lesions.
Diabetes Insipidus
Diabetes insipidus results from lesions that destroy the
majority of neurons of the supraoptic and paraventricu- DISORDERS OF CALORIC BALANCE
lar nuclei (sites of ADH secretion) or that interrupt the
supraoptic-neurohypophyseal tract. Affected patients pass large Diencephalic Syndrome of Infancy (Russell
volumes of dilute urine (polyuria). Because the thirst mechanism Syndrome, Batten-Russell-Collier Disease)
is intact, patients drink large amounts of fluid (polydipsia). Such
patients drink over 10 liters of water per day and excrete a simi- This condition is characterized by progressive emaciation during
lar amount of urine. In contrast to diabetes mellitus, values for the first year of life despite a reasonable food intake.
glucose in blood and urine are normal in diabetes insipidus. The Despite their emaciation, such children are characteristi-
two types of diabetes were differentiated by Thomas Willis in cally happy and active. Other associated clinical signs
1674. The relation of diabetes insipidus to the neurohypophysis include poor temperature regulation, vomiting, and nys-
was recognized by the German physiologist Alfred Frank. tagmus. Growth hormone may be normal or elevated. The etiol-
Diabetes insipidus can be caused by a variety of disease processes, ogy of this syndrome is usually a slowly growing tumor of the an-
including hypothalamic tumors, trauma, storage diseases, and terior hypothalamus. Other lesions interrupting projections
infection. A familial variety of diabetes insipidus may be due to a from or to the anterior hypothalamus can produce the syn-
defect in the neurophysin gene precluding normal production of drome. The syndrome was best described by A. Russell in 1951.
ADH. Treatment of diabetes insipidus consists of intranasal ad-
ministration of a long-acting vasopressin analogue, desmopressin Fröhlich Syndrome (Babinski-Fröhlich
acetate (des-amino-D-arginine vasopressin, DDAVP). Syndrome, Dystrophia-Adiposogenitalis)
Fröhlich syndrome is characterized by obesity, genital hypopla-
Syndrome of Inappropriate Secretion sia, and stunted growth as a result of hypothalamic or pituitary
of ADH (SIADH) lesion. Obesity in this syndrome is attributed to damage to the
This syndrome is due to lesions in the region of the supraoptic ventromedial nucleus of the hypothalamus (satiety center) and
and paraventricular nuclei that impair hypothalamic osmorecep- hypogonadism to the involvement of the adjacent infundibu-
tors and that result in elevated ADH release. The syndrome lum. Although the syndrome is attributed to a report by Fröhlich
is characterized by (1) hyponatremia, (2) low serum osmolarity, in 1901, the main features of the syndrome had been described
(3) normal renal excretion of sodium, (4) elevated urine osmo- in 1900 by Babinski and in 1840 by the German physician
larity, and (5) absence of volume depletion. Berhard Mohr.
DISORDERS OF EMOTIONAL BEHAVIOR

DISORDERS OF THERMOREGULATION
Lesions in the ventromedial region of the hypothalamus have
Hypothermia been associated with rage, whereas lesions in the posterior hypo-
Hypothermia of hypothalamic origin may be chronic or periodic thalamus have been associated with fear and apathy. Stimulation
(episodic). Chronic hypothermia is associated with pos- of the lateral regions of the anterior hypothalamus elicits a flight
terior hypothalamic injury from trauma, tumor, infec- response. Pleasurable as well as unpleasant responses have been
tion, or metabolic or vascular disease. Episodic hy- elicited from hypothalamic stimulation. The reciprocal connec-
pothermia (Shapiro syndrome, diencephalic epilepsy) is tions between the limbic prefrontal cortex and the hypothalamus
characterized by spontaneous episodic hypothermia lasting min- are an important link for autonomic response to emotion.
utes to days occurring at variable intervals (daily or decades).
The hypothermia is usually associated with polydipsia, polyuria, DISORDERS OF SLEEP
hyponatremia, and autonomic paroxysms characterized by hy-
Sleep disturbances associated with hypothalamic lesions were at-
pertension, tachycardia, and diaphoresis. The condition may re-
tributed previously to concomitant involvement of the ascend-
spond to antiepileptic drug therapy. The lesion in the hypothala-
ing reticular pathways. Accumulating evidence, however, points
mus may involve the arcuate nucleus and the premamillary area.
to the existence of a waking center in the posterior hypothala-
Agenesis of the corpus callosum is often present.
mus and a sleep center in the anterior hypothalamus. Lesions of
Hyperthermia the posterior hypothalamus provoke lethargy and hyper-
somnia, whereas lesions in the anterior hypothalamus
Hyperthermia of hypothalamic origin may be sustained or cause insomnia. The lateral hypothalamus contains a ma-
episodic (periodic). Sustained hyperthermia usually is associated jor excitatory neuromodulatory system (orexin/hypocretin) which
with head trauma or with surgery adjacent to the anterior hypo- controls activities of monoaminergic and cholinergic systems that
thalamus. It usually lasts 1 to 2 days but may last up to 2 weeks. control vigilance. Lesions in the orexin/hypocretin system are asso-
Episodic hyperthermia has been associated with lesions in the ven- ciated with a state of irresistible sleep known as narcolepsy.
278 / CHAPTER 20
Table 20–1. Hypothalamic Disorders
Hypothalamic function Hypothalamic disorder Site of pathology
Water balance Diabetes insipidus Supraoptic and paraventricular nuclei

Syndrome of inappropriate secretion Supraoptic and paraventricular nuclei
of antidiuretic hormone or neighborhood
Thermoregulation Hypothermia
Chronic Posterior hypothalamus
Episodic Arcuate nucleus, premamillary area
Hyperthermia
Sustained Anterior hypothalamus
Episodic Ventromedial hypothalamus
Poikilothermia Posterior hypothalamus
Caloric balance Diencephalic syndrome of infancy Anterior hypothalamus
Fröhlich syndrome Ventromedial nucleus, infundibulum
Emotional behavior Rage Ventromedial nucleus
Fear, apathy Posterior hypothalamus
Sleep Hypersomnolence Posterior hypothalamus
Insomnia Anterior hypothalamus
Memory Loss of episodic memory Mamillary bodies, fornix
Kleine-Levin Syndrome diuretic hormone. The condition was distinguished from dia-
betes mellitus by Thomas Willis, the English physician in 1674.
Hypothalamic lesions have been associated with Kleine-Levin The relation of the condition to lesions in the neurohypophysis
syndrome which is characterized by episodic compulsive eating is attributed to the German physiologist Alfred Frank.
(bulimia), hypersomnolence, and hypersexuality in adolescent
Fröhlich syndrome. A hypothalamic syndrome characterized
males and, rarely, in females. A similar syndrome occurs with le-
by obesity, genital hypoplasia, and stunted growth. Named after
sions in the medial thalamus. Each episode lasts days to weeks at
Alfred Fröhlich (1871–1953), the Viennese neurologist and phar-
intervals of 3 to 6 months between episodes. The episodes de-
macologist. Also known as Babinski-Fröhlich syndrome.
crease in frequency with age and usually disappear by the fourth
decade. Some evidence indicates that the dopaminergic tone of Kleine-Levin syndrome. A hypothalamic syndrome occurring
the hypothalamus is reduced during the symptomatic phase of in adolescent males and, less frequently, in females, characterized
the syndrome. Although credit is given to the German neuropsy- by episodic hypersomnolence, hypersexuality, and compulsive
chiatrist Kleine and the American neurologist Levin for describ- eating. The syndrome was described by Willi Kleine, the German
ing the syndrome in 1925 and 1929, a similar syndrome of neuropsychiatrist, in 1925. Max Levin, the American neurolo-
episodic hypersomnolence and morbid hunger was described by gist, reported another case in 1929 and summarized the features
Antimoff in 1898. of the syndrome in 1936.
Poikilothermia (Greek poikilos, “varied”; therme, “heat”).
DISORDERS OF MEMORY Variation of body temperature with environmental temperature.
Polydipsia (Greek polys, “many”; dipsa, “thirst”). Chronic
Hypothalamic lesions in the posterior hypothalamus involving excessive thirst as in diabetes insipidus and mellitus.
the mamillary bodies or the fornix are associated with inability to Polyuria (Greek polys, “many”; ouron, “urine”). The passage
establish (encode) new memories for personally experi- of a very large volume of urine, characteristic of diabetes.
enced, context- and time-specific events (episodic mem- Shapiro syndrome. A hypothalamic syndrome characterized
ory) such as the memory of eating a specific dish at a by recurrent hypothermia and agenesis of the corpus callosum.
specific restaurant. The connections of the mamillary bodies Named after W.R. Shapiro, who described the syndrome in
with the hippocampus (via the fornix) and with the anterior 1969.
thalamic nucleus (via the mamillothalamic tract) make them
crucial to the process of acquisition of recent memory.
The different hypothalamic disorders discussed herein and
corresponding sites of hypothalamic pathology are summarized
SUGGESTED READINGS
in Table 20–1. Arroyo HA et al: A syndrome of hyperhidrosis, hypothermia, and bradycardia
possibly due to central monoaminergic dysfunction. Neurology 1990;
40:556–557.
TERMINOLOGY Bartter FC, Schwartz WB: The syndrome of inappropriate secretion of anti-
diuretic hormone. Am J Med 1967; 42:790–806.
Bulimia (Greek bous, “ox”; limos, “hunger”). A disorder of
Bauer HG: Endocrine and other clinical manifestations of hypothalamic dis-
eating occurring predominantly in adolescent females, character- ease. J Clin Endocrinol Metab 1954; 14:13–31.
ized by morbid hunger and binge eating that continue until ter- Burr IM et al: Diencephalic syndrome revisited. J Pediatr 1976; 88:439–444.
minated by abdominal pain, vomiting, or sleep.
Chesson AL et al: Neuroendocrine evaluation in Kleine-Levin syndrome:
Diabetes insipidus (Greek diabetes, “a syphon”). A condition Evidence of reduced dopaminergic tone during periods of hypersomno-
of excessive production of urine from deficiency of the anti- lence. Sleep 1991; 14:226–232.
HYPOTHALAMUS: CLINICAL CORRELATES / 279
Culebras A: Neuroanatomic and neurologic correlates of sleep disturbances. LeWitt PA et al: Episodic hyperhidrosis, hypothermia, and agenesis of the cor-
Neurology 1992; 42(suppl 6):19–27. pus callosum. Neurology 1983; 33:1122–1129.
Gaffan EA et al: Amnesia following damage to the left fornix and to other Maghnie M et al: Correlation between magnetic resonance imaging of poste-
sites. Brain 1991; 114:1297–1313. rior pituitary and neurohypophyseal function in children with diabetes
Gamstorp I et al: Diencephalic syndrome of infancy. J Pediatr 1967; 70:383– insipidus. J Clin Endocrinol Metab 1992; 74:795–800.
390. Perry RJ, Hodges JR: Spectrum of memory dysfunction in degenerative
Gillberg C: Kleine-Levin syndrome: Unrecognized diagnosis in adolescent disease. Curr Opin Neurol 1996; 9:281–285.
psychiatry. J Am Acad Child Adolesc Psychiatry 1987; 26:793–794. Reeves AG, Plum F: Hyperphagia, rage, and dementia accompanying a
Harris AS: Clinical experience with desmopressin: Efficacy and safety in central ventromedial hypothalamic neoplasm. Arch Neurol 1969; 20:616–624.
diabetes insipidus and other conditions. J Pediatr 1989; 114:711–718. Russell A: A diencephalic syndrome of emaciation in infancy and childhood.
Hirayama K et al: Reverse Shapiro’s syndrome. A case of agenesis of corpus Arch Dis Child 1951; 26:274.
callosum associated with periodic hyperthermia. Arch Neurol 1994; Shapiro WR et al: Spontaneous recurrent hypothermia accompanying agenesis
51:494–496. of the corpus callosum. Brain 1969; 92:423–436.
Limbic System 21
Definition of Terms: Limbic Lobe, Limbic System, The Papez Circuit

and Rhinencephalon Limbic System
Rhinencephalon (Smell Brain) Hippocampal Formation
Olfactory Nerve Rootlets Fornix
Olfactory Bulb Entorhinal-Hippocampal Circuitry
Olfactory Tract Amygdala
Olfactory Striae Septal Area
Olfactory Cortex Overview of the Limbic System
Limbic Lobe
KEY CONCEPTS
The term limbic lobe refers to the structures that form a and the ventral amygdalofugal pathway (ventrofugal
limbus (ring or border) around the brain stem. These bundle).
structures include the subcallosal gyrus, cingulate gyrus,
The amygdala plays an important role in a variety of
isthmus, parahippocampal gyrus, and uncus.
functions, including autonomic and orienting responses,
The term limbic system refers to the limbic lobe and the emotional behavior, food intake, arousal, sexual activity,
structures connected to it. and motor activity.
Limbic system structures play important roles in emo- The term septal area refers to the septum pellucidum
tional behavior, memory, homeostatic responses, sexual and the septum verum. The septum pellucidum is a thin
behavior, and motivation. glial partition between the lateral ventricles; the septum
verum is a group of basal nuclei that includes the septal
The term hippocampal formation refers to the hippo-
nuclei.
campus, dentate gyrus, and subiculum.
Reciprocal connections with the hippocampus (via the
The bulk of extrinsic input to the hippocampal formation
fornix) constitute the major connection of the septal
comes from the entorhinal area and the septal area.
area. Other connections include those with the amyg-
The major targets of the hippocampal formation’s output dala, hypothalamus, thalamus, brain stem, and cingulate
are the entorhinal cortex, the hypothalamus, and the sep- gyrus.
tal area.
The septal area plays an important role in emotional be-
The entorhinal area is reciprocally connected with the havior, learning, reward, autonomic responses, drinking
hippocampus and serves as a gateway between the cere- and feeding, and sexual behavior.
bral cortex and the hippocampus.
The limbic system plays a major role in integrating extero-
The hippocampus plays a role in declarative or associa- ceptive and interoceptive information by serving as a link
tive memory, attention and alertness, and behavioral, en- between cortical sensory association areas, the subcorti-
docrine, and visceral functions. cal autonomic and endocrine centers, and the prefrontal
association cortex. It thus mediates the effects of emotion
Output from the amygdala is carried in two pathways:
on motor function.
the stria terminalis (dorsal amygdalofugal pathway)
280
LIMBIC SYSTEM / 281
DEFINITION OF TERMS: LIMBIC LOBE, RHINENCEPHALON (SMELL BRAIN)

LIMBIC SYSTEM, AND RHINENCEPHALON The rhinencephalon (Figures 21–1 and 21–2) consists of the fol-
The concept of the limbic system is derived from the limbic lowing structures:
lobe. The term le grande lobe limbique (limbic lobe), coined by 1. Olfactory nerve rootlets
the French anthropologist, anatomist, and surgeon Pierre-Paul 2. Olfactory bulb
Broca in 1878, refers to a number of structures on the medial
and basal surfaces of the hemisphere that form a limbus (bor- 3. Olfactory tract
der or ring) around the brain stem. Broca was possibly unaware 4. Olfactory striae
that Thomas Willis (of Circle of Willis fame) had designated 5. Primary olfactory cortex
the cortical border encircling the brain stem as the cerebri lim-
bus in 1664, 200 years earlier. The limbic lobe and all the Olfactory Nerve Rootlets
structures connected to it constitute the limbic system, which
plays a major role in visceral function, emotional behavior, and The olfactory nerve is composed of unmyelinated thin processes
memory. (rootlets) of the olfactory hair cells (receptors) in the nasal mu-
Because of the large size of the limbic lobe in phylogenetically cosa. Fascicles of the olfactory nerve pierce the cribriform plate
lower animals, Broca postulated that it might have an olfactory of the ethmoid bone, enter the cranial cavity, and terminate on
function; hence, the terms limbic lobe and smell brain (rhinen- neurons in the olfactory bulb.
cephalon) were used synonymously. In humans, the limbic lobe
has very little if any primary olfactory function. The rhinen- Olfactory Bulb
cephalon, by contrast, is primarily concerned with olfaction but
has some reciprocal relationships with parts of other limbic sys- The olfactory bulb is the main relay station in the olfactory
tem regions. pathways.
Olfactory Groove
Olfactory Bulb Gyrus Rectus
Olfactory Tract
Orbital Gyri
Olfactory Stria: Optic Nerve

lateral
Optic Chiasma
Optic Tract
Olfactory Stria:
medial Oculomotor
Nerve
Anterior
Perforate Infundibulum
Substance Tuber Cinereum (Pituitary Stalk)
Figure 21–1. Ventral view of the brain showing components of the rhinencephalon.
282 / CHAPTER 21
Olfactory 4. Diagonal band of Broca

receptors 5. Anterior olfactory nucleus
The output from the olfactory bulb is composed of axons of
Olfactory Anterior mitral cells and tufted cells (principal neurons), which project to
nerves commissure the following areas:
1. Contralateral olfactory bulb
Olfactory 2. Subcallosal gyrus
bulb 3. Anterior perforated substance
4. Primary olfactory cortex
Olfactory
5. Anterior entorhinal cortex
tract
Olfactory Tract
The olfactory tract is the outflow pathway of the olfactory bulb.
Olfactory striae
Lateral It is composed of the axons of principal neurons (mitral and
Intermediate tufted cells) of the olfactory bulb and centrifugal axons originat-
Medial ing from central brain regions. The olfactory tract also contains
the scattered neurons of the anterior olfactory nucleus, the axons
of which travel in the olfactory tract, cross in the anterior com-
missure, and project on the contralateral anterior olfactory nu-
cleus and the olfactory bulb. At its caudal extremity, just anterior
to the anterior perforated substance, the olfactory tract divides
into the olfactory striae.
Primary Anterior Subcallosal
olfactory perforated gyrus Olfactory Striae
cortex substance
Figure 21–2. Schematic diagram of olfactory pathways. At its caudal extremity, just rostral to the anterior perforated sub-
stance, the olfactory tract divides into three striae:
1. Lateral olfactory stria
2. Medial olfactory stria
A. LAMINATION AND CELL TYPES
3. Intermediate olfactory stria.
In histologic sections (Figure 21–3), the olfactory bulb appears
to be laminated into the following layers: Each stria is covered by a thin layer of gray matter known as
an olfactory gyrus.
1. The olfactory nerve layer is composed of incoming olfactory
nerve fibers.
2. In the glomerular layer synaptic formations occur between
the olfactory nerve axons and the dendrites of olfactory bulb Olfactory nerve
neurons (mitral and tufted neurons). rootlets
3. The external plexiform layer consists of tufted neurons, some
granule cells, and a few mitral cells with their processes. Olfactory nerve
4. The mitral cell layer is composed of large neurons (mitral layer
neurons).
5. The granule layer is composed of small granule neurons and Glomerulus Glomerular layer
processes of granule and mitral cells; it also contains incom-
ing fibers from other cortical regions.
Tufted neuron Plexiform layer
The mitral cells and tufted cells are the principal neurons of
the olfactory bulb. Their dendrites establish synaptic relationships
with olfactory nerve fibers within the glomeruli. Mitral neuron
The granule cells are the intrinsic neurons of the olfactory Mitral cell layer
bulb. These cells have vertically oriented dendrites but no axon
and exert their action on other cells solely by means of dendrites.
Another type of intrinsic neuron, the short axon neuron, is found Granule neuron Granule layer
in the glomerular layer (periglomerular short axon neuron) and
the granular layer.
Short axon neuron
The olfactory bulb receives fibers (input) from the following
sources: Axons of mitral
1. Olfactory hair cells in the nasal mucosa and tufted neurons
2. Contralateral olfactory bulb Figure 21–3. Schematic diagram of olfactory bulb showing
3. Primary olfactory cortex laminae and types of cells.
LIMBIC SYSTEM / 283
The lateral olfactory stria projects to the primary olfactory LIMBIC LOBE
cortex in the temporal lobe. The medial olfactory stria projects
on the medial olfactory area, which also is known as the septal As described by Broca in 1878, the limbic lobe refers
area, on the medial surface of the frontal lobe, ventral to the to the gray matter in the medial and basal parts of the
genu and rostrum of the corpus callosum and anterior to the hemisphere that forms a limbus (border) around the
lamina terminalis. The medial olfactory area is closely related to brain stem. The limbic lobe is a synthetic lobe whose component
the limbic system and thus is concerned with emotional re- parts are derived from different lobes of the brain (frontal, pari-
sponses elicited by olfactory stimuli. It does not play a role in etal, temporal). There is no general agreement on all the parts
the perception of olfactory stimuli. The medial and intermedi- that enter into the formation of the limbic lobe. The following,
ate striae are poorly developed in humans. The intermediate however, are generally accepted as limbic lobe components
stria blends with the anterior perforated substance. The thin (Figure 21-4):
cortex at this site is designated the intermediate olfactory area. 1. Subcallosal gyrus, inferior to the genu and rostrum of the
The three areas of olfactory cortex are interconnected by the corpus callosum, just anterior to the lamina terminalis
diagonal band of Broca, a bundle of subcortical fibers in front of
the optic tract. 2. Cingulate gyrus
3. Isthmus of the cingulate gyrus, posterior and inferior to the
Olfactory Cortex splenium of the corpus callosum
4. Parahippocampal gyrus (and the underlying hippocampal
The olfactory cortex is located within the temporal lobe and is formation and dentate gyrus)
composed of the pyriform cortex, the periamygdaloid area, and 5. Uncus
part of the entorhinal area. The pyriform cortex is the region on
each side of and beneath the lateral olfactory stria; hence, it is The limbic lobe is formed of archicortex (hippocampal for-
also called the lateral olfactory gyrus. The periamygdaloid area mation and dentate gyrus), paleocortex (rostral parahippocam-
is dorsal and rostral to the amygdaloid nuclear complex. The pal gyrus and uncus), and juxtallocortex or mesocortex (cingu-
pyriform cortex and the periamygdaloid area constitute the pri- late gyrus).
mary olfactory cortex. The entorhinal area, which is situated Originally, the limbic lobe was assigned a purely olfactory
in the rostral part of the parahippocampal gyrus, corresponds to function. It has been established that only a minor part of the
Brodmann’s area 28. It constitutes the secondary olfactory cor- limbic lobe has an olfactory function. The rest of the limbic lobe,
tex. The olfactory cortex is relatively large in some animals, such which forms part of the limbic system, plays a role in emotional
as the rabbit, but in humans it occupies a small area. The pri- behavior and memory.
mary olfactory cortex in humans is concerned with the conscious
perception of olfactory stimuli. In contrast to all other primary THE PAPEZ CIRCUIT
sensory cortices (vision, audition, taste, and somatic sensibility),
the primary olfactory cortex is unique in that afferent fibers from In 1937, James Papez, an American neuroanatomist, described a
the receptors reach it directly without passing through a relay closed circuit of connections starting and ending in the hippo-
in the thalamus. campus that later became known as the Papez circuit. It was
The primary olfactory cortex contains two types of neurons: suggested that the structures connected by this circuit play a
(1) principal neurons (pyramidal cells) with axons which leave role in emotional reactions. The circuit consisted of outflow of
the olfactory cortex and project to nearby or distant regions and impulses from the hippocampus via the fornix to the mamillary
(2) intrinsic neurons (stellate cells) with axons which remain bodies of the hypothalamus; from there, via the mamillotha-
within the olfactory cortex. lamic tract, to the anterior thalamic nucleus; and, via the
The major input to the primary olfactory cortex is from (1) the thalamocortical fiber system, to the cingulate gyrus, from which
olfactory bulb via the lateral olfactory stria and (2) other central impulses returned to the hippocampus via the entorhinal area.
brain regions. The circuit which has been modified since its introduction, pro-
The output from the primary olfactory cortex is via axons of vided the basis for the concept of the limbic system introduced
principal neurons which project to (1) the secondary olfactory by McLean in 1952.
cortex in the entorhinal area, (2) the amygdaloid nucleus, and
(3) the dorsomedial nucleus of the thalamus. LIMBIC SYSTEM
The output of the secondary olfactory cortex, the entorhinal
area, is to the (1) hippocampal formation and (2) the anterior in- The limbic system is defined as the limbic lobe and all
sular and frontal cortices. the cortical and subcortical structures related to it. These
The connections of the olfactory cortex with the thalamus, include the following structures:
the amygdaloid nucleus, the hippocampal formation, and the in- 1. Septal nuclei
sular and frontal cortices provide the anatomic basis for a role of
olfaction in emotional behavior, visceral function, and memory. 2. Amygdala
Quantitative studies of the primary olfactory cortex have re- 3. Hypothalamus (particularly the mamillary body)
vealed that (1) there is a predominance of principal neurons 4. Thalamus (particularly the anterior and medial tha-lamic
(compared with the intrinsic variety) and (2) the number of nuclei)
principal neurons far exceeds the number of fibers in the lateral 5. Brain stem reticular formation
olfactory stria. Thus, in contrast to the olfactory bulb, in which 6. Epithalamus
there is a high convergence ratio, the ratio of input to output in
the primary olfactory cortex is low. This is similar to the pattern 7. Neocortical areas in the basal frontotemporal region
in the neocortex and the climbing fiber system of the cerebellar 8. Olfactory cortex
cortex. 9. Ventral parts of the striatum
284 / CHAPTER 21
Cingulate Cingulate
Gyrus Sulcus
ALLOSUM
PUS C
COR
Isthmus
Subcallosal
Gyrus
Parahippocampal
Gyrus
Uncus
Figure 21–4. Midsagittal view of brain showing components of the limbic lobe.
This conglomerate of neural structures, which con- tata), and subiculum. The dentate gyrus occupies the interval be-
stitute the old part of the brain and are highly intercon- tween the hippocampus and subiculum part of the parahip-
nected, seems to play a role in the following processes: pocampal gyrus. The dentate gyrus and subiculum are separated
by the hippocampal sulcus (Fig. 21–7). The name dentate gyrus
1. Emotional behavior
is derived from its toothed or beaded surface. The subiculum is
2. Memory the part of the parahippocampal gyrus that is in direct continu-
3. Integration of homeostatic responses such as those related to ity with the hippocampus.
preservation of the species, securing food, and the fight or Of the three components of the hippocampal formation, the
flight response. hippocampus is the largest and the best studied in humans.
4. Sexual behavior Therefore, it is presented in this chapter as the prototype of this
5. Motivation segment of the limbic system.
The underlying mechanisms for these different functions are Hippocampus
very complex and are inadequately understood. Furthermore, it
has become difficult to define the extent of the limbic system The hippocampus appears as a C-shaped structure in coronal
with precision and to attribute common connections and func- sections, bulging into the inferior horn of the lateral ventricle.
tions to its individual components. Some researchers have advo- The hippocampus is closely associated with the adjacent dentate
cated the theory that the limbic system is not useful as a scientific gyrus (Figures 21–5 to 21–7), and together they form an S-shaped
or clinical concept. structure.
The presentation of the limbic system in this chapter focuses
on the following components: hippocampal formation, amyg- A. HIPPOCAMPAL TERMINOLOGY
dala, and septal area. These are the regions that are most closely
related to the limbic lobe. In the late 1500s, the anato-mist Arantius exposed a convoluted
structure in the floor of the temporal horn of the lateral ventri-
HIPPOCAMPAL FORMATION cle. He called this structure the hippocampus because of its
resemblance to a sea horse. A century later the term pes hippo-
The hippocampal formation (Figures 21–5 and 21–6) is an in- campus was used to describe the same structure, and two cen-
folding of the parahippocampal gyrus into the inferior turies later anatomists likened the structure to a ram’s horn or the
(temporal) horn of the lateral ventricle and consists of horns of the ancient Egyptian deity Ammon, who had a ram’s
three regions: hippocampus, dentate gyrus (fascia den- head, hence the name Ammon’s horn or cornu Ammonis. Ter-
LIMBIC SYSTEM / 285
Lateral Medial
Geniculate Geniculate Posterior
Body Body Pulvinar Commissure Fimbria Alveus
Hippocampus
Midbrain
Dentate
Gyrus
Basis
Pontis
Parahippocampal Gyrus
(Subiculum) Parahippocampal Gyrus
(Entorhinal Cortex)
Figure 21–5. Coronal section of the brain showing the hippocampus and dentate gyrus (components of the hippocampal for-
mation), the alveus, and fimbria. Adjacent to the hippocampal formation are the subiculum and entorhinal cortex (components of
the parahippocampal gyrus).
minology over the years became abundant and often confusing. ary between the compact and less compact zones of the pyrami-
Table 21–1 lists the preferred terminology and synonyms used dal layer separates the two divisions of the hippocampus (Figure
for hippocampal structures. 21–7) into the superior division (compact zone) and the inferior
division (less compact zone).
B. LAMINATION AND DIVISIONS The hippocampus has been subdivided further into fields
Although Ramón y Cajal described seven laminae in the hip- (Figure 21–7) designated as cornu Ammonis 1, 2, 3, and 4 (CA1
pocampus, it is customary to combine the different laminae into through CA4). CA1, the largest hippocampal field in humans, is
three major layers (Figure 21–7): the molecular layer, the pyra- located in the superior division at the interface between the hip-
midal cell layer, and the stratum oriens (polymorphic layer). pocampus and the subiculum. CA2 and CA3 are in the inferior
The pyramidal cell layer is divided into a zone in which the division within the hippocampus. CA4 constitutes the transi-
pyramidal cells are compact and a zone (rostral to the compact tion zone between the hippocampus and the dentate gyrus.
zone) in which the pyramidal cells are less compact. The bound- Field CA1 (also known as Sommer’s sector and the vulnerable
sector) is of interest to neuropathologists because its pyramidal
neurons are highly sensitive to anoxia and ischemia and because
it is the trigger zone for some forms of temporal lobe epilepsy.
Hippocampus CA2 and CA3 have been referred to as resistant sectors because
they are less sensitive to anoxia. CA4 (the Bratz sector) is also
called the medium vulnerability sector because of its medium
sensitivity to hypoxia.
C. NEURONAL POPULATION
Dentate
gyrus There are basically two types of neurons in the hippocampus: the
principal neurons (pyramidal cell) and the intrinsic neurons (poly-
morphic cell, basket cell) (Figure 21–8).
1. Principal Neurons. The pyramidal neurons in the pyramidal
cell layer are the principal neurons of the hippocampus. They are
Subiculum
the only neurons with axons which contribute to the outflow
tract from the hippocampus. Pyramidal neurons vary in size and
Figure 21–6. Schematic diagram showing the components of density in different regions of the hippocampus. They are
the hippocampal formation. smaller and more densely packed in the superior region than in
286 / CHAPTER 21
HIPPOCAMPUS Lateral ventricle
Stratum
oriens CA 3
CA
Inferior
Pyramidal CA 2
CA
layer Hippocampal
regions
Molecular C
CAA4 Superior
layer
CA 1
CA
DENTATE
GYRUS
Hippocampal
sulcus
SUBICULUM Figure 21–7. Schematic diagram

showing layers of the hippocam-
pus and the division of the hippo-
PARAHIPPOCAMPAL GYRUS campus into superior and inferior
(Entorhinal cortex) regions, and four fields (CA1 to CA4).
the inferior region. The largest neurons in the inferior region are It is estimated that the hippocampus of humans contains 1.2
referred to as the giant pyramidal cells of the hippocampus. million principal neurons on each side, a figure close to the num-
Basal dendrites of pyramidal neurons are oriented toward the ber of pyramidal tract fibers.
ventricular surface; apical dendrites are oriented toward the mol- 2. Intrinsic Neurons. Intrinsic neurons have axons which re-
ecular layer. Both types of dendrites arborize extensively and are main within the hippocampus. Because of the irregularity of
rich in dendritic spines. their perikarya and dendrites, they are referred to as polymor-
Axons of pyramidal cells are directed toward the ventricular phic neurons. They are situated in the stratum oriens (Figure
surface, where they gather to form the alveus and fimbria and fi- 21–8). Their irregularly oriented dendrites arborize locally, while
nally join the fornix as the outflow tract from the hippocampus. their axons ramify between pyramidal neurons and arborize
Recurrent axon collaterals terminate within the stratum oriens or around the perikarya of pyramidal neurons in a basket formation
reach the molecular layer. They exert a facilitatory influence. (hence the term basket cells). They are inhibitory (GABAergic)
to pyramidal cell activity. There are no estimates of the exact
number of intrinsic neurons in the hippocampus. It has been es-
Table 21–1. Terminology of Hippocampal Structures. timated, however, that one basket cell is related to about 200 to
500 pyramidal cells. Thus, it is believed that the intrinsic neu-
Structure Preferred Synonyms rons are much fewer in number than are the principal neurons.
terminology
Hippocampus Hippocampus Hippocampal formation Dentate Gyrus

Ram’s horn
Ammon’s horn Like the hippocampus, the dentate gyrus is a three-layered struc-
Cornu ammonis ture composed of a molecular layer, a granular cell layer, and a
Pes hippocampus polymorphic layer. The molecular layer is continuous with that of
Pes hippocampus major the hippocampus. The granular layer is made up of small, densely
Cornu ammonis Cornu ammonis Ammon’s horn packed granular cells whose axons form the mossy fiber system
Hippocampus proper which links the dentate gyrus and the hippocampus. The cells in
Hippocampus the polymorphic layer are varied and include pyramidal and bas-
Cornu ammonis 1 CA1 Sommer’s sector ket cells. Unlike the hippocampus, the output of the dentate
Vulnerable sector gyrus does not leave the hippocampal formation.
Cornu ammonis 2 CA2
Cornu ammonis 3 CA3 Resistent sector
Spielmeyer sector Subiculum
Cornu ammonis 4 CA4 Hilus of fascia dentata
End folium Like the hippocampus and the dentate gyrus, the subiculum is
Bratz sector composed of three layers: a molecular layer, a pyramidal layer,
Dentate gyrus Dentate gyrus Gyrus dentatus and a polymorphic layer. The polymorphic layer originates in
Fascia dentata the adjoining entorhinal cortex. Axons of pyramidal neurons in
Commissure Hippocampal Psalterium the subiculum, like those in the hippocampus, contribute to the
of fornix commissure Lyre of David
output of the hippocampal formation.
LIMBIC SYSTEM / 287
Fornix Lateral ventricle modality sensory-specific, and multimodal association cortices)

in the frontal, temporal, parietal, and occipital lobes conveying
Alveus visual, auditory, and somatosensory information converges on
the entorhinal cortex and the posterior parahippocampal gyrus.
The entorhinal cortex in turn conveys this cortical information
to the hippocampus. Reciprocally, hippocampal output originat-
ing in CA1 and the subiculum is relayed back to the entorhinal
cortex. The entorhinal cortex is the most heavily damaged in
Alzheimer’s disease and is the site of early onset of the disease.
Principal Fibers from the septal nuclei reach the hippocampus via the
neuron Intrinsic fornix. Compared with the input from the entorhinal area, the
neuron septal input is modest.
Axons of small pyramidal neurons (granule cells) in the den-
tate gyrus reach the hippocampus via the mossy fiber pathway.
The two hippocampi are in communication via the hippocam-
pal commissure (commissure of the fornix). Interhippocampal
Figure 21–8. Schematic diagram showing the major types of communication in humans is minimal, and the hippocampal
neurons in the hippocampus and their interrelationships. commissure is thus rudimentary.
Fibers from the hypothalamus originate from cell groups in
the vicinity of the mamillary body and exert a strong inhibitory
influence on the hippocampus.
Afferent Pathways Amygdalohippocampal connections travel in the adjacent
temporal lobe white matter and may form the anatomic basis for
The bulk of extrinsic input to the hippocampal forma- the effect of emotion on memory function.
tion comes from the entorhinal area (Brodmann’s area Thalamic input to the hippocampus has been shown to orig-
28) of the parahippocampal gyrus and, to a lesser extent, inate in the anterior thalamic nucleus.
the septal area (Figure 21–9). Other inputs include those from Noradrenergic fibers from the locus ceruleus have been traced
the contralateral hippocampus, hypothalamus, amygdala, thalamus, to the hippocampus and the dentate gyrus.
locus ceruleus, raphe nuclei, and ventral tegmental area of Tsai. Serotonergic fibers from the raphe nuclei and dopaminergic
Fibers from the parahippocampal gyrus arise mainly from its fibers from the ventral tegmental area of Tsai in the midbrain
rostral part, the entorhinal area (Brodmann’s area 28). They con- also have been traced to the hippocampus.
stitute the major input to the hippocampus, dentate gyrus, and The noradrenergic, serotoninergic, and dopaminergic inputs
subiculum, which they reach by two routes. The main input, exert a modulatory effect on memory function in the hippocampus.
first described by Ramón y Cajal, travels through (perforates) the
adjacent subicular area en route to the hippocampus and dentate
gyrus and is therefore called the perforant path. A smaller input Efferent Pathways
arrives in the hippocampus at the ventricular surface, where the
The output from the hippocampal formation consists of axons
alveus (axons of hippocampal pyramidal neurons) is formed, and
of pyramidal neurons in the hippocampus and subicu-
is therefore called the alvear path. The entorhinal area serves as
lum (Figure 21–10). Axons of granule neurons in the
an important gateway between the cerebral cortex and the hip-
dentate gyrus have no extrinsic connections but termi-
pocampus. Information from many cortical areas (limbic,
nate locally as mossy fibers on hippocampal pyramidal neurons.
Both the hippocampus and the subiculum project on the en-
torhinal cortex. From there, impulses are mediated to limbic, sen-
LIMBIC,
sory-specific, and multimodal association cortical areas. Another
SENSORY SPECIFIC, and major output from the hippocampus is to the subiculum. Both
MULTIMODAL ASSOCIATION the hippocampus and the subiculum contribute fibers to the
CORTICES fornix, the output tract of the hippocampal formation.
Subiculum-originating fibers constitute the major component of
the fornix and are distributed, via its postcommissural division,
Septal area Entorhinal area to the mamillary bodies of the hypothalamus and the anterior
nucleus of the thalamus. Hippocampal originating fibers in the
fornix constitute its smaller precommissural division and are dis-
HIPPOCAMPAL
FORMATION
tributed to the septal nuclei, the medial area of the frontal cor-
tex, the anterior and preoptic hypothalamic nuclei, and the ven-
tral striatum.
Dentate gyrus Amygdala
FORNIX (FIGURE 21–11)

Thalamus Locus ceruleus
Hypothalamus Raphe nuclei The fornix is a fiber bundle that reciprocally connects the hip-
Ventral tegmental area pocampal formation with a number of subcortical areas, includ-
ing the thalamus, the hypothalamus, and the septal region. It
Figure 21–9. Schematic diagram showing the major afferents thus has both hippocampofugal and hippocampopetal fibers.
to the hippocampal formation. The hippocampofugal fibers are axons of pyramidal neurons in
288 / CHAPTER 21
HIPPOCAMPUS
ENTORHINAL AREA
SUBICULUM
LIMBIC,
FORNIX SENSORY SPECIFIC, and
MULTIMODAL ASSOCIATION
CORTICES
PRECOMMISSURAL POSTCOMMISSURAL
FORNIX FORNIX
MAMILLARY BODY
ANTERIOR NUCLEUS
SEPTAL NUCLEI OF THALAMUS
MEDIAL FRONTAL CORTEX
HYPOTHALAMUS
ANTERIOR AND PREOPTIC NUCLEI
showing the major efferents of the
VENTRAL STRIATUM hippocampus.
the subiculum and hippocampus which gather at the ventricular columns of the fornix, which arch ventrally. Most of the fibers
surface of the hippocampus as the alveus. Fibers in the alveus (75 percent) in each anterior column descend caudal to the ante-
converge farther on to form a flattened ribbon of white matter, rior commissure to form the postcommissural fornix. The ma-
the fimbria. Traced posteriorly on the floor of the inferior horn jority of fibers in this component of the fornix terminate in the
of the lateral ventricle, the fimbria, at the posterior limit of the mamillary body, and the rest terminate in the anterior nucleus of
hippocampus, arches under the splenium of the corpus callosum the thalamus and the midbrain tegmentum. A small component
to form the crus of the fornix. The two crura converge to form (25 percent) of each anterior column descends rostral to the an-
the body of the fornix, which is attached to the inferior surface terior commissure to form the precommissural fornix. Fibers in
of the septum pellucidum to the level of the rostral thalamus. As this component of the fornix terminate in the septal nuclei, me-
the crura converge to form the body, a small number of fibers dial frontal cortex, anterior hypothalamus, and ventral striatum.
cross to the other side (hippocampal commissure, fornical com- Fibers in the postcommissural fornix originate in the subiculum,
missure, lyra, psalterium). The hippocampal commissure is rudi- whereas those in the precommissural fornix originate in both the
mentary in humans. Just above the interventricular foramen of hippocampus and the subiculum.
Monro, the body of the fornix splits to form the two anterior Each fornix contains 1.2 million axons of pyramidal neurons
in humans.
ENTORHINAL-HIPPOCAMPAL CIRCUITRY
(FIGURE 21–12)
Using a variety of neuroanatomic and neurophysiologic tech-
niques, the entorhinal-hippocampal-entorhinal circuit of
connections has been defined. The circuit starts in the
entorhinal area, which projects via the perforant path-
way to granule cells in the dentate gyrus and pyramidal cells in
the hippocampus. Axons of granule cells in the dentate gyrus
form the mossy fiber system, which projects on pyramidal neu-
rons in the CA3 field of the hippocampus. The CA3 pyramidal
neurons send Schaffer collaterals to the pyramidal cells of the
CA1 hippocampal field. Axons of pyramidal neurons in CA1
project on neurons in the subiculum. The subiculum in turn
projects back to the entorhinal area, thus closing the circuit. The
synapses in this circuit are all excitatory; the only inhibitory
synapses are those from hippocampal basket neurons in the stra-
Figure 21–11. Schematic diagram of the component parts of tum oriens whose axons terminate on the perikarya of pyramidal
the fornix. neurons.
LIMBIC SYSTEM / 289
Granule Cells
Dentate Gyrus
2 Mossy Fibers
Perforant 1
Entorhinal CA3
Hippocampus 3
Cortex Pathways Pyramidal Schaffer's
Neurons CA1 Collaterals
entorhinal-hippocampal circuit showing the
perforant pathway (1) from the entorhinal
cortex to the dentate gyrus, hippocampus, 4
and subiculum; mossy fibers (2) connecting
the dentate gyrus with CA3 neurons of the
hippocampus; Schaffer collaterals (3) link-
ing CA3 neurons with CA1 neurons within Subiculum
the hippocampus; hippocampal-subiculum
pathway (4); and finally the circuit is closed
by connections from the subiculum back to
the entorhinal cortex (5). 5
FUNCTIONAL CONSIDERATIONS memory and the inability to store newly learned facts (antero-
grade amnesia). Remote or long-term memories, how-
In considering the functions of the hippocampus, it is important ever, remain intact. Unilateral ablation of the hippocam-
to emphasize the complex relationships of the hippocampus with pus in humans does not affect memory to a significant
other brain regions, as was outlined above. The effects of stimula- degree. Studies of humans with brain lesions indicate that the hip-
tion or ablation of the hippocampus cannot be evaluated in isola- pocampus is important for declarative (explicit) memory, the
tion from the elaborate systems of hippocampal communication. memory of facts, words, and data that can be brought to mind and
The hippocampus is no longer believed to play a role in ol- consciously inspected. Declarative (associative) memory includes
faction. The hippocampus is very well developed in humans, who episodic, semantic, and familiarity-based recognition, with the ad-
are microsmatic; it is also present in the whale, which is anos- ditional suggestion that the hippocampus plays a time-limited role
matic. No direct pathways from the primary olfactory cortex can (being needed only for recently acquired information). Episodic
be traced to the hippocampus, although a multisynaptic pathway memory (recall of past events with a sense of personal familiarity)
through the primary olfactory cortex and the parahippocampal is usually more severely disrupted in hippocampal lesions than se-
gyrus (entorhinal area) exists. Olfactory bulb stimulation results mantic memory (memory for general declarative information such
in excitatory postsynaptic potential (EPSP) activity but no action as for vocabulary or arithmetic facts). Similar to hemispheric spe-
potential firing in the hippocampus. This is consistent with a cialization, the left hippocampus is specialized for verbal memory
polysynaptic pathway from the olfactory bulb to the hippocam- and the right hippocampus for nonverbal memory.
pus. It has been suggested that this subthreshold EPSP activity The hippocampus has a low threshold for seizure (epileptic)
may be comparable to a conditional stimulus that plays a role in activity; however, the spread of such epileptic activity to the non-
memory and learning. specific thalamic system, and hence all over the cortex, is not
Action potentials, in contrast, have been recorded in the hip- usual. This may explain why temporal lobe epilepsy (psychomo-
pocampus after stimulation of various areas, both centrally and tor epilepsy) in humans does not become generalized.
peripherally. Hippocampal responses have been elicited after vi-
sual, acoustic, gustatory, and somatosensory stimulation as well AMYGDALA (FIGURE 21–13)
as after stimulation of various cortical and subcortical areas. Such
responses are characteristically labile and are easily modified by a The amygdalar (from the Greek amygdala, “almonds”) nuclei, a
variety of factors. major component of the limbic system, resemble almonds in
Stimulation and ablation of the hippocampus give rise to shape and are located in the tip of the temporal lobe beneath the
changes in behavioral, endocrine, and visceral functions. The cortex of the uncus and rostral to the hippocampus and the infe-
same effects may follow either ablation or stimulation. rior horn of the lateral ventricle. There are two main groups of
The hippocampus has been implicated in the processes of at- these nuclei: the corticomedial and central and the basolateral.
tention and alertness. Stimulation of the hippocampus in animals The corticomedial-central group is relatively small and is phyloge-
produces glancing and searching movements that are associated netically older. It maintains connections with the phylogenetically
with bewilderment and anxiety. older regions of the central nervous system, such as the olfactory
The important role of the hippocampus in memory was not bulb, hypothalamus, and brain stem. The basolateral group is
apparent until the late 1950s, when Scoville and Milner described larger and phylogenetically more recent. It has extensive connec-
memory loss following bilateral anterior temporal lobectomies. tions with the cerebral cortex. Several neurotransmitters have been
Bilateral ablation of the hippocampus in humans (usually in- demonstrated in the amygdala, including acetylcholine, gamma-
volving adjacent regions as well) results in a loss of recent (60 s) aminobutyric acid (GABA), noradrenaline, serotonin, dopamine,
290 / CHAPTER 21
Caudate Nucleus
(Body)
Putamen
Thalamus
Third Ventricle Amygdala
Mamillary
Bodies
Figure 21–13. Coronal section of the brain showing the amygdala and adjacent structures.
substance P, and enkephalin. The amygdala was first identified by interoceptive stimuli from a variety of autonomic areas (Figure
the German physician Burdach in the early 19th century. 21–14). Most of the amygdalar connections are reciprocal.
The basolateral nuclear group, the largest in humans, receives in-
Afferent Pathways puts from the following cortical and subcortical sources: (1) cortical
input from the prefrontal, temporal, occipital, and insular cortices,
The amygdala receives a broad range of exteroceptive afferents (ol- which convey to the amygdala highly processed somatosensory,
factory, somatosensory, auditory, and visual) for integration with auditory, and visual sensory information from modality-specific
O us
b
alamus
Figure 21–14. Schematic diagram of the major afferent connections of the amygdala.
LIMBIC SYSTEM / 291
and multimodal association areas as well as visceral information, the hypothalamus and the lateral hypothalamic area, and (3) bed
(2) the thalamus (dorsomedial nucleus), (3) the olfactory cortex, nucleus of the stria terminalis (a scattered group of nuclei at the
and (4) cholinergic input from the nucleus basalis of Meynert. rostral extremity of the stria terminalis).
The basolateral nuclear group is intimately and reciprocally con-
nected with the prefrontal cortex via the uncinate fasciculus. B. VENTRAL AMYGDALOFUGAL PATHWAY
The corticomedial and central nuclear complex receives in-
puts from the following sources: (1) olfactory bulb (directly via The ventral amygdalofugal pathway is a ventral outflow tract
the lateral olfactory stria and indirectly via the olfactory cortex), that originates from the basolateral and central amygdalar nuclei.
(2) thalamus (dorsomedial nucleus), (3) hypothalamus (ventro- It proceeds along the base of the brain beneath the lentiform nu-
medial nucleus and lateral hypothalamic area), (4) septal area, cleus and distributes fibers to the following areas. Fibers originat-
and (5) brain stem nuclear groups concerned with visceral func- ing from the basolateral amygdalar nucleus project to the follow-
tion (periaqueductal gray matter, parabrachial nucleus, and nu- ing cortical and subcortical areas: (1) prefrontal, inferior
cleus of the solitary tract). temporal (entorhinal area and subiculum), insular, cingulate,
and occipital cortices, (2) ventral striatum, (3) thalamus (dorso-
Efferent Pathways medial nucleus), (4) hypothalamus (preoptic and lateral hypo-
thalamic areas), (5) septal area, and (6) substantia innominata
A large number of amygdalar efferents terminate in nuclei that (nucleus basalis of Meynert), from which a diffuse cholinergic
regulate endocrine and autonomic function, and others are di- system activates the cerebral cortex in response to significant
rected to the neocortex. Output from the amygdala is conveyed stimuli.
via two main pathways: (1) stria terminalis (dorsal amyg- Fibers in the ventral amygdalofugal pathway originating in
dalofugal pathway) and (2) ventral amygdalofugal path- the central amygdalar nucleus are distributed to brain stem nu-
way (ventrofugal bundle). clei concerned with visceral function (dorsal motor nucleus of
A. STRIA TERMINALIS the vagus, raphe nuclei, locus ceruleus, parabrachial nucleus, and
periaqueductal gray matter).
The stria terminalis (Figure 21–15) is the main outflow tract of the The two amygdala communicate with each other through the
amygdala. It arises predominantly from the corticomedial group of stria terminalis and the anterior commissure. Fibers leave one
amygdalar nuclei. From its sites of origin, it follows a C-shaped amygdaloid nuclear complex and travel via the stria terminalis to
course caudally, dorsally, anteriorly, and ventrally along the medial the level of the anterior commissure, where they cross and join the
surface of the caudate nucleus to reach the region of the anterior other stria terminalis and return to the contralateral amygdaloid
commissure, where it branches out to supply the following areas: nuclear complex. Nuclear groups within each amygdaloid nuclear
(1) septal nuclei, (2) anterior, preoptic, and ventromedial nuclei of complex communicate with each other via short fiber systems.
leus of
minalis
minalis
edullaris
A a
o
n
alamus
Figure 21–15. Schematic diagram of the major efferent connections of the amygdala.
292 / CHAPTER 21
Intra-Amygdaloid Connections recognition of social cues from faces. Bilateral amygdalar damage
in humans is associated with impaired recognition of facial ex-
Tract tracing studies have revealed extensive intranuclear and in- pressions. Functional imaging studies have demonstrated activa-
ternuclear connectivity between amygdalar nuclei. Most of the tion of the amygdala during presentation of emotional facial ex-
connections are glutamatergic. These observations indicate that pressions. These findings are most evident for negatively
there is extensive local processing of information entering the valenced emotions (fear, anger, and sadness).
amygdala before it leads to the appropriate behavioral outcomes.
E. AROUSAL RESPONSE
Functional Considerations Stimulation of the basolateral nuclear group of the amygdala pro-
The functions of the amygdala are somewhat elusive. Stimula- duces an arousal response that is similar to but independent of the
tion and ablation experiments usually involve adjacent arousal response that follows stimulation of the reticular activat-
neural structures. The intricate neural connectivity of the ing system of the brain stem. The amygdalar response is indepen-
amygdala makes it difficult to ascribe an observed be- dent of the reticular activating system response, since it can be
havior purely to the amygdala. The following manifestations, elicited after lesions have been made in the reticular formation of
however, have been noted to occur after stimulation or ablation the brain stem. Stimulation of the corticomedial nuclear group of
of the amygdala. the amygdala, by contrast, produces the reverse effect (a decrease
in arousal and sleep). The net total effect of the amygdala, how-
A. AUTONOMIC EFFECTS ever, is facilitatory, since ablation of the amygdala results in a
sluggish, hypoactive animal which is placid and tame. Such ani-
Changes in heart rate, respiration, blood pressure, and gastric mals avoid social interaction and may become social isolates.
motility have been observed after amygdalar stimulation. Both
an increase and a decrease in these functions have been observed, F. SEXUAL ACTIVITY
depending on the area that is stimulated.
The amygdala contains the highest density of receptors for sex
B. ORIENTING RESPONSE hormones. Stimulation of the amygdala has been associated with
a variety of sexual behaviors, including erection, ejaculation, cop-
Stimulation of the amygdala enhances the orienting response to ulatory movements, and ovulation. Bilateral lesions of the amyg-
novel events. Such animals arrest ongoing activity and orient dala produce hypersexuality and perverted sexual behavior.
their bodies to the novel situation. Animals with amygdalar le-
sions manifest reduced responsiveness to novel events in the vi- G. MOTOR ACTIVITY
sual environment. Their responsiveness, however, is improved if
they are rewarded for the response. Stimulation of the corticomedial nuclear group of the amygdala
produces complex rhythmic movements related to eating, such
C. EMOTIONAL BEHAVIOR AND FOOD INTAKE as chewing, smacking of the lips, licking, and swallowing.
Animal experiments support the importance of the amygdala
There seem to be two regions in the amygdala that are antago- in the organization of fear-related behavior. Bilateral removal of
nistic to each other with regard to emotional behavior and eat- the amygdala abolishes naturally occurring fear-related responses
ing. Lesions in the corticomedial nuclear group of the amygdala in animals. Electric stimulation of the amygdala elicits defensive
result in aphagia, decreased emotional tone, fear, sadness, and or fear-related behavior. The amygdaloid projections to the hypo-
aggression. Lesions of the basolateral nuclear group, by contrast, thalamus via the ventral amygdalofugal pathway seem to be es-
produce hyperphagia, happiness, and pleasure reactions. Stim- sential for fear-related behavior.
ulation of the basolateral nuclear group of the amygdala is asso- Stimulation of the amygdala during brain surgery in humans
ciated with fear and flight. Stimulation of the corticomedial nu- is associated with a variety of autonomic and emotional reactions
clear group produces a defensive and aggressive reaction. The and a feeling of fear and anxiety. Some of these patients report a
attack behavior elicited by amygdalar stimulation differs from memorylike delusion of recognition known as the déjà vu phe-
that elicited by hypothalamic stimulation in its gradual buildup nomenon (a French term meaning “already seen”). The déjà vu
and gradual subsidence upon the onset and cessation of stimula- phenomenon, as well as olfactory and gustatory hallucinations,
tion. Attack behavior elicited from the hypothalamus, in con- is frequently experienced as auras in patients who experience
trast, begins and subsides almost immediately after the onset and temporal lobe seizures.
cessation of the stimulus. Of interest also is the fact that prior Destruction of both amygdalas in humans has been done to
septal stimulation prevents the occurrence of aggressive behavior relieve intractable epilepsy and treat violent behavior. Such pa-
elicited from both the amygdala and the hypothalamus. tients usually become complacent and sedate and show signifi-
D. FACIAL EXPRESSION cant changes in emotional behavior.
It should be pointed out that many, if not all, of these func-
Several areas in the brain are specialized for processing of faces. tions can be observed after stimulation or ablation of other brain
Foremost among them are the sectors of extrastriate visual cor- regions, notably the hypothalamus and the septal regions. It has
tex, notably in the fusiform and superior temporal gyri, and the been proposed that the amygdala plays an integrative role in all
amygdala. Whereas the extrastriate visual cortices participate pri- these functions.
marily in constructing detailed perceptual representation of
faces, the amygdala is required to link the perception of the face SEPTAL AREA
to the retrieval of knowledge about its emotional and social
meaning. Lesions of the amygdala in monkeys impair the ability The septal area (Figures 21–16 and 21–17) has two divisions:
to evaluate social and emotional meaning of visual stimuli. the septum pellucidum and the septum verum. The sep-
Bilateral amygdalar lesions in humans result in alteration in so- tum pellucidum is a thin leaf that separates the lateral
cial behavior and social cognition, especially as related to the ventricles. It is made up of glia and lined by ependyma.
Septum Pellucidum Corpus Callosum
Anterior
Commissure
Lamina Subcallosal
Terminalis Gyrus
Hypothalamus
Septal Area
Figure 21–16. Midsagittal view of the brain showing the septal area ventral to the septum pellucidum, between the subcallosal
gyrus rostrally and the anterior commissure, hypothalamus and lamina terminalis caudally.
Lateral
Ventricle
Corpus Callosum
Candate
Septum Nucleus
Pellucidum
Putamen
Septal
Globus
Nuclei
Pallidus
Fornix
(Columns)
Thalamus
Third
Ventricle
Hippocampus
Splenium
Figure 21–17. Axial brain section showing septal nuclei and septum pellucidum between the corpus callosum and fornix.
293
294 / CHAPTER 21
Cingulate Reciprocal connections with the hypothalamus travel in the

gyrus medial forebrain bundle. The hypothalamic nuclei involved in-
clude the preoptic, anterior, paraventricular, and lateral. The me-
Corpus
callosum
dial forebrain bundle is an ill-defined bundle of short nerve fibers
that courses through the lateral hypothalamus, interconnecting
Stria nuclei located close together and extending from the septal area
medullaris into the midbrain.
Fibers between the septal area and the midbrain travel in the
medial forebrain bundle. The periaqueductal gray region and the
Habenula
ventral tegmental area are the primary brain stem areas involved
Thalamus in this connection.
Septal area Hypothalamus
Stria The stria medullaris thalami reciprocally connects the septal
terminalis area and the habenular nuclei. From the habenular nuclei, the
habenulointerpeduncular tract connects the septal area indirectly
Medial Fornix with the interpeduncular nucleus of the midbrain.
forebrain The thalamic nuclei involved in the septothalamic connec-
bundle tion are the dorsomedial and the anterior nuclei.
Amygdala Midbrain Functional Considerations

The functional importance of the septal area lies in providing a
site of interaction between limbic and diencephalic structures.
Hippocampus
Stimulation and ablation experiments have provided
the following information about the role of the septal
Figure 21–18. Schematic diagram showing afferent and effer- region.
ent connections of the septal area.
A. EMOTIONAL BEHAVIOR
Lesions of the septal area in animal species such as rats and mice
The septum verum is ventral to the septum pellucidum, between produce rage reactions and hyper-emotionality. These behavioral
the subcallosal gyrus rostrally and the anterior commissure and alterations usually are transitory and disappear 2 to 4 weeks after
the anterior hypothalamus caudally. Most authors include the the lesion.
following structures in the septum verum: the septal nuclei, the
diagonal band of Broca, the bed nucleus of the stria terminalis, B. WATER CONSUMPTION
and the nucleus accumbens septi.
The septal nuclei are made up of medium-size neurons which Animals with lesions in the septal area tend to consume in-
are grouped into medial, lateral, and posterior groups. The lat- creased amounts of water. There is evidence to suggest that this
eral group receives most of the septal afferents and projects to the is a primary effect of the lesion and is caused by disruption of a
medial septal group. The medial group gives rise to most of the neural system concerned with water balance in response to
septal efferents. The posterior group receives input from the hip- changes in total fluid volume. Chronic stimulation of the septal
pocampus and directs its output to the habenular nuclei. The area tends to decrease spontaneous drinking even in animals
septal nuclei are poorly developed in humans. that have been deprived of water for a long time.
Connections C. ACTIVITY
The septal area has reciprocal connections (Figure 21–18) with Animals with septal lesions demonstrate a high initial state of ac-
the following areas: (1) hippocampus, (2) amygdala, (3) hy- tivity in response to a novel situation. This heightened activity,
pothalamus, (4) midbrain, (5) habenular nucleus, (6) cin- however, rapidly declines almost to immobility.
gulate gyrus, and (7) thalamus.
The reciprocal connections between the septal area and the D. LEARNING
hippocampus constitute the major connection of the septal
Animals with septal lesions tend to learn tasks quickly and per-
area and travel via the fornix. The hippocampal-septal relation-
form them effectively once they have been learned.
ship is topographically organized so that specific areas of the
hippocampus project on specific regions of the septum (CA1 of
the hippocampus to the medial septal region; CA3 and CA4 of E. REWARD
the hippocampus to the lateral septal region, medial septal re- Stimulation of several regions of the septal area gives rise to plea-
gion to CA3 and CA4). When one adds to this the intrinsic sure or rewarding effects.
connection between the medial and lateral septal regions and
between CA1 and CA3–CA4 of the hippocampus, it becomes F. AUTONOMIC EFFECTS
evident that a neural circuit is established connecting these two
limbic regions. Stimulation of the septal region has an inhibitory effect on auto-
The reciprocal connections between the septal area and the nomic function. Cardiac deceleration ensues after septal stimula-
amygdala travel via the stria terminalis and the ventral amyg- tion and is reversed by the drug atropine, suggesting that septal
dalofugal pathway. effects are mediated via the cholinergic fibers of the vagus nerve.
LIMBIC SYSTEM / 295
Primary Sensory Frontal Primary 2. Emotional behavior (including fear, rage, pleasure, and sad-
sensory association
ciation association motor ness) and feeling
cortex cortex cortex cortex 3. Memory
4. Matching up sensory input with autonomic-endocrine drives
and putting it into the context of the situation
LIMBIC CENTERS
5. Motivation
Different functions of the limbic system are not distributed
Sensory Motor equally among its components. The hippocampus is especially
Input Autonomic and
output concerned with memory, the amygdala with emotion and sexual-
endocrine centers
ity, the anterior cingulate gyrus with motivation, and the or-
Figure 21–19. Schematic diagram showing the anatomic sub- bitofrontal cortex with social behavior.
strate for the integrative function of the limbic system (the lim-
bic loop). TERMINOLOGY
Alveus (Latin, “a trough or canal”). The alveus of the hip-
pocampus is the thin layer of white matter that covers the ven-
G. SEPTAL SYNDROME tricular surface of the hippocampus.
Amnesia (Greek, “forgetfulness”). Lack or loss of memory.
Destruction of the septal nuclei gives rise to behavioral overreac- Amnesia was an old term for loss of memory. The modern use of
tion to most environmental stimuli. Behavioral changes occur in the word dates from about 1861 and the work of Broca, who di-
sexual and reproductive behavior, feeding, drinking, and the rage vided disorders of speech caused by central lesions into aphemia
reaction. and verbal amnesia. The term first appeared in English in 1862.
Relatively few discrete septal lesions or stimulations have Broca’s use of the term verbal amnesia (impaired word finding) is
been reported in humans. Chemical stimulation in the septal no longer current.
area using acetylcholine results in euphoria and sexual orgasm.
Recordings from the septal area during sexual intercourse have Amygdala (Greek amygdale, “almond”). The amygdaloid nu-
shown spike and wave activity during orgasm. Markedly in- cleus is an almond-shaped nuclear mass in front of the tail of the
creased sexual activity has been reported in humans after septal caudate nucleus.
damage. Associative memory. The conscious recollection of specific
events and facts. Also known as declarative memory and data-
base memory.
OVERVIEW OF THE LIMBIC SYSTEM Bratz sector. Cornu Ammonis field CA4. Also known as the
medium vulnerability (to anoxia) sector.
It is evident that the limbic system is a highly complex system Broca, Pierre-Paul (1824–1880). French anthropologist, anat-
that is interconnected by a multiplicity of pathways and recip- omist, and surgeon, and later a politician. He described hemi-
rocal circuits among its component parts, notably the spheric dominance for language. He described muscular dystro-
hypothalamus. phy before Duchenne, and the use of hypnotism in surgery. The
The main components of the limbic system (hip- speech area in the left hemisphere is named after him.
pocampal formation, amygdala, septal area, and entorhinal cor-
tex) are densely interconnected and are connected with neural Burdach, Karl Friedrich (1776–1847). German physician,
systems that subserve somatosensory, somatomotor, and auto- anatomist and physiologist. He introduced the terms biology and
nomic and endocrine functions. They are thus in a unique posi- morphology. He is credited with naming many structures, includ-
tion to integrate exteroceptive and interoceptive information and ing the fasciculus cuneatus (Burdach column), globus pallidus,
are essential for the maintenance of emotional stability, learning putamen, internal capsule, lenticular nucleus, red nucleus, cin-
ability, and memory function. A limbic loop (Figure 21–19) has gulum, cuneus, and amygdaloid nucleus. He also classified the
been proposed as the anatomic substrate for the integrative role of thalamic nuclei.
the limbic system. The afferent limb of the loop consists of col- Cingulate gyrus (Latin, “belt or girdle”). A four-layered paleo-
laterals to the limbic system from the pathway connecting neocortex above the corpus callosum. Part of the limbic lobe.
cortical association cortices with the prefontal cortex. Autonomic Cornu Ammonis. Ammon’s horn. Anatomists likened the hip-
and endocrine centers are reciprocally connected with the same pocampus to a ram’s horn or to the horns of the ancient Egyptian
limbic system centers that receive cortical collaterals. The efferent deity Ammon, who had a ram’s head.
limb of the loop consists of projections from the limbic centers to Crus fornix (Latin, “leg or shin, arch”). The flattened band of
the prefrontal association cortex. The prefrontal cortex plays a white beneath the splenium of the corpus callosum. The two
role in guiding behavior and is indirectly involved in the initia- crura join to form the body of the fornix.
tion of movement. The input from the limbic centers into the Declarative memory. The conscious recollection of specific
prefrontal cortex subserves the effects of emotion on motor func- events and facts. Also known as associative memory and database
tion. At best, one can define the overall functions of the limbic memory.
system in the most general terms as subserving the following: Déjà vu (French, “already seen”). An illusion in which a new
1. Homeostatic mechanisms for preservation of the individual situation is incorrectly viewed as a repetition of a previous situa-
(flight or defensive response, eating, drinking) and preservation. Usually an aura of a temporal lobe seizure.
tion of the species (sexual and social behavior). In this the Dentate gyrus (Latin dentatus, “having teeth”; Greek gyros,
limbic system serves a protective function of assuring graded “circle”). The three-layered archicortex of the temporal lobe. A
and considered autonomic and endocrine responses. component of the hippocampal formation.
296 / CHAPTER 21
Entorhinal cortex. The rostral part of the parahippocampal Ben-Ari Y et al: Regional distribution of choline acetyltransferase and acetyl-
gyrus in the temporal lobe. It corresponds to Brodmann’s area 28. cholinesterase within the amygdaloid complex and stria terminalis sys-
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Fimbria (Latin, “fringe, border, edge”). The band of white
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Limbic System: Clinical Correlates 22
Abnormalities of Olfaction Transient Global Amnesia

Memory Klüver-Bucy Syndrome
Types of Memory Temporal Lobe Epilepsy
Anatomic Correlates of Memory Schizophrenia
Types of Memory Loss (Amnesia) Alzheimer’s Disease
Wernicke-Korsakoff Syndrome Herpes Simplex Encephalitis
KEY CONCEPTS
Anosmia may be the earliest clinical sign of a subfrontal Various manifestations of the Klüver-Bucy syndrome can
meningioma. be explained as defects in relating sensory information to
past experience or in evaluating sensory stimuli in terms
There are two types of memory: explicit and implicit.
of their biologic significance.
Temporal lobe epilepsy is characterized by a combination
Amnesia (memory loss) may be anterograde, retrograde,
of psychological and motor manifestations.
global, or modality-specific. It may be transient or per-
manent. Schizophrenia is a mental illness with undefined neuro-
pathology. Cortical and subcortical limbic structures are
Wernicke-Korsakoff’s syndrome, a thiamine deficiency syn-
likely sites of the neuropathology.
drome seen in chronic alcoholics,is characterized by amne-
sia (anterograde and retrograde) and in confabulation. Alzheimer’s disease is a degenerative brain disease charac-
terized by severe memory loss, disorientation, and behav-
Transient global amnesia is caused by ischemia in mem-
ioral changes.The brunt of the pathology is in the entorhi-
ory structures in the medial temporal lobe. Spreading cor-
nal cortex, which isolates the hippocampal formation
tical depression in the medial temporal lobe is another,
from the rest of the cerebral cortex.
more recently reported mechanism.
ABNORMALITIES OF OLFACTION the earliest clinical manifestation of a subfrontal menin-

gioma. Pathologic processes in the region of the primary
Rhinencephalic structures can be affected in several sites, result- olfactory cortex (uncus of the temporal lobe) usually give
ing in derangement of the sense of smell. rise to hallucinations of smell (uncinate fits). The odor experi-
Olfactory receptors in the nose are involved in common colds, enced in such cases often is described as unpleasant. Such halluci-
resulting in bilateral diminution or loss of smell (anosmia). nations may herald an epileptic seizure or be part of it.
Olfactory nerve fibers may be affected in their course through the
cribriform plate of the ethmoid bone after fractures of the plate MEMORY
and severe falls. The anosmia in such cases results from the shear-
ing of the fine olfactory nerve fibers as they pass through the crib- The term memory refers to the encoding, storage, and retrieval
riform plate. The olfactory bulb and tract may be involved in in- of information. A defect in one or more of these processes results
flammatory processes of the meninges (meningitis) or tumors in memory impairment (amnesia).
(meningiomas) in the inferior surface of the frontal lobe or the The role of the nervous system in memory has been studied
anterior cranial fossa. Unilateral loss of smell (anosmia) may be by using neurosurgical techniques (ablation of selective areas of
297
298 / CHAPTER 22
the brain), electrophysiologic methods (neural pathways and Table 22–1. Memory Types
mechanisms), biochemical studies (the role of RNA and other
proteins), a neuropharmacologic approach (the effect of drugs Explicit
on synaptic transmission and intracellular processes), and studies Semantic
of humans with a memory deficit (amnesia). Memory seems to Episodic
depend on two distinct changes: an electric membrane event of a Short term
temporary nature and a more stable, permanent change in the Long term
chemistry of the nervous system. The discovery that DNA and Anterograde
RNA can act as codes for synaptic transmission has led to the Retrograde
theory that those substances are responsible for transforming Implicit
short-term memories into permanent stores. Procedural
Priming
Types of Memory
Memories are either explicit or implicit. of these alterations have been described in different experimental
situations, including changes in the number and size of synaptic
terminals as well as their chemical composition. Changes in post-
A. EXPLICIT (DECLARATIVE) MEMORY synaptic neurons also have been described. Such changes in the
Explicit memory refers to conscious retrieval of information. It pre- or postsynaptic components of the synapse have been thought
supports the learning and retention of facts and the conscious to facilitate the transmission of impulses at the synapse and thus
recollection of prior events (knowing that). Thus, it is consciously establish a memory code, or ingram.
accessed. There are two subtypes of explicit memory: (1) episodic Several biochemical studies have suggested a role for protein
and (2) semantic. and RNA in memory mechanisms. Evidence for this role has
Episodic (unique) memory is the memory of personally expe- been obtained from (1) experiments in which protein and RNA
rienced facts and events with special spatial and temporal local- syntheses were increased or blocked by drugs, (2) measurement
ization, such as the memory of eating a specific type of food in a of the protein and RNA content of stimulated neuronal systems,
restaurant. and (3) experiments in which learned tasks were presumably
Semantic (nonunique, generic) memory refers to the memory transferred from a trained animal to an untrained animal after the
of culturally and educationally acquired encyclopedic knowledge injection of RNA or protein from the brain of the trained subject.
such as the meaning of words, arithmetical facts, and geographic
and historical information, for example, that Paris is the capital Anatomic Correlates of Memory
of France and that bistro is French for “restaurant.” The different types of memory are supported by different neural
Episodic memory can be short or long term. systems.
1. Short-Term (Immediate, Recent, Working) Memory.
Short-term memory refers to the memory of a limited amount A. EPISODIC MEMORY
of information (e.g., a seven-digit telephone number) held con- The mesial temporal cortex (hippocampus, entorhinal cortex,
tinuously in consciousness for a short period (less than 60 s). perirhinal cortex, and parahippocampal gyrus) are critical for
This type of memory decays in seconds if it is not refreshed episodic memory. Patients with bilateral hippocampal resection
continuously. (for treatment of intractable epilepsy) or acquired lesions (herpes
2. Long-Term (Remote) Memory. Long-term memory refers simplex encephalitis) are unable to acquire new explicit (declara-
to the memory retrieved after delays longer than one minute, tive) memory (anterograde amnesia). In these patients, no new
and in the case of remote memory, for more distant past. information is ever retained beyond the span of 40–60 seconds.
Lesions extending beyond the hippocampus to involve adjacent
B. IMPLICIT MEMORY mesial temporal regions are associated with severe anterograde
Implicit memory supports the learning and retention of skills and/or retrograde amnesia. Besides the mesial temporal cortex,
(knowing how). It is the memory of experience-affected behav- the following brain regions are implicated in episodic memory:
iors that are performed unconsciously. There are two types of (1) cortico-cortical connections from posterior and anterior neo-
implicit memory: (1) procedural memory and (2) priming. cortices to the entorhinal cortex, (2) hippocampus-mamillary
1. Procedural Memory. Procedural memory (skill learning) is body-anterior and medial thalamic nuclei via the fornix and
the phenomenon in which repeated performance of a motor act, mamillothalamic tract, and 3) basal forebrain cholinergic nuclei
such as driving or riding a bike, enhances and automates future (nucleus basalis of Meynert).
skill for the same act. It is characteristically resistant to forgetting, B. SEMANTIC MEMORY
hence its preservation in patients who are otherwise amnesic. The temporal, parietal, and occipital lobes, particularly the tem-
2. Priming. Priming refers to short-lived enhancement of per- poral neocortex, are associated with semantic memory. Semantic
ceptually based performance following recent exposure to visu- memory impairment is seen in patients with bilateral lesions in
ally similar material, such as completing a three-letter item with the above cortices as occurs in herpes simplex encephalitis and
a word that has been presented previously or recognizing a word Alzheimer’s disease. Right hemisphere damage is more impor-
or picture faster or more accurately because of prior exposure. tant than left hemisphere damage.
Table 22–1 is a summary of the types of memory.
Immediate memory may be explained as a transient electric al- C. SHORT-TERM (WORKING) MEMORY
teration at the synapse; longer-lasting memory may be explained Studies on short-term memory point to two separate neural sys-
as an actual physical or chemical alteration of the synapse. Several tems that handle verbal and nonverbal information. In patients
LIMBIC SYSTEM: CLINICAL CORRELATES / 299
with left hemisphere dominance for language, the left pre- WERNICKE-KORSAKOFF SYNDROME
frontal cortex subserves working memory for verbal material,
and the right prefrontal cortex subserves working memory for The Wernicke-Korsakoff syndrome, which was described by
nonverbal material. Working memory is unaffected in mesial Wernicke in 1881 and Korsakoff in 1887, is characterized by se-
temporal lesions. vere anterograde and retrograde amnesia and confabula-
tion. The cause of this syndrome is vitamin B1 (thiamine)
D. PROCEDURAL (SKILL LEARNING) MEMORY deficiency resulting from malnutrition associated with
Skill learning memory is a function of subcortical circuits, par- chronic alcohol intake. The lesion in Korsakoff ’s syndrome in-
ticularly in the basal ganglia and cerebellum, and is thus unaf- volves the dorsomedial and midline nuclei of the thalamus,
fected by mesial temporal pathology. mamillary body, and frontal cerebral cortex.
E. PRIMING
The neural basis of priming is not certain but is most probably TRANSIENT GLOBAL AMNESIA
related to unimodal sensory association areas. Transient global amnesia is a short-term neurologic condition that
is characterized by sudden memory loss of recent events, transient
Types of Memory Loss (Amnesia) inability to retain new information (anterograde amnesia), and ret-
rograde amnesia of variable extension. Immediate and very remote
Several types of amnesia are recognized: (1) retrograde, memories are unaffected. Complete recovery usually occurs within
(2) anterograde, (3) global, (4) modality-specific, (5) per- a few hours. The term transient global amnesia was coined by Fisher
manent, and (6) transient. and Adams in 1964. The exact mechanism of transient global am-
Retrograde amnesia is amnesia for information learned before nesia remains controversial. This type of amnesia has been associ-
the onset of an illness. Anterograde amnesia is amnesia for infor- ated with epilepsy, migraine headache, and tumor. Most reports
mation that should have been acquired after the onset of an ill- emphasize bilateral transient ischemia in the territory of the poste-
ness. Anterograde amnesia is the most common type of amnesia. rior cerebral circulation affecting medial temporal lobe
It usually affects verbal and nonverbal (visual) materials equally, structures that are important for memory. More recent
although unilateral left temporal lobe damage may selectively af- studies on transient global amnesia implicate spreading
fect acquisition of verbal information, whereas right temporal cortical depression in medial temporal structures in the pathogene-
lobe damage may selectively affect nonverbal information, such sis of the amnesia. The episodes of transient amnesia may be pre-
as faces and location of items. Retrograde amnesia occurs usually ceded by characteristic events or activities such as exertion, intense
in association with anterograde amnesia and is most pronounced emotion, sexual intercourse, temperature extremes, and bathing.
for events in the years just preceding the lesion. Global amnesia
is an acute, transient (minutes to hours) severe anterograde, with
variable periods of retrograde amnesia in which information can- KLÜVER-BUCY SYNDROME
not be retrieved through any sensory channel. Transient global The Klüver-Bucy syndrome is a clinical syndrome observed in
amnesia was first described in 1956 by Morris Bender, and the humans and other animals after bilateral lesions in the temporal
term was coined by C. Miller Fisher and Raymond Adams in lobe that involve the amygdala, hippocampal formation, and ad-
1964. Modality-specific amnesia is the inability to retrieve infor- jacent neural structures. The syndrome was first described by
mation through a specific channel, such as vision. Amnesia may Klüver and Bucy in 1939 in monkeys after bilateral temporal
be permanent, as in Alzheimer’s disease, or transient, as in post- lobectomy. The human counterpart was described by Terzian
traumatic and global amnesia. and Dalle Ore in 1955 and by Marlowe in 1975. The syndrome
Much of our knowledge about memory loss has come from is manifested by the following symptoms:
careful observations of patients with amnesia. Although a relation-
ship between the temporal lobe and loss of memory was recognized 1. Visual agnosia or psychic blindness (inability to differentiate
at around the turn of the century by the Russian neuropathologist between friends, relatives, and strangers).
Vladimir Bekhterev, it was William Scoville in 1953 who estab- 2. Hyperorality (tendency to examine all objects by mouth).
lished a precise relationship between bilateral anterior temporal 3. Hypersexuality (normal as well as perverted sexual activity).
lobe lesions and anterograde amnesia. Scoville’s patient underwent Such patients and animals manifest heightened sexual drives
bilateral anterior temporal lobectomies for the treatment of in- toward either sex of their own or other species and even in-
tractable seizures. The lesion included the anterior hippocampal animate objects.
formation and parahippocampal gyrus and the amygdala. While
the seizures responded favorably, the patient was left with severe de- 4. Docility.
clarative memory loss and anterograde memory loss. His retrograde 5. Lack of emotional response, blunted affect, and apathy.
memory and implicit (procedural) memory were not affected. 6. Increased appetite, bulimia.
Pathologic processes in the brain may affect one type of 7. Memory deficit.
memory and spare others. Older people lose the ability to recall
what they ate earlier in the day but can recall, in the minutest de- The various manifestations of this syndrome reflect a defect
tail, experiences they had many years earlier. People who suffer in relating sensory information to past experience or
head trauma in a car accident are unable to recall what transpired evaluating sensory stimuli in terms of their biologic sig-
for minutes to hours before the accident, but the recall of older nificance.
memories remains intact.
Severe impairment of episodic memory is the hallmark of TEMPORAL LOBE EPILEPSY
Alzheimer’s disease. However, other types of memory are affected
in this disease, including semantic memory, some aspects of im- Another manifestation of limbic lesions in humans is temporal
plicit memory, and short-term memory. lobe epilepsy, which also is known as psychomotor seizures,
300 / CHAPTER 22
uncinate fits, and complex partial seizures. During the lobe epilepsy. This has been attributed to autonomic changes in
seizure, the patient may manifest one or more of the fol- cardiovascular function during a seizure. Autonomic cardiovas-
lowing symptoms: cular responses have been elicited on stimulation of the insular
cortex in humans. Stimulation of the right insular cortex pro-
1. Olfactory hallucinations consisting of transient and recurrent
duces sympathetic effects on cardiovascular function (tachycar-
episodes of unpleasant olfactory experiences such as smelling
dia and pressor effects). Stimulation of the left insular cortex, in
burning rubber.
contrast, produces parasympathetic effects (bradycardia and de-
2. Gustatory hallucinations consisting of a transient unpleasant pressor effects).
taste sensation.
3. Auditory hallucinations.
4. Visual hallucinations (déjà vu).
SCHIZOPHRENIA
5. Rhythmic movements related to feeding (chewing, licking, Schizophrenia is a severe mental illness characterized by disorga-
swallowing). nized thought processes, hallucinations, delusions, and cogni-
6. Complex motor acts such as walking, undressing, and twist- tive deficits. Vulnerability to schizophrenia is 60% genetic and
ing movements of trunk and extremities. 40% environmental. Although the definitive neuropathology of
7. Amnesia, which may last several hours or days. schizophrenia has not been defined, it includes ventriculo-
megaly, diffuse neuronal loss and disorganization, and decreased
8. Aggressive behavior. During the seizure, such patients may frontal blood flow and metabolism. Neurochemical studies have
commit violent or even criminal acts. strongly supported a dysfunctional dopaminergic neu-
The pathology in temporal lobe seizures involves the hippo- rotransmission. Thus, the pathology involves both cor-
campus, entorhinal cortex, and amygdala. Magnetic resonance tical and subcortical structures. Numerous pathologic
imaging (MRI) is useful in identifying temporal lobe pathology, mechanisms have been proposed for schizophrenia. The currently
such as mesial temporal lobe sclerosis and tumor (Figure 22–1). predominant hypothesis is abnormal neurodevelopment that
Unexplained death has been reported in patients with temporal becomes manifest in adolescence. The alternative hypothesis is
Figure 22–1. Gadolinium-enhanced T1-weighted magnetic

resonance image of the brain showing an enhancing lesion
(tumor) (arrow) in the temporal lobe.
a neurodegenerative one. Cytoarchitectural studies in schizo- in limbic and multimodal association cortices compared with
phrenic brains point to abnormal laminar organization in lim- primary association, primary sensory, and primary motor cortices.
bic structures that are suggestive of abnormal neuronal migra- The most affected areas are the anterior parts of the parahippo-
tion during brain development. Findings from different studies campal gyrus and particularly in the entorhinal cortex (area 28).
suggest a “miswiring” of neural connections in the schizo- It is well established that the entorhinal cortex serves as a link
phrenic brain. between the hippocampal formation (important for memory)
and the rest of the cerebral cortex. Severe neuropathology in the
ALZHEIMER’S DISEASE entorhinal cortex, as occurs in Alzheimer’s disease, thus isolates
or disconnects the hippocampal formation from the remainder of
Alzheimer’s disease is a degenerative brain disorder that is char- the cortex and results in severe memory loss. Alzheimer’s disease
acterized by memory loss severe enough to impair everyday ac- thus is a disorder where there is a breakdown of cortical neural
tivities; disorientation to time, place, and person; and behavioral systems critical for higher cognitive behaviors (thought, reason-
changes such as depression, paranoia, and aggressive- ing, memory).
ness. Memory loss starts with recent (short-term) mem- Alzheimer’s disease has been shown to be a polygenetic disease.
ory such as remembering to keep appointments, and Mutations in chromosomes 21, 14, and 1 have been associated
progresses to involve remote (long-term) memory such as forget- with the disorder. All three chromosomes have been related to
ting names of children and spouses, and finally, in the end stage, early onset autosomal dominant Alzheimer’s disease. Chromo-
to nearly total loss of memory. The gross neuropathologic hall- some 19 has been associated with late onset familial and sporadic
marks of Alzheimer’s disease consist of atrophic gyri and widened Alzheimer’s disease.
sulci (Figure 22–2) most prominent in the limbic cortex. The
association cortices are heavily affected, whereas primary sensory
cortices are minimally affected and the motor cortex is least af- HERPES SIMPLEX ENCEPHALITIS
fected. Microscopically, the neuropathologic hallmarks of the dis-
ease consist of neurofibrillary tangles and senile plaques. Neuro- Herpes simplex encephalitis is a viral encephalitis caused by her-
chemical studies have demonstrated abnormal accumulation in pesvirus and characterized by focal seizures, focal neurologic signs,
senile plaques of a breakdown product of amyloid precursor pro- and progressive deterioration of consciousness. It is the single
tein known as beta-amyloid or A4 amyloid as well as accumu- most important cause of fatal sporadic encephalitis in the United
lation of tau protein in neurons destined to have neurofibrillary States. The neuropathology consists of a severe focal necrotizing
tangles. The cognitive deficit in Alzheimer’s disease has been at- process with a predilection for the limbic system. A brain biopsy
tributed to an abnormality in the cholinergic system. In support is diagnostic in showing characteristic intranuclear viral inclu-
of this hypothesis are the loss in Alzheimer’s brains of choliner- sions (Figure 22–3) (Cowdry type A inclusions) and inflamma-
gic projection neurons in the nucleus basalis of Meynert and the tion. MRI is the most sensitive noninvasive test for the early di-
loss throughout the cerebral cortex of choline acetyltransferase agnosis of herpes simplex encephalitis and the demonstration of
activity. pathology in the limbic system (Figure 22–4). Early diagnosis is
Careful studies on the distribution of neurofibrillary tangles crucial because there is an effective antiviral treatment for this
in Alzheimer’s brains have shown a preponderance of these tangles type of encephalitis.
Figure 22–2. Lateral view of the

brain showing prominence of sulci
(arrows) and atrophy of gyri (stars)
in Alzheimer’s disease.
302 / CHAPTER 22
Bulimia (Greek bous, “ox”; limos, “hunger”). An eating dis-

order characterized by episodes of binge eating that continue un-
til they are terminated by abdominal pain, sleep, or self-induced
vomiting.
Cribriform (Latin cribrum, “sieve”; forma, “form”). The crib-
riform plate of the ethmoid bone is perforated with small aper-
tures, resembling a sieve. Ancient anatomists were especially in-
terested in the perforations of the ethmoid bone because of their
theory that pituita (mucous brain secretions) entered the nose
through these channels.
Déjà vu (French, “already seen”). An illusion in which a new
situation is incorrectly viewed as a repetition of a previous situa-
tion. Usually an aura of temporal lobe seizures.
Klüver-Bucy syndrome. A clinical syndrome characterized by
visual agnosia, hyperorality, hypersexuality, docility, blunted af-
fect, bulimia, and memory deficit. First described in monkeys by
H. Klüver, and P.C. Bucy in 1937.
Korsakoff ’s syndrome (Wernicke-Korsakoff syndrome). A
syndrome of thiamine deficiency in chronic alcoholics that is
characterized by loss of memory and confabulation. The syn-
drome was first described by Magnus Huss, a Swedish physician.
Strumpell, in 1883, and Charcot, in 1884, called attention to
this syndrome. Charles Gayet described the pathology in 1875.
Karl Wernicke, a German neuropsychiatrist, described three cases
in 1881 and named the disorder acute superior hemorrhagic po-
lioencephalitis. Sergi Korsakoff, a Russian neuropsychiatrist, sum-
marized the syndrome and described it as an entity between
1887 and 1889. The role of vitamin deficiency in the etiology of
the syndrome was established by Peters in 1936.
Figure 22–3. Electron micrograph showing intranuclear viral

inclusions (Cowdry type A) (arrow) in brain biopsy of a patient
with herpes simplex encephalitis.
TERMINOLOGY
Alzheimer’s disease. A progressive degenerative brain disorder
characterized by severe loss of memory, disorientation, and be-
havioral changes. Named after Alois Alzheimer, a German neuro-
psychiatrist and pathologist who described the disorder verbally
in 1906 and in writing in 1907.
Amnesia (Greek, “forgetfulness”). Lack of or loss of memory.
Amnesia was an old term for loss of memory. The modern use of
the word dates from about 1861 and the work of Broca, who di-
vided disorders of speech caused by central lesions into aphemia
and verbal amnesia. The term first appeared in English in 1862.
Broca’s use of the term verbal amnesia (impaired word finding)
is no longer current.
Anosmia (Greek an, “negative”; osme, “smell”). Absence of
the sense of smell. The condition was first mentioned by Galen.
Bekhterev, Vladimir Mikhailovitch (1857–1927). Russian
neuropathologist and psychiatrist whose contributions include
descriptions of the superior vestibular nucleus (Bekhterev nu-
cleus), the relationship between temporal lobe and memory, Figure 22–4. T2-weighted magnetic resonance image of the
and spasmodic laughter and weeping in hemiplegic patients brain showing increased signal intensity (arrows) in components
(Bekhterev-Brissaud sign), among other findings. of the limbic system in a patient with herpes simplex encephalitis.
Nucleus basalis of Meynert. A group of neurons in the substantia Horel JA: The neuroanatomy of amnesia: A critique of the hippocampal mem-
innominata below the globus pallidus. This nucleus is the source ory hypothesis. Brain 1978; 101:403–445.
of cholinergic innervation of the cerebral cortex. Loss of neurons Jafek BW et al: Post-traumatic anosmia: Ultrastructural correlates. Arch Neurol
in the nucleus occurs in patients with Alzheimer’s disease. Named 1989; 46:300–304.
after Theodor Hermann Meynert, an Austrian psychiatrist. Klüver H, Bucy PC: Preliminary analysis of functions of the temporal lobes in
monkeys. Arch Neurol Psychiatry 1939; 42:979–1000.
Psychic blindness (visual agnosia). A disorder in which pa- Kritchevsky M et al: Transient global amnesia: Characterization of anterograde
tients with normal vision fail to comprehend the nature or and retrograde amnesia. Neurology 1988; 38:213–219.
meaning of nonverbal visual stimuli. Laloux P et al: Technetium-99m HM-PAO single photon emission computed
Rhinencephalon (Greek rhin, “nose”; enkephalos, “brain”). tomography imaging in transient global amnesia. Arch Neurol 1992; 49:
The smell brain. 543–546.
Uncinate fits (Latin, “hook”). Uncinate fits arise from the area Marlow WB et al: Complete Klüver Bucy syndrome in man. Cortex 1975; 11:
53–59.
of the uncus, the medially curved (like a hook) anterior end of
Mesulam M-M: Large-scale neurocognitive networks and distributed process-
the parahippocampal gyrus. ing for attention, language, and memory. Ann Neurol 1990; 28:597–
613.
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of schizophrenia. Acta Neuropathol (Berl ) 1996; 92:217–231. graphic distinction. Arch Neurol 1987; 44:629–633.
Blass JP, Gibson GE: Abnormality of a thiamine-requiring enzyme in patients Nissen MJ et al: Neurochemical dissociation of memory systems. Neurology
with Wernicke-Korsakoff syndrome. N Engl J Med 1977; 297:1367–1370. 1987; 37:789–794.
Bossi L et al: Somatomotor manifestations of temporal lobe seizures. Epilepsia Perani D et al: Evidence of multiple memory systems in the human brain:
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Neurology 1995; 45:1546–1550. Curr Opin Neurol 1994; 7:294–298.
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Special Senses 23
Olfaction Synaptic Organization of the Retina

Olfactory Epithelium Photochemistry and Physiology of the Retina
Olfactory Nerve Dark and Light Adaptation
Olfactory Bulb Color Vision
Olfactory Tract Visual Pathways
Olfactory Striae Hearing
Primary Olfactory Cortex The Ear
Olfactory Mechanisms Sound Transmission
Taste Cochlea
Taste Buds Auditory End Organ (Organ of Corti)
Physiology of Taste Auditory Physiology
Central Transmission of Taste Sensations Otoacoustic Emissions
Vision Audiometry
The Retina Deafness
Variations in Retinal Structure Vestibular Sensation
KEY CONCEPTS
The olfactory sense organ is located in the roof of the nose terior medial) before reaching the primary gustatory cor-
and the upper part of the lateral wall and septum. tex in the inferior part of the somesthetic cortex.
Olfactory nerve fibers synapse on mitral and tufted neu- The visual receptor cells are located in the retina.
rons of the olfactory bulb.
The olfactory tract subdivides into three striae. Axons of ganglion cells form the optic nerve.
The gustatory (taste) sense organs (taste buds) are distrib- Crossed and uncrossed optic nerve fibers join caudal to
uted in the tongue, soft palate, oropharynx, and epiglottis. the optic chiasma to form the optic tract.
Taste buds in different locations of the tongue respond Axons of neurons in the lateral geniculate nucleus form
best to different tastes. Those at the tip of the tongue re- the geniculocalcarine tract (optic radiation).
spond best to sweet and salty substances; those at the
Geniculocalcarine fibers terminate,in a retinotopic fashion,
margins and posterior part of the tongue respond best to
in the primary visual (striate) cortex in the occipital lobe.
sour and bitter substances.
The sense organs for hearing and equilibrium are in the
Taste sensations are transmitted centrally via three cra-
inner ear.
nial nerves: facial, glossopharyngeal, and vagus.
Efferent nerves originating from the superior olivary com-
Central taste pathways establish synapses in several brain
plex modulate activity in hair cells.
stem nuclei (nucleus solitarius,reticular nuclei,ventral pos-
304
SPECIAL SENSES / 305
(continued from previous page) Central vestibular pathways are directed to several neural
structures: spinal cord, cerebellum, thalamus, nuclei of ex-
Central auditory pathways synapse in several brain stem traocular movement, and the cerebral cortex.
nuclei before terminating in the primary auditory cortex
The vestibular system is essential for the coordination of
(transverse gyri of Heschl) in the temporal lobe.
motor responses, eye movement, and posture.
Receptors of the vestibular sense organ are located in the
inner ear (semicircular canals, utricle, saccule).
The different sensations perceived by the human body are grouped Each cell has a single dendrite that reaches the surface of the ep-
into two major categories: those concerned with general sensations ithelium and forms a knoblike expansion that extends beyond
(touch, pressure, pain, and temperature) and those concerned with the epithelial surface. From this expansion, 10 to 20 nonmotile
special sensations (olfaction, taste, vision, audition, and sense of po- cilia project into a layer of fluid covering the epithelium. The
sition and movement). This chapter is devoted to a consideration olfactory cilia contain receptors for odorant molecules. From
of the organs of special senses. Whereas nerve endings concerned the basal part of the perikaryon, a nonmyelinated axon emerges
with general sensibility are distributed widely, those concerned and joins with axons of adjacent receptor cells to form the olfac-
with special sensations are limited to specific areas of the body. tory nerve (first cranial nerve). Olfactory nerve bundles pene-
trate the cribriform plate of the ethmoid bone to reach the ol-
OLFACTION factory bulb.
It is estimated that there are more than 100 million receptor
Olfactory stimuli are received by receptors of the olfactory epi- cells in the olfactory mucosa. The specialized nerve cells of the
thelium in the nasal wall and are conveyed via olfactory nerve olfactory epithelium are highly sensitive to different odors.
fibers through the cribriform plate of the ethmoid bone to the Olfactory neurons are produced continuously from basal cells of
olfactory bulb inside the cranial cavity (see Figure 21–2). Within the olfactory epithelium and are lost continuously by normal
the olfactory bulb, axons of the olfactory nerve synapse with mi- wear and tear. It is estimated that olfactory receptor cells have an
tral and tufted cells in a complex structure known as the olfac- average life span of 30–60 days. The presence of these nerve cells
tory glomerulus (see Figure 21–3). Axons of mitral and tufted at the surface exposes them unduly to damage; it is estimated
neurons form the olfactory tract, which lies in the olfactory sul- that 1 percent of the fibers of the olfactory nerves (axons of ol-
cus on the undersurface of the frontal lobe. Close to the anterior factory neurons) are lost each year of life because of injury to the
perforated substance, the olfactory tract divides into the lateral, perikarya. The sense of smell thus diminishes in the elderly as a
intermediate, and medial olfactory striae (see Figures 21–1 and result of exposure of the olfactory epithelium to repeated infec-
21–2). The lateral olfactory stria terminates in the primary olfac- tions and trauma in life. The presence of olfactory neurons at
tory cortex, where olfaction is perceived. The medial olfactory the surface represents the only exception to the evolutionary rule
stria joins the anterior commissure to reach the contralateral ol- by which nerve cell bodies of afferent neurons migrate along
factory tract and bulb. It also projects on limbic system struc- their axons to take up more central and well-protected positions.
tures. The intermediate olfactory stria blends with the anterior The surface of the olfactory epithelium is moistened constantly
perforated substance. The medial and intermediate olfactory by secretions of Bowman’s glands. This moistening helps dis-
striae are not well developed in humans and do not play a role in solve the gaseous substances, facilitating stimulation of the ol-
perception of olfactory stimuli.
Olfactory Epithelium
Receptor cell
The olfactory epithelium is located in the mucous membrane lin-
ing the roof of the nasal cavity on the inferior surface of the cribri-
form plate of the ethmoid bone. From the roof, the olfac-
tory epithelium extends down both sides of the nasal Supporting cell
cavity to cover most of the superior concha laterally and
1 cm of nasal septum medially. Humans are microsmatic animals
Gland of Bowman
in whom the surface area of olfactory mucous membrane in both
nostrils is small (approximately 5 cm2). Though microsmatic, hu-
mans are able to distinguish large numbers of odors, some at very
Basal cell
low concentrations.
The olfactory epithelium contains three types of epithelial
Olfactory axon
cells: receptor cells, supporting cells, and basal cells (Figure 23–1).
Interspersed among epithelial cells are ducts of Bowman’s glands.
A. RECEPTOR CELLS
Olfactory receptor cells are bipolar sensory neurons. Their Figure 23–1. Schematic diagram of the cellular components of
perikarya are located in the lower part of the olfactory epithelium. the olfactory mucosa.
306 / CHAPTER 23
factory epithelium. The continuous secretion also cleanses the Granule layer. Composed of small granule neurons and
receptors of accumulated odorous substances and prevents their processes of granule and mitral cells, this layer also contains
retention. incoming fibers from other cortical regions.
It is believed that different basic odors stimulate different The mitral and tufted cells are considered the principal neu-
olfactory neurons. Stimulation of different combinations of re- rons of the olfactory bulb. Their dendrites establish synaptic re-
ceptors for basic odors is believed to be the basis for humans’ lationships with the olfactory nerve fibers within the glomeruli.
ability to recognize all the varieties of odors to which they are The granule cells (GABAergic inhibitory neurons) are con-
exposed. sidered to be the intrinsic neurons of the olfactory bulb. These
B. SUPPORTING (SUSTENTACULAR) CELLS cells have vertically oriented dendrites but no axon and exert
their action on other cells solely by dendrites. The olfactory bulb
Supporting cells are columnar epithelial cells that separate the ol- contains two other varieties of intrinsic neurons. These are the
factory receptor cells. The surface of supporting cells is special- periglomerular short axon cells in close proximity to the glomeruli
ized into microvilli that project into the fluid layer covering the in the glomerular layer and the deep short axon cells located in
epithelium. As their name suggests, supporting cells provide me- the granule layer.
chanical support to the receptor cells. In addition, they contribute, Dopamine has been reported to be present in the olfactory
along with Bowman’s gland, to the elaboration of the overlying bulb. Its depletion in patients with Parkinson’s disease may ex-
mucus. In contrast to the relatively short life span of olfactory re- plain the decrease of the sense of smell in patients with Parkinson’s
ceptor cells, supporting cells remain stable. disease.
C. BASAL CELLS The olfactory bulb receives fibers (input) from the following
sources:
Basal cells are polygonal cells limited to the basal part of the ep-
ithelium. They are the source of new epithelial cells. Mitotic ac- 1. Olfactory hair cells in the nasal mucosa
tivity persists in these cells through maturity. 2. Contralateral olfactory bulb
3. Primary olfactory cortex
D. BOWMAN’S GLANDS 4. Diagonal band of Broca
Bowman’s glands contain serous and mucous cells and are lo- 5. Anterior olfactory nucleus
cated beneath the epithelium. They send their ducts in between
epithelial cells to pour their secretion onto the surface of the epi- The output from the olfactory bulb is the olfactory tract.
thelium, bathing the cilia of receptor cells and the microvilli of
supporting cells. The secretion of Bowman’s glands plays an im- Olfactory Tract
portant role in dissolving odorous substances and diffusing them
to receptor cells. The olfactory tract (see Figures 21–1 and 21–2) is the outflow
pathway of the olfactory bulb. It is composed of the axons of
principal neurons (mitral and tufted cells) of the olfactory bulb
Olfactory Nerve and centrifugal axons originating from the contralateral olfac-
tory bulb, as well as from central brain regions. The olfactory
The olfactory nerve (see Figure 21–2) is composed of unmyeli- tract also contains the scattered neurons of the anterior olfactory
nated thin processes (rootlets) of the olfactory hair cells nucleus, the axons of which contribute to the olfactory tract. At
in the nasal mucosa. Fascicles of the olfactory nerve its caudal extremity, just anterior to the anterior perforated sub-
pierce the cribriform plate of the ethmoid bone, enter stance, the olfactory tract divides into the olfactory striae (see
the cranial cavity, and terminate on neurons in the olfactory Figures 21–1 and 21–2).
bulb.
Olfactory Striae
Olfactory Bulb At its caudal extremity, just rostral to the anterior perforated sub-
The olfactory bulb (see Figures 21–1 and 21–2) is the main relay stance, the olfactory tract divides into three striae:
station in the olfactory pathways. It is located on the cribriform 1. Lateral olfactory stria
plate of the ethmoid and beneath the inferior surface of the
2. Medial olfactory stria
frontal lobe.
3. Intermediate olfactory stria.
A. LAMINATION AND CELL TYPES (SEE FIGURE 21–3) Each of the striae is covered by a thin layer of gray matter, the
In histologic sections, the olfactory bulb appears laminated into olfactory gyri.
the following layers (see Figure 21–3): The lateral olfactory stria projects to the primary olfactory
Olfactory nerve layer. This layer is composed of incoming cortex in the temporal lobe. The medial olfactory stria projects on
olfactory nerve fibers. the medial olfactory area, also known as the septal area, located
on the medial surface of the frontal lobe, ventral to the genu and
Glomerular layer. In this layer, synaptic formations occur rostrum of the corpus callosum (subcallosal gyrus) and anterior to
between olfactory nerve axons and dendrites of olfactory bulb the lamina terminalis. The medial olfactory area is closely related
neurons (mitral and tufted neurons). to the limbic system and hence is concerned with emotional re-
Plexiform layer. This layer consists of tufted neurons, some sponses elicited by olfactory stimuli. It does not play a role in the
granule cells, and a few mitral cells with their processes. perception of olfactory stimuli. The medial and intermediate
Mitral cell layer. This layer is composed of large neurons striae are poorly developed in humans. The intermediate stria
(mitral neurons). blends with the anterior perforated substance. The thin cortex at
this site is designated the intermediate olfactory area. The pri- Olfactory receptors adapt rather quickly to a continuous
mary terminal stations of the three olfactory striae (olfactory cor- stimulus. Although the olfactory mucosa can discriminate among
tices) are interconnected by the diagonal band of Broca, a bundle a large number of different odors, its ability to detect changes in
of subcortical fibers in front of the optic tract, and with a number concentration of an odorous substance is rather poor. It is esti-
of cortical and subcortical areas concerned with visceral function mated that the concentration of an odorous substance must
and emotion (hippocampus, thalamus, hypothalamus, epithala- change by 30 percent before it can be detected by receptor cells.
mus, and brain stem reticular formation). Through these connec- The mechanism of discrimination is poorly understood but is
tions, the olfactory system exerts influence on visceral function probably related to a spatial pattern of stimulation of the recep-
(salivation, nausea) and behavioral reactions. tor cells.
Primary Olfactory Cortex TASTE

The primary olfactory cortex is located within the uncus of the The gustatory (taste) sense organs in higher vertebrates are lim-
temporal lobe and is composed of the prepiriform cortex, peri- ited to the cavity of the mouth. Taste receptors are located within
amygdaloid area, and part of the entorhinal area. The prepiri- taste buds in the tongue (circumvallate and fungiform papillae),
form cortex is the region on each side of and beneath the lateral as well as in the soft palate, oropharynx, and epiglottis.
olfactory stria; hence it is also called the lateral olfactory gyrus. It Circumvallate papillae are distributed in the back of the
is considered the major part of the primary olfactory cortex. The tongue, whereas fungiform papillae are scattered on the
primary olfactory cortex is relatively large in some animals, such anterior two-thirds of the tongue. There are about 2000 taste
as the rabbit, but in humans it occupies a small area. The pri- buds in the human tongue. This number decreases progressively
mary olfactory cortex in humans is concerned with the conscious with age. It is estimated that taste buds are lost at a rate of 1%
perception of olfactory stimuli. In contrast to all other primary per year with increased rate after 40 years of age. Taste sensations
sensory cortices (vision, audition, taste, and somatic sensibility), are conveyed centrally via three cranial nerves: the facial (CN
the primary olfactory cortex is unique in that afferent fibers VII), glossopharyngeal (CN IX), and vagus (CN X) cranial
from the receptors reach it directly without passing through a nerves.
relay in the thalamus.
The primary olfactory cortex contains two types of neurons. Taste Buds (Figure 23–2)
These are (1) principal neurons (pyramidal cells) with axons that
leave the olfactory cortex and project to nearby or distant regions Taste buds are barrel-like structures distributed in the epithelium
and (2) intrinsic neurons (stellate cells) with axons that remain of the tongue, soft palate, oropharynx, and epiglottis. Each taste
within the olfactory cortex. bud is composed of receptor (neuroepithelial), supporting and
The major input to the primary olfactory cortex is from (1) the basal cells, and nerve fibers.
olfactory bulb via the lateral olfactory stria and (2) other central A. RECEPTOR CELLS
brain regions. The output from the olfactory cortex is via axons
of principal neurons that project to nearby areas surrounding the Two types of receptor cells can be identified in taste buds, clear
primary olfactory cortex, as well as to more distant areas, such as receptor cells and dense receptor cells. Clear receptor cells con-
the thalamus and hypothalamus, which play important roles in tain clear vesicles; dense receptor cells contain dense-core vesicles
behavior and emotion. that store glycosaminoglycans. Both cell types presumably func-
tion as receptors. They are believed to represent two stages in the
development of receptor elements, the dense cell being the more
Olfactory Mechanisms mature. The apex of each receptor cell is modified into micro-
villi, which increase the receptor surface area and project into an
Olfaction is a chemical sense. For a substance to be detected, it
should have the following physical properties:
• Volatility, so that it can be sniffed
• Water solubility, so that it can diffuse through the olfactory
epithelium Supporting cell
• Lipid solubility, so that it will interact with the lipids of the
membranes of olfactory receptors
After an odorous substance is dissolved in the fluid bathing
the surface of the olfactory mucosa, it interacts with receptor Receptor cell
sites located on the cilia of receptor cells. The binding of a single
appropriate molecule to one receptor site causes a change in
membrane permeability. The ion flux that ensues gives rise to
a slow surface negative wave (receptor or generator potential)
that can be detected at the surface of the receptor cell. An all- Basal cell
or-none action potential, however, can be detected in the axons
of receptor cells.
The olfactory receptors show a marked variability in sensitiv-
ity to different odors. They can detect methyl mercaptan (garlic Nerve
odor) in a concentration of less than one-millionth of a milli-
gram per liter of air but ethyl ether in a concentration of 5.8 mg Figure 23–2. Schematic diagram of the cellular components of
per liter of air. the taste bud.
308 / CHAPTER 23
opening, the taste pore. Approximately 4 to 20 receptor cells are Although humans can taste a large number of substances, only
located in the center of each taste bud. Receptor elements de- four primary taste sensations are identified:
crease in number with age. Receptor cells are stimulated by sub- • Sour
stances in solution.
• Salty
B. SUPPORTING CELLS • Sweet
These are spindle-shaped cells that surround the receptor cells. • Bitter
They are located at the periphery of the taste bud. They have
both an insulating function and a secretory function. They are Most taste receptors respond to all four primary taste modal-
believed to secrete the substance that bathes the microvilli in ities at varying thresholds but respond preferentially at a very
the taste pore. low threshold to only one or two. Thus taste buds at the
tip of the tongue respond best to sweet and salty sub-
C. BASAL CELLS stances, and those at the lateral margins and posterior
Basal cells are located at the base of the taste bud and, by divi- part of the tongue respond best to sour and bitter substances,
sion, replenish the receptor cells that are lost continually with an respectively.
average life span of 10–14 days. The ability of taste buds to detect changes in concentration of
a substance is poor, similar to the response of olfactory receptors.
D. NERVE FIBERS A difference in taste intensity remains undetected until the con-
The nerve fibers in the taste bud are terminal nerve fibers of centration of a substance has changed by 30 percent. Substances
the facial (chorda tympani branch), glossopharyngeal (lingual- in solution enter the pore of the taste bud and come in contact
tonsillar branch), and vagus nerves (superior laryngeal branch). with the surface of taste receptors located on microvilli of taste
They are peripheral processes of sensory neurons in the genicu- receptor cells. This contact induces a change in the electrical po-
late ganglion of the facial nerve and in the inferior ganglia of the tential of the membrane of the receptor cells (receptor or genera-
glossopharyngeal and vagus nerves (petrosal and nodose gan- tor potential). The receptor potential in turn generates an action
glia, respectively). They enter the taste bud at its base and wind potential in nerve terminals in apposition to the receptor cell
themselves around the receptor cells in close apposition to re- surface.
ceptor cell membranes. Synaptic vesicles cluster on the inner
surfaces of receptor cell membranes at sites of apposition to
nerve terminals. Central Transmission of Taste
Sensations (Figure 23–3)
Physiology of Taste Taste sensations from the anterior two-thirds of the tongue are
mediated to the central nervous system via the chorda tympani of
Although all taste buds look alike histologically, sensitivity to the the seventh (facial) cranial nerve, those from the poste-
four basic taste modalities is different in different regions of the rior one-third of the tongue via the ninth (glossopharyn-
tongue. Like olfaction, the sense of taste is a chemical sense. geal) cranial nerve, and those from the epiglottis and
PRIMARY GUSTATORY CORTEX
Gustatory
cortex
Ventral posterior
Medial thalamic
nucleus
Nucleus
solitarius
Glossopharyngeal
nerve
Facial nerve
Vagus
nerve
Figure 23–3. Schematic diagram of the gustatory

Epiglottis Tongue
pathways.
lower pharynx via the tenth (vagus) cranial nerve. These nerves The Retina
contain the peripheral processes of pseudounipolar sensory nerve
cells located in the geniculate ganglion (seventh nerve), petrous Light rays falling on the eye pass through its refractive media
ganglion (ninth nerve), and nodose ganglion (tenth nerve). These (cornea, lens, and anterior and posterior chambers) before reach-
peripheral processes enter the deep ends of the taste buds and es- ing the visual receptor cells (the rods and cones) in the
tablish intimate contact with the neuroepithelial cells of the buds. retina. The refractive media help focus the image on the
The central processes of these sensory neurons pro- retina.
ject to the nucleus of the tractus solitarius (the rostral The retina (Figure 23–4), an ectodermal derivative, is an out-
part of the nucleus, the gustatory subnucleus) in the ward extension of the brain, to which it is connected by the op-
brain stem. Axons of neurons in the nucleus solitarius project on tic nerve. The human retina is made up of the following ten lay-
a number of reticular nuclei (especially the parabrachial nucleus ers, starting with the outermost:
in the pons) before crossing the midline to reach the ventral pos- • Layer of pigment epithelium
terior medial (VPM) nucleus of the thalamus, giving on their • Layer of rods and cones
way collateral branches to such nuclei as the nucleus ambiguus
and salivatory nuclei for reflex activity. From the VPM nucleus, • External limiting membrane
axons project (via the posterior limb of the internal capsule) to • Outer nuclear layer
the cerebral cortex to terminate on neurons in the inferior part of • Outer plexiform layer
the somesthetic cortex, just anterior to the face area (primary • Inner nuclear layer
gustatory cortex). • Inner plexiform layer
• Layer of ganglion cells
VISION • Optic nerve layer
• Internal limiting membrane
Vision is by far the most important of the human senses. Most of
our perception of the environment around us comes through our Five types of neurons are distributed throughout these layers:
eyes. Our visual system is capable of adapting to extreme changes • Receptor cells
in light intensity to allow us to see clearly; it is also capable of • Bipolar cells
color discrimination and depth perception. The organ of vision
• Ganglion cells
is the eye; accessory structures are the eyelids, lacrimal glands,
and extrinsic eye muscles. • Horizontal cells
The eye has been compared with a camera. Although struc- • Amacrine cells
turally the two are similar, the camera lacks the intricate auto-
matic control mechanism involved in vision. As an optic instru- A. LAYER OF PIGMENT EPITHELIUM (FIGURE 23–4)
ment, the eye has four functional components: a protective coat, The pigment epithelium is a single layer of melanin-containing,
a nourishing lightproof coat, a dioptric system, and a receptive pigmented cuboidal cells firmly bound at their bases to the
integrating layer. The protective coat is the tough, opaque sclera, choroid layer. The cell membrane at the apices of these epithelial
which covers the posterior five-sixths of the eyeball; it is continu- cells is specialized into slender microvilli that interdigitate with
ous with the dura mater around the optic nerve. The anterior the outer segments of photoreceptor cells. The lateral walls show
one-sixth is covered by a transparent cornea, which belongs to conspicuous zonulae occludentes and zonulae adherentes as well
the dioptric system. The nourishing coat is made up of the vas- as desmosomes and gap junctions. The function of this layer in-
cular choroid, which supplies nutrients to the retina and, be- cludes providing nutrients and mechanical support for the photo-
cause of its rich content of melanocytes, acts as a light-absorbing receptors and protecting retinal receptors from the damaging
layer. It corresponds to the pia-arachnoid layer of the nervous effect of excessive light by absorption of excess light. Retinal de-
system. Anteriorly, this coat becomes the ciliary body and iris. tachment, essentially a splitting of this layer from the other reti-
The iris ends at a circular opening, the pupil. nal layers, is nowadays treated with laser surgery.
The dioptric system comprises the cornea, the lens, the aque-
ous humor within the anterior eye chamber, and the vitreous B. LAYER OF RODS AND CONES (FIGURE 23–4)
body. The dioptric system helps focus the image on the retina.
The greatest refraction of incoming light takes place at the air- The rods and cones are the light-sensitive parts of the photo-
cornea interface. The lens is supported by the suspensory liga- receptors. The human retina contains approximately 100 million
ment from the ciliary body, and changes in its shape permit rods and 6 to 7 million cones. The rods and cones differ in their
change of focus. This is a function of the ciliary muscle, which is distribution along the retina. In humans, a modified region called
supplied by the parasympathetic nervous system. In late middle the fovea contains only cones and is adapted for high visual acuity.
age, the lens loses its elastic properties, and a condition known as At all other points along the retina, rods greatly outnumber cones.
presbyopia results, wherein accommodative power is diminished, 1. Rods (Figure 23–4). The rod photoreceptor cell is a modi-
especially for near vision. The amount of light entering the eye is fied neuron having as components the cell body, axonal process,
regulated by the size of the pupil. Pupillary size is controlled by and photosensitive process. The cell body contains the nucleus.
the action of the constrictor and dilator smooth muscles of the This part of the rod is located in the outer nuclear layer. The ax-
iris. The constrictor muscle is supplied by the parasympathetic onal process is located in the outer plexiform layer. The photo-
nervous system and the dilator muscle by the sympathetic ner- sensitive process is located in the layer of rods and cones. The
vous system. photosensitive process of the rod is made up of two segments,
The receptive integrating layer of the eye is the retina, which outer and inner, connected by a narrow neck containing cilia.
is an extension of the brain, to which it is connected by the optic The outer segment has been shown by electron microscopy to be
nerve. The rods and cones are the sensory retinal receptors. filled with stacks of double-membrane disks containing the
310 / CHAPTER 23
Rod
Rod and cone Cone
Outer nuclear
Horizontal cell
Amacrine cell
Bipolar cell
Inner plexiform
Ganglion cell
Optic nerve Figure 23–4. Schematic diagram

of the layers of the retina and their
cellular components.
visual pigment rhodopsin. The disks are not continuous with the ergy is produced. Extremely sensitive to light, rods are the recep-
cell membrane. The function of the outer segment is to trap the tors used when low levels of light are available, such as at night.
light that reaches the retina. The visual pigment molecules are
positioned within the disk membranes in such a way as to maxi- 2. Cones (Figure 23–4). Cones have the same structural com-
mize the probability of their interacting with the path of inci- ponents as the rods (cell body, axonal process, and photosensitive
dent light. The extensive invagination of the disk membranes in- process). The photosensitive processes of cones, like those of
creases the total surface area available for visual pigment. rods, contain outer and inner segments. The disks in the outer
Rhodopsin is composed of a vitamin A aldehyde (retinal) com- segments, unlike those of rods, are attached to the cell mem-
bined with the protein scotopsin. Exposure to light breaks the brane and are not shed. They contain iodopsin, an unstable,
bond between retinal and the protein. This chemical change trig- light-sensitive visual pigment composed of vitamin A aldehyde
gers a change in the electric potential and produces a generator conjugated to a specific protein (cone opsin). Cones are sensitive
(receptor) potential. The stacked disks in the outer segment are to light of higher intensity than that required for rod vision.
shed continually and are replaced by the infolding of the cell
membrane. The outer segments are separated and supported by
C. EXTERNAL LIMITING MEMBRANE (FIGURE 23–4)
processes from the layer of pigment epithelium. A sievelike sheet, the external limiting membrane, is fenestrated
The inner segment of the rod’s photosensitive process con- to allow the passage of processes that connect the photosensitive
tains mitochondria, glycogen, endoplasmic reticulum, and Golgi processes of rods and cones with their cell bodies. It also contains
apparatus. It is the site of formation of the protein scotopsin, the outer processes of Müller’s (supporting) cells.
which subsequently moves to the outer segment. The inner seg-
ment is connected to the cell body of the rod fiber, which tra- D. OUTER NUCLEAR LAYER (FIGURE 23–4)
verses the external limiting membrane. The outer segment of The outer nuclear layer of the retina contains the cell bodies of
rods is the photosensitive part, where the receptor potential is rods and cones with their nuclei. Cone nuclei are ovoid and lim-
generated, whereas the inner segment is the site of metabolic ac- ited to a single row close to the external limiting membrane. Rod
tivity, where protein and phospholipids are synthesized and en- nuclei are rounded and distributed in several layers.
E. OUTER PLEXIFORM LAYER (FIGURE 23–4) both sites, the ganglion cell layer, inner plexiform layer, and bipo-
Also known as the outer synaptic layer, the outer plexiform layer lar cell layer are absent.
contains axonal processes of rods and cones, as well as dendrites The fovea centralis represents the area of greatest visual acuity,
of bipolar cells and processes of horizontal cells. and its center contains only cones arranged in multiple rows.
The cones of the fovea are slender and resemble rods. The thin-
F. INNER NUCLEAR LAYER (FIGURE 23–4) ning of the retina at the fovea centralis reduces to a minimum
The inner nuclear layer contains cell bodies and nuclei of bipolar tissue through which light passes, hence improving visual acuity.
cells and association cells (horizontal and amacrine) as well as Cones in this area function for sharp vision and color percep-
supporting (Müller’s) cells. The layer has three zones: an outer tion. Surrounding the fovea centralis in the posterior pole of the
zone containing horizontal cells, an intermediate zone contain- eye on the temporal side of the optic disk is a 1-mm yellowish
ing bipolar cells, and an inner zone containing amacrine cells. area, the macula lutea.
Three types of bipolar cells are recognized. Rod bipolar cells Near the ora serrata, at the periphery of the retina, rods pre-
are related to several rod axons, midget bipolar cells are related to dominate, increase in thickness, and become shorter. The cones
one cone axon, and flat bipolar cells are related to several cone decrease in number and also become shorter.
axons. The retina receives its vascular supply from two sources. The
The horizontal association cells are larger than bipolar cells. outer retina is vascularized by the choriocapillaris layer of the
Their axons and dendrites are located in the outer plexiform choroid. The inner retina receives its blood supply from the cen-
layer. Their axons establish synapses with rod and cone axons, tral artery of the retina and its branches. The foveal area, the area
whereas their dendrites establish relationships with cone axons. of most acute vision, is vascularized mostly by the underlying
Thus they connect cones of one area with cones and rods of an- choriocapillaries of the choroid. If the retina surrounding the
other area. fovea becomes semiopaque, as in occlusion of the central retinal
The amacrine association cells are pear shaped. Each has a sin- artery or in some of the lipid storage diseases (e.g., Tay-Sachs dis-
gle process that terminates on a bipolar or ganglion cell process in ease), the choroid underlying the thin avascular fovea appears as
the inner plexiform layer. Müller’s supporting cells send their a bright red circle called a cherry red spot.
processes to the outer plexiform layer.
G. INNER PLEXIFORM LAYER (FIGURE 23–4) Synaptic Organization of the Retina
The inner plexiform, also called synaptic, layer contains axons (Figure 23–5)
of bipolar cells, dendrites of ganglion cells, and processes of the The human retina is considered to be a simple retina in which
association (amacrine) cells. there is relatively little processing of information, compared with
H. LAYER OF GANGLION CELLS (FIGURE 23–4) complex retinas, such as the frog’s, in which information pro-
cessing is more extensive. The different types of cells encoun-
The perikarya of multipolar ganglion cells constitute the eighth
tered in the retina can be divided into three categories:
layer of the retina. Two types of ganglion cells are recognized on
the basis of their dendritic connections: a monosynaptic (midget) • Input elements (rods and cones)
ganglion cell related to a single bipolar midget cell and a diffuse • Output elements (ganglion cells)
(polysynaptic) ganglion cell related to several bipolar cells. The • Intrinsic elements (bipolar, horizontal, and amacrine cells)
axons of ganglion cells traverse the inner surface of the retina and
collect at the papilla, where they penetrate the sclera to form the It is estimated that the human retina contains 100 million
optic nerve. This part of the retina contains no receptor cells and rods, 6 to 7 million cones, and 1 million ganglion cells. This pro-
is called the blind spot. In humans, the number of ganglion cells vides input-to-output ratios of 100:1 for rods and 5:1 for cones.
is estimated to be 1 million. This difference correlates well with the function of cones, namely,
high-acuity vision. The input-to-output ratio is lowest (approxi-
I. OPTIC NERVE LAYER (FIGURE 23–4) mately 1:1) in the fovea centralis, where visual acuity is highest.
The optic nerve layer is composed of axons of ganglion cells that Synaptic interaction in the retina takes place in two layers,
form the optic nerve, as well as some Müller’s fibers and neuroglial the outer plexiform layer and the inner plexiform layer.
cells. Axons of ganglion cells in this layer are unmyelinated but
have a glial sheath around them. They run toward the posterior A. SYNAPTIC INTERACTION IN THE OUTER PLEXIFORM LAYER
pole of the eye, where they form the optic disk and penetrate the (FIGURE 23–5)
sclera to form the optic nerve. In the outer plexiform layer, synaptic interaction occurs both
J. INTERNAL LIMITING MEMBRANE (FIGURE 23–4) vertically and horizontally. The vertical interaction is represented
The expanded inner ends of the processes of Müller’s cells form by the rod and cone terminals on bipolar cell dendrites. The hor-
the internal limiting membrane. Müller’s cells, the cell bodies of izontal interaction is represented by the interaction of horizontal
which are located in the inner nuclear layer, send processes both cell processes with both rod and cone axons. Axon terminals of
outward to the external limiting membrane and inward to the rods (rod spherules) are smaller than cone terminals; the latter
internal limiting membrane. They are thus homologous to glial are flat or pyramidal and large (cone pedicles).
cells of the central nervous system. 1. Receptor–Bipolar Cell Interaction. Bipolar cells provide a
link between photoreceptor cells (rods and cones) and ganglion
Variations in Retinal Structure cells.
As stated previously, there are three varieties of bipolar cells.
The retinal structure just described is maintained throughout the A rod bipolar cell forms synapses with several rod spherules. A
retina except at two sites, the fovea centralis in the central area of midget bipolar cell forms synapses with one cone pedicle. A flat
the retina and the ora serrata at the periphery of the retina. In bipolar cell forms synapses with several cone pedicles.
312 / CHAPTER 23
Rods Cones
Rod bipolar Horizontal cell

cell
Midget
Flat bipolar bipolar cell
cell
Amacrine cell
Midget
ganglion cell
Polysynaptic Figure 23–5. Schematic diagram

ganglion cell of the types of synaptic activity
DIFFUSE OLIGOSYNAPTIC
PATHWAY PATHWAY within the retina.
2. Horizontal Cell–Receptor Interaction. Horizontal cell C. CHARACTERISTICS OF SYNAPTIC INTERACTION

processes form synapses with several cones or rods, relating cones It is apparent, from the preceding description, that synaptic ac-
of one area to rods and cones of another area. Processes of hori- tivity in the retina has the following characteristics:
zontal cells are not classified as either axons or dendrites and pos-
sibly transmit bidirectionally. • It is oriented both vertically (receptor-bipolar-ganglion cell
Horizontal cells receive excitatory (glutaminergic) input from axis) and horizontally (via horizontal and amacrine cell
photoreceptor cones, and in turn form inhibitory GABAergic connections).
contact with adjacent photoreceptor rods and cones. They thus • It is carried out by both diffuse (flat bipolar– or rod bipolar–
serve to sharpen transmission by surround inhibition. polysynaptic ganglion cell) and oligosynaptic (midget bipolar–
midget ganglion cell) pathways (Figure 23–5).
B. SYNAPTIC INTERACTION IN THE INNER PLEXIFORM LAYER
(FIGURE 23–5) Photochemistry and Physiology of the Retina
In the inner plexiform layer, synaptic interaction occurs verti- The retina contains two types of photoreceptors, the rods and
cally, between bipolar and ganglion cells, as well as horizontally, the cones. The rods are highly sensitive to light, have a low
among amacrine, bipolar, and ganglion cells. threshold of stimulation, and are thus best suited for dim-light
1. Bipolar Cell–Ganglion Cell Interaction. Rod bipolar cells vision (scotopic vision). Such vision, however, is poor in detail
project on several ganglion cells. Midget bipolar cells relate to and does not differentiate colors (achromatic). The cones, how-
one ganglion cell (midget ganglion cell). Flat bipolar cells relate ever, have a high threshold of stimulation and function best in
to several ganglion cells. strong illumination (daylight) (photopic vision). They provide
the substrate for acute vision as well as color vision.
2. Amacrine, Bipolar, and Ganglion Cell Interaction. On exposure to light, the visual pigments in the outer seg-
Amacrine cells relate to axons of bipolar cells as well as to den- ments of the rods and cones (rhodopsin and cone opsin, respec-
drites and perikarya of ganglion cells. Amacrine cell processes, tively) break down into two components, retinal (colorless pig-
like horizontal cell processes, probably conduct bidirectionally. ment) and the protein opsin. The degradation of visual pigment
triggers a change in the electric potential of the photoreceptors red light waves interfere with cone stimulation, so the individual
(receptor or generator potential). The generator potential of rods can still see in bright light. The process of dark adaptation has
and cones (unlike similar potentials in other receptors) is in the two components, a fast one attributed to adaptation of cones
hyperpolarizing direction. This unique response of the photo- and a slower one attributed to adaptation of rods.
receptors has been attributed to the fact that the photoreceptor Conversely, when an individual moves from a dark environ-
membrane is depolarized in the resting state (darkness) by a con- ment to a bright one, it takes time to adapt to the bright envi-
stant entry of sodium ions into the outer segment through cyclic ronment. This process, called light adaptation, takes about 5 min
guanosine monophosphate (cGMP)–gated ionophores. Exposure to be effective.
to light closes the cGMP-gated ionophores and reduces the per-
meability of the membrane to sodium ions, lowers the electric A. NIGHT BLINDNESS
current, and hyperpolarizes the membrane. Thus hyperpolariz- Night blindness (nyctalopia) is encountered in individuals with
ing currents in photoreceptors are produced by turning off depo- vitamin A deficiency. As mentioned previously, photoreceptor
larizing sodium ion conductance, whereas the orthodox hyper- pigment is formed of two substances, vitamin A aldehyde (reti-
polarization—inhibitory postsynaptic potential (IPSP)—seen in nal) and the protein opsin. In vitamin A deficiency, the total
other neurons is produced by turning on hyperpolarizing potas- amount of visual pigment is reduced, thus decreasing the sensi-
sium ion conductance in the neuronal membrane. tivity to light of both rods and cones. Although this reduction
The generator potential of photoreceptors leads to hyper- does not interfere with bright-light (daylight) vision, it does sig-
polarization or depolarization of the bipolar and horizontal cells. nificantly affect dim-light (night) vision, because the amount of
Neither of these cell types, however, is capable of triggering a light is not enough to excite the depleted visual pigment. This
propagated action potential. condition is treatable by administration of vitamin A.
On the basis of their hyperpolarizing or depolarizing response,
two types of bipolar cells are identified. One type (off cell) re- Color Vision
sponds by hyperpolarization to a light spot in the center of its
receptive field and by depolarization to a light spot in the area Color vision is a function of the retina, lateral geniculate nu-
surrounding the center (the surround). The other type (on cell) cleus, and cerebral cortex. In the retina, the cone receptors and
responds in a reverse fashion by depolarization to a light spot in the horizontal cells as well as ganglion cells take part in the inte-
the center of its receptive field and by hyperpolarization to the gration of color vision. According to the Young-Helmholtz the-
surround. The bipolar cell is the first of the retinal elements to ory of color vision, there are three varieties of retinal cone recep-
show this variation of response in relation to the spatial position tors: those which respond maximally to long wavelengths in the
of the stimulus in its receptive field. red end of the spectrum (L-cones), those which respond maxi-
The amacrine cell responds to a light stimulus by a propa- mally to medium wavelengths in the green end of the spectrum
gated, all-or-none action potential. It is the first cell of the retinal (M-cones), and those which respond maximally to short wave-
elements to generate a propagated action potential. lengths in the blue range of the spectrum (S-cones). A mono-
Ganglion cells discharge continuously at a slow rate in the ab- chromatic color (red, green, or blue) stimulates one variety of
sence of any stimulus. On superimposition of a circular beam of cones maximally and the other varieties of cones to a variable but
light, ganglion cells may behave in a variety of ways. Some cells lesser degree. Blue light, for example, stimulates blue cones max-
increase their discharge in response to the superimposed stimu- imally, green cones much less so, and red cones not at all. This
lus (“on” cells). Others inhibit their discharge in response to the pattern is interpreted centrally as blue color. Two monochro-
superimposed stimulus but discharge again with a burst when matic colors stimulating two types of cones equally and simulta-
the stimulus is turned off (“off ” cells). Still others increase their neously are interpreted as a different color; thus, if green and red
discharge when the stimulus is turned both on and off (“on-off ” lights stimulate green and red cones simultaneously and equally,
cells). Furthermore, the behavior of ganglion cells, like that of they are interpreted as yellow. Simultaneous and equal stimula-
bipolar cells, is regulated by the spatial position of the stimulus tion by red, green, and blue lights is interpreted as white.
in their receptive field. “On” cells, which increase their discharge The horizontal cells respond to a particular monochromatic
in response to a spot of light in the center of their receptive field, color by either depolarization or hyperpolarization. A red-green
inhibit their discharge when light is shone in the area surround- horizontal cell responds by depolarization to red light and by
ing the center. The same principle applies to “off ” cells, which hyperpolarization to green light. Such a cell is turned off by equal
inhibit their discharge in response to a light stimulus in the cen- and simultaneous stimulation by red and green light. There are also
ter of the receptive field but increase their discharge when the yellow-blue horizontal cells, accounting for the four hues—red,
stimulus is shone in the surround. green, blue, and yellow. The depolarization and hyperpolarization
Furthermore, some ganglion cells respond only to a steady responses of horizontal cells also explain why red with green and
stimulus of light in their receptive field, whereas others respond blue with yellow are complementary colors, which, when mixed
only to a change in intensity of illumination; still others respond together in proper amounts, result in the cancellation of color.
only to a stimulus moving in a particular direction. Ganglion cells of the retina respond in an “on-off” manner to
monochromatic light. Thus there are green “on” and red “off”
Dark and Light Adaptation ganglion cells, blue “on” and yellow “off” ganglion cells, and so on.
Furthermore, there are color-sensitive neurons in the lateral
When an individual moves from an environment of bright light geniculate nucleus and occipital cortex that respond maximally
to dim light or darkness, the retina adapts and becomes more to color in one part of the spectrum. They also play a role in
sensitive to light. This process, called dark adaptation, takes color discrimination. The color-contrast cells in the striate cortex
about 20 min to become maximally effective. The time required form a distinct population separate from cells concerned with
for maximal adaptation to darkness can be shortened by wearing brightness contrast. As with cells concerned with brightness dis-
red glasses. Light waves in the red end of the spectrum do not ef- crimination, the color-contrast cells can be divided into simple,
fectively stimulate the rods, which remain dark-adapted. Nor do complex, and hypercomplex cells.
314 / CHAPTER 23
A. COLOR BLINDNESS VISUAL

FIELD
Some people have a deficiency in or lack of a particular color cone.
Such people have color weakness or color blindness, respectively.
Most color-blind persons are red-green blind; a minority are blue
blind. Among the group blind to red-green, there is a prepon-
derance of green color blindness. EYE Nasal Temporal
Color blindness for red and green is inherited by an X-linked
recessive gene; thus there are more males with red-green color
blindness than females. Color blindness for blue is inherited
through an autosomal gene and is much less common. Pure red
color blindness is known as protanopia. Pure green color blind-
Ipsilateral
ness is known as deuteranopia. Blue-yellow blindness is known A blindness
as tritanopia.
Color blindness was first described, in 1794, by John Dalton, OPTIC NERVE
a color-blind English chemist. The phenomenon may have been
reported earlier, in 1777, by Joseph Huddard.
B Bitemporal
OPTIC CHIASMA
Visual Pathways hemianopia
Axons of ganglion cells in the retina gather together at the optic

disk in the posterior pole of the eye, penetrate the sclera, and
form the optic nerve. At the point of exit of ganglion OPTIC TRACT C
cell axons from the retina the optic disk is devoid of re-
ceptor elements (blind spot). There are approximately Homonymous
hemianopia
one million axons in the optic nerve. Outside the sclera, the op-
tic nerve is covered by extensions of the meninges that en- Lateral
sheathe the brain. Marked increase in intracranial pressure from geniculate
tumors or bleeding inside the cranial cavity or an increase in nucleus
cerebrospinal fluid pressure around the nerve sufficient to in-
terfere with venous return from the retina results in swelling of Geniculocalcarine
the optic disk (papilledema). This swelling can be seen using a tract D
special instrument, an ophthalmoscope, which views the retina
through the pupil. The optic nerve enters the cranial cavity Homonymous
through the optic foramen. Thus tumors of the optic nerve (op- hemianopia
tic glioma) may be diagnosed by taking radiographs of the optic
foramen, which appears enlarged in such conditions. Lesions of
the optic nerve produce unilateral blindness on the side of the
lesion (Figure 23–6). VISUAL CORTEX
The two optic nerves come together at the optic chiasma,
where partial crossing of optic nerve fibers takes place. Optic Figure 23–6. Schematic diagram of the visual pathways show-
nerve fibers from the nasal half of each retina cross at the optic ing clinical manifestations of lesions in various sites.
chiasma. Fibers from the temporal halves remain uncrossed. The
optic chiasma is related to the hypothalamus above and pituitary
gland below. Thus tumors in the pituitary gland encroaching (as
they do initially) on the crossing fibers of the optic nerve cause from the upper halves of both retinae course directly backward
degeneration of optic nerve fibers arising in the nasal halves of around the lateral ventricle in the inferior part of the parietal
both retinae. This results in loss of vision in both temporal fields lobe to reach the visual cortex. Geniculocalcarine fibers from the
of vision (bitemporal hemianopia) (Figure 23–6). lower halves of both retinae course forward toward the tip of the
The crossed and uncrossed fibers from both optic nerves join temporal horn of the lateral ventricle and then loop backward
caudal to the optic chiasma to form the optic tract. Le- (Meyer’s loop, Flechsig’s loop, Archambault’s loop) in the tempo-
sions of the optic tracts, therefore, cause degeneration of ral lobe to reach the visual cortex. Lesions of the geniculocal-
optic nerve fibers from the temporal half of the ipsilat- carine tract give rise to a contralateral homonymous hemianopia
eral retina and nasal half of the contralateral retina. This pro- similar to that occurring with lesions of the optic tract (Figure
duces loss of vision in the contralateral half of the visual field 23–6). Because of the spread of geniculocalcarine fibers in the
(homonymous hemianopia) (Figure 23–6). parietal and temporal lobes, a lesion involving part of this fiber
The lateral geniculate nucleus is laminated into six layers. system at these sites produces a contralateral quadrantic visual
Not all parts of the retina are represented equally in the lateral field defect (upper if the temporal fibers are affected and lower if
geniculate nucleus. Proportionally much more of the nucleus is the parietal fibers are affected) (Figure 23–7).
devoted to the representation of the central area than of the pe- The geniculocalcarine fibers project on neurons in the primary
riphery of the retina. visual cortex (area 17 of Brodmann). As described in the chapter
Axons of neurons in the lateral geniculate nucleus project to on cerebral cortex (Chapter 17), fibers from the upper retina ter-
the visual cortex in the occipital lobe via the geniculocal- minate in the upper calcarine gyrus, those from the lower retina
carine tract (optic radiation). Geniculocalcarine fibers in the lower calcarine gyrus, those from the macular area of the
nferior quadrantic
hemianopia
Superior quadrantic
hemianopia
Figure 23–7. Schematic diagram showing the clinical manifestations of lesions in the optic radiation in the temporal and
parietal lobes.
retina posteriorly, and those from the peripheral retina anteriorly tough connective tissue made up of collagen and elastic fibers
in the visual cortex. Thus a lesion destroying the whole and fibroblasts.
of the visual cortex on one side produces contralateral
homonymous hemianopia, whereas a lesion destroying the B. MIDDLE EAR
upper or lower calcarine gyrus will produce only a contralateral The middle ear (tympanic cavity) is located within the temporal
lower or an upper quadrantic visual field defect. As stated in bone. It communicates with the nasopharynx anteriorly via the
Chapter 17, vascular lesions in the occipital cortex tend to spare eustachian (auditory) tube and with the mastoid air cells posteri-
the macular area because of its two sources of blood supply (pos- orly. The tympanic membrane separates the middle ear medially
terior and middle cerebral arteries). from the external ear laterally. Two windows (oval and round)
In addition to the classic geniculostriate visual pathway that separate the middle ear from the inner ear. The middle ear cavity
terminates in the primary visual (striate) cortex, a second visual is traversed by three bony ossicles. The malleus is attached to the
pathway has been described; this is the retinocolliculopulvinar- tympanic membrane, the stapes fits into the foramen ovale (oval
cortical pathway, which terminates in extrastriate cortical areas, window), and the incus is in between. The three ossicles transmit
including areas 18 and 19 and the temporal lobe. The classic sound vibrations from the tympanic membrane to the oval win-
geniculostriate pathway is concerned with the identification of dow. The cavity also contains two muscles, the tensor tympani and
objects, whereas the second visual pathway is important for pro- stapedius. The tensor tympani muscle inserts into the malleus
cessing highly abstracted visual perceptions. and the stapedius muscle into the stapes.
HEARING C. INNER EAR

The Ear The inner ear, located within the petrous portion of the tempo-
ral bone, contains two systems of canals or cavities, the
The ear has three compartments: external, middle, and internal. osseous labyrinth and the membranous labyrinth. Both
Each component plays a specific role in the hearing process. The systems contain fluids, perilymph in the osseous labyrinth
organs of hearing and equilibrium are located within the internal and endolymph in the membranous labyrinth. Perilymph has a
compartment of the ear. high concentration of sodium ions, whereas endolymph has a
high concentration of potassium ions. The osseous labyrinth has
A. EXTERNAL EAR a large central cavity, the vestibule, located medial to the tympanic
The external ear is formed of the auricle or pinna, external audi- cavity. Three semicircular canals open into the vestibule posteri-
tory canal, and tympanic membrane. The auricle collects sound orly, and a coiled winding tube, the cochlea, communicates with
and funnels it into the external auditory meatus. The external the vestibule anteriorly.
auditory canal is a narrow tube through the temporal bone. The membranous labyrinth, located within the osseous laby-
The tympanic membrane (eardrum) delimits the external au- rinth, maintains a similar configuration. The central cavity of
ditory canal medially. The core of the tympanic membrane is the membranous labyrinth (within the vestibule of the osseous
316 / CHAPTER 23
labyrinth) contains two cavities. The utricle, the posterior cavity, The tensor tympani muscle, attached to the handle of the
communicates with the membranous labyrinth of the semicircu- malleus, and the stapedius muscle, attached to the neck of the
lar canals (semicircular ducts). The saccule, the anterior cavity, stapes, have a damping effect on sound waves. Loud sounds cause
communicates with the membranous labyrinth of the cochlea these muscles to contract reflexively, to prevent strong sound
(cochlear duct). At the junction of the membranous semicircular waves from excessively stimulating the hair cells of the organ of
canals (semicircular ducts) with the utricle, the epithelium of the Corti; this is the tympanic reflex. When this damping effect is lost,
semicircular ducts becomes specialized to form a receptive sen- as in lesions of the facial nerve (which supplies the stapedius mus-
sory area (neuroepithelium) for equilibrium, the crista ampullaris. cle), or the trigeminal nerve (which supplies the tensor tympani)
Similar sensory receptive areas in the utricle and saccule are the sound stimuli are augmented unpleasantly (hyperacusis).
macula utriculi and the macula sacculi. The macula sacculi is lo- Because of the marked difference in elasticity and density be-
cated in the floor of the saccule, whereas the macula utriculi is in tween air and fluid, almost 99 percent of acoustic energy is re-
the lateral wall of the utricle at right angles to the saccule. The flected back at the air-fluid interface between the middle ear and
sensory receptive organ for hearing is the organ of Corti within inner ear. This is counteracted by two mechanisms. First, the ratio
the cochlear duct. between the surface areas of the tympanic membrane and the foot-
plate of the stapes is approximately 25:1. However, because the
Sound Transmission (Figure 23–8) tympanic membrane is not a piston but a stretched membrane at-
tached around its edge, its effective area is 60 to 75 percent of its
Our current knowledge of sound transmission started in the sixth actual area. Thus the ratio between the effective area of the tym-
century B.C. when Pythagoras, the Greek mathematician, intro- panic membrane and the area of the footplate of the stapes is only
duced the concept that sound was a vibration in the air. Seven 14:1. Second, the lever effect counteracts energy lost at the air-
centuries later, in 175 A.D., Galen, the Greek physician, recog- fluid interface. The movements of the tympanic membrane are
nized that the sensation of sound was transmitted to the brain via transmitted to the malleus and incus, which move as one unit. The
nerves. The gap in knowledge between Pythagoras’s sound as air manubrium of the malleus is a longer lever than the long process
vibration and Galen’s nerves transmitting sound to the brain was of the incus. The force exerted at the footplate of the stapes is thus
filled in 1543 by the Belgian anatomist Andreas Vesalius, who greater than that at the tympanic membrane by a ratio of 1.3:1.
discovered the malleus and incus bones in the middle ear. Several The total pressure amplification via the two mechanisms just
years later, in 1546, Ingrassias discovered the third middle ear os- described thus counteracts the energy lost at the air-fluid inter-
sicle, the stapes. In 1561, the Italian anatomist Gabriello face. The total gain in force per unit area achieved by conduc-
Fallopius named the cochlea, and in 1851, Alfonso Corti, the tance in the middle ear is a factor of about 18.
Italian anatomist, discovered the organ of Corti.
Sound waves traverse the external ear and middle ear before Cochlea
reaching the inner ear, where the auditory end organ (organ of
Corti) is located. The tympanic membrane between the external The cochlea is a snail-shaped structure consisting of two and
ear and middle ear vibrates in response to pressure changes pro- one-half spirals filled with fluid. It has three compartments
duced by the incoming sound waves. Vibrations of the tympanic (Figure 23–9), the scala vestibuli, scala tympani, and scala media
membrane are transmitted to the bony ossicles of the middle ear (cochlear duct). The three compartments wind together in a cir-
(malleus, incus, and stapes). The handle of the malleus is at- cular pattern around a central core, the modiolus which contains
tached to the tympanic membrane, and the footplate of the the spiral ganglion. The scala vestibuli and scala tympani are sep-
stapes is attached to the oval window between the middle ear and arated by a bony shelf (osseous spiral lamina) projecting from the
inner ear. Vibrations of the footplate of the stapes are then trans- modiolus across the osseous canal of the cochlea.
mitted to the membrane of the oval window and subsequently to The scala media, lying between the scala vestibuli (above) and
the fluid medium (perilymph) of the inner ear. the scala tympani (below), contains the auditory end organ (organ

of the three compartments of the
ear showing transmission of sound
waves.
Oval Scala vestibuli Reissner's membrane forms the base of the cochlear duct and gives support
window (perilymph) membrane Helicotrema to the organ of Corti (Figure 23–10). The organ of Corti con-
tains the following cellular elements (Figure 23–11).
A. HAIR CELLS
The auditory receptor cells, the hair cells, are of two types: inner
hair cells, which number approximately 3500 arranged in a single
row, and outer hair cells, which number approximately 20,000
arranged in three to four rows. The “hairs” (or stereocilia) of the
hair cells are in contact with the tectorial membrane, which trans-
mits to them vibrations from the endolymph. The hair cells are
columnar or flask shaped, with a basally located nucleus and
ilar about 50 to 100 hairlike projections emanating from their apical
mbrane surfaces. Cochlear nerve fibers establish synapses with their basal
Round Scala tympani Scala media membranes.
window (perilymph) (endolymph)
B. SUPPORTING CELLS
Figure 23–9. Schematic diagram showing the three compo- Supporting cells are tall, slender cells extending from the basi-
nents of the cochlea and their interrelationships. lar membrane to the free surface of the organ of Corti. They in-
clude the following cell types: pillar or rod cells (outer and in-
ner), phalangeal (Deiters’) cells (outer and inner), and cells of
of Corti). The scala vestibuli and scala tympani are continuous Hensen.
through the helicotrema at the apex of the coil. The oval window 1. Pillar Cells. Pillar cells are filled with tonofibrils. The apices of
and round window separate, respectively, the scala vestibuli and the inner and outer pillar cells converge at the free surface of the
scala tympani from the middle ear (Figure 23–9). organ of Corti and fan out as a cuticle to form, along with a simi-
Vibrations of the oval window are transmitted to the peri- lar formation of Deiters’ cells, a thin plate through which the
lymph in the scala vestibuli and, subsequently, via Reissner’s apices of the inner and outer hair cells pass. The space between in-
membrane (which separates the scala vestibuli from the scala me- ner and outer pillar cells comprises a fluid-filled tunnel of Corti.
dia), to the endolymph of the scala media. Vibrations in the en-
dolymph are then transmitted via the basilar membrane (which 2. Phalangeal (Deiters’) Cells. Arranged in three to four outer
separates the scala media from the scala tympani) to the peri- rows and one inner row, Deiters’ cells give support to the outer
lymph of the scala tympani and out through the round window. and inner hair cells, respectively. They extend from the basilar
membrane, like all supporting cells, to the free surface of the or-
gan of Corti, where they contribute to the formation of the cu-
Auditory End Organ (Organ of Corti) ticular plate through which the hairs of the hair cells pass.
The organ of Corti (Figure 23–10) is located in the scala media Phalangeal cells are flask shaped and contain tonofibrils. Some of
(cochlear duct), which is separated from the underlying scala the tonofibrils support the base of the hair cells; others extend
tympani by the basilar membrane and from the scala vestibuli by along their sides to the free surface of the organ.
Reissner’s (vestibular) membrane. The cochlear duct is part of 3. Cells of Hensen. Cells of Hensen are columnar cells located
the endolymphatic system and contains endolymph. The basilar adjacent to the outermost row of outer phalangeal cells. They
Reissner's membrane Scala media
Tectorial
membrane
Scala vestibuli Organ of Corti

gram of the cochlear compart- Basilar
membrane
ments showing the organ of Corti
Scala tympani
in the scala media.
318 / CHAPTER 23
Basilar Inner Outer Cells duce vibrations in the tympanic membrane, which are transmit-
membrane hair cells hair cells of Hensen ted to the bony ossicles of the middle ear and through them to
the footplate of the stapes. The energy lost at the air-fluid inter-
face in the oval window is counteracted by the factors outlined
Border previously.
cells
2. Air Route. An alternate route, the air route, is used when the
orthodox ossicular route is not operative owing to disease of the
ossicles. In this situation, vibrations of the tympanic membrane
are transmitted through air in the middle ear to the round win-
dow. This route is not effective in sound conduction.
3. Bone Route. Sound waves also may be conducted via the
bones of the skull directly to the perilymph of the inner ear. This
Inner Inner Tunnel Outer Outer Cells
route plays a minor role in sound conduction in normal individ-
phalangeal pillar of Corti pillar phalangeal of Claudius uals but is utilized by deaf people who can use hearing aids.
cells cells cells cells
B. FLUID VIBRATION
Figure 23–11. Simplified schematic diagram of the cellular Vibrations of the footplate of the stapes are transmitted to the
components of the organ of Corti. perilymph of the scala vestibuli. Pressure waves in the perilymph
are transmitted via Reissner’s membrane to the endolymph of
the scala media and, through the helicotrema, to the perilymph
constitute the outer border of the organ of Corti. They merge lat- of the scala tympani (Figure 23–9).
erally with cuboidal cells (cells of Claudius). Similar (cuboidal)
cells adjacent to the inner phalangeal cells, known as border cells, C. VIBRATIONS OF BASILAR MEMBRANE
constitute the inner border of the organ. Pressure waves in the endolymph of the scala media produce
4. Tectorial Membrane. The tectorial membrane is a gelatinous traveling waves in the basilar membrane of the organ of Corti.
structure in which filamentous elements are embedded. It ex- The basilar membrane varies in width and degree of stiffness in
tends over the free surface of the organ of Corti. The hairs of the different regions. It is widest and more flaccid at its apex and
hair cells are attached to the tectorial membrane. Vibrations in thinnest and more stiff at its base.
the endolymph are transmitted to the tectorial membrane, re- Pressure waves in the endolymph initiate a traveling wave in
sulting in deformation of the hairs attached to it. Such deforma- the basilar membrane that proceeds from the base toward the
tion initiates an impulse in the afferent nerve fibers in contact apex of the membrane. The amplitude of the traveling waves
with the basal part of the hair cells. varies at different sites on the membrane depending on the fre-
5. Nerve Supply. The hair cells of the organ of Corti receive two quency of sound waves. High-frequency sounds elicit waves with
types of nerve supply, afferent and efferent. The afferent fibers highest amplitude toward the base of the membrane. With low-
are peripheral processes of bipolar neurons in the spiral ganglion frequency sounds, the waves with highest amplitude occur toward
located in the bony core (modiolus) of the cochlear spiral. There the apex of the membrane. Similarly, each sound frequency has a
are about 30,000 bipolar neurons in the spiral ganglion, 90 per- site of maximum amplitude wave on the basilar membrane. The
cent of which (type I neurons) innervate the inner hair cells. frequency of the wave, measured in cycles per second or hertz
Each inner hair cell receives contacts from about ten fibers; each (Hz), determines its pitch. The amplitude of the wave is corre-
fiber contacts only one inner hair cell. The remaining 10 percent lated with its loudness; a special scale, the decibel (dB) scale, is
(type II neurons) innervate the outer hair cells; each fiber diverges used to measure this aspect of sound. Thus the basilar membrane
to innervate many outer hair cells. exhibits the phenomenon of tonotopic localization seen along the
The efferent fibers originate in the contralateral superior olive central auditory pathways all the way to the cortex.
and periolivary nuclei in the pons. These fibers form the
olivocochlear bundle of Rasmussen, which leaves the D. RECEPTOR POTENTIAL
brain stem via the vestibular component of the vestibu- Vibrations of the basilar membrane produce displacement of
locochlear (eighth cranial) nerve, joins the cochlear component the hair cells, the hairs of which are attached to the tectorial
(vestibulocochlear anastomosis), and terminates peripherally on membrane. The shearing force produced on the hairs by the dis-
the outer hair cells and the afferent terminal boutons innervating placement of hair cells is the adequate stimulus for the receptor
inner hair cells. These fibers have an inhibitory effect on audi- nonpropagated potential of the hair cells. Hair cells, like all ex-
tory stimuli. citable nerve cells, have an excess of negatively charged ions in-
side and an excess of positively charged ions in the surrounding
Auditory Physiology endolymph. The displacement of the stereocilia of hair cells
opens pores on the stereocilia, which allows positive ions to rush
A. CONDUCTION OF SOUND WAVES inside, causing depolarization. This receptor potential is also
Sound waves may reach the inner ear via three routes: known as the cochlear microphonic potential. It can be recorded
from the hair cells and their immediate neighborhood and is a
• Ossicular route faithful replica of the mechanical events of sound waves described
• Air route previously.
• Bone route E. ACTION POTENTIAL
1. Ossicular Route. The ossicular route normally conducts The receptor potential causes the hair cell to release neurotrans-
sound. Sound waves entering the external auditory meatus pro- mitter substances that interact with receptors on nerve terminals
and thus initiates an action potential in the afferent nerves in includes deafness due to obstruction of the external auditory
contact with hair cells. meatus by wax, as well as middle ear diseases, such as chronic oti-
Increasing the intensity of sound of a particular frequency tis media and ossicle sclerosis. The second group includes condi-
raises the number of hair cells stimulated, the number of affer- tions in which hair cells are affected (advancing age, strepto-
ent nerve fibers activated, and the rate of discharge of impulses. mycin toxicity), as well as diseases of the auditory nerve, such as
A single nerve fiber responds to a range of frequencies but is nerve tumors (acoustic neuroma).
most sensitive to a particular frequency, called its characteristic The two types of deafness can be identified clinically by use
frequency; this is related to the region of the basilar membrane of the tuning fork. A vibrating tuning fork is placed in front of
that the fiber innervates. Fibers innervating the part of the the ear and then on a bony prominence over the skull. A person
basilar membrane near the oval window have high characteristic with normal hearing can hear the tuning fork better when it is
frequencies, whereas those innervating the part of the basilar placed in front of the ear. A subject with conductive deafness
membrane near the apex of the cochlea have low characteristic hears the tuning fork better when it is placed over a bony promi-
frequencies. nence, because sound waves bypass the site of obstruction in the
external auditory meatus or the middle ear and reach the audi-
F. CENTRAL TRANSMISSION tory end organ via the round window or directly through skull
Action potentials generated in the afferent nerve fibers travel via bones to the perilymph.
the central components (axons) of bipolar neurons in the spiral In patients with unilateral sensorineural deafness, a tuning fork
ganglion to reach the cochlear nuclei in the pons. The placed over the forehead will be heard best in the healthy ear, since
cochlear nuclei contain a variety of physiologic cell types. air conduction in such patients is better than bone conduction.
In addition to cells that respond to tone bursts in a man- Patients with severe sensorineural deafness may be helped by
ner similar to primary eighth nerve fibers, there are cells that re- cochlear implants.
spond only to the onset of the stimulus, some in which the rate
of firing builds up slowly during the course of the stimulus and
others that pause, showing no response to the onset of the stim- VESTIBULAR SENSATION
ulus. Axons of cochlear nuclei synapse in some or all of several
brain stem nuclei (nucleus of the trapezoid body, superior olive, The receptors of the vestibular sense organ are located in the
nucleus of the lateral lemniscus, inferior colliculus, reticular nu- semicircular canals, utricle, and saccule in the inner ear. The
clei of the brain stem, medial geniculate nucleus) before termi- utricle and saccule are located in the main cavity of the
nating in the primary auditory cortex (transverse gyri of Heschl) bony labyrinth, the vestibule; the semicircular canals,
in the temporal lobe. The central auditory pathways are orga- three in number, are extensions of the utricle (Figure
nized into two systems: core pathways, and belt pathways. Core 23–12). Vestibular sensory receptors are located in the floor of
pathways are direct, fast conducting, and tonotopically orga- the utricle, wall of the saccule, and dilated portions (ampullae)
nized. Belt pathways are less tonotopically organized. of each of the three semicircular canals. The optimal stimulus
for receptors in the utricle and saccule is linear acceleration of
the body (as occurs in body motion on a swing when coupled
Otoacoustic Emissions with gravity to change the direction and degree of the acceler-
Recent research on the cochlea has suggested that the cochlea ation and head tilt), whereas receptors in the semicircular
not only receives sounds but also produces sound. The term canals respond to angular acceleration resulting from head or
otoacoustic emission has been coined to describe this observation. body turns.
It is now believed that the outer hair cells are the source of oto-
acoustic emissions.
Semicircular canals
Audiometry
The quantitative clinical assessment of hearing acuity is known
as audiometry; the resulting record is the audiogram. In audiome-
try, pure tones of known frequency and varying intensity are pre-
sented via earphones to the individual, who is asked to signal a
response when he or she hears a tone. The examiner records the
audible frequencies and intensities on a chart. The record is then
examined to compare the audible range of the individual with
that of normal individuals.
Deafness
The range of audible frequencies in the normal adult is 20 to
20,000 Hz. With advancing age, there is a decrease in perception
of high frequencies (high-frequency deafness). This loss corre-
lates with the loss of hair cells in the basal turns of the cochlea.
Similar high-frequency deafness is encountered in individuals in-
toxicated by the antibiotic streptomycin. Rock band performers,
on the other hand, develop middle-frequency deafness. Saccule
Deafness disorders generally are separated into two groups,
conductive deafness and sensorineural deafness. The first group Figure 23–12. Schematic diagram of the vestibular end organ.
320 / CHAPTER 23
The vestibular receptor in the semicircular canal (crista am- nal. The efferent terminals in type I hair cells are applied to the
pullaris) is composed of hair cells and supporting cells (Figure external surface of the calyx.
23–13). The hair cells are of two types. The type I hair cell is Type I hair cells receive vestibular nerve fibers that are large in
flask shaped and is surrounded by a nerve terminal (calyx). The diameter and fast conducting. Each vestibular nerve fiber inner-
type II hair cell is cylindrical and is not surrounded by a calyx. vates a small number of type I hair cells. Thus type I hair cells are
Both types of hair cells show on their free surfaces about 40 to regarded as more discriminative than type II hair cells, which re-
100 short stereocilia (modified microvilli) and one long kino- ceive small-diameter, slow-conducting vestibular nerve fibers
cilium attached to one border of the cell. The short stereocilia in- projecting on a large number of hair cells.
crease progressively in length toward the kinocilium. The stereo- The stimulus adequate to discharge hair cells is movement of
cilia are nonmotile; the kinocilium is motile. the cupula or otolithic membrane, which bends or deforms the
Supporting cells are slender columnar cells that reach the basal stereocilia. Deformation of stereocilia toward the kinocilium trig-
lamina; their free surfaces are specialized into microvilli. The sub- gers inflow of potassium ions into the hair cells from the en-
apical parts of supporting cells are related to adjacent hair cells by dolymph and depolarization of cell membrane. Deflection of
junctional complexes. stereocilia away from the kinocilium allows potassium ions to flow
The apical processes of hair and supporting cells are embed- out of cells and hyperpolarization of hair cell membrane. The rest-
ded in a dome-shaped, gelatinous protein-polysaccharide mass, ing vestibular end organ has a constant discharge of impulses de-
the cupula. The cupula swings from side to side in response to tected in afferent vestibular nerve fibers. This resting activity is
currents in the endolymph that bathes it. modified by mechanical deformation of the stereocilia. Bending
The vestibular receptor organ of the utricle and saccule (mac- the stereocilia toward the kinocilium increases the frequency of
ula) is similar in structure to that of the semicircular canals. The resting discharge, whereas bending the stereocilia away from the
gelatinous mass into which the apical processes of hair and sup- kinocilium lowers the frequency. The signals emitted by hair cells
porting cells project is the otolithic membrane. It is flat and con- of the vestibular end organ are transmitted to the central nervous
tains numerous small crystalline bodies, the otoliths or otoconia, system via processes of bipolar cells in Scarpa’s ganglion that ter-
composed of calcium carbonate and protein. minate on neurons in the four vestibular nuclei in the
The hair cells of the semicircular canals, utricle, and saccule pons. Output of vestibular nuclei is directed to several
receive both afferent and efferent nerve terminals (Figure 23–13). central nervous system regions, including the spinal cord,
The afferent terminals contain clear vesicles, whereas efferent ter- cerebellum, thalamus, and nuclei of extraocular movements. The
minals contain dense-core vesicles. In type II hair cells, both af- pathway to the primary vestibular cortex in the temporal lobe is
ferent and efferent terminals are related to the cell body and are not well defined but most likely passes through the thalamus.
sites of neurochemical transmission. In type I hair cells, the calyx Although we are normally not aware of the vestibular
that surrounds the hair cell is regarded as the afferent nerve termi- component of our sensory experience, this component is
essential for the coordination of motor responses, eye
movements, and posture.
TERMINOLOGY
Amacrine (Greek a, “negative”; makros, “long”). Having no
long processes. The amacrine cells of the retina have no long
processes.
Bowman’s gland. Branched and tubuloalveolar glands located be-
neath the olfactory epithelium. Secretions of the glands are impor-
tant in dissolving odorous substances and diffusing them to ol-
factory receptor cells. Named after Sir William Bowman (1816–
1892), an English ophthalmologic surgeon and anatomist.
Cells of Hensen. Type of cells in the organ of Corti. Named af-
ter Viktor Hensen (1835–1924), a German physiologist.
Chiasma (Greek chiasma, “two-crossing line,” from the
shape of the letter chi, “X”). The decussation of the fibers of
the optic nerve. The decussation was described by Galen without
naming it. It was named by Rufus of Ephesus.
Ciliary muscle (Latin cilium, “eyelid or eyelash”). Smooth
muscles of the ciliary body; the circumferential fibers were de-
scribed by Heinrich Müller in 1858 and the radial fibers by
William Bowman in 1847. Together they control the aperture of
the pupil and the degree of curvature of the lens.
Circumvallate (Latin circum, “around”; vallare, “to wall”).
Surrounded by a trench or wall.
Cochlea (Latin, “snail shell,” from Greek “a winding stair-
case”). The coiled winding tube of the cochlea in the inner ear
Figure 23–13. Schematic diagram of the vestibular sensory resembles a snail shell. It was first described by Eustachio (1552)
receptor. and named cochlea by Fallopius about 1561.
Cornea (Latin corneus, “horny”). The transparent structure Macula lutea (Latin, “a small spot, yellow”). The portion of
forming the anterior part of the fibrous tunic of the eye. the retina on the temporal side of the optic disk. It contains the
Corti, Alfonso Marchese (1822–1888). Italian histologist who greatest concentration of cone receptors.
described the end organ of hearing, the organ of Corti. Malleus (Latin malleus, “a hammer”). One of the bones of the
Cribriform (Latin cribrum, “a sieve”; forma, “form”). The middle ear. So named by Vesalius in 1543, but probably seen
cribriform plate of the ethmoid bone is so named because of the much earlier.
numerous perforations. Meatus (Latin meo, “passage”). The external auditory meatus
Cupula. (Latin, “a small inverted cup or dome-shaped cap”). is a path or a way for sound waves.
Deiters’ cells. Also known as phalangeal cells. One type of cell in Meyer, Adolph (1866–1950). Swiss neuropsychiatrist who im-
the organ of Corti. Described by Otto Friedrich Karl Deiters migrated to the United States and was on the faculty of Cornell
(1834–1863), a German anatomist. and Johns Hopkins. Described the part of the optic radiation
that loops around the tip of the temporal horn (Meyer’s loop).
Deuteranopia (Greek deuteros, “second”; an, “negative”;
opia, “vision”). Complete insensitivity to green. Patients con- Mitral (Latin mitra, “a kind of a hat with two cusps, a turban,
fuse red and green but are sensitive to red light. or head band”).
Eustachian tube. The auditory tube, a connection between Modiolus (Latin, “the hub of a wheel”). The central pillar of
the middle ear and nasopharynx. Named after Bartolommeo the cochlea. Described and so named by Eustachio in 1563. Its
Eustachio, the Italian anatomist who provided the classic de- structure suggests the hub of the wheel with radiating spokes
scription of this structure in 1563. The term eustachian tube was (lamina spiralis) attached to it.
coined by Val Salva in 1704. The eustachian tube was known to Nyctalopia (Greek nyx, “night”; alaos, “blind”; opia, “eye”).
the ancients. Alcmaeon (500 B.C.) had dissected it. It was de- Night blindness.
scribed by Aristotle and other early writers. Olfactory (Latin olfacere, “to smell”). Pertaining to the sense
Fallopius, Gabriel (1523–1563). Italian anatomist. Credited of smell. The olfactory nerve, the first cranial nerve in today’s
with description of the facial canal and of the trochlear, trigemi- classification, was proposed by Soemmerring (1755–1830), the
nal, glossopharyngeal, and vagus nerves as well as the cochlea in German anatomist, although it was not included as a cranial
the inner ear. He is believed to have, in his drawings, noted the nerve by Galen. The olfactory nerves were first noted by
circle of Willis before Thomas Willis. Theophilus Protospatharius, physician to the Emperor Heraclius
in the seventh century A.D. The function of the olfactory nerve
Flechsig, Paul Emile (1847–1929). Bohemian neurologist and
was correctly stated by Achillini, and its relationship to the
psychiatrist. Defined the dorsal spinocerebellar tract (Flechsig
neuroepithelium of the nasal mucosa was demonstrated by Max
tract) in 1876 and the part of the optic radiation (known as
Schultze in 1856.
Meyer’s loop or Flechsig loop) that loops around the tip of the
temporal horn. Organ of Corti. Auditory end organ in the inner ear. Named af-
ter Marchese Alfonso Corti (1822–1888), the Italian histologist
Fovea (Latin, “a pit, a small hollow”). The part of the macula who is known for his investigations of the mammalian cochlea in
that receives light from the central part of the visual field and 1851.
which contains high concentration of cones.
Pinna (Latin, “a feather”). The part of the external ear that pro-
Fungiform. Shaped like a fungus or mushroom. jects from the side of the head. So named by Rufus of Ephesus.
Galen, Claudius (130–201 A.D.). Greek physician and founder Protanopia (Greek protos, “first”; an, “negative”; opia, “vi-
of the galenical system of medicine. Among his many contribu- sion”). Absence of red sensitive pigment in cones. Patients are
tions are the descriptions of the Great Vein of Galen, seven pairs insensitive to red light and confuse red and green light.
of cranial nerves, CSF production from choroid, CSF circula-
tion, and transmission of sound to the brain via nerves. Pythagoras. Greek mathematician. Proposed that sound is an
air vibration. He also was the first to advance the concept that
Gustatory (Latin gustatorius, “pertaining to the sense of taste”). the power of reasoning is in the brain.
Helicotrema (Greek helix, “a spiral”; trema, “a hole”). The Reissner’s membrane. The membrane that separates the scalae
passage or hole that connects the scala vestibuli at the apex of the vestibuli and media. Described in 1851 by Ernst Reissner
cochlea with the scala tympani. First described in 1761 by (1824–1878), a German anatomist.
Cotugno and so named by Breschet. Scala (Latin, “stairway or ladder”). The scala tympani and
Hemianopia (Greek hemi, “half ”; a, “without”; opia, “eye”). scala vestibuli are so named because of their circular staircase
Loss of vision in one-half the visual field. appearance.
Homonymous (Greek homos, “same”; onoma, “name”). Per- Sclera (Greek skleros, “hard”). The outermost, tough, fibrous
taining to the corresponding halves of the visual fields. coat of the eyeball. The term was first used to refer to the whole
Incus (Latin anvil, “one of the bones in the middle ear”). So white outer layer by Salomon Albertus, professor of anatomy in
named by Vesalius in 1543, although probably seen much earlier. Wittenburg in 1585.
Ingrassias, Giovanni Filipo (1510–1580). Italian anatomist. Stapes (Latin, “a stirrup”). The stapes of the middle ear resem-
Described the stapes bone in the middle ear in 1546. He called it bles a stirrup. So named by Ingrassias in 1546.
“stapha.” Eustachio later asserted (1564) that he had found the Tectorial membrane (Latin tego, “a covering”).
bone before Ingrassias. Tritanopia (Greek tritos, “third”; an, “negative”; opia, “vi-
Labyrinth (Greek labyrinthos, “a system of interconnecting sion”). Absence of blue sensitive pigment in retinal cones. Patients
cavities or canals,” as in the inner ear). are insensitive to blue light but do not confuse red and green.
Lens (Latin lentil, “a bean”). The lens of the eye resembles a Vesalius, Andreas (1514–1564). Belgian anatomist. Considered
lentil. one of the greatest anatomists of all time.
322 / CHAPTER 23
SUGGESTED READINGS Mafee MF et al: Large vestibular aqueduct and congenital sensorineural hear-
ing loss. AJNR 1992; 13:805–819.
Barbur JL et al: Human visual responses in the absence of the geniculo- Merigan WH, Maunsell JHR: How parallel are the primate visual pathways:
calcarine projection. Brain 1980; 103:905–928. Annu Rev Neurosci 1993; 16:369–402.
Brown KT: Physiology of the retina. In Mountcastle VB (ed): Medical Physiol- Nelson GM: Biology of taste buds and the clinical problem of taste loss. The
ogy, 14th ed, vol 1. St. Louis, Mosby, 1980:504. Anat Rec (New Anat) 1998; 253:70–78.
Goldstein MH: The auditory periphery. In Mountcastle VB (ed): Medical Shepherd GM: Synaptic organization of the mammalian olfactory bulb.
Physiology, 14th ed, vol 1. St. Louis, Mosby, 1980:428. Physiol Rev 1972; 52:864–917.
Hubel DH, Wiesel TN: Functional architecture of macaque monkey visual Uesaka Y et al: The pathway of gustatory fibers of the human ascends ipsilater-
cortex. Proc R Soc Lond [B ] 1977; 198:1–59. ally in the pons. Neurology 1998; 50:827–828.
Hubel DH, Wiesel TN: Brain mechanisms of vision. Sci Am 1979; 241(3): Zeki S: The representation of colours in the cerebral cortex. Nature 1980;
150–162. 284:412–418.
Hudspeth AJ: The hair cells of the inner ear. Sci Am 1983; 248:54–64. Zihl J, von Cramon D: The contribution of the “second” visual system to di-
Kaneko A: Physiology of the retina. Annu Rev Neurosci 1979; 2:169–191. rected visual attention in man. Brain 1979; 102:835–856.
Lim DJ: Functional structure of the organ of Corti: A review. Hear Res 1986;
22:117–146.
Special Senses: Clinical Correlates 24
Disorders of Olfaction Disorders of Hearing

Abnormalities in Taste Vestibular Disorders
Disorders of Vision
KEY CONCEPTS
The olfactory system may be involved in disease processes Lesions of the upper or the lower bank of the calcarine
at the olfactory receptors (common cold), olfactory nerve sulcus are associated with contralateral quadranta-
(fractures of the cribriform plate of the ethmoid), olfac- nopia.
tory bulb and tract (inflammation, tumors), and olfactory
Lesions of the primary visual cortex (both banks of the
cortex (tumor, epilepsy).
calcarine sulcus) are associated with contralateral homony-
Taste may be affected in lesions of the facial, glossopha- mous hemianopia.
ryngeal, and vagus cranial nerves and in lesions of or near
In vascular lesions of the primary visual cortex (occlusion
the primary gustatory cortex. Taste loss is also associated
of posterior cerebral artery), macular (central) vision is
with a variety of medical conditions, drugs, and radiation.
preserved (macular sparing).
Lesions of the optic nerve are associated with monocular
Sensorineural deafness results from disorders that inter-
blindness. Lesions of the optic chiasma are associated
fere with function of the auditory end organ, cochlear
with bitemporal hemianopia. Lesions of the optic tract are
nerve, cochlear nuclei, or central auditory pathways.
associated with contralateral homonymous hemianopia.
Vestibular disorders (peripheral and central) are associ-
Lesions of the optic radiation in the temporal and parietal
ated with vertigo, nystagmus, and truncal ataxia.
lobes are associated with contralateral quadrantanopia.
DISORDERS OF OLFACTION Pathologic processes in the region of the primary olfactory

cortex (the uncus of the temporal lobe) usually give rise to hallu-
The olfactory system can be affected in several sites with result- cinations of smell (uncinate fits). The odor experienced in such
ing derangements in the sense of smell. Olfactory receptors are cases is often described as unpleasant. Such hallucinations may
decreased in number with age and are affected in common colds, herald an epileptic seizure or be part of it. They also may be a
resulting in bilateral diminution or loss of smell (anos- manifestation of a tumor in that region.
mia). Olfactory nerve fibers may be affected in their
course through the cribriform plate of the ethmoid bone ABNORMALITIES IN TASTE
in fractures of the plate.
The olfactory bulb and tracts may be involved in inflamma- Abnormal taste sensations (usually unpleasant sensations) occur
tory processes of the meninges (meningitis) or tumors (menin- preceding a temporal lobe seizure or as part of the seizure, espe-
gioma) in the frontal lobe or the anterior cranial fossa. Unilateral cially if the epileptic focus is close to the uncus of the temporal
loss of smell may be the earliest clinical manifestation in such lobe (uncinate seizures) or to the primary gustatory cortex in the
processes. Loss of dopamine in the olfactory bulb of Parkinson’s inferior part of the somesthetic cortex.
patients is responsible for the decrease of the sense of smell in Taste loss (ageusia), decrease in taste (hypogeusia),
such patients. and abnormal taste (dysgeusia) are common disorders.
323
324 / CHAPTER 24
They occur as a natural phenomenon of aging or in association tralateral homonymous hemianopia. If the lesion is vas-
with pregnancy, menopause, and a variety of illnesses. cular (occlusion of posterior cerebral or calcarine arter-
Taste sensations are impaired ipsilateral to lesions in the facial ies), there will be macular sparing due to collateral sup-
(CN VII), glossopharyngeal (CN IX), and vagus (CN X) nerves. ply of the macular area from the middle cerebral artery.
These nerves convey taste sensations from the anterior two-
thirds of the tongue (CN VII), posterior third of the tongue (CN
IX), and the epiglottis (CN X). DISORDERS OF HEARING
Patients with xerostomia (dry mouth), Sjögren syndrome Disorders of hearing are generally of two types: conductive and
(salivary glands inflammation) diabetes, and zinc deficiency may sensorineural. Conductive hearing loss is associated with pro-
experience loss of taste. cesses that interfere with conduction of sound waves in the ex-
Chemotherapeutic agents (methotrexate) used in the treat- ternal and middle ears. Such processes include wax (cerumen)
ment of cancer, as well as numerous drugs (dexamethasone, anti- accumulations in the external auditory meatus, chronic otitis
hypertensive agents, H2 receptor agonists, antimicrobial agents), media, and ossicle sclerosis (otosclerosis).
can also induce loss of taste. Sensorineural hearing loss is associated with lesions of the
Taste loss usually follows radiation therapy to the oral cavity. hair cells in the organ of Corti, the cochlear nerve (tumors of the
nerve, such as in cerebellopontine angle tumors,
labyrinthine artery occlusion), cochlear nuclei in the
DISORDERS OF VISION pons, or the central auditory pathways. Hearing loss is
The visual system can be affected in several sites. Alterations in ipsilateral to the lesion in disorders of the hair cells, cochlear
length of the eyeball result in refraction errors. Normally, distant nerve, and cochlear nuclei. Lesions of the central auditory path-
objects are brought to focus on the retina. In persons with elon- ways (lateral lemniscus, medial geniculate body, auditory cortex)
gated eyeballs, distant objects are brought to focus in front of the result in a bilateral decrease in hearing more marked contralat-
retina (myopic eyes). In such persons, only near objects can be eral to the lesion. Ringing, buzzing, hissing, or paper crushing
brought to focus on the retina (nearsightedness). In persons with noises (tinnitus) in the ear are early signs of diseases of the
flattened eyeballs, distant objects are brought to focus behind the cochlea.
retina (hyperopic eyes). Both conditions can be corrected by use The two types of hearing disorders (conductive and sen-
of appropriate lenses. sorineural) are differentiated by placing a vibrating tuning fork
Night blindness (nyctalopia) is encountered in individuals on the vertex in the midline of the skull (Weber test) or alter-
with vitamin A deficiency. Photoreceptor pigment is formed of nately on the mastoid process and next to the auricle (Rinne
vitamin A aldehyde and a protein. Thus, in vitamin A deficiency test). Using the Weber test, a person with normal hearing will
states, the total amount of visual pigment is reduced, decreasing hear the sound of the vibrating tuning fork equally well in both
the sensitivity to light of both rods and cones. This reduction in ears. A person with conductive deafness in one ear will hear the
visual pigment, while not affecting bright-light (daylight) vision, sound louder in the deaf ear because the masking effect of envi-
does significantly interfere with dim-light (night) vision. This ronmental noises is absent on the affected side. A person with
condition is treatable by vitamin A administration. sensorineural deafness will hear the sound louder in the normal
Color blindness is associated with deficiency or lack of a par- ear. With the Rinne test, a person with normal hearing will con-
ticular color cone. Most color blind persons are red-green blind; tinue to hear the sound of the vibrating tuning fork placed next
a minority are blue blind. Color blindness for red and green is to the ear (air conduction) after he or she stops hearing the
inherited by X-linked recessive gene; hence it is more prevalent sound of the tuning fork placed on the mastoid process (bone
in males. Color blindness for blue is inherited by autosomal re- conduction). A person with conductive deafness will not hear
cessive gene. the vibrations of the tuning fork in air after bone conduction is
Lesions of the optic nerve (tumor, demyelination) over. A person with sensorineural deafness will continue to hear
(see Fig. 23–6) result in monocular blindness (blindness vibrations in air after bone conduction is over.
in one eye). Lesions of the optic chiasma (see Fig. 23–6), Cochlear implants are used today to treat patients with sen-
where partial crossing of optic nerve fibers occurs, result in sorineural loss resulting from cochlear disease provided the audi-
bitemporal hemianopia (blindness in both temporal visual fields) tory nerve and central auditory pathways are intact.
due to involvement of the crossing fibers. Such a visual defect is
seen in association with lesions in the pituitary gland (pituitary VESTIBULAR DISORDERS
adenoma) or tumors in the hypothalamus. Lesions in the optic
tract result (see Fig. 23–6) in homonymous hemianopia con- The vestibular system can be affected in several sites, including
tralateral to the lesion in the optic tract due to involvement of the peripheral end organ in the inner ear, vestibular
crossed fibers from the contralateral retina and uncrossed fibers nerve, vestibular nuclei, and central vestibular pathway,
from the ipsilateral retina. Lesions of the direct path of the optic and by a variety of disease processes, including infection,
radiation in the parietal lobe or of the indirect path of demyelination, vascular disorders, and tumor. Disorders of the
the optic radiation (Meyer’s loop) in the temporal lobe vestibular system are manifested by an illusory sensation of mo-
(see Fig. 23–6) result in quadrantic hemianopia. The in- tion (vertigo), oscillatory involuntary eye movements (nystag-
ferior quadrants of the visual field will be affected in parietal lobe mus), and postural disequilibrium (truncal ataxia).
lesions and the superior quadrants in temporal lobe le- Lesions of the semicircular canals induce rotatory vertigo,
sions. Similarly, lesions of the upper or lower banks of whereas disease of the utricle or saccule produces sensations of
the calcarine sulcus will result in a quadrantic visual field tilt or levitation. An example of end-organ vertigo is sea sickness,
defect, inferior in upper bank lesions and superior in which is caused by irregular continuous movement of endo-
lower bank lesions. Lesions of the primary visual cortex lymph in susceptible individuals. Vertigo also may occur with
(upper and lower banks) (see Fig. 23–6) result in con- disease of vestibular structures in the brain stem. This is usually
SPECIAL SENSES: CLINICAL CORRELATES / 325
associated with other signs of brain stem damage such as hemi- Nystagmus (Greek nystagmos, “drowsiness,” from nystazein,
paresis, hemisensory loss, and cranial nerve signs. “to nod”). Involuntary, rapid rhythmic oscillations of the eyes.
Both central and peripheral vestibular lesions induce nystag- Otosclerosis (Greek otos, “ear”; sklerosis, “hardening”). Conduc-
mus, an involuntary back-and-forth movement of the eyes in tive hearing loss due to sclerosis of the ossicles in the middle ear.
horizontal, vertical, or rotatory pattern. Peripheral and central Rinne test. Hearing test to compare air and bone conduction of
nystagmus are differentiated from each other by the following: sound by placing a vibrating tuning fork on the mastoid process
(1) fixation of the eyes suppresses peripheral but not central nys- and in front of the ear. Named after H. A. Rinne (1819–1868),
tagmus, and (2) pure vertical or torsional nystagmus is usually a German otolaryngologist who described the test.
central.
Truncal (vestibular) ataxia occurs in association with periph- Tinnitus (Latin “ringing”). Hallucinatory sound associated with
eral and central vestibular disease. A dramatic feature of such pa- cochlear disorders.
tients is the inability to stand upright without support and a Uncinate (Latin, “hooked”). Pertaining to the uncus. Uncinate
staggering gait with a tendency to fall toward the side of the fits are complex partial seizures in which olfactory or gustatory
lesion. hallucinations occur. The term was used by Hughlings-Jackson,
a British neurologist in 1899.
TERMINOLOGY Vertigo (Latin vertigo, “turning or whirling around”).
Hallucination of movement, a sign of peripheral or central
Anosmia (Greek a, “negative”; osme, “smell”). Loss of sense of vestibular system disorders.
smell. Weber test. A hearing test to differentiate conductive and sen-
Calcarine (Latin calcarinus, “spur-shaped”). Pertaining to the sorineural deafness by placing a vibrating tuning fork on the ver-
calcar, a structure resembling a spur. tex of the skull. Named after Ernest Heinrich Weber, a German
Cribriform plate (Latin cribrum, “a sieve”; forma, “form”). anatomist who described the test in 1834.
The cribriform plate of the ethmoid bone has many holes (like a
sieve) through which olfactory nerve fibers pass.
Gustatory (Latin gustatorius, “pertaining to the sense of
taste”). Relating to the sense of taste. SUGGESTED READINGS
Hemianopia (Greek hemi, “half ”; an, “negative”; opia, “eye”). Borruat FX et al: Congruous quadrantanopia and optic radiation lesion.
Loss of vision in one-half the visual field of each eye. Neurology 1993; 43:1430–1432.
Brandt T: Man in motion: Historical and clinical aspects of vestibular func-
Homonymous (Greek homo, “same”; onoma, “name”). Per- tion. Brain 1991; 114:2159–2174.
taining to the corresponding halves of the visual field.
Brandt T, Daroff RB: The multisensory physiological and pathological vertigo
Hyperopia (Greek hyper, “above”; opia, “eye”). An error of syndromes. Ann Neurol 1980; 7:195–203.
refraction (farsightedness) in which the entering light rays are Collard M, Chevalier Y: Vertigo. Curr Opin Neurol 1994; 7:88–92.
focused behind the retina as a result of a short eyeball from front D’Amico DJ: Disease of the retina. N Engl J Med 1994; 331:95–106.
to back. Luxon LM: Disorders of hearing. In Asbury AK et al (eds): Diseases of the
Meyer’s loop. Also known as Flechsig loop. The part of the optic Nervous System: Clinical Neurobiology. Philadelphia, Saunders, 1992:434.
radiation that loops around the tip of the temporal horn before Masdeu JC: The localization of lesions in the oculomotor system. In Brazis
reaching the primary visual cortex in the occipital lobe. Named PW et al (eds): Localization in Clinical Neurology. Boston, Little, Brown,
after Adolph Meyer (1866–1950), a Swiss-American neurologist 1985:118.
and psychiatrist who described this loop. Nelson GM: Biology of taste buds and the clinical problem of taste loss. The
Anat Rec (New Anat) 1998; 253:70–78.
Myopia (Greek myein, “to shut”; opia, “eye”). An error of re-
Newman NJ: Neuro-ophthalmology: The afferent visual system. Curr Opin
fraction (shortsightedness) in which light rays fall in front of the Neurol 1993; 6:738–746.
retina as a result of a too long eyeball from front to back. Sharpe JA, Johnston JL: Vertigo and nystagmus. Curr Opin Neurol Neurosurg
Nyctalopia (Greek nyx, “night”; alaos, “blind”; opia, “eye”). 1990; 3:789–795.
Impairment of night vision. The original Greek usage referred to Troost BT: Nystagmus: A clinical review. Rev Neurol 1989; 145:417–428.
the ability to see by night only. Galen changed the meaning to Zeki S: The visual image in mind and brain. Sci Am 1992; 267(September):
impairment of night vision. 69–76.
Central Nervous System Development 25
Development Postnatal Brain Performance

Embryogenesis Myths and Facts
Histogenesis Aging
Regional Development Morphologic Alterations
Myelination Functional Alterations
Prenatal Brain Performance
Postnatal Development and Growth
Functional Maturation
Cerebral Oxygen Consumption
Cerebral Blood Flow
Cerebral Metabolic Rate for Glucose
KEY CONCEPTS
Embryogenesis includes three developmental events: The alar plate of the neural tube gives rise to sensory
induction, neurulation, and vesicle formation. structures in the spinal cord and brain stem. The basal
plate gives rise to motor structures.
Almost all of the central nervous system develops by
primary neurulation.The sacral and coccygeal spinal cord Layers II to VI of the cerebral hemisphere develop from the
segments develop by secondary neurulation. cortical plate by an “inside-out” process.
Dysraphic (neural tube) defects result from defective Cerebral commissures develop from the commissural
neurulation. plate, a specialized area in the lamina terminalis.
Histogenesis includes two processes: cellular differentia- Myelination follows a caudal-rostral sequence in which
tion and cellular maturation. motor and sensory systems myelinate before association
systems do.
Cells migrate from the ventricular zone to other zones of
the neural tube by using glial cell guides (radial glia).
Exposure of a fetus to radiation or infection early in devel-
opment leaves the fetus with serious defects.
DEVELOPMENT A. INDUCTION
The development of the central nervous system occurs in two Induction is a process of cell-to-cell signaling by which the un-
stages: (1) embryogenesis and (2) histogenesis. derlying mesoderm induces the ectoderm to become neuroecto-
derm and form the neural plate, which gives rise to most of the
Embryogenesis nervous system. Neuroectodermal induction is believed to be
due to the actions of hormones, neurotransmitters, and growth
Embryogenesis includes the following developmental events: factors. The specific biochemical mechanisms are unknown. The
(1) induction, (2) neurulation, and (3) vesicle formation. process of induction takes place in the ectoderm of the head
326
CENTRAL NERVOUS SYSTEM DEVELOPMENT / 327
process overlying the notochord at about the seventeenth day of Through these orifices, the lumen of the neural tube (the
intrauterine life. neural canal) communicates with the amniotic cavity. The ante-
rior neuropore closes on about the twenty-fourth day of intrauter-
B. NEURULATION ine life, and the posterior neuropore closes 2 days later. The
The process by which the neural plate folds over on itself and neural canal persists as the future ventricular system.
fuses in a zipperlike fashion to become a neural tube is known as 2. Secondary Neurulation. Secondary neurulation is the process
neurulation (Figure 25–1). There are two neurulation by which the caudal parts of the spinal cord (lower lumbar,
processes: (1) primary, by which most of the neural tube sacral, and coccygeal segments) are formed. Secondary neurula-
is formed, and (2) secondary, by which the most caudal tion begins on about the twenty-sixth day of intrauterine life as
part of the neural tube is formed. the posterior neuropore is closing. At about that time a mass of
1. Primary Neurulation. Primary neurulation is the process by cells, the caudal eminence, develops caudal to the neural tube.
which the brain and most (cervical, thoracic, upper lumbar) of The caudal eminence then enlarges and develops a cavity within
the spinal cord form. Primary neurulation begins when the noto- itself. Eventually, the caudal eminence joins the neural tube and
chord induces the overlying embryonic ectoderm to form a its cavity becomes continuous with that of the neural tube.
neural plate. On about the eighteenth day of intrauterine life, Defective primary neurulation leads to a group of congenital
the neural plate begins to thicken at its lateral margins. Rapid central nervous system malformations known as dys-
growth at these margins results in elevation of the margins and raphic defects. They include anencephaly, in which the
formation of neural folds as well as invagination of the neural brain fails to form; encephalocele, in which the intracra-
plate to form the neural groove. The elevated lateral margins of nial contents, including the brain, herniate through a defect in
the neural tube (the neural folds) then approximate each other in the cranium; and spina bifida cystica, in which the contents of
the midline and fuse to form the neural tube. the spinal canal, including the spinal cord, herniate through a
In the human embryo, fusion of the margins of the neural defect in the vertebral column. Defects associated with sec-
groove begins on the twenty-first day in the region of the fourth ondary neurulation (myelodysplasias) include the tethered cord
somite (middle of the embryo, presumptive cervical region) and syndrome, in which the conus medullaris and the filum terminale
proceeds in both directions; it is completed by the twenty-fifth are abnormally fixed to the vertebral column.
day. Two orifices delimit the completed neural tube, one at its Two theories have been proposed for fusion sites in the for-
rostral end (anterior neuropore) and the other at its posterior end mation of the neural tube. The traditional theory (zipper model)
(posterior neuropore). states that the neural tube closes in a continuous bidirectional
process beginning in the cervical region. The other theory
(multisite closure model) states that neural tube fusion occurs at
multiple sites along the neural tube.
3. Neural Crest. As the neural tube is being formed, a cluster of
Neural plate
ectodermal cells that originally was at the margins of the neural
groove separate to form the neural crest. The neural crest gives
rise to the dorsal root (spinal) ganglia, including their satellite
cells; the sensory ganglia of cranial nerves V, VII, VIII, IX, and
X; the parasympathetic ganglia of cranial nerves VII, IX, and X;
the autonomic ganglia (paravertebral, prevertebral, enteric); the
Schwann cells; the melanocytes; the chromaffin cells of the
adrenal medulla; and the pia and arachnoid layers of the meninges.
Ectoderm
C. VESICLE FORMATION
After closure of the anterior neuropore at about the twenty-
fourth day of intrauterine development, the rostral, larger portion
of the neural tube subdivides into three vesicles (Figure 25–2):
the prosencephalon (forebrain), mesencephalon (midbrain), and
rhombencephalon (hindbrain).
Ectoderm At about the thirty-second day, the prosencephalon and
rhombencephalon subdivide further into two parts each, while the
Neural groove Neural crest
mesencephalon remains undivided. The prosencephalon divides
into an anterior telencephalon and a posterior diencephalon. The
telencephalon differentiates further into two telencephalic vesi-
cles which extend beyond the anterior limit of the original neural
tube (lamina terminalis) and eventually become the cerebral
hemispheres. From the diencephalon, two secondary bulges (the
optic vesicles) appear, one on each side. These structures differ-
entiate to form the optic nerves and retinas. The rhomben-
cephalon divides into an anterior metencephalon and a posterior
Neural tube Neural crest myelencephalon. The metencephalon eventually becomes the
pons and cerebellum, and the myelencephalon is differentiated
into the medulla oblongata.
Figure 25-1. Schematic diagram showing the stages of forma- Thus, the five vesicles that develop from the rostral part of the
tion of the neural tube. neural tube eventually give rise to the whole brain. Table 25–1
328 / CHAPTER 25
Diencephalon Midbrain flexure

Telencephalon
Prosencephalon Diencephalon
Mesencephalon Mesencephalon Metencephalon
Metencephalon Telencephalon
Rhombencephalon
Myelencephalon Pontine flexure Myelencephalon
Spinal cord
SPINAL CORD
Cervical flexure
Figure 25–2. Schematic diagram showing the vesicle stages of Figure 25–3. Schematic diagram showing the formation of
brain development. flexures in brain development.
summarizes the sequence of events leading to the development prosocele undergoes corresponding divisions (Figure 25–4), re-
of the various regions of the brain. sulting in the formation of the following structures:
As a result of the unequal growth of the different parts of the 1. Two telencephalic cavities, one on each side (lateral teloceles)
developing brain, three flexures appear (Figure 25–3).
2. A midline cavity between the telencephalic vesicles (median
1. Midbrain Flexure. The midbrain flexure develops in the re- telocele)
gion of the midbrain. As a result, the forebrain (prosencephalon)
bends ventrally until its floor lies almost parallel to the floor of 3. A diencephalic cavity (diocele)
the hindbrain (rhombencephalon). The two lateral teloceles develop into the two lateral ventricles.
2. Cervical Flexure. The cervical flexure appears at the junction The median telocele and the diocele develop into the third ventri-
of the hindbrain (rhombencephalon) and the spinal cord. cle. The cavity of the mesencephalon (mesocele) remains undivided
(Figure 25–4) and eventually becomes the aqueduct of Sylvius.
3. Pontine Flexure. The pontine flexure appears in the region
After the division of the rhombencephalon into a meten-
of the developing pons.
cephalon and a myelencephalon, its cavity (rhombocele) divides
The midbrain and cervical flexures are concave ventrally,
into the metacele, the cavity of the metencephalon, and the my-
whereas the pontine flexure is convex ventrally.
elocele, the cavity of the myelencephalon (Figure 25–4). The
D. VENTRICULAR SYSTEM metacele and myelocele become the fourth ventricle.
After the appearance of the three vesicles in the rostral part of the As the different parts of the brain change shape, correspond-
neural tube, cavities develop within the vesicles. Initially, three ing changes in the cavities follow. The connections between the
cavities are visible, corresponding to the three vesicles: (1) the
prosocele, the cavity of the prosencephalon; (2) the mesocele, the
cavity of the mesencephalon; and (3) the rhombocele, the cavity
of the rhombencephalon. Lateral
Simultaneous with the division of the prosencephalon into telocele
the two telencephalic vesicles and the diencephalic vesicle, the
Median
telocele
Diocele
Table 25–1. Developmental Sequence of Brain Regions
Three-vesicle stage Five-vesicle stage Brain region Mesocele
Prosencephalon Telencephalon Cerebral hemisphere

Metacele
Diencephalon Diencephalon
Optic nerve
and retina Myelocele
Mesencephalon Mesencephalon Mesencephalon
Rhombencephalon Metencephalon Pons
Cerebellum Figure 25–4. Schematic diagram showing the formation of
Myelencephalon Medulla oblongata
brain cavities.
lateral ventricles and the third ventricle become smaller and con- Marginal Mantle
stitute the interventricular foramina of Monro. The median layer layer
aperture (of Magendie) in the roof of the fourth ventricle appears
during the third month of intrauterine life, followed by the ap-
pearance of the lateral apertures (of Luschka). Table 25–2 sum-
marizes the sequence of events leading to the formation of the
various ventricles.
E. CHOROID PLEXUS
The choroid plexus develops in the floor and roof of the lateral
ventricle, and the roofs of the third and fourth ventricles by a
process of invagination of blood vessels. As the neural tube thick-
ens, the blood vessels on the surface of the pia mater penetrate
Ependymal Central
the brain surface carrying the pia mater with them. At sites of layer canal
formation of choroid plexus in the ventricles, the pial sheaths re-
main apposed to the penetrating blood vessels and are adherent Figure 25–5. Schematic diagram of the three basic layers of
to the ependymal lining of the ventricles. The choroid plexus is the neural tube.
thus formed by a core of blood vessels surrounded by pia which
is adherent to the ependymal lining of the ventricles.
Histogenesis
(mantle), and marginal. The intermediate (mantle) and marginal
Neurons and macroglia arise from a single precursor cell from layers are the primordia of the future gray and white matter,
which two lineage cells arise: the neuroblast, which gives respectively.
rise to neurons, and the glioblast, from which macroglia A full-term fetus is born with a full complement of neurons.
(astrocytes and oligodendroglia) develop. Microglia are It has been estimated that roughly 20,000 neurons are formed
derived not from neuroectoderm but from mesoderm-derived each minute during the period of prenatal development. The
monocytes. Histogenesis includes two main processes: (1) cellu- rate varies in different growth periods. In general, there are two
lar differentiation and (2) cellular maturation. growth spurts in the human embryo. The first extends from the
A. CELLULAR DIFFERENTIATION tenth week to the eighteenth week of gestation. The second be-
gins in the thirtieth week of gestation and extends through the
Once it has been determined that a region will become part of second year of life. The first growth spurt is vulnerable
the nervous system, its cells begin to differentiate. Differentiation to irradiation, chromosomal anomalies, and viral infec-
involves three phases: cellular proliferation, migration of cells to tions; these factors may leave the fetus with serious de-
characteristic positions, and maturation of cells with specific inter- fects. Congenital infection with toxoplasma, rubella, cytomega-
connections. lovirus (CMV), and herpes simplex at this stage may damage the
When the neural tube is formed, the cells of the germinating developing heart, brain, and eyes of the fetus, resulting in a new-
epithelium around the lumen of the tube (ventricular zone) pro- born with congenital heart disease, mental retardation, and blind-
liferate actively between the seventh and sixteenth weeks of ges- ness. The second growth spurt is sensitive to factors such as mal-
tation to form an ependymal layer of columnar cells lining the nutrition. Within any given neural region, different cell types are
cavity of the neural tube. Some of these cells migrate pe- generated during specific periods. In general, large nerve cells de-
ripherally to form the intermediate (mantle) layer. Pro- velop before small cells do, motor neurons develop before sen-
cesses of cells in the mantle layer extend to the periphery sory neurons do, and interneurons are the last to develop. Glial
to form the marginal layer. Cell migration from the periventric- cells proliferate after the neurons and continue to grow rapidly
ular zone to the periphery of the neural tube occurs between the after birth.
twelfth and twenty-fourth weeks of gestation and utilizes tran- During histogenesis, one and a half to two times more neu-
sient glial cell guides (radial glia). Radial glia subsequently disap- rons are produced than are present in the mature brain. The ex-
pear and may be transformed into astrocytes. As development cess neurons are disposed of during development by a genetically
continues, the central cavity diminishes in size, the mitotic activ- determined process of programmed cell death (apoptosis). Apop-
ity of the ependymal cells decreases, and three distinct layers tosis is characterized morphologically by condensation of nuclear
are established (Figure 25–5): the ependymal, intermediate chromatin, fragmentation of DNA, and formation of encapsu-
lated cell fragments that are then phagocytosed. Apoptosis in the
spinal cord occurs before 25 weeks of gestation, whereas cortical
Table 25–2. Developmental Sequence of Ventricular apoptosis occurs late in gestation. Apoptosis serves two purposes:
Cavities (1) elimination of redundancy in number of neurons and
(2) regulation of neural connectivity, matching the size of input
Three-vesicle stage Five-vesicle stage Adult structure population of neurons (usually in excess) with the number or
size of the target population.
Prosocele Lateral telocele Lateral ventricle
Median telocele Third ventricle B. CELLULAR MATURATION
Diocele Neuronal maturation consists of four stages: (1) outgrowth and
Mesocele Mesocele Aqueduct of Sylvius elongation of axons, (2) elaboration of dendritic processes, (3)
Rhombocele Metacele Fourth ventricle
expression of appropriate biochemical properties, and (4) forma-
Myelocele
tion of synaptic connections.
330 / CHAPTER 25
(motor) and dorsal (sensory) horns of the adult spinal cord, re-
Alar plate spectively. The intermediate zone of the adult spinal cord devel-
ops from the interface of the alar and basal plates. By the four-
teenth week of gestation all the cell groups in the central gray
matter can be recognized. Axons of motor neurons in the ventral
Central canal
horn develop in the fourth week of gestation and form the ven-
tral root. Later in the fourth week, axons from the dorsal root
ganglia grow into the dorsal horn.
Sulcus limitans
Early in development, the spinal cord and the vertebral col-
umn, which develop from the surrounding mesoderm, grow at
the same rate. At the end of the first trimester of pregnancy, the
Basal plate spinal cord occupies the entire length of the vertebral column
and the spinal nerves travel at right angles to exit at their corre-
Figure 25–6. Schematic diagram showing the stage of plate sponding intervertebral foramina. In the fourth month of gesta-
formation in central nervous system development. tion, however, growth of the spinal cord slows in comparison
with that of the vertebral column. By term, the tip of the spinal
cord lies at the level of the third lumbar vertebra, and in the
adult it lies at the lower border of the first or second lumbar ver-
tebra. As a result, the spinal roots, which originally were hori-
Axons grow out before any other sign of neuronal maturation zontal, become oblique, being dragged down by the growth of
occurs. Axonal growth is guided by specialized structures that are the vertebral column. The degree of obliquity increases from the
rich in actin filaments important for motility at the tip of the lower cervical segment caudally, particularly in the lumbar and
growing process (growth cones) and is influenced by factors that sacral segments, where the roots form the cauda equina, extend-
guide the neuron toward its target (tropic factors) and factors ing well below the end of the cord.
that maintain the metabolism of the neuron (trophic factors).
Axonal growth is not random but is aimed toward a specific target. C. MEDULLA OBLONGATA AND PONS
Dendrites grow after axons have developed. Unlike axons, The medulla oblongata and the pons are derivatives of the em-
which have few branches if any, dendrites may form elaborate bryologic myelencephalon and metencephalon, respectively. At
branches. the junction of the spinal cord and the medulla oblongata, the
When axonal growth cones arrive at their targets, they un- central canal opens to form the fourth ventricle. This forces the
dergo biochemical and morphologic changes to establish synapses. alar plate to rotate dorsolaterally. Thus, sensory neurons of the
Similarly, the target cells undergo changes to enhance synaptic alar plate come to lie lateral or dorsolateral to motor neurons of
interaction involving neurotransmitter receptors and second the basal plate (Figure 25–7). A thin single cell layer of ependyma
messenger molecules. Normally, more synapses are produced (roof plate) also is formed, supported by a richly vascularized
than are needed. Subsequently, many synapses are lost. The use mesenchymal tissue (tela choroidea). The sulcus limitans, which
and disuse of synapses are important factors in their growth and disappears in the spinal cord during development, is retained in
regression. the floor of the fourth ventricle between alar plate and basal plate
neuronal derivatives. The same pattern of organization is main-
Regional Development tained in the pons. The alar plate gives rise to the following cra-
nial nerve nuclei in the medulla and pons: spinal trigeminal nu-
A. ALAR AND BASAL PLATES cleus, principal (main) sensory trigeminal nucleus, nucleus
During the formation of the neural tube, a longitudinal groove solitarius, and vestibular and cochlear nuclei. The alar plate also
appears on each side of the lumen. This groove, known as the gives rise to the following structures in the medulla and pons: the
sulcus limitans, divides the neural tube into a dorsal area, the alar
plate, and a ventral area, the basal plate (Figure 25–6). Alar and
basal plates give rise to all the elements destined to make up the
spinal cord, medulla oblongata, pons, and mesencephalon. The Fourth
regions of the brain rostral to the mesencephalon (diencephalon ventricle Sulcus limitans
and cerebral cortex) develop from the alar plate, as does the cere-
bellum. The mantle layer of the alar plate generally gives rise to
sensory neurons and interneurons, whereas that of the basal plate
gives rise to motor neurons and interneurons.
B. SPINAL CORD
The adult spinal cord maintains the organizational pattern of the Alar plate derivatives
embryologic neural tube, with a central canal (neural canal), the
ependyma (ventricular zone), and central gray matter (interme-
diate, or mantle, zone) surrounded by white matter (marginal
zone). The cervical, thoracic, and upper lumbar segments de-
velop from the neural tube by the process of primary Basal plate derivatives
neurulation. The lower lumbar, sacral, and coccygeal seg-
ments develop from the caudal eminence by the process Figure 25–7. Schematic diagram showing reorganization of
of secondary neurulation. The cord matures from the cervical re- basal and alar plate derivatives induced by formation of the
gion caudally. The basal and alar plates give rise to the ventral fourth ventricle.
inferior olivary nucleus of the medulla and the pontine nuclei in G. BASAL GANGLIA
the basis pontis. The basal plate gives rise to the following cranial The caudate and putamen nuclei develop from a ventral telen-
nerve nuclei in the medulla and pons: hypoglossal nucleus, nu- cephalic swelling, the ganglionic eminence, in the floor of the fu-
cleus ambiguus, dorsal motor nucleus of the vagus, inferior sali- ture cerebral hemispheres. In addition to the caudate and the
vatory nucleus, abducens nucleus, superior salivatory nucleus, putamen, the ganglionic eminence contributes cells to the amyg-
trigeminal motor nucleus, and facial motor nucleus. daloid nucleus and the bed nucleus of the stria terminalis.
D. CEREBELLUM Initially, the caudate and putamen appear as a single cellular
mass. With the development of the internal capsule, which con-
The cerebellum, like the pons, is a derivative of the meten- nects the cerebral hemispheres with subcortical structures, the
cephalon. It arises from an alar plate structure (the rhombic lip) single cell mass is divided into a medial caudate nucleus and a
in the dorsolateral wall of the fourth ventricle, which also gives lateral putamen.
rise to the inferior olive, cochlear, and vestibular nuclei. The cere- The derivation of the globus pallidus is controversial. It is
bellar primordia in each rhombic lip grow outward to form the probably derived from telencephalic anlage as well as diencephalic
cerebellar hemispheres and inward toward the midline, where anlage. The external (lateral) segment of the globus pallidus is
they meet to form the cerebellar vermis in the roof of the fourth derived partly from the telencephalic ganglionic eminence and
ventricle. partly from the diencephalon, whereas the internal segment of
Neurons of the cerebellum are derived from neuroblasts in the the globus pallidus is derived from the diencephalon. The portions
ventricular zone of the cerebellar primordium. Some of these neu- of the globus pallidus that are derived from the diencephalon are
roblasts migrate outward along radial glia to form the deep cere- subsequently incorporated in the telencephalon.
bellar nuclei (dentate, emboliform, globose, and fastigii) and the
Purkinje and Golgi cells. Another group of periventricular neuro- H. CEREBRAL HEMISPHERE
blasts from the lateral edges of the rhombic lip move across the The cerebral hemispheres develop from the telencephalic vesi-
rhombic lip to the subpial zone and from there to the external sur- cles. Early in development, each telencephalic vesicle is com-
face of the cerebellum to form the external granular layer. These posed of three zones: ventricular, intermediate (mantle), and
neuroblasts retain their proliferative potential and give rise to cells marginal. The marginal zone develops into the acellular, most
that migrate inward to form the granule, basket, and stellate cells superficial layer I of the mature cerebral cortex. Layers II to VI
of the adult cerebellum. Some external granular layer cells (those develop from the cortical plate, a group of cells that migrate
destined to form granule cells of the internal granular layer) de- from the ventricular zone to the outer part of the intermediate
velop tangentially oriented axonal processes (future parallel fibers (mantle) zone (Figure 25–8). The development of layers II to VI
of granule cells) before migrating inward along radial glial guides from the cortical plate is accomplished by an “inside-out” se-
to form the granule cells of the internal granular cell layer in the quence in which newly arrived cells migrate outward past their
adult cerebellum. The external granular layer generates neurons predecessors in the cortical plate. Thus, in the mature
throughout the last 7 months of gestation and the first 7 months of adult cerebral cortex, acellular layer I is the oldest; cellu-
postnatal life. The cerebellum remains relatively small during devel- lar layer VI is formed by the first wave of neuroblast mi-
opment; the main growth spurt in humans occurs from 30 weeks gration, followed in chronologic sequence by cellular layers V,
of gestation through the first year of postnatal life. IV, III, and II (Table 25–3). Unlike the spinal cord, where gray
E. MESENCEPHALON (MIDBRAIN) matter is centrally placed compared with white matter, the re-
verse is true in the cerebral cortex, where gray matter is superfi-
The midbrain is a derivative of the embryologic mesencephalic cial to the white matter core. Defects in the inside-out migration
vesicle. The tectum (superior and inferior colliculi) and the cen- sequence result in a variety of developmental brain disorders,
tral (periaqueductal) gray matter are derivatives of the alar plate; such as heterotopias, lissencephaly, and schizencephaly. Because
the tegmentum, which contains the oculomotor and trochlear
nuclei, the red nucleus, and the substantia nigra, is a derivative of
the basal plate. Some authors limit the basal plate derivatives to
the oculomotor and trochlear nuclei and suggest that the red nu-
cleus and substantia nigra are derived from alar plate neuroblasts Chronological order
that migrate to the basal plate. Thickening of the walls of the of development
embryologic mesencephalon reduces the central ventricular space
Marginal Layer I Oldest
into a narrow passage, the aqueduct of Sylvius. zone
Layer II Fifth wave
F. DIENCEPHALON Cortical
plate Layer III Fourth wave
The diencephalon develops solely from the alar plate. Three
swellings in the wall of the central cavity (future third ventricle)
develop into the future epithalamus, thalamus, and hypothala- Intermediate Layer IV Third wave
mus. After further development, the area of the epithalamus di- zone
Layer V Second wave
minishes in size, whereas the thalamus and hypothalamus grow.
The two thalami are connected across the midline (massa inter- Ventricular Layer VI First wave
media) in about 80 percent of individuals. The hypothalamic zone
sulcus separates the thalamus and hypothalamus. This sulcus is
TELENCEPHALIC MATURE
not a rostral continuation of the sulcus limitans, which termi- VESICLE CEREBRAL
nates at the rostral mesencephalon. Within the thalamus, later- CORTEX
ally placed nuclei (lateral and medial geniculate, ventral lateral,
ventral anterior, and ventral posterior) develop before the medi- Figure 25–8. Schematic diagram showing origin of mature
ally placed nuclei (dorsomedial, anterior) do. cerebral cortical layers from the telencephalic vesicle.
332 / CHAPTER 25
Table 25–3. Development of Cortical Layers: The Inside- related anatomically and functionally to the anterior hypothala-
Out Process mus, arise from an area of the anterior diencephalon just ventral
to the lamina reuniens.
Layer Origin Chronologic age
Myelination
I Periventricular layer Oldest
II Cortical plate Fifth wave of neuroblast migration In the central nervous system, myelin is formed by oligodendro-
III Cortical plate Fourth wave of neuroblast migration cytes. Myelin formation in the central nervous system begins at
IV Cortical plate Third wave of neuroblast migration about the sixth month of gestation and continues into adult-
V Cortical plate Second wave of neuroblast migration hood. The factors that initiate myelin formation have not been
VI Cortical plate First wave of neuroblast migration fully elucidated. It is known, however, that myelination is re-
tarded when the conduction of nerve impulses through axons is
interrupted and that myelin production by oligodendrocytes is
enhanced when neural cell extracts are added to cul-
tures. It appears that both neural impulses and some un-
of the rapid accumulation of cells, the telencephalic vesicles grow known cellular communication between neurons and
rapidly forward, upward, and backward to form the frontal, pari- oligodendrocytes (surface markers, chemotactic factors) stimu-
etal, occipital, and temporal lobes. In the process of rapid late the process of myelination. Different fiber systems myelinate
growth, the newly formed cortex covers cortical and subcortical at different developmental periods. In general, motor and sen-
structures such as the insula and the diencephalon. Local varia- sory tracts myelinate before association tracts do. Myelination
tions in the rate of growth result in the formation of the gyri, proceeds in a caudal-to-rostral order. The spinal cord and spinal
sulci, and fissures that demarcate different cortical convolutions nerve roots begin to myelinate during the second trimester in
and lobes. The sylvian fissure is the first to develop, at about the utero. Toward the end of the second trimester and the beginning
fourteenth week of gestation. The central (rolandic) and cal- of the third trimester, myelination begins in the brain stem. No
carine sulci appear between 24 and 26 weeks of gestation. The myelin is detectable in the cerebral hemisphere until the first
formation of the cortical gyri proceeds rapidly near the thirtieth postnatal month.
week of gestation, and the entire hemisphere surface is gyrated by Using T1-weighted magnetic resonance imaging, myelin ap-
the thirty-second week of gestation. pears at birth in the posterior limb of the internal capsule and
middle cerebellar peduncle (brachium pontis). Myelin appears in
I. CEREBRAL COMMISSURES the anterior limb of the internal capsule and in the centrum
At about the sixth week of gestation, the dorsal part of the lam- semiovale between the second and fourth months. The splenium
ina terminalis (site of the embryologic anterior neuropore) thick- of the corpus callosum myelinates between the third and fourth
ens to form a densely cellular cell mass, the lamina reuniens (lam- months and the genu follows at between the fourth and sixth
ina of His). The lamina reuniens increases rapidly in size months. Myelin appearance is evident in the occipital white mat-
to form the commissural plate, from which the cerebral ter between the fourth and seventh months and in the frontal
commissures and the septum pellucidum develop. Pioneer white matter between the fourth and eleventh months. Myelin
cerebral commissure fibers cross the midline with the help of appearance on T2-weighted magnetic resonance imaging usually
early glial cells and are guided either by cell surface markers or by occurs 1 to several months after its appearance on T1-weighted
chemotactic substances that are expressed into the extracellular images.
space. The anterior commissure is the first to form at about the Myelination undergoes dramatic changes in the first 2 post-
sixth gestational week and the first to cross in the anterior por- natal years. Multiple rules govern the chronologic and topo-
tion of the commissural plate at about the tenth week of gesta- graphic sequences of central nervous system myelination during
tion. The hippocampal commissure is the next structure to form. this period. These rules include the following: (1) Sensory path-
It crosses further dorsally in the commissural plate at about the ways myelinate before motor pathways, (2) projection pathways
eleventh week of gestation. The first fibers of the corpus callo- myelinate before association pathways, (3) central telencephalic
sum begin to cross at approximately the twelfth gestational week. sites myelinate before telencephalic poles, (4) occipital poles
Growth of the corpus callosum continues over the next 5 to 7 myelinate before frontal and temporal poles, (5) the posterior
weeks in an anterior to posterior direction with the formation of limb of the internal capsule myelinates earlier and faster than the
the genu anteriorly followed by development of the body and, fi- anterior limb, (6) the body and splenium of the corpus callosum
nally, the splenium. The rostrum is the last part of the corpus myelinate earlier and faster than the rostrum, and (7) the central
callosum to form after the genu, body, and splenium. This se- segment of the cerebral peduncle myelinates earlier than both
quence of callosal growth is reflected in patients with callosal hy- the lateral and medial segments. The lateral segment (from pos-
pogenesis, who may manifest the presence of the early formed terior cerebral hemisphere sites) myelinates before the medial
portions of the corpus callosum (genu, body, splenium) and the segment (from anterior cerebral hemisphere sites) does.
absence of the portion that forms later (rostrum).
The septum pellucidum, another derivative of the commis- PRENATAL BRAIN PERFORMANCE
sural plate, is a thin structure that separates the anterior horns of
the lateral ventricles. At about 8 weeks of gestation, the central The cardiovascular and nervous systems are the first systems to
part of the commissural plate undergoes cystic necrosis and function in an embryo. The heart begins to beat 3 weeks after con-
forms the thin leaves of the septum pellucidum with the cavum ception. The earliest detectable reflex in the nervous system ap-
septum pellucidum between them. pears in about the eighth week of intrauterine life. If a stimulus is
Congenital absence of the corpus callosum and septum pellu- applied to the lip region at this time, the hand region exhibits a
cidum is at times associated with hypothalamic abnormalities. withdrawal reflex. Touching the lips at 11 weeks of gestation elicits
This can be explained by the fact that the septal nuclei, which are swallowing movements. At 14 weeks of gestation, the reflexogenic
zones spread so that touching the face of the embryo results in a about 50 percent of the child’s total oxygen consumption. With
complex sequence of movements consisting of head rotation, gri- further development, cerebral oxygen consumption decreases to
macing, stretching of the body, and extension of the extremities. reach the adult level of 3.5 ml/100 g of brain tissue per minute.
At 22 weeks of gestation, the embryo manifests stretching out The low cerebral oxygen consumption of the brain at birth ex-
movements and pursing of the lips; at 29 weeks, sucking move- plains the ability of a newborn brain to tolerate states of anoxia.
ments become apparent. At birth almost all reflexes are of brain This tolerance to anoxia also may be explained by the depen-
stem origin; cortical control of these reflexes is minimal. dence of the brain before birth on anaerobic glycolysis as a
source of energy. Just before birth, the level of enzymes needed
POSTNATAL DEVELOPMENT AND GROWTH for aerobic glycolysis (succinodehydrogenase, succinoxidase,
adenylphosphatase, etc.) increases in preparation for the change
The brain of a human newborn weighs 350 g, which is approxi- in brain metabolism from anaerobic to aerobic processes.
mately 10 percent of its body weight; in contrast, the brain of an
adult weighs about 1400 g (roughly 2 percent of body weight).
This difference in weight between the adult brain and the new-
Cerebral Blood Flow
born brain is accounted for by the laying down of myelin, which Cerebral blood flow in a newborn brain is low. It increases with
occurs mainly in the first 2 years of life, as well as by an increase age to reach a maximum of 105 ml/100 g per minute between
in the size of neurons, the number of glial elements, and the the ages of 3 and 5 years. It then decreases to reach the adult rate
complexity of neuronal processes. Virtually no neurons are added of 54 ml/100 g per minute.
after birth, since the human newborn has the full complement of
neurons. Structurally, in the brain of a newborn all the lobes are
clearly distinguishable. The central lobe (insula, island of Reil) is Cerebral Metabolic Rate for Glucose
not covered by the frontal and temporal opercula. The color of Studies using positron emission tomography to study local cere-
the cortex at birth is pale, approximating that of white matter. bral metabolic rates for glucose in infants and children have
Histologically, a newborn brain shows the six-layered cytoarchi- shown a pattern of glucose utilization in the neonatal brain that
tectonic lamination of the adult cerebral cortex. In contrast to is markedly different from that in the adult brain. Typically, four
the adult cortex, however, the cells of the newborn cortex are brain regions are metabolically prominent: sensorimotor cortex,
tightly packed together with few if any processes to separate thalamus, brain stem, and cerebellar vermis. By 1 year of age, lo-
them. Nissl substance is sparse in cortical neurons and abundant cal cerebral metabolic rates for glucose resemble qualitatively
in brain stem and spinal cord neurons. Dendritic development those of young adults. Quantitatively, however, glucose meta-
in the newborn cortex is poor, and this correlates with the ab- bolic rates mature slowly. In a neonate, the local cerebral meta-
sence of alpha activity in the electroencephalogram of a new- bolic rate for glucose is 70 percent that of an adult. It increases
born. At birth, most of the synapses are of the axodendritic vari- and exceeds the adult rate by 2 to 3 years of life. It remains at
ety; axosomatic synapses develop later. these high levels until 9 or 10 years of life, and then it declines to
At 3 months of age, the brain weighs approximately 500 g. reach the adult rate by 16 to 18 years. The stage of decline in the
The island of Reil is completely covered by the frontal and tem- cerebral metabolic rate for glucose between 9 and 18 years of age
poral opercula. Although the gray matter and white matter re- corresponds to the stage of a notable decrease in brain plasticity
main poorly demarcated and the cortical Nissl substance remains after injury.
scanty, the neurons are not as closely packed as they are in the
newborn brain.
At 6 months of age, the brain weighs approximately 660 g. POSTNATAL BRAIN PERFORMANCE
The cytoplasm of neurons is more abundant. Nissl material is
more prominent, and the distinction between gray matter and Brain performance after birth proceeds through several stages of
white matter can be made easily. increasing complexity.
At 1 year of age, the brain weighs approximately 925 g. The The first stage spans the first 2 years of life. During this stage,
density of cortical neurons is reduced as a result of an increase in the infant changes from a baby with no awareness of the envi-
neuronal and glial processes between neuronal perikarya; Nissl ronment to a child who is aware of the environment and is able
substance within the cell bodies is well developed. to discriminate among varying environmental stimuli.
By the third postnatal year, average brain weight (1080 g) The second stage occurs between 2 and 5 years of age. This is
triples compared to birth weight, and by 6 to 14 years, average a stage of preconceptual representation in which the child devel-
brain weight (1350 g) approximates that of an adult. Even when ops picture images as symbols and begins to use language as a
adult brain weight has been reached, maturational changes con- system of symbol signs.
tinue to occur in the brain. Although active myelination in the The third stage is noted between 5 and 8 years of age. This is
human brain continues throughout the first decade, remodeling a stage of conditional representation in which the child becomes
of myelin continues throughout life. The electroencephalogram aware that he or she is not alone in the universe and begins to in-
and stimulus-evoked potentials undergo maturational changes teract with other features and forces of the universe.
that continue into the second decade of life. The fourth stage, which extends from 7 to 12 years of age, is
a stage of operational thinking in which the child begins to rec-
ognize the relationships between objects and appreciate their rel-
FUNCTIONAL MATURATION ative values, such as more or less, heavier or lighter, and longer or
Cerebral Oxygen Consumption shorter.
Along with these stages of behavioral development, the child
Oxygen consumption is relatively low in the newborn brain and proceeds through stages of motor and sensory development of
increases gradually with maturation. It reaches approximately increasing complexity. In general, motor development precedes
5 ml/100 g of brain tissue per minute, which is equivalent to sensory development. Starting as a subcortical creature at 1 month
334 / CHAPTER 25
Table 25–4. Brain Development: Anatomic, Functional, and Behavioral Correlations
Age (mo) Brain weight (g) Local cerebral metabolic rate Behavior
for glucose
Neonate 150 Primary sensorimotor cortex, thalamus, brain Subcortical reflexes (Moro’s, grasp, rooting)
stem, cerebellar vermis
2–3 500 Parietal cortex, temporal cortex, primary visual Visuospatial and visuosensorimotor integrative
cortex, basal ganglia, cerebellar hemispheres functions
6–8 660 Lateral frontal cortex Higher cortical and cognitive functions, inter-
8–12 925 Prefrontal cortex

} action with surroundings, phenomenon
of stranger anxiety
of age, the child proceeds to grasp, raise its head, smile, focus its Morphologic Alterations
eyes, hear, roll over, crawl, pick up small objects, stand, and
walk. The following structural alterations have been described in the
As these behavioral, motor, and sensory developments proceed, aging nervous system.
the central nervous system develops nerve processes, synapses, and 1. Cortical atrophy manifested by broadening of sulci, a de-
myelinated pathways. It is difficult, however, to match each of these crease in the size of gyri, and widening of ventricular cavities.
developmental stages with a definitive structural change. 2. A reduction in the number and size of neurons. This is best
Table 25–4 presents a simplified summary correlating ana- seen in larger neurons such as the pyramidal cells of Betz and
tomic, functional, and behavioral developments in the first year Purkinje neurons.
of life.
Functional imaging studies have revealed that early stimula- 3. A reduction in the amount of Nissl material.
tion enhances brain function whereas lack of early stimulation 4. Thickening and clumping together of neurofibrils.
leads to loss of brain function. Developmental research has shown 5. An increase in the number of amyloid bodies (corpora am-
that there are developmental windows of opportunity for differ- ylacea), particularly around the ventricular surface. The ori-
ent brain functions. Thus, the windows of opportunity are 0 to gin of amyloid bodies has not been established with cer-
2 years for emotional development, 0 to 4 years for mathematics tainty, but they are believed to represent products of
and logic, 0 to 10 years for language, and 3 to 10 years for music. neuronal degeneration.
It has been found that accent-free second language acquisition is 6. An increase in lipofuscin pigment in both neurons and glia.
not possible after mid adolescence. Another example of a critical Among the glia, the astrocytes are particularly affected,
period effect relates to absolute pitch, a skill important for musi- whereas the oligodendroglia and microglia are relatively
cians, which is unlikely to develop if music training is started af- spared. The predominant involvement of astrocytes in this
ter the age of 10 years. aging process has a deleterious effect on neuronal function.
7. Thickening of the walls of cerebral blood vessels.
MYTHS AND FACTS
Functional Alterations
Several myths about brain development have been corrected by
The following functional alterations are believed to contribute to
new knowledge:
some of these structural alterations or result from such structural
Myth #1: Brain develops at a steady pace throughout childhood. modifications.
Fact: Brain development is not linear but episodic, with win- 1. A decrease in cerebral blood flow. The reduction in cerebral
dows of opportunity to be utilized. blood flow can be the end product of the thickening of
blood vessel walls, which in turn can lead to ischemia and
Myth #2: Brain development is affected primarily by biolog- dropout of neuronal elements.
ical factors.
2. A reduction in oxygen utilization by cerebral tissues.
Fact: Brain development can be altered by abuse, neglect,
3. A reduction in glucose utilization by cerebral tissues.
poverty, and institutionalization.
4. An increase in cerebrovascular resistance.
Myth #3: Brain development is very slow before age 3 years.
Fact: Brain development during the first 3 years is rapid. TERMINOLOGY
Myth #4: Genes control brain development. Anencephaly (Greek an, “negative”; enkephalos, “brain”).
Fact: Genes and experience determine brain development. Congenital absence of the cranial vault with failure of the cerebral
hemispheres to develop as a result of a defect in the development
of the rostral neural tube. A condition incompatible with life.
AGING Apoptosis (Greek apo, “off ”; ptosis, ”fall”). A genetically
determined process of cell death. The fragmentation of a cell
Aging in the nervous system is associated with characteristic into membrane-bound particles that are then eliminated by
morphologic and functional alterations. phagocytosis.
Aqueduct of Sylvius (Latin aqua, “water”; ductus, “canal”). Metacele (Greek meta, “after, beyond, over”; koilos, “hollow”).
The narrow passage in the midbrain linking the third and fourth The cavity of the metencephalon.
ventricles. Described by Jacques Dubois (Sylvius) in 1555. Metencephalon (Greek meta, “after, beyond, over”; enkephalos,
Cauda equina (Latin, “horse’s tail”). A bundle of lumbosacral “brain”). The anterior portion of the most caudal primary vesi-
nerve roots beyond the tip of the spinal cord that form a cluster cle of the embryologic neural tube (the rhombencephalon).
in the spinal canal which resembles the tail of a horse. Develops into the pons and the cerebellum.
Corpora amylacea (Latin corpus, “body”; amylaceus, Moro’s reflex. Abduction and extension of the arms and open-
“starchy”). Starchlike bodies. Basophilic structures found in astro- ing of the hands followed by adduction of the arms in response
cytic processes with advancing age and in various degenerative dis- to sudden withdrawal of support of the head. Normally present
eases. The name was applied by Virchow to certain “amyloid” bod- from birth to 5 months of age. Named after E. Moro, an Austrian
ies in the central nervous system that had been noted by Purkinje. pediatrician who described it in 1918.
Cortical plate. The part of the intermediate (mantle) zone of Myelencephalon (Greek myelos, “medulla, marrow”; enkephalos,
the telencephalic vesicle that gives rise to layers II to VI of the “brain”). The caudal part of the rhombencephalon. Develops
cerebral hemispheres. into the medulla oblongata.
Diocele (Greek dis, “twice”; koilos, “hollow”). The cavity of Myelocele (Greek myelos, “medulla, marrow”; koilos, “hol-
the diencephalon, the third ventricle. low”). The cavity of the myelencephalon. The fourth ventricle.
Dysraphic defects (Greek dys, “abnormal, disordered”; raphe, Myelodysplasia (Greek myelos, “medulla, marrow”; dys, “ab-
“seam”). Defects caused by incomplete closure of the neural normal”; plassein, “to form”). Defective development of the
tube, such as anencephaly and spina bifida cystica. caudal spinal cord and vertebral column.
Embryogenesis (Greek embryo, “seed that develops into an Neurulation. A stage of embryogenesis that includes the forma-
individual”; genesis, “production, generation”). The process tion and closure of the neural tube.
of embryo formation. Prosencephalon (Greek prosos, “before”; enkephalos, “brain”).
Encephalocele (Latin encephalon, “brain”; Greek kele, “her- The most anterior of the three primary brain vesicles of the em-
nia”). A congenital developmental defect characterized by extra- bryologic neural tube. Gives rise to the diencephalon and the
cranial herniation of part of the cerebral hemisphere through a cerebral hemispheres.
midline skull defect. Prosocele (Greek prosos, “before”; koilos, “hollow”). The fore-
Ganglionic eminence. A swelling in the ventral telencephalon most cavity of the brain. The ventricular cavity of the prosen-
from which the basal ganglia develop. cephalon.
Grasp reflex. Flexion of the fingers when an object is placed Rhombencephalon (Greek rhombos, “rhomb”; enkephalos,
gently in the palm. Normally present in infants from birth to “brain”). The most caudal of the three primary brain vesicles.
about 6 months of age. It is also found in adults with bifrontal Gives rise to the medulla oblongata, pons, and cerebellum.
lesions. Rhombic lip. Part of the alar plate in the dorsolateral wall of the
Heterotopia (Greek heteros, “other, different”; topos, “place”). fourth ventricle. Gives rise to the cerebellum.
Displacement of parts; the presence of tissue in an abnormal lo- Rhombocele (Greek rhombos, “rhomb”; koilos, “hollow”). The
cation. Neuronal heterotopia refers to the presence of gray matter cavity of the rhombencephalon.
within white matter as a result of abnormal neuronal migration Rooting reflex. Mouth opening and head turning in response to
during histogenesis. stroking of the corner of the mouth. An exploratory reflex of the
His, Wilhelm (1831–1904). A Swiss anatomist who was inter- mother’s skin to locate the nipple. A normal reflex from birth to
ested in the development of the nervous system. He described 6 months of life.
the lamina reunions (lamina of His) from which cerebral com- Schizencephaly (Greek schizein, “to divide”; enkephalos,
missures develop. He is also credited for originating the follow- “brain”). A developmental brain anomaly characterized by the
ing terms: dendrite, neuropil, neuroblast, and spongioblast. presence of unilateral or bilateral clefts in the cerebral hemi-
Histogenesis (Greek histos, “web”; genesis, “production, gen- sphere. A neuronal migration defect.
eration”). The formation of tissues from undifferentiated germi- Tela choroidea (Latin tela, “a web”; chorion, “membrane”;
nal cells in the embryo. epidos, “form”). A membrane of pia and ependyma that con-
Induction (Latin inductio, “the process of inducing or caus- tributes to the formation of choroid plexus inside the ventricles.
ing to occur through the influence of organizers”). The forma- Telencephalon (Greek telos, “end”; enkephalos, “brain”). The
tion of the neural plate is induced by the underlying mesoderm. anterior of the two vesicles that develop from the prosencephalon.
Lamina reuniens (lamina of His). The dorsal part of the lam- Gives rise to the cerebral hemispheres.
ina terminalis, from which the cerebral commissures develop. Telocele (Greek telos, “end”; koilos, “hollow”). The cavity of
Described by Wilhelm His (1831–1904), a Swiss anatomist. the telencephalon. The lateral ventricles.
Lissencephaly (Greek lissos, “smooth”; enkephalos, “brain”). Tethered cord. A developmental defect of the caudal spinal cord
A developmental brain anomaly characterized by a smooth brain in which the conus medullaris is low in the vertebral canal and is
surface devoid of gyral convolutions or a paucity of convolu- anchored to the sacrum.
tions. Also known as agyria. A defect of neuronal migration.
Mesencephalon (Greek mesos, “middle”; enkephalos, “brain”). SUGGESTED READINGS
The midbrain. Developed from the middle of the three primary
Bangert BA: Magnetic resonance techniques in the evaluation of the fetal and
brain vesicles of the embryologic neural tube. neonatal brain. Semin Pediatr Neurol 2001; 8:74–88.
Mesocele (Greek mesos, “middle”; koilos, “hollow”). The cav- Barkovich AJ et al: Formation, maturation, and disorders of white matter.
ity of the mesencephalon, the aqueduct of Sylvius. AJNR 1992; 13:447–461.
336 / CHAPTER 25
Chugani HT: Functional maturation of the brain. Int Pediatr 1992; 7:111– Link E: Time is of the essence: Early stimulation and brain development. Care
117. for Kids EPSDT Newsletter 1998; 5:1,2,6. Available at http://www.medi-
Cowan WM: The development of the brain. Sci Am 1979; 241:112–133. cine.uiowa.edu/uhs/EPSDT/archive.cfm#1998.
Crelin ES: Development of the nervous system. Ciba Clin Symp 1974; 26:2– Marin-Padilla M: Prenatal development of human cerebral cortex: An overview.
32. Int Pediatr 1995; 10(suppl):6–15.
Moore K: The nervous system. In Moore K (ed): The Developing Human.
Dorovini-Zis K, Dolman CL: Gestational development of the brain. Arch
Philadelphia, Saunders, 1982:375–412.
Pathol Lab Med 1977; 101:192–195.
Naidich TP: Normal brain maturation. Int Pediatr 1990; 5:81–86.
Friede RL: Gross and microscopic development of the central nervous system.
In Friede RL (ed): Developmental Neuropathology. Berlin, Springer- Norman MG et al: Embryology of the central nervous system. In Norman
Verlag, 1989; 2–20. MG et al (eds): Congenital Malformations of the Brain: Pathological,
Embryological, Clinical, Radiological, and Genetic Aspects. New York,
Hayflick L: The cell biology of human aging. Sci Am 1980; 242:58–65. Oxford University Press, 1995:9–50.
Hutchins JB, Barger SW: Why neurons die: Cell death in the nervous system. O’Rahilly R, Muller F: The Embryonic Human Brain: An Atlas of Developmental
Anat Rec 1998; 253:79–90. Stages. New York, Wiley-Liss, 1994.
Huttenlocher PR: Basic neuroscience research has important implications for Rockstein M: Development and Aging in the Nervous System. New York,
child development. Nat Neurosci 2003; 6:541–543. Academic Press, 1973.
Leech RW: Normal development of central nervous system. In Leech RW, Yakovlev PI, Lecours AR: The myelogenetic cycles of regional maturation of
Brumback RA (eds): Hydrocephalus, Current Clinical Concepts. St. Louis, the brain. In Mikowski A (ed): Regional Development of the Brain in
Mosby Year Book, 1991:9–17. Early Life. Philadelphia, Davis, 1967:3–70.
Central Nervous System Development: 26

Clinical Correlates
Neurulation (Neural Tube) Defects Polymicrogyria

Primary Neurulation Defects Cortical Heterotopias
Secondary Neurulation Defects Schizencephaly
Neuronal and Glial Proliferation Defects Midline Defects
Microcephaly (Micrencephaly) Holoprosencephaly
Macrocephaly (Megalencephaly) Agenesis of the Corpus Callosum
Hemimegalencephaly Septo-optic Dysplasia (DeMorsier Syndrome)
Neuroblast Migration Defects
Lissencephaly (Agyria)
Pachygyria (Macrogyria)
KEY CONCEPTS
Congenital malformations of the brain have exogenous Malformations associated with neuroblast migration in-
and endogenous causes and occur in 0.5 percent of live clude lissencephaly (agyria), pachygyria, polymicrogyria,
births. cortical heterotopias, and schizencephaly.
Malformations associated with defective neurulation in- Agenesis of the corpus callosum is commonly associated
clude anencephaly, encephalocele, myelomeningocele, with other congenital brain malformations. It may be to-
diastematomyelia, and tethered cord. tal or partial.
Neural tube defects can be detected prenatally by exam-
ining alpha-fetoprotein and acetylcholinesterase in the
amniotic fluid and by ultrasonography.
Congenital malformations of the brain occur in approximately cephaly, (2) encephalocele, (3) myelomeningocele, (4) diastemato-
0.5 percent of live births and 3 percent of stillbirths. myelia, and (5) tethered cord. The first three are associated with
They are generally attributed to one of two types of primary neurulation defects, and the last two with secondary
causes: exogenous and endogenous. Exogenous causes neurulation defects.
include nutritional factors, radiation, viral infections, chemicals, Two features of human neural tube defects point to failure
ischemic insults, and medications. Endogenous causes are mainly of closure of the neural tube as the more likely cause of mal-
genetic. The different etiologic factors affect the embryo ad- formations: (1) Pathologic studies show that the neural tube is
versely during specific periods of development. Since the same open at the area of the defect, with continuity of the neural
malformation may be produced by both exogenous and endoge- epithelium and surface epithelium, suggesting failure of fu-
nous causes, it is customary to classify the different malforma- sion of the neural tube, and (2) neural tube malformations oc-
tions according to the developmental stage at which they occur. cur mostly at the rostral and caudal regions of the neural tube
just proximal to the areas of final neural tube fusion, suggest-
NEURULATION (NEURAL TUBE) DEFECTS ing that the malformations result from a defect in neural tube
closure.
Congenital malformations associated with defective In experimental animals, neural tube defects can be produced
neurulation are among the most commonly encoun- by introducing a variety of teratogens during the stage of closure
tered malformations in humans. They include (1) anen- of the anterior and posterior neuropores.
337
338 / CHAPTER 26
Early prenatal detection of neural tube defects is possible

by the determination of alpha-fetoprotein (AFP) and
acetylcholinesterase in amniotic fluid. AFP is synthe-
sized in fetal liver and excreted in urine. It increases in
amount in the amniotic fluid in patients with various malforma-
tions, in particular those resulting from neural tube defects. AFP
elevation in maternal serum is not as reliable as similar elevations
in amniotic fluid. Acetylcholinesterase is produced in nervous
tissue, is excreted in cerebrospinal fluid, and passes into the am-
niotic fluid only in cases of neural tube defects. Neural tube de-
fects also can be detected early by ultrasonography.
The incidence of neural tube defects varies worldwide from
about 1 to about 9 per 1000 births. The incidence in the
United States is 1 per 2000 births. Northern Ireland and South
Wales are among the areas with the highest incidence (8.6 and
7.6 per 1000 births, respectively). The incidence also varies
with ethnic origin. In the United States, African Americans
have lower incidence rates than whites. Asian Americans have
lower incidence rates than African Americans or whites. His-
panic Americans have the highest incidence rates. Neural tube
defects are known to cluster in families. The occurrence in sib-
lings of an affected child is approximately 3 percent, and it
doubles with the birth of each additional child with a neural
tube defect.
The risk of neural tube malformation can be reduced by daily
intake of folic acid.
Primary Neurulation Defects

Primary neurulation refers to the formation of the neural tube
from approximately the caudal lumbar level to the cranial end of
the embryo. Most of the central nervous system is thus devel- Figure 26–1. Photograph of a neonate with anencephaly.
oped by primary neurulation, which occurs during the third and
fourth weeks of gestation. Three malformations are generally
associated with defective primary neurulation: (1) anencephaly, B. ENCEPHALOCELE (ENCEPHALOMENINGOCELE)
(2) encephalocele, and (3) myelinomeningocele. An encephalocele (Figure 26–2) consists of a protrusion of brain
and meninges through a skull defect. Rarely, only the meninges
A. ANENCEPHALY (meningocele) protrude through the skull defect (Figure 26–3).
Anencephaly (Figure 26–1) is characterized by the absence or Encephaloceles may occur in the occipital, parietal, frontal,
underdevelopment of the cranial vault, maldevelopment of the nasal, and nasopharyngeal sites but are most common (75 to 85
skull base, and a constant anomaly of the sphenoid bone that percent) in the occipital area. The incidence of encephaloceles is
resembles “a bat with folded wings.” The orbits are shallow, approximately 0.8 to 3.0 per 10,000 births. They account for
causing protrusion of the eyes. The anomaly of the skull im- 0.07 percent of all pediatric admissions and about 10 percent
parts a froglike appearance to the patient when viewed face on. of all craniospinal malformations. Occipital encephaloceles are
The forebrain is absent and is replaced by a reddish irregular more common in females, whereas encephaloceles in other sites
mass of vascular tissue with multiple cavities containing cere- occur more frequently in males. Most encephaloceles occur spo-
brospinal fluid. The primary defect is failure of closure of the radically. They typically present at birth and usually come to
rostral part of the neural tube. The onset of the malformation medical attention within the first days or weeks of life. Encepha-
is estimated to occur no later than at 24 days of gestation. loceles typically have an intact skin cover but are variable in size,
Anencephaly was known in Egyptian antiquity. Affected infants shape, and consistency. Occipital encephaloceles are usually large.
are stillborn or die early (a few days) in the neonatal period. The outcome is poor. Seventy-five percent of occipital encepha-
The incidence of anencephaly varies from 0.5 to 2.0 per 1000 locele and 100 percent of parietal encephalocele infants die or
live births, and anencephaly accounts for approximately 30 per- are severely retarded.
cent of all major abnormal live births. Females are affected
more frequently than are males. Epidemiologic studies have C. MYELOMENINGOCELE
shown a high incidence of anencephaly in Northern Ireland A myelomeningocele (Figure 26–4) is characterized by hernia-
and South Wales. Both environmental and genetic factors oper- tion of the lower spinal cord and overlying meninges through a
ate in the genesis of the malformation. Familial cases have been large midline defect in the vertebral column. The protruding
reported; the mode of transmission, however, is poorly under- mass consists of a distended meningeal sac filled with cere-
stood. brospinal fluid containing spinal cord tissue. The sac is covered
The incidence of anencephaly has been declining. This has by a thin membrane or skin. The malformation results from
been attributed to early detection by ultrasonography, AFP, and a defect in closure of the caudal neural tube. Approximately
acetylcholinesterase determination, and elective termination of 80 percent of myelomeningoceles are in the lumbar region, the
pregnancy when the fetus is found to have anencephaly. last region of the neural tube to close.
CENTRAL NERVOUS SYSTEM DEVELOPMENT: CLINICAL CORRELATES / 339
Figure 26–2. Magnetic resonance image (MRI) of the brain

showing an occipital encephalomeningocele (arrow).
The onset of the malformation occurs not later than the

twenty-sixth day of gestation. The incidence is approximately 2
to 3 per 1000 births. As with anencephaly, the incidence is Figure 26–4. MRI of the spinal canal showing a myelome-
higher in Ireland and Wales. Most cases are sporadic. There is in- ningocele (arrow).
creased risk of the malformation in families with a history of
neural tube defects. Females are affected about twice as often as
are males. Other frequently associated malformations include
the Arnold-Chiari malformation, hydrocephalus, syringohydro-
myelia, and diastematomyelia. The clinical picture is character-
ized by sensorimotor deficits in the lower extremities. IQ is nor-
mal in 90 percent of patients. Recent advances in the care of
children with myelomeningocele have resulted in increased sur-
vival. Early surgery involves closure of the spinal lesion and fre-
quently the placement of a shunt.
Secondary Neurulation Defects

Secondary neurulation refers to the process by which the sacral
and coccygeal segments of the spinal cord are developed. Two
malformations are generally associated with defective secondary
neurulation: diastematomyelia and tethered cord.
A. DIASTEMATOMYELIA
Diastematomyelia is characterized by the presence of two hemi-
cords within a single dural sac separated by a vascular mass of con-
nective tissue or in two separate dural sacs between which there
may be a bony septum. The malformation usually occurs in the
lower thoracic or lumbar cord segments but may occur at any
spinal level. Seventy percent of cases occur between the first and
fifth lumbar cord segments. The cord is normal above and below
the level of the split. The central canal bifurcates to extend into
each hemicord and reunites below the split. Similarly, the anterior
cerebral artery divides at the level of the split so that each hemi-
Figure 26–3. Photograph of a child with frontal meningocele. cord has an independent arterial supply. This condition may be
340 / CHAPTER 26
asymptomatic in neonates and become symptomatic later in venting its upward displacement. The clinical picture is charac-
childhood, between 2 and 10 years of age. Females are affected terized by progressive motor and sensory deficits in the lower
more than males are. Although not an inherited disorder, diastem- extremities, scoliosis, back pain, and a neurogenic bladder.
atomyelia has been reported to occur in members of the same fam- Associated cutaneous signs in the lumbosacral region include a
ily. The malformation frequently is associated with spina bifida. hairy skin patch, a hemangioma, and a dimple.
On imaging studies, diastematomyelia may be difficult to dis-
tinguish from diplomyelia, a rare condition characterized by a NEURONAL AND GLIAL
duplicated spinal cord instead of two facing hemicords, as in di-
astematomyelia. PROLIFERATON DEFECTS
The oldest known specimen of diastematomyelia, dating Microcephaly (Micrencephaly)
back to the Roman period, approximately A.D. 100, was recov-
ered from a burial site in the Negev desert in Palestine. The term Microcephaly is a term used generally to describe head circum-
diastematomyelia was coined by Ollivier, a French neurologist, ference 2 standard deviations (SD) or less below the mean, or
in 1837. head circumference below the third percentile. It refers to a small
cranial vault of varying etiologies. Micrencephaly, in contrast,
B. TETHERED CORD refers to small brain size (head circumference 5 to 6 SD below
The tethered cord malformation (Figure 26–5) is characterized the mean). Micrencephaly may occur as a result of genetic im-
by an abnormally low conus medullaris tethered (anchored) by pedance of neuronal proliferation or environmental factors that
one or more forms of intradural abnormalities, such as a short interfere with brain development. In practice, the two terms are
thickened filum terminale, fibrous bands, or adhesions, or a to- used interchangeably. Micrencephalic children have a small cra-
tally intradural lipoma. The underlying pathologic anomaly is a nial vault, compared with the size of the face, and thickened
dural defect through which the spinal cord comes in contact skull bones. Affected children are developmentally delayed.
with the subcutaneous tissue early in embryonic development. Micrencephaly occurs sporadically or in families with autosomal
The spinal cord thus is anchored to subcutaneous tissue, pre- recessive, autosomal dominant, or X-linked transmission.
Macrocephaly (Megalencephaly)
Macrocephaly is generally used to describe head circumference
of more than 2 SD above the mean, irrespective of etiology.
Megalencephaly, however, implies increased brain weight sec-
ondary to an increase in neural elements, both neuronal and
glial. The term megalencephaly was introduced in 1900 by
Fletcher to designate true hyperplasia of brain tissues. Megalen-
cephalic brains have bulky gyri with increased cortical thickness
and white matter volume. Ventricles are usually of normal size.
No significant microscopic alterations are found in the cortex.
Minor migrational anomalies (heterotopias) may be present.
Hemimegalencephaly
Hemimegalencephaly is a rare congenital malformation of the
brain in which an enlarged hemisphere is the main pathologic
finding (Figure 26–6). Traditionally regarded as a defect in neu-
roblast migration, it is now believed to be a defect in cellular pro-
liferation, cellular lineage, and establishment of hemispheral
symmetry (which occurs in the third week of gestation). Hemi-
megalencephaly may be isolated or may be part of a neurological
syndrome (syndromic). It is associated with mental retardation,
intractable epilepsy, macrocephaly, and hemiparesis. Magnetic
resonance imaging (MRI) reveals a dysplastic hemisphere with
overall increased size of the involved hemisphere, increased vol-
ume of white matter of the affected hemisphere, abnormal gyral
pattern, ventriculomegaly, and displacement of the occipital lobe
across the midline (occipital sign).
The first description of hemimegalencephaly was by Sims in
1835. Hemimegalencephaly may occur alone or associated with
hypertrophy of the face or entire half body.
NEUROBLAST MIGRATION DEFECTS

Neuroblast migration is a critical stage in normal histogenesis in
which neuroblasts migrate, guided by radial glial processes, from
Figure 26–5. MRI of the spinal canal showing a low-lying the ventricular or periventricular zone to their proper position.
conus medullaris (arrow) in a tethered cord. In many regions, the migratory pathway is long and migration
Figure 26–6. Axial MRI showing a hemimegalencephalic dysplastic left cerebral hemisphere (stars).
occurs over a protracted period. The time involved is the third somal dominant, autosomal recessive, or X-linked. Most cases of
month to the sixth month of gestation. lissencephaly are secondary to a deletion of 17p13 chromosome.
Congenital malformations associated with defective Genes involved with lissencephaly include LIS1, located at
neuroblast migration include (1) lissencephaly (agyria), 17p13.3 (Miller-Dieker syndrome), and double cortin (DCX,
(2) pachygyria, (3) polymicrogyria, (4) cortical hetero- XLIS), located at Xq22.3 (X-linked lissencephaly). Recurrence
topias, and (5) schizencephaly. The causes of these malforma- risk in lissencephaly varies between 5 and 12 percent and may be
tions are varied and include genetic (maternal), and environ- as high as 25 percent in recessive cases. Cases not caused by
mental factors. Many are associated with agenesis or hypoplasia 17p13 deletion show higher recurrence risk.
of the corpus callosum. A prevalence for lissencephaly of 11.7 per million births has
been ascertained.
Lissencephaly (Agyria)
Pachygyria (Macrogyria)
Lissencephaly (Figure 26–7) is characterized by a smooth brain
surface resulting from the absence or paucity of gyri and sulci. Pachygyria (Figure 26–8) is characterized by a reduced number
The cerebral cortex is composed of four layers, similar to that of of coarse, broad, shallow gyri and sulci. The gyral malformation
a 3-month fetus: (1) an outermost, relatively acellular molecular differs from lissencephaly only in degree. Both malformations
layer, (2) a thick, richly cellular intermediate (mantle) zone, may be found in different areas of the same hemisphere. The
(3) an innermost thin band of white matter, and (4) a layer of pachygyric cortex is made up of four layers: (1) an outermost
periventricular gray matter. The migratory defect of this malfor- normal-appearing molecular layer, (2) a layer of neurons of de-
mation occurs between 12 and 16 weeks of gestation. It has been creased population which has not received its full complement of
proposed that late-migrating neuroblasts that are destined to be- neurons by radial migration, (3) a much thicker layer of neurons,
come cortical layers II and IV are arrested by a deep cortical and usually poorly organized and arranged in broad columns, which
subcortical laminar necrosis at about the fourth fetal month. represent heterotopic neurons arrested in their migration, and
Neurologic abnormalities are evident at birth or shortly after- (4) a relatively thin layer of white matter encroached on by het-
ward. Affected infants are hypotonic and microcephalic and have erotopic neurons. The migration defect resulting in pachygyria
intractable seizures. Neurologic development is severely im- occurs at a slightly later stage of development than is the case in
paired. Most cases of lissencephaly are sporadic; some are associ- lissencephaly. Affected infants are hypotonic at birth, develop
ated with genetic syndromes such as the Miller-Dieker and seizures within the first year of life, and are severely neurologi-
Walker-Warburg syndromes. Inheritance pattern may be auto- cally retarded.
342 / CHAPTER 26
Figure 26–7. MRI of the brain showing the smooth

surface of the cerebral hemisphere (arrows) in a pa-
tient with lissencephaly.
Polymicrogyria both hemispheres. It is most commonly seen in the perisylvian

region. On imaging studies, polymicrogyria appears as cortical
Polymicrogyria is characterized by a large number of very small thickening with multiple small gyri. In some cases, the gyri are so
gyri without intervening sulci or with shallow sulci bridged by small that the appearance is one of broad, flat gyri with shallow
the overlying molecular layers of adjacent gyri. Polymicrogyria sulci simiar to pachygyria. The migration defect that leads to
results when neurons reach the cortex but distribute in an abnor- polymicrogyria occurs in the fifth month of gestation, later than
mal fashion. Because of this, some classify polymicrogyria as a that responsible for lissencephaly and pachygyria. The clinical
malformation of abnormal cortical organization rather than a presentation of patients with polymicrogyria varies with the ex-
malformation of abnormal neuronal migration. The appearance tent of the malformation. Patients with diffuse polymicrogyria
of the polymicrogyric cortex has been compared to that of a cau- involving the entire cortex present with microcephaly, hypoto-
liflower. The polymicrogyric malformation may cover the entire nia, seizures, and developmental retardation, similar to the pre-
surface of the hemisphere or occur in limited areas of one or sentation in patients with lissencephaly. Patients with bilateral
Figure 26–8. MRI of the brain showing wide gyri

(arrows) in pachygyria.
focal polymicrogyria usually are moderately developmentally de-

layed and spastic. Patients with unilateral focal polymicrogyria
most often have congenital hemiplegia, mild to moderate devel-
opmental delay, and focal motor seizures.
Cortical Heterotopias
A cortical heterotopia (Figure 26–9) is characterized by islands of
gray matter along the route of neuroblast migration. The islands
consist of a collection of normal neurons in abnormal locations
secondary to an arrest of the radial migration of neuroblasts. The
onset of the migration defect occurs no later than the latter part
of the fifth month of gestation. Heterotopias have been associ-
ated with a wide variety of genetic, vascular, and environmental
causes. Heterotopias are clinically divided into three groups: (1)
subependymal, periventricular (nodular), (2) focal subcortical
(laminar), and (3) diffuse (band) (double cortex). Subependymal
(nodular) heterotopias are subependymal masses of gray matter
which form clusters of rounded nodules that are well separated
from the cortex by normally myelinated white matter. They usu-
ally are localized at the corners of the lateral ventricles. Focal sub-
cortical (laminar) heterotopias are separated from both the cor-
tex and the ventricles by thick layers of white matter. Diffuse
(band) heterotopias (double cortex) consist of bilateral symmet-
ric layers of heterotopic neurons between the lateral ventricles
and the cerebral cortex. The heterotopic neurons are separated
from the cortex by a band of white matter, giving the appearance
of double cortex. Patients with subependymal heterotopias tend
to have normal development and mild clinical symptoms. The
onset of seizures usually occurs in the second decade of life.
Patients with focal subcortical heterotopias have variable symp-
toms and signs that depend on the extent of their heterotopias.
Those with large heterotopias have moderate to severe develop-
mental delay and hemiplegia, whereas those with smaller or thin-
Figure 26–10. MRI of the brain showing schizencephalic cleft
(arrows).
ner subcortical heterotopias may have normal development and

motor function. Patients with diffuse band heterotopias (double
cortex) have moderate or severe developmental delay and in-
tractable seizures.
Schizencephaly
The term schizencephaly (Figure 26–10) was coined by Yakovlev
and Wadsworth in 1946 to describe gray matter–lined clefts in
the cerebral hemispheres extending from the pia to the ependy-
mal lining of the lateral ventricle. The walls of the clefts may be
in apposition (closed lip, type I) or separated (open lip, type II).
The onset of the malformation is considered to occur at 3 to
5 months of gestation. A focal watershed infarct in the cerebral
mantle during early development has been proposed as a cause of
schizencephaly. Familial occurrence raises the possibility of a ge-
netic mechanism in the causation of this malformation. Previous
reports of this malformation, derived primarily from pathologic
specimens, suggested that this malformation was extremely rare,
seen primarily in institutionalized patients with severe motor
and intellectual deficits. The introduction of and improvements
in imaging techniques such as computed tomography (CT) and
MRI have enhanced awareness and increased recognition of the
Figure 26–9. MRI of the brain showing cortical heterotopia disorder. The clinical presentation varies with the extent of the
(arrows). malformation. Patients with bilateral malformations usually are
344 / CHAPTER 26
developmentally delayed and have seizures. Patients with unilat- somal aberrations range from 24 to 45 percent. Most cases of
eral malformations may have only a motor deficit (hemiplegia) holoprosencephaly, however, are sporadic.
and seizures or may be developmentally delayed, depending on Because formation of the face parallels the formation of the
the extent of the malformation. Patients with small unilateral forebrain, malformations of the face are frequently noted in holo-
clefts, particularly those not involving the frontal lobe, usually prosencephaly. Traditionally, holoprosencephaly has been divided
have no symptoms. into three types: (1) alobar, (2) semilobar, and (3) lobar. Alobar
Mutations in the human homeobox gene, EMX2 (empty cases (Figure 26–11) have a single large, horseshoe-shaped ventri-
spiracles 2), are responsible for familial schizencephaly, and the cle, no interhemispheric fissure, and absent corpus callosum. They
inheritance may be autosomal dominant with variability. are the most severe type. Semilobar cases have partially formed in-
terhemispheric fissure and falx cerebri posteriorly and remnant
MIDLINE DEFECTS lobes. The monoventricle shows minimal differentiation and rudi-
mentary temporal horns. Lobar cases (the least severe) have nor-
Holoprosencephaly mal lobes, interhemispheric fissure, and falx, but the frontal lobes
are fused and communication between ventricles persists.
Holoprosencephaly is a midline malformation caused by failure
of cleavage of the prosencephalon into discrete telencephalic and Agenesis of the Corpus Callosum
diencephalic structures. The malformation develops between the
fourth and sixth weeks of gestation, when the hemispheric vesi- Corpus callosum malformations are commonly associated with
cles cleave. It is a rare malformation occurring in 1 per 16,000 other congenital brain malformations, suggesting a causal rela-
live births. The term holoprosencephaly was introduced in 1963 tionship. Both neurulation and migration defect malfor-
by DeMyer and Zeman. The malformation was recognized in mations have been associated with agenesis of the corpus
1882 by Kundrat, who described it as arhinencephaly, a term not callosum (Figure 26–12). Agenesis of the corpus callo-
now generally accepted. Yakovlev in 1959 proposed the term sum may be total or partial. In total absence of the corpus callo-
holotelencephaly to describe the malformation. The malforma- sum, the medial surface of the hemisphere has an abnormal ra-
tion is extremely heterogeneous, with both teratogenic and dial gyral pattern. The cingulate gyrus is poorly outlined, and
genetic etiologies. Maternal diabetes, alcohol, salicylates, and most of the gyri extend perpendicularly to the roof of the third
anticonvulsants have been associated with the malformation. ventricle. The axons destined to form the corpus callosum in-
Eighteen to 25 percent of holoprosencephaly cases have a recog- stead turn parallel to the interhemispheric fissure and form the
nized monogenic syndrome. Estimates of frequency of chromo- longitudinal callosal bundles of Probst (Figure 26–13). The bun-
Figure 26–11. Coronal brain section showing a single ventricle (arrow) in holoprosencephaly.
Figure 26–12. MRI of the brain showing

agenesis of the corpus callosum (arrows).
Figure 26–13. Coronal MRI showing Probst bundle (stars) in a patient with agenesis of the corpus callosum.
346 / CHAPTER 26
dle of Probst indents the superomedial borders of the lateral ven- Lissencephaly (Greek lissos, “smooth”; enkephalos, “brain”).
tricles, giving them a characteristic crescent shape. In partial age- A developmental brain anomaly characterized by a smooth brain
nesis, the posterior portion (splenium) or the rostrum (late to surface devoid of gyral convolutions or a paucity of convolu-
develop) is missing. Absence of the corpus callosum may be an tions. Also known as agyria. A defect of neuronal migration.
isolated anomaly with no clinical symptoms or may be associated Miller-Dieker syndrome. The association of lissencephaly
with mental retardation and seizures. Sporadic as well as familial (smooth brain) with dysmorphic facial features, renal anomalies,
cases have been reported. polydactyly, seizures, and microcephaly. Described by J. Q.
Miller in 1963 and H. Dieker in 1969. The term was introduced
Septo-optic Dysplasia (DeMorsier Syndrome) by Jones in 1980.
Septo-optic dysplasia is a congenital malformation of the ante- Myelomeningocele (Greek myelos, “marrow”; meninx, “mem-
rior midline structures of the brain that occurs between 4 and brane”; koilos, “hollow”). A severe defect of neural tube closure
6 weeks of gestation. The malformation includes agenesis of sep- in which the spinal cord and meninges herniate through a mid-
tum pellucidum and optic nerve hypoplasia. Pituitary gland and line defect in the vertebral column.
hypothalamic insufficiencies may be present. Agenesis of the sep- Neurulation. A stage of embryogenesis that includes the forma-
tum pellucidum was first described by Tenchini in 1881 and in tion and closure of the neural tube.
association with optic nerve hypoplasia by Reeves in 1941. Pachygyria (Greek pachys, “thick”; gyros, “ring”). Thick,
DeMorsier in 1956 reported the frequent association of optic broad, shallow gyral convolutions in the cerebral hemisphere.
nerve hypoplasia and agenesis of the septum pellucidum, and Polymicrogyria (Greek polys, “many”; mikros, “small”; gyros,
coined the term septo-optic dysplasia. “ring or circle, convolution”). A malformation of the brain
The malformation has been associated with a wide variety of characterized by numerous small gyri.
cerebral anomalies but most consistently with schizencephaly. Schizencephaly (Greek schizein, “to divide”; enkephalos,
Approximately half of patients with septo-optic dysplasia will “brain”). A developmental brain anomaly characterized by the
have schizencephaly. Patients usually present with congenital presence of unilateral or bilateral clefts in the cerebral hemi-
nystagmus or decrease in visual acuity. Some may also have en- sphere. A neuronal migration defect.
docrine abnormalities.
Syringohydromyelia (Greek syrinx, “pipe or tube”; hydor,
“water”; myelos, “marrow”). A cavitation within the spinal
TERMINOLOGY cord filled with cerebrospinal fluid.
Teratogenic (Greek teratos, “monster”; genesis, “production”).
Agyria (Greek a, “negative”; gyros, “ring”). A malformation in Tending to produce anomalies of formation.
which the brain surface is devoid of gyri and has a smooth ap- Tethered cord. A type of spinal dysraphism in which the lower
pearance. Also known as lissencephaly. part of the spinal cord (conus medullaris) is anchored to the
Anencephaly (Greek an, “negative”; enkephalos, “brain”). sacrum.
Congenital absence of the cranial vault with failure of the cere- Walker-Warburg syndrome. A lethal autosomal recessive con-
bral hemispheres to develop as a result of a defect in the develop- genital syndrome with brain, eye, and muscle abnormalities.
ment of the rostral neural tube. A condition incompatible with Most of these children die in the neonatal period secondary to
life. defects in brain development. Those who survive are severely
Arnold-Chiari malformation. A brain malformation character- mentally retarded.
ized by cerebellar and brain stem elongation and protrusion
through the foramen magnum. This malformation was first ob- SUGGESTED READINGS
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Cerebral Circulation 27
Sources of Supply Cerebral Dural Venous Sinuses

Internal Carotid Artery Factors Regulating Cerebral Circulation
Vertebral Artery Extrinsic Factors
Basilar Artery Intrinsic Factors
Circle of Willis Neural Factors
Conducting and Penetrating Vessels Neuropeptides
Histology of Cerebral Vessels Mean and Regional Cerebral Blood Flow
Collateral Circulation Steal Syndrome
Cerebral Venous Drainage Autoregulation and Hypertension
Superficial Venous System Cerebral Blood Flow in Epilepsy
Deep Venous System Cerebral Blood Flow in Coma
KEY CONCEPTS
Irreversible brain damage (brain death) occurs if blood sup- Two prominent superficial anastomotic venous channels
ply to the brain is interrupted for more than a few minutes. are the anastomotic vein of Trolard and the inferior anas-
tomotic vein of Labbé.
The internal carotid arteries provide blood supply to the
rostral parts of the brain, whereas the vertebral arteries The deep venous system drains via two main veins (the in-
provide blood supply to the posterior parts of the brain. ternal cerebral vein and the basal vein of Rosenthal) into
the great cerebral vein of Galen.
The anterior cerebral artery and its branches provide
blood supply to the medial surface of the hemisphere as The dural venous sinuses include the superior and inferior
far back as the parietooccipital fissure. sagittal, straight, confluence, transverse, sigmoid, occipi-
tal, petrosal, and cavernous sinuses.
The middle cerebral artery and its branches provide blood
supply to most of the lateral surface of the hemisphere. Extrinsic factors that regulate cerebral circulation in-
clude systemic blood pressure, blood viscosity, and vessel
The posterior cerebral artery, the terminal branch of the
lumen.
basilar artery, supplies the medial surfaces of the occipi-
tal, temporal, and the caudal part of the parietal lobes. Intrinsic factors that regulate cerebral circulation include
autoregulation (the most effective) and biochemical al-
The circle of Willis comprises the major site of intracranial
terations in carbon dioxide, oxygen, and pH.
collateral circulation.
The constantly active brain requires a rich blood supply to sus- nervous system due to interruption of blood supply constitute
tain its ongoing activity. Irreversible brain damage (brain death) the most common type of central nervous system disorders.
results if the blood supply to the brain is interrupted for It is estimated that about 15 percent of cardiac output reaches
more than a few minutes; consciousness is lost if the the brain; about 20 percent of oxygen utilization of the body is
blood supply is interrupted for about 5 s. Lesions of the consumed by the adult brain and as much as 50 percent by the
348
CEREBRAL CIRCULATION / 349
infant brain. The blood flow through the human brain is esti- gives rise to the ophthalmic, anterior choroidal, anterior cerebral,
mated to be 800 ml/min, or approximately 50 ml/100 g of brain middle cerebral, and posterior communicating branches. Within
tissue per minute. This average value increases with an increase the cavernous sinus, the internal carotid artery lies close to the
in functional activity of the brain or regions within it. The blood medial wall immediately adjacent to the abducens nerve (CN
flow is markedly increased in the sensory motor area on vigorous VI). Other cranial nerves in the sinus, situated along the lateral
exercise of the contralateral limb. Cerebral blood flow is faster in wall include the oculomotor (CN III), trochlear (CN IV), oph-
gray matter (70 to 80 ml/100 g per min) than in white matter thalmic, and maxillary divisions of the trigeminal (CN V).
(30 ml/100 g per min). Irreversible brain damage will occur if From its site of origin from the common carotid artery to its
the cerebral blood flow is less than 15 ml/100 g per min. site of bifurcation into the anterior and middle cerebral arteries,
the internal carotid artery is divided into four segments: (1) the
SOURCES OF SUPPLY cervical segment extends from the origin of the internal carotid
artery from the common carotid to the site where it enters the
The brain receives its blood supply from four arterial trunks: two carotid canal, (2) the intrapetrosal segment is the part of the
internal carotid arteries and two vertebral arteries. On the right artery as it courses through the petrous portion of the temporal
side, the brachiocephalic trunk gives rise to the right subclavian bone, (3) the intracavernous segment courses through the cav-
and right common carotid arteries. The right subclavian artery ernous sinus, and (4) the cerebral (supraclinoid) segment extends
gives rise to the right vertebral artery, and the right common from the site of exit of the artery from the cavernous sinus to its
carotid artery bifurcates into the right internal and external bifurcation into the anterior and middle cerebral arteries. The
carotid arteries. On the left side, the vertebral artery arises from intracavernous and cerebral segments are collectively known as
the left subclavian artery, and the internal carotid artery arises the carotid siphon because of their characteristic S-shaped con-
from the left common carotid artery. A knowledge of normal figuration. All the major branches of the internal carotid artery
cerebral vascular anatomy is essential for understanding and arise from the cerebral segment.
localizing cerebrovascular disorders. This chapter will focus on
blood supply of the cerebral cortex. It is worth noting that A. OPHTHALMIC ARTERY
nomenclature of the various branches of cerebral vessels varies The ophthalmic artery is the first intracranial branch of the in-
from author to author. Blood supplies of the spinal cord and ternal carotid as it courses through the cavernous sinus (Figure
brain stem are discussed in their respective chapters: Chapters 3, 27–1). The ophthalmic artery supplies the optic nerve and gives
5, 7, 9, 11, 13, and 15. rise to the central artery of the retina. Thus interruption of the
blood supply from the internal carotid system may result in dis-
Internal Carotid Artery turbances in visual acuity. The ophthalmic artery is also of im-
portance because of its anastomotic connections with branches
The internal carotid arteries arise at the bifurcation of the com- of the external carotid system; this anastomotic relationship is es-
mon carotid arteries in the neck (Figure 27–1), ascend sential in establishing collateral circulation when the internal
in front of the transverse processes of the upper three carotid system is occluded in the neck.
cervical vertebrae, and enter the base of the skull
through the carotid canal. Within the cranium, the internal B. ANTERIOR CHOROIDAL ARTERY
carotid artery lies in the cavernous sinus. It then pierces the dura The anterior choroidal artery arises from the internal carotid
to begin its subarachnoid course. The internal carotid artery artery after it emerges from the cavernous sinus (Figure 27–1). It
Anterior
Cerebral Mi le Cerebral
Artery
dd
Artery
Internal Carotid Artery
(cerebral segment)
Anterior Choroidal Artery
Ophthalmic Artery
Internal Carotid Arter y Internal Carotid
(intracavernous segment) Artery (cervical segment)
Internal Carotid Arter y
(intrapetrosal segment)
Common Caroti d
Artery
Figure 27–1. Lateral view of carotid arteriogram showing the four segments of the internal carotid artery
and four of its intracranial branches: ophthalmic, anterior choroidal, anterior cerebral, and middle cerebral.
350 / CHAPTER 27
passes ventral to the optic tract and supplies the optic tract, cere- gyri at the base of the frontal lobe and part of the septal area.
bral peduncles, lateral geniculate body, posterior part of the pos- The orbitofrontal artery or its branches may be displaced by
terior limb of the internal capsule, tail of the caudate nucleus, subfrontal tumors, thus providing a clue, in cerebral angiograms,
uncus, amygdala, anterior hippocampus, choroid plexus of the to the extracerebral location of the tumor (e.g., subfrontal
temporal horn, and sometimes the globus pallidus. The anterior meningioma).
choroidal artery is prone to occlusion by thrombus because of its 3. Frontopolar Artery (Figure 27–2). Arising at the level of
small caliber. the genu of the corpus callosum, this artery supplies most of the
pole of the frontal lobe.
C. ANTERIOR CEREBRAL ARTERY
4. Callosomarginal Artery (Figure 27–2). This is the major
The anterior cerebral artery (Figures 27–1, 27–2, and 17–26) branch of the anterior cerebral artery. It passes backward and up-
originates from the internal carotid artery lateral to the optic ward and gives off internal frontal branches before terminating
chiasm and courses dorsal to the optic nerve to reach the inter- in the paracentral branch around the paracentral lobule.
hemispheric fissure, where it curves around the genu of the cor-
pus callosum and continues as the pericallosal artery dorsal to 5. Pericallosal Artery (Figure 27–2). This is the terminal
the corpus callosum. As the two anterior cerebral arteries ap- branch of the anterior cerebral artery. It courses fairly close to the
proach the interhemispheric fissure, they are joined by the ante- corpus callosum. It ordinarily gives rise to the paracentral artery,
rior communicating artery. The following are among its major which also may be derived from the callosomarginal artery. The
branches. pericallosal artery terminates as the precuneal branch, which
supplies the precuneus gyrus of the parietal lobe.
1. Recurrent Artery of Heubner (Medial Striate Artery) The anterior cerebral artery supplies the medial surface
(Figure 27–2). This artery arises from the anterior cerebral of the cerebral hemisphere as far back as the parietooc-
artery either proximal or distal to the anterior communicating cipital fissure. This area includes the paracentral lobule,
artery. It supplies the anterior limb and genu of the internal cap- which contains cortical centers for movement and sensation from
sule and parts of the head of the caudate, rostral putamen, and the contralateral lower extremity, and the ventromedial prefrontal
globus pallidus. It also provides blood supply to the posterior cortex important for executive functions, including short-term
portions of the gyrus rectus and orbitofrontal cortex. Thus oc- memory, planning, and decision making. Unilateral occlusion of
clusion of this artery will result in subcortical and cortical in- the anterior cerebral artery is manifested in contralateral lower
farcts. The recurrent artery of Heubner varies in number from extremity weakness or paralysis and sensory deficit.
one to three. Occlusion of both anterior cerebral arteries results in bilateral
2. Orbitofrontal Artery (Figure 27–2). This branch arises dis- lower extremity paralysis and impaired sensations that mimic a
tal to the anterior communicating artery and supplies the orbital spinal cord lesion.
Pericallosal Branch Callosomarginal Branch
Frontopolar
Branch
Orbitofrontal
Branch
Medial Striate Branch Anterior Cerebral

(Recurrent Artery Artery Stem
of Heubner)
Figure 27–2. Midsagittal view of the brain showing anterior cerebral artery distribution.
Because of the bilateral involvement of the ventromedial pre- 2. Central (Perforating) Branches. These include the lenticu-
frontal cortex in such lesions, affected patients show loss of initia- lostriate arteries, which supply the major parts of the caudate,
tive and spontaneity, apathy, memory and emotional disturbances, putamen, globus pallidus, internal capsule, and thalamus. The
and difficulty in control of their urinary and anal sphincters. perforating branches are involved in basal ganglia and internal
capsule hemorrhages and infarcts. Charcot’s artery, the artery of
D. MIDDLE CEREBRAL ARTERY cerebral hemorrhage, is one of the perforating branches of the
The middle cerebral artery (Figures 27–1, 27–3, and 17–27) is a middle cerebral artery.
continuation or the main branch of the internal carotid artery. It The perforating arteries range in number from two to twelve
is divided into four segments: the M1 (sphenoidal) segment and in size from 80 to 1400 m.
courses posterior and parallel to the sphenoid ridge; the M2 (in- The middle cerebral artery thus supplies the following impor-
sular) segment lies on the insula (island of Reil); the M3 tant neural structures: primary and association motor and so-
(opercular) segment courses over the frontal, parietal, matosensory cortices, Broca’s area of speech, prefrontal cortex,
and temporal opercula; and the M4 (cortical) segment primary and association auditory cortices (including Wernicke’s
spreads over the cortical surface. It courses within the lateral (syl- area), and the major association cortex (supramarginal and angu-
vian) fissure and divides into a number of branches that supply lar gyri). Occlusion of the middle cerebral artery results in con-
most of the lateral surface of the hemisphere. The middle cere- tralateral paralysis (more marked in the upper extremity and
bral artery territory does not reach the occipital or frontal poles face), contralateral loss of kinesthesia and discriminative touch,
or the upper margin of the hemisphere along the superior longi- changes in mentation and personality, and aphasia when the left
tudinal fissure but does extend around the inferior margin of the (dominant) hemisphere is involved.
cerebral hemisphere onto the inferior surfaces of the frontal and
temporal lobes. The following are some of the more important E. POSTERIOR COMMUNICATING ARTERY
branches. The posterior communicating artery (Figure 27–4) connects
1. Cortical Branches. These include the frontal branch, includ- the internal carotid artery with the posterior cerebral artery.
ing the rolandic (which supplies the primary sensory motor cor- Some anatomists consider the posterior cerebral artery as a con-
tex); the temporal branch; and the parietal branch, including the tinuation of the posterior communicating artery. Branches of
angular (which supplies the supramarginal and part of the angu- the posterior communicating artery supply the genu and ante-
lar gyri). The most rostral cortical division of the middle cerebral rior part of the posterior limb of the internal capsule, the ante-
artery is known as the candelabra branch because of its division rior part of the thalamus, and parts of the hypothalamus and
into two segments, resembling a candelabra. subthalamus.
Parietal
Frontal Branches Rolandic Branch Branches
Angular
Branch
Temporal
Branches
Middle Cerebral Artery
Figure 27–3. Lateral Surface of the cerebral hemisphere showing the middle cerebral artery and its cortical
branches.
352 / CHAPTER 27
Anterior comm Anterior cerebral

artery artery
Internal carot Middle cerebral

artery artery
Posterior Posterior cerebral

communicatin artery
artery
Superior cerebellar
artery
Basilar
artery Pontine
arteries
Anterior Labyrinthine artery

spinal
artery Anterior inferior
cerebellar artery

Vertebral Posterior inferior
artery cerebellar artery of the major branches of the ver-
tebral and basilar arteries and the
circle of Willis and arteries that
contribute to the formation of the
circle.
Vertebral Artery spinal cord. Occlusion of this artery in the spinal cord results in
sudden onset of paralysis below the occlusion.
The vertebral artery arises from the subclavian artery. It ascends
within the foramina of the transverse processes of the upper C. POSTERIOR INFERIOR CEREBELLAR ARTERY (PICA)
six cervical vertebrae (intraosseous segment), curves backward Asymmetric in level of origin and diameter, these arteries (Figure
around the lateral mass of the atlas (atlantoaxial segment), and 27–4) follow an S-shaped course over the olive and inferior cere-
enters the cranium through the foramen magnum (intracranial bellar peduncle to supply the inferior surface of the cerebellum,
segment). Within the cranium, the vertebral arteries lie on the dorsolateral surface of the medulla oblongata, choroid plexus of
inferior surface of the medulla oblongata (Figure 27–4). The two the fourth ventricle, and part of the deep cerebellar nuclei.
vertebral arteries join at the caudal end of the pons to form the Occlusion of this artery gives rise to a characteristic group of
basilar artery. The vertebral artery gives rise to the posterior signs and symptoms comprising the lateral medullary syndrome
spinal, anterior spinal, and posterior inferior cerebellar branches. (Wallenberg syndrome). The posterior inferior cerebellar artery
Meningeal branches supply the meninges of the posterior fossa, may have common origin with the anterior inferior cerebellar
including the falx cerebelli. artery from the basilar artery.
The intraosseous segment is affected by osteoarthritis and
atherosclerosis. The atlantoaxial segment is affected in fractures, Basilar Artery
dislocations, subluxations, birth trauma, and chiropractic adjust-
ments. The intracranial segment is involved more frequently Formed by the union of the two vertebral arteries at the caudal
than other segments in thrombotic occlusions. end of the pons, the basilar artery (Figure 27–4) runs in the pon-
tine groove on the ventral aspect of the pons and terminates at
A. POSTERIOR SPINAL ARTERY the rostral end by dividing into the two posterior cerebral arter-
The two posterior spinal arteries pass caudally over the medulla ies. Branches include a series of paramedian (penetrating) arter-
and the posterior surface of the spinal cord. They supply the pos- ies that supply the paramedian zone of the basilar portion of the
terior aspect of the medulla below the obex, as well as the poste- pons (basis pontis) and the adjacent pontine tegmentum and a
rior column and posterior horns of the spinal cord. One or both series of short and long circumferential arteries.
posterior spinal arteries may arise from the posterior inferior
cerebellar arteries. A. PARAMEDIAN PENETRATING ARTERIES
These branches travel for variable distances caudally before pen-
B. ANTERIOR SPINAL ARTERY etrating the brain stem; hence a lesion in the brain stem may ap-
The anterior spinal artery (Figure 27–4) starts as two vessels that pear at levels more caudal than that of the occluded vessel.
join to form a single artery that descends on the ventral aspect of
the medulla and into the anterior median fissure of the spinal B. SHORT CIRCUMFERENTIAL ARTERIES
cord. It supplies the medullary pyramids and the paramedian These branches supply the anterolateral and posterolateral parts
medullary structures, as well as the anterior two-thirds of the of the pons.
C. LONG CIRCUMFERENTIAL ARTERIES the cerebral peduncle and supply the medial surfaces of the oc-
There are three long circumferential arteries. cipital lobe, including the primary and association visual cor-
tices, temporal lobe, caudal parietal lobe, and the splenium of
1. Auditory (Labyrinthine) Artery. This artery (Figure 27–4) the corpus callosum. The main trunk of the posterior cerebral
accompanies the facial (CN VII) and vestibulocochlear (CN artery bifurcates into medial and lateral branches (Figure 27–5).
VIII) cranial nerves and supplies the inner ear and root fibers of The lateral branch gives rise to anterior and posterior temporal
the facial nerve. Occlusion of this artery gives rise to deafness. It branches, which supply the medial surface of the temporal lobe
has variable origin from the basilar, anterior inferior cerebellar, except for its most rostral part, which is supplied by the middle
and the posterior inferior cerebellar arteries. cerebral artery. The medial branch gives rise to parietooccipital
2. Anterior Inferior Cerebellar Artery (AICA). This artery and occipital (including calcarine) branches, which supply the
(Figure 27–4) supplies the inferior surface of the cerebellum, the medial surface of the occipital lobe, part of the posterior parietal
brachium pontis, and the restiform body, as well as the tegmen- lobe, and the splenium of the corpus callosum.
tum of the lower pons and upper medulla. It may arise from a Occlusion of one posterior cerebral artery results in contralat-
common stem with the auditory artery or the posterior inferior eral loss of vision (homonymous hemianopia), with sparing of
cerebellar artery. macular vision because of collateral circulation from the middle
3. Superior Cerebellar Artery. This is the last branch of the cerebral artery to the occipital pole, where macular vision is rep-
basilar artery before its terminal bifurcation into the two posterior resented. Bilateral occlusion of the posterior cerebral artery re-
cerebral arteries (Figure 27–4). The oculomotor nerve exits the sults in prosopagnosia (loss of face recognition) and achromatop-
brain stem between the superior cerebellar and posterior cerebral sia (loss of color vision). Perforating branches supply the cerebral
arteries. It supplies the superior surface of the cerebellum, part of peduncle, mamillary bodies, and the mesencephalon. Other
the dentate nucleus, the brachium pontis and conjunctivum, the branches include the thalamogeniculate artery, which supplies
tegmentum of the upper pons, and the inferior colliculus. the lateral geniculate body and posterior thalamus, and the pos-
terior choroidal artery, which supplies the choroid plexus of the
D. POSTERIOR CEREBRAL ARTERIES (Figures 27–5 and 17–26) third and lateral ventricles, tectum, and thalamus. Posterior cere-
These constitute the terminal branches of the basilar artery in bral artery branches also pass over the dorsal edge of the cerebral
70 percent of cases; they may arise from the carotid hemisphere to supply a small part of the lateral surface of the
artery of one side in 20 to 25 percent of cases and on caudal parietal lobe and occipital lobe and the inferior temporal
both sides in 5 to 10 percent of cases. They pass around gyrus. The posterior cerebral artery may be compressed by herni-
Medial Branch
Parietooccipital
Branch
Calcarine
Branch
Lateral
Branch
Posterior
Temporal
Branches
Posterior Cerebral
Artery Anterior Temporal
Branches
Figure 27–5. Medial and inferior view of the cerebral hemisphere showing the posterior cerebral artery and its
branches.
354 / CHAPTER 27
ation of the uncus in cases of increased intracranial pressure. As a 2. Extracranial-intracranial anastomoses occur between branches
consequence, the circulation of the visual cortex is impaired, re- of the external carotid and the ophthalmic artery. This is a
sulting in cortical blindness. major site of communication between extracranial and in-
tracranial circulations. Thus, when the internal carotid is
CIRCLE OF WILLIS obstructed proximal to the origin of the ophthalmic artery,
flow is reversed in the ophthalmic artery. Another site of
The proximal portions of the anterior, middle, and posterior extracranial-intracranial anastomosis is through the rete
cerebral arteries connected by the anterior and posterior commu- mirabile, a group of small vessels that connect meningeal
nicating arteries form a circle, the circle of Willis (Figure 27–4), and ethmoidal branches of external carotid arteries with lep-
around the infundibulum of the pituitary and the optic chiasm. tomeningeal branches of cerebral arteries.
The circle constitutes an important anastomotic channel be- 3. Intracranial anastomoses occur in the circle of Willis. Under
tween the internal carotid and the vertebral basilar systems. normal conditions, there is very little side flow or flow from
When either the internal carotid arteries (anterior circula- posterior to anterior segments in the circle of Willis. In
tion) or the vertebral basilar system (posterior circulation) be- the presence of major occlusion, however, the commu-
comes occluded, collateral circulation in the circle of Willis will nications across the anterior or posterior communicat-
provide blood to the area deprived of blood supply. The circle of ing artery become a very important channel for collateral cir-
Willis is complete in only 20 percent of individuals. In the ma- culation. Other sites of intracranial anastomoses include
jority of individuals, variation in size and/or origin of vessels is those among the superior cerebellar, anterior inferior cere-
the rule. bellar, and posterior inferior cerebellar in the cerebellum.
CONDUCTING AND PENETRATING VESSELS CEREBRAL VENOUS DRAINAGE

The arteries of the brain fall into two general types. The con- Cerebral venous drainage occurs through two systems, the super-
ducting or superficial arteries are those which run in the pia ficial and the deep.
arachnoid and include the internal carotid and vertebral basilar
systems and their branches. These vessels receive autonomic
nerves and function as pressure-equalization reservoirs to main- Superficial Venous System
tain an adequate perfusion pressure for the penetrating arteries.
It is estimated that the drop in the pressure head from large ves- The superficial system of veins (Figure 27–6) is divided into
sels to the penetrating arterioles does not exceed 10 to 15 per- three groups.
cent. The penetrating arterioles supply the cortex and white mat- A. SUPERIOR CEREBRAL GROUP
ter and are organized in vertical and horizontal patterns. These These veins drain the dorsolateral and dorsomedial surfaces of
are presumed to be the primary sites of regional autoregulation the hemisphere and enter the superior sagittal sinus at a forward
and do not receive a significant neural supply. angle against the flow of blood. Conventionally, the
most prominent of these veins in the central sulcus is
HISTOLOGY OF CEREBRAL VESSELS called the superior anastomotic vein of Trolard, which
interconnects the superior and middle groups of veins.
Cerebral arteries differ from arteries elsewhere in the body in the
following features: B. MIDDLE CEREBRAL GROUP
1. Thinner walls These veins run along the sylvian fissure, drain the inferolateral
surface of the hemisphere, and open into the cavernous sinus.
2. Absent external elastic laminae
3. Presence of astrocytic processes
4. Presence of a perivascular reticular sheath consisting of
arachnoid trabeculae (the latter acquire an outer pial mem-
Superior Vein of Trolard
brane when the vessel penetrates the brain substance). cerebral
Cerebral capillaries are structurally similar to capillaries else- veins
where, except for being surrounded by perivascular glial (astro-
cytic) processes. Cerebral veins have thinner walls and are devoid
of valves and muscle fibers. The absence of valves allows reversal
of blood flow when occlusion of the lumen occurs in disease.
COLLATERAL CIRCULATION
Anastomotic channels are present in all parts of both the arterial Middle cerebral
and venous circulations. Their main purpose is to ensure a con- vein
tinuing blood flow to the brain in case of a major occlusion of a Vein of Labbé
feeding vessel. Some of these channels, however, are not very ef-
fective in collateral circulation because of their small caliber. The Inferior cerebral veins
following are the major sites of collateral circulation. Figure 27–6. Schematic diagram of lateral surface of the cere-
1. Extracranial anastomoses are found between cervical vessels, bral hemisphere showing the system of superficial venous
such as the vertebral and external carotids of the same side. drainage.
C. INFERIOR CEREBRAL GROUP Visualization of the cerebral veins, particularly the deep
These veins drain the inferior surface of the hemisphere and group, is used during cerebral angiography in the localization of
open into the cavernous and transverse sinuses. The middle and deep brain lesions.
inferior groups are interconnected by the inferior anas- C. GREAT CEREBRAL VEIN (OF GALEN)
tomotic vein of Labbé, which crosses the temporal lobe
about 5 cm behind its tip. The medial surface of the This vein receives the internal cerebral vein and the basal vein of
hemisphere is drained by a number of veins that open into the Rosenthal and a number of other smaller veins (occipital, posterior
superior and inferior sagittal sinuses, as well as into the basal vein callosal) and extends for a short distance under the splenium of the
and the great cerebral vein of Galen. corpus callosum to empty into the straight sinus (rectus sinus).
Because of the many anastomotic interconnections within
the deep venous system, only simultaneous obstruction of the
Deep Venous System great cerebral vein of Galen and the basal vein of Rosenthal will
The deep venous system (Figure 27–7) consists of a number of effectively obstruct deep venous flow. This can occur in tentorial
veins that drain into two main tributaries; these are the internal herniation associated with displacement of the midbrain as a re-
cerebral vein and the basal vein (of Rosenthal). The two join be- sult of brain edema, bleed, or tumor. Complete obstruction of
neath the splenium of the corpus callosum to form the great the vein of Galen and basal vein leads to rapid death.
cerebral vein of Galen, which opens into the straight sinus.
CEREBRAL DURAL VENOUS SINUSES
A. INTERNAL CEREBRAL VEIN
This vein receives two tributaries. Cerebral dural venous sinuses (see Figure 2–4) are lined by endo-
thelium and are devoid of valves. They lie between the periosteal
1. Terminal Vein (Thalamostriate). Draining the caudate nu- and meningeal layers of the dura mater. They serve as low-pressure
cleus and possibly the thalamus, this vein passes forward in a channels for venous blood flow back to the systemic circulation.
groove between the caudate nucleus and thalamus in the body of The superior sagittal sinus and the inferior sagittal si-
the lateral ventricle and empties into the internal cerebral vein at nus lie in the superior and inferior margins of the falx
the interventricular foramen of Monro. cerebri, respectively. The superficial cerebral veins drain
2. Septal Vein. This vein drains the septum pellucidum, the ante- into the superior and inferior sagittal sinuses. The superior sagit-
rior end of the corpus callosum, and the head of the caudate nu- tal sinus, in addition, drains cerebrospinal fluid from the sub-
cleus and passes backward from the anterior column of the fornix to arachnoid space via arachnoid granulations, evaginations of the
open at the interventricular foramen into the internal cerebral vein. arachnoid matter (arachnoid villi), into the superior sagittal si-
The internal cerebral vein of each side runs along the roof of nus. Caudally, the inferior sagittal sinus is joined by the great
the third ventricle in the velum interpositum. It extends from cerebral vein of Galen to form the straight sinus (rectus sinus) lo-
the region of the foramen of Monro rostrally to between the cated at the junction of the falx cerebri and tentorium cerebelli.
pineal body (below) and the splenium of the corpus callosum The straight sinus drains into the confluence of sinuses. The two
(above) caudally. The two internal cerebral veins join below the transverse sinuses arise from the confluence of sinuses (torcular
splenium of the corpus callosum to form the great vein of Galen. Herophili) and pass laterally and forward in a groove in the oc-
cipital bone. At the occipitopetrosal junction, they curve down-
B. BASAL VEIN OF ROSENTHAL
ward and backward as the sigmoid sinus, which drains into the
This vein begins under the anterior perforated substance near internal jugular vein. The occipital sinus connects the confluence
the medial part of the anterior temporal lobe and runs backward of sinuses (torcular Herophili) to the marginal sinus at the fora-
to empty into the great cerebral vein. It drains blood from the men magnum. The superior petrosal sinus lies in the dura at the
base of the brain. anterior border of the tentorium cerebelli. It connects the pe-
trosal vein and transverse sinus to the cavernous sinus. The infe-
rior petrosal sinus joins the cavernous sinus to the jugular bulb
and extends between the clivus and the petrous bone. The cav-
Thalamostriate vein Great cerebral
vein of Gale
en
ernous sinus lies on each side of the sphenoid sinus, the sella tur-
cica, and the pituitary gland. The medial wall of the sinus con-
tains the internal carotid artery and the abducens cranial nerve.
The lateral wall contains the oculomotor and trochlear cranial
nerves and the ophthalmic and maxillary divisions of the trigem-
inal cranial nerve. The two cavernous sinuses intercommunicate
via the basilar venous plexuses and via venous channels anterior
and posterior to the pituitary gland. Anteriorly, the ophthalmic
vein drains into the cavernous sinus. Posteriorly, the cavernous
sinus drains into the superior and inferior petrosal sinuses.
Laterally, it joins the pterygoid plexus at the foramen ovale.
FACTORS REGULATING CEREBRAL

CIRCULATION
Septaal Basal vein Internal
vein of Rosenthal cerebral vein
Cerebral blood flow is a function of the pressure gradient and
cerebral vascular resistance. The pressure gradient is determined
Figure 27–7. Schematic diagram of the deep system of venous primarily by arterial pressure. Resistance is a function of blood
drainage of the brain. viscosity and size of cerebral vessels.
356 / CHAPTER 27
Extrinsic Factors B. BIOCHEMICAL FACTORS

A. SYSTEMIC BLOOD PRESSURE Several biochemical factors regulate cerebral circulation.
Arterial pressure is regulated by several circulatory re- 1. Carbon Dioxide. Arterial PCO2 is a major factor in the regu-
flexes, the most important of which are the barorecep- lation of cerebral blood flow. Hypercapnia (high PCO2) produces
tor reflexes. Baroreceptors in the aortic arch and carotid marked vasodilatation and an increase in cerebral blood flow.
sinus are tonically active when arterial pressure is normal and The reverse occurs in hypocapnia (low PCO2). Thus inhalation of
vary their impulse frequency directly with fluctuations in blood carbon dioxide increases cerebral blood flow, whereas hyperven-
pressure. An increase in arterial pressure increases impulses tilation decreases cerebral blood flow. Under normal conditions,
from baroreceptors, with inhibition of sympathetic efferents to it is estimated that a change of 1 mmHg in PCO2 will induce a
the cardiovascular system and stimulation of the cardiac vagus 5 percent change in cerebral blood flow.
nerve, leading to a decrease in arterial pressure. The reverse oc- The control of cerebral blood flow by carbon dioxide is medi-
curs if the arterial pressure is decreased. Baroreceptor regulation ated via the cerebrospinal fluid bathing cerebral arterioles. The
of arterial pressure ceases when arterial pressure falls below 50 to pH of the cerebrospinal fluid (CSF) reflects the arterial PCO2 and
60 mmHg. is also influenced by the level of bicarbonate in the CSF.
Fluctuations in systemic arterial blood pressure in the healthy The effect of carbon dioxide on cerebral blood flow is impor-
young individual have very little, if any, effect on cerebral blood tant in dampening the effects of tissue PCO2 in areas of brain is-
flow. Cerebral blood flow will be maintained with fluctuations in chemia. The increase in cerebral blood flow in such areas helps to
systolic blood pressure between 200 and 50 mmHg. A fall in sys- wash out metabolically produced carbon dioxide and thus
tolic blood pressure below 50 mmHg may be accompanied by a reestablishes homeostasis of brain pH.
reduction in cerebral blood flow; however, because more oxygen 2. Oxygen. Moderate changes in arterial PO2 do not alter cere-
is extracted, consciousness is usually not impaired. Cerebral bral blood flow. However, more marked changes in arterial PO2
blood flow also may decrease if systolic pressure rises above 200 alter cerebral blood flow in a manner that is the reverse of that
mmHg or diastolic pressure rises above 110 to 120 mmHg. The described for PCO2. Thus low PO2 (below 50 mmHg) will in-
range of blood pressure fluctuations beyond which cerebral crease cerebral blood flow, and high PO2 will decrease cerebral
blood flow is affected is narrower in individuals with arterioscle- blood flow. Although the exact mechanism of this effect is not
rosis of cerebral vessels. known, it is believed to be independent of changes in PCO2.
3. pH. Cerebral blood flow increases with the lowering of the
B. BLOOD VISCOSITY pH and decreases in alkalosis.
Cerebral blood flow is inversely proportional to blood viscosity
in humans. A major factor controlling blood viscosity is the con- Neural Factors
centration of red blood cells. A reduction in blood viscosity, as
occurs in anemia, will increase cerebral blood flow. On the other A. SYMPATHETIC SUPPLY
hand, an increase in viscosity, as occurs in polycythemia, will de- Sympathetic innervation of conducting vessels is amply docu-
crease cerebral blood flow. Venesection in polycythemic patients mented from the cervical sympathetic chain. In contrast, very
has been shown to increase cerebral blood flow by 30 percent few, if any, penetrating vessels receive adrenergic nerves. Both
concomitant with a drop in viscosity and hematocrit. myelinated preganglionic and unmyelinated postganglionic nerve
plexuses have been demonstrated in the periadventitial tissue.
C. VESSEL LUMEN Synaptic terminals also have been traced to the outer part of the
Minor reductions in the lumina of carotid and vertebral arteries muscular media. The number of nerve plexuses and terminals de-
are without effect on cerebral circulation. The vessel lumen must creases with reduction in the caliber of the conducting vessel.
be reduced by 70 to 90 percent before a reduction in cerebral cir- Stimulation of the sympathetic system produces vasoconstriction
culation occurs. and a decrease in cerebral blood flow. The effect is greater in the
internal carotid artery system than in the vertebral basilar system.
Intrinsic Factors B. PARASYMPATHETIC SUPPLY
A. AUTOREGULATION Although parasympathetic nerve fibers have been demonstrated
in cerebral vessels of the conducting variety, a physiologic role
The single most important factor controlling cerebral for this system in the regulation of cerebral circulation is yet to
circulation is the phenomenon of autoregulation, by be found. The vasoactive effects of sympathetic stimulation are
which smooth muscles in small cerebral arteries and ar- counteracted by a minor change in pH. Thus neural factors in
terioles can change their tension in response to intramural pres- the regulation of cerebral blood flow are believed to be of minor
sure to maintain a constant flow despite alterations in perfusion importance when compared with the biochemical factors.
pressure. Thus cerebral blood vessels constrict in response to an
increase in intraluminal pressure and dilate in response to a re- Neuropeptides
duction in intraluminal pressure. This phenomenon is particu-
larly useful in shunting blood from healthy regions where intra- Nerve fibers containing neuropeptide Y, vasoactive intestinal
luminal pressure is higher to ischemic regions where a reduction peptide (VIP), substance P (SP), and calcitonin gene-related
in blood flow has occurred, resulting in a reduction in intra- peptide (CGRP) have been reported in adventitia or at the ad-
luminal pressure. Autoregulation operates independently of but ventitia–media border of human cerebral arteries. In vitro stud-
synergistically with other intrinsic factors such as biochemical ies reveal that neuropeptide Y causes vasoconstriction, whereas
changes. The mechanism of autoregulation is poorly under- VIP, SP, and CGRP cause relaxation of precontracted vessels.
stood. In general, three theories have been proposed; these are The effect of neuropeptides on cerebral blood vessels is not me-
the neurogenic, myogenic, and metabolic theories. diated via adrenergic, cholinergic, or histaminergic receptors.
MEAN AND REGIONAL CEREBRAL Carotid (Greek karotis, “deep sleep”). The arteries of the neck
BLOOD FLOW are so called because it was known in ancient times that animals
became sleepy when these vessels were compressed.
Mean cerebral blood flow is rather constant during the perfor- Cavernous (Latin cavernosus, “containing caverns or hollow
mance of daily physiologic activities, such as muscular exercise, spaces”).
changes in posture, mental activity, and sleep. It is altered, how- Circle of Willis. The anastomotic ring of arteries that encircles
ever, in some pathologic conditions such as convulsions (in- the pituitary stalk. It was first depicted by Johann Vesling in
creased), coma (decreased), anemia (increased), and cerebral ves- 1647 and further defined by Thomas Willis in 1664.
sel sclerosis (decreased). In contrast, regional cerebral blood flow
Great cerebral vein of Galen. A major deep cerebral vein that
is altered during the performance of physiologic activities; thus
drains into the straight sinus. Named after Claudius Galen,
the regional blood flow in the occipital cortex is increased with
the Roman physician and founder of the galenical system of
visual activity and in the motor cortex during limb movement.
medicine.
Studies of regional cerebral blood flow in normal individuals
have contributed significantly to a better understanding of the Recurrent artery of Heubner. A branch of the anterior cerebral
role of different brain regions in the performance of physiologic artery. Named after Otto Johann Leonhard Heubner, a German
activities, such as reading, speaking, hearing, and movement. pediatrician.
Determinations of regional cerebral blood flow also have eluci- Torcular Herophili (Latin torcula, “wine press”). A cistern or
dated regional derangements of distribution of blood flow in dis- well to collect the liquor from the wine press. Herophilus was the
ease states, such as cerebral stroke. ancient Greek anatomist who described this region of the brain.
The confluence of sinuses.
Steal Syndrome Vein of Labbé. An anastomotic cerebral vein that interconnects
the middle and inferior groups of superficial cerebral veins.
Ischemia of brain tissue, in which cerebral blood flow is below Named after Charles Labbé, the French anatomist.
20 ml/100 g per min, results in accumulation of lactic acid and Vein of Trolard. An anastomotic cerebral vein that interconnects
secondary loss of tone of the regional blood vessels. These vessels the superior and middle groups of superficial cerebral veins.
are not capable of responding normally, in view of vasomotor Named after Paulin Trolard, professor of anatomy in Algiers,
paralysis, to factors that alter cerebral blood flow, such as carbon who described the vein in his graduation thesis from the Univer-
dioxide and oxygen. In such patients, administration of a vaso- sity of Paris in 1868.
dilator drug or induction of a state of hypercapnia dilates the
normal vessels and increases blood flow in the brain regions sup-
plied by such vessels at the expense of the ischemic region (steal SUGGESTED READINGS
syndrome). These agents should be used with great caution in Andeweg J: Consequences of the anatomy of deep venous outflow from the
such patients to avoid a serious and possibly fatal reduction in brain. Neuroradiology 1999; 41:233–241.
cerebral blood flow in the already ischemic region. Brown MM et al: Fundamental importance of arterial oxygen content in the
regulation of cerebral blood flow in man. Brain 1985; 108:81–93.
Damasio H: A computed tomographic guide to the identification of cerebral
Autoregulation and Hypertension vascular territories. Arch Neurol 1983; 40:138–142.
Edvinsson L et al: Peptide-containing nerve fibers in human cerebral arteries:
Cerebral blood flow is normal in patients with moderate hyper- Immunocytochemistry, radioimmunoassay, and in vitro pharmacology.
tension. Such patients therefore do not have cerebral symptoms. Ann Neurol 1987; 21:431–437.
It has been found that the autoregulatory mechanism in such pa- Gibo H et al: Microsurgical anatomy of the middle cerebral artery. J Neurosurg
tients is set at a higher threshold than that in normal individuals. 1981; 54:151–169.
However, if the blood pressure is increased acutely, then autoreg- Glasberg MD et al: Increase in both cerebral glucose utilization and blood
ulatory mechanisms break down and cerebral symptoms appear. flow during execution of a somatosensory task. Ann Neurol 1988; 23:
152–160.
Ingvar DH, Schwartz MS: Blood flow patterns induced in the dominant
Cerebral Blood Flow in Epilepsy hemisphere by speech and reading. Brain 1974; 97:273–288.
During an epileptic attack, mean cerebral blood flow increases Lassen NA: Control of cerebral circulation in health and disease. Circ Res 1974;
two- to threefold. This is a response to increased metabolic de- 34:749–760.
mands of brain tissues during such attacks. Lister JR et al: Microsurgical anatomy of the posterior inferior cerebellar
artery. Neurosurgery 1982; 10:170–199.
Kuschinsky W, Wahl M: Local chemical and neurogenic regulation of cerebral
Cerebral Blood Flow in Coma vascular resistance. Physiol Rev 1978; 58:656–689.
Marinkovic SV et al: Perforating branches of the middle cerebral artery:
The mean cerebral blood flow is severely reduced in states of un- Microanatomy and clinical significance of their intracerebral segments.
consciousness. Attempts to correlate the degree of reduction of Stroke 1985; 16:1022–1029.
cerebral blood flow with the chances of recovery from the co- Marinkovic S et al: Anatomical bases for surgical approach to the initial seg-
matose state have not been successful. ment of the anterior cerebral artery: Microanatomy of Heubner’s artery
and perforating branches of the anterior cerebral artery. Surg Radiol Anat
1986; 8:7–18.
TERMINOLOGY Marinkovic S et al: Interpeduncular perforating branches of the posterior cere-
bral artery: Microsurgical anatomy of their extracerebral and intracere-
Basal vein of Rosenthal. A deep cerebral vein that serves as a bral segments. Surg Neurol 1986; 26:349–359.
landmark for neuroradiologists in identifying pathology in deep Marinkovic SV et al: Distribution of the occipital branches of the posterior
cerebral structures. It was described by Friedrich Rosenthal, a cerebral artery: Correlation with occipital lobe infarcts. Stroke 1987; 18:
German anatomist. 728–732.
358 / CHAPTER 27
Marinkovic S et al: Anatomic and clinical correlations of the lenticulostriate Waddington MM: Atlas of Cerebral Angiography with Anatomic Correlation.
arteries. Clin Anat 2001; 14:190–195. Boston: Little, Brown, 1974.
Martin RG et al: Microsurgical relationships of the anterior inferior cerebellar Wade JPH: Transport of oxygen to the brain in patients with elevated hemat-
artery and the facial–vestibulocochlear nerve complex. Neurosurgery 1980; ocrit values before and after venesection. Brain 1983; 106:513–523.
6:483–507. Zhang R et al: Autonomic neural control of dynamic cerebral autoregulation
Soh K et al: Regional cerebral blood flow in aphasia. Arch Neurol 1978; 35: in humans. Circulation 2002; 106:1814–1820.
625–632.
Tatu L et al: Arterial territories of the human brain: Cerebral hemispheres.
Neurology 1998; 50:1699–1708.
Cerebral Vascular Syndromes 28
Cerebrovascular Occlusion Syndromes Anterior Choroidal Artery Syndrome

Middle Cerebral Artery Syndrome Posterior Cerebral Artery Syndrome
Lenticulostriate Artery Syndrome Vertebral-Basilar Artery Syndromes
Anterior Cerebral Artery Syndrome Lacunar Syndromes
Recurrent Artery of Heubner Syndrome Cerebral Hemorrhage Syndromes
Internal Carotid Artery Syndrome
KEY CONCEPTS
Cerebrovascular disorders include cerebral infarcts (most Lacunar syndromes result from occlusion of small pene-
common) and cerebral hemorrhages. trating end arteries. Five well-defined lacunar syndromes
occur: pure motor, pure sensory, ataxic hemiparesis,
The clinical picture of cerebral infarcts reflects the affected
dysarthria–clumsy hand, and état lacunaire.
vessel, the location, and the size of the lesion.
Intracranial hemorrhage results from rupture of an arter-
Fairly consistent, though not absolute, anatomicoclinical
ial wall because of longstanding hypertension, congeni-
correlations occur for each of the following vascular
tal aneurysm, arteriovenous malformation, trauma, or a
occlusion syndromes: middle cerebral artery, lenticulostri-
bleeding disorder.
ate artery, anterior cerebral artery, recurrent artery of
Heubner, internal carotid artery, anterior choroidal artery,
posterior cerebral artery, and vertebral-basilar arteries.
Cerebrovascular disorders (strokes) constitute the most common CEREBROVASCULAR OCCLUSION

cause of brain lesions. The most common cerebrovascu- SYNDROMES
lar disorders are cerebral infarcts resulting from occlu-
sion of cerebral vessels by thrombosis or embolism. Less Middle Cerebral Artery Syndrome
common is hemorrhage, usually from rupture of a congenitally (Figure 28–1)
abnormal sacculation of a cerebral blood vessel (aneurysm).
Strokes are characterized by a relatively abrupt onset of a focal This is the most frequently encountered stroke syndrome. The
neurologic deficit. The conglomeration of sensory, motor, and clinical picture varies according to the site of occlusion of the
behavioral clinical signs of the neurologic deficit usually re- vessel and to the availability of collateral circulation. The con-
flects the affected vessel as well as the location and size of glomerate clinical signs and symptoms of this syndrome consist
the cerebral lesion. Despite this predictable pattern of of the following:
clinical signs with specific arterial territory, there is also
sufficient variation in vascular patterns to produce perplexing 1. Contralateral hemiplegia or hemiparesis (complete or partial
clinicoanatomic and clinicopathologic syndromes. paralysis) affecting primarily the face and upper extremity
359
360 / CHAPTER 28
Cingulate Gyrus
Caudate Nucleus,
Head
Internal Capsule,
Anterior Limb
External Capsule
Putamen Middle Cerebral

Artery Infarct
Insular Cortex
Claustrum
Globus Pallidus
Anterior Commissure
Optic Tract
Figure 28–1. Coronal brain section showing middle cerebral artery territory infarct and secondary enlargement of the
lateral ventricle (star).
and, to a lesser degree, the lower extremity. Weakness is great- 7. Spatial perception disorders if the right, nondominant hemi-
est in the contralateral hand because more proximal limb sphere is involved. This includes such difficulties as copying
and trunk muscles as well as facial muscles have greater rep- simple pictures or diagrams (constructional apraxia), inter-
resentation in both hemispheres. preting maps or finding one’s way out (topographagnosia),
2. Contralateral sensory deficit, also more prominent in the and putting on clothes properly (dressing apraxia).
face and upper extremity than in the lower extremity. Posi- 8. Gerstmann syndrome (finger agnosia, acalculia, right-left
tion, vibration, deep touch, two-point discrimination, and disorientation, and pure dysgraphia).
stereognosis are more affected than pain and temperature be-
Language and spatial perception deficits tend to follow occlu-
cause the latter two sensory modalities may be perceived at
sion not of the proximal stem of the middle cerebral artery but of
the thalamic level.
one of its several main branches. In such circumstances, other
3. Contralateral visual field deficit because of damage to the op- signs such as weakness or visual field defects may not be present.
tic radiation, the tract that connects the lateral geniculate nu- Similarly, occlusion of the rolandic branch of the middle cerebral
cleus with the visual cortex. Depending on where the lesion artery produces motor and sensory deficits without disturbances
in the optic tract is located, the visual field deficit may be a of vision, language, or spatial perception. Hearing is unimpaired
homonymous hemianopia (half-field deficit) or a quadrant- because of its bilateral representation.
anopia (quadrant-field deficit). In general, parietal lesions are
associated with inferior quadrantanopia, whereas temporal le-
sions are associated with superior quadrantanopia. Occipital Lenticulostriate Artery Syndrome
lesions are usually associated with a hemianopia.
4. Contralateral conjugate gaze paralysis because of the involve- Infarction in the territory of the lenticulostriate artery, a branch
ment of the frontal eye field (area 8 of Brodmann). The gaze of the middle cerebral artery, is associated with pure motor
paralysis is usually transient for 1 to 2 days. The reason for hemiplegia because of involvement of the internal capsule.
this transient duration is not clear.
5. Aphasia (with impairment of repetition) if the dominant Anterior Cerebral Artery Syndrome
(left) hemisphere is involved. The aphasia may be of Broca’s,
Wernicke’s, or global variety depending on the involved cor- The clinical manifestations of this syndrome vary according to
tical region. Lesions in the inferior frontal gyrus affecting the site of occlusion along the artery, the availability of collateral
Broca’s area are associated with Broca’s aphasia. Lesions af- circulation, and whether there is unilateral or bilateral occlusion.
fecting Wernicke’s area in the superior temporal gyrus are as-
sociated with Wernicke’s aphasia. Global aphasia is usually A. UNILATERAL ANTERIOR CEREBRAL ARTERY SYNDROME
associated with extensive lesions involving much of the dom-
inant hemisphere. Unilateral occlusion of the anterior cerebral artery is associated
with the following clinical picture:
6. Inattention and neglect of the contralateral half of body or
space and denial of illness if the nondominant (right) hemi- 1. Contralateral hemiplegia or hemiparesis affecting primarily the
sphere is involved. lower extremity and to a lesser extent the upper extremity
CEREBRAL VASCULAR SYNDROMES / 361
2. Contralateral sensory deficit affecting primarily the lower ex- Recurrent Artery of Heubner Syndrome
tremity and to a lesser extent the upper extremity
Infarction in the territory supplied by the recurrent artery of
3. Transcortical motor aphasia when the left (dominant) hemi-
Heubner (medial striate artery), which is a branch of the anterior
sphere is affected
cerebral artery, results in the following signs:
B. BILATERAL ANTERIOR CEREBRAL ARTERY SYNDROME 1. Contralateral face and arm weakness without sensory loss
(Figure 28–2)
2. Behavioral and cognitive abnormalities, including abulia, ag-
This syndrome occurs when both anterior cerebral arteries arise itation, neglect, and aphasia
anomalously from a single trunk. In addition to the signs en-
countered in the unilateral syndrome, the following signs and The clinical signs reflect involvement of the anterior limb of
symptoms occur in the bilateral syndrome due to involvement of the internal capsule, rostral basal ganglia (caudate nucleus and
orbitofrontal cortex, limbic structures, supplementary motor cor- putamen), and the basal frontal lobe.
tex, and cingulate gyrus:
1. Loss of initiative and spontaneity Internal Carotid Artery Syndrome
2. Profound apathy
Occlusion of the internal carotid artery in the neck may be
3. Memory and emotional disturbances
asymptomatic in the presence of adequate collateral circula-
4. Akinetic mutism (complete unresponsiveness with open eyes tion and slow occlusion or may result in the following clinical
only) picture:
5. Disturbance in gait and posture
1. Transient monocular blindness (amaurosis fugax) due to in-
6. Grasp reflex volvement of the ophthalmic artery, the first intracranial
7. Disorder of sphincter control branch of the internal carotid artery
The explanation for the occurrence of sphincter control dis- 2. Contralateral motor and sensory deficits equally severe in the
order is not certain. It has been variably attributed to involve- face, upper extremity, and lower extremity
ment of the motor and sensory cortices on the medial surface of 3. Contralateral visual field deficit (homonymous hemianopia)
the hemisphere (paracentral lobule) or to involvement of more 4. Aphasia if the dominant hemisphere is involved
anterior regions of the frontal lobe concerned with inhibition of
5. Perceptual deficits if the nondominant (right) hemisphere is
bladder emptying.
involved
Involvement of the anterior part of the corpus callosum may
cause apraxia and tactile anomia of the left arm attributed to dis- The internal carotid artery syndrome is thus a combination
connection of the left (dominant) hemisphere language area from of the middle and anterior cerebral artery syndromes to which is
the right motor and sensory cortices. added transient monocular blindness.
Superior Frontal Anterior Cerebral

Gyrus Artery Infarct
Cingulate Gyrus
Corpus Callosum
Insular Cortex
Thalamus
Putamen
Globus Pallidus
Third Ventricle
Figure 28–2. Coronal brain section showing bilateral anterior cerebral artery territory infarct (stars).
362 / CHAPTER 28
Anterior Choroidal Artery Syndrome cal features and causes have not been studied as extensively as in
(Figure 28–3) other vascular territories.
Occlusion of the anterior choroidal artery, a branch of the inter- A. UNILATERAL POSTERIOR CEREBRAL ARTERY SYNDROME
nal carotid artery, may be asymptomatic or may result in one or Unilateral occlusion of the posterior cerebral artery is associated
more of the following: with the following:
1. Contralateral motor deficit (hemiplegia) involving the face, 1. Contralateral visual field deficit (hemianopia) due to in-
arm, and leg due to involvement of the posterior part of the volvement of the calcarine cortex. Macular (central) vision is
posterior limb of the internal capsule and the cerebral pe- usually spared because macular representation in the occipi-
duncle. This is the most consistent and persistent deficit. tal pole receives additional blood supply from the middle
2. Contralateral hemisensory deficit, usually transient, involv- cerebral artery.
ing, in most cases, all sensory modalities (hemianesthesia) 2. Visual and color agnosia, the inability to name a color or
due to involvement of the sensory tracts within the posterior point to a color named by the examiner because of involve-
limb of the internal capsule. ment of the inferiomesial aspect of the occipitotemporal lobe
3. Contralateral visual field defect (hemianopia or quadrant- in the dominant hemisphere.
anopia) due to involvement of the retrolenticular part of the 3. Contralateral sensory loss of all modalities with concomitant
internal capsule (visual radiation) or the lateral geniculate pain (thalamic syndrome) due to involvement of the ventral
nucleus. This is the most variable feature of the syndrome. posterolateral and ventral posteromedial nuclei of the thala-
mus, which are supplied by deep penetrating branches of the
Posterior Cerebral Artery Syndrome posterior cerebral artery.
(Figure 28–4) 4. Pure alexia (alexia without agraphia) with a left-sided lesion
The clinical picture of posterior cerebral artery occlusion is vari- affecting the posterior corpus callosum and the left visual
able depending on whether it is unilateral or bilateral, the site of cortex.
occlusion, and the availability of collateral circulation. Only a As a rule, the posterior cerebral artery syndrome is not associ-
few large series of posterior cerebral artery stroke exist, and clini- ated with motor deficit. The hemiplegia reported occasionally in
Putamen
Caudate Nucleus,
Head
Globus Pallidus
Internal Capsule,
Posterior Limb
Thalamus
Figure 28–3. T2-weighted magnetic resonance image (MRI) showing bright signal intensity infarct (arrow) in
the anterior choroidal artery territory.
Caudate Nucleus,
Head
Putamen
Internal Capsule,
Thalamus Posterior Limb
Lateral Ventricle
Visual Cortex
Figure 28–4. T2-weighted MRI showing bright signal intensity infarct (arrow) in the posterior cerebral
artery territory.
these patients is attributed to involvement of the midbrain by specific branch affected and the brain stem territory involved
the infarct. (e.g., lateral medullary syndrome, medial medullary syndrome,
Benedikt syndrome, Weber’s syndrome, etc.). Common to all
B. BILATERAL POSTERIOR CEREBRAL ARTERY SYNDROME
vertebral-basilar artery syndromes are the following:
This syndrome results from occlusion at the point of origin of
both posterior cerebral arteries from the basilar artery. The syn- 1. Bilateral long tract (motor and sensory) signs
drome is characterized by the following: 2. Crossed motor and sensory signs (e.g., facial weakness or
numbness combined with contralateral extremity weakness
1. Cortical blindness, visual loss in both eyes in the presence of or numbness)
normal pupillary reactivity and normal fundus examination
3. Cerebellar signs
2. Disturbance in facial recognition (prosopagnosia) due to bi-
lateral involvement of the inferior occipitotemporal region 4. Cranial nerve signs
(lingual and fusiform gyri) 5. Alteration in state of consciousness (stupor or coma)
3. Balint syndrome (optic ataxia, psychic paralysis of fixation), 6. Disconjugate eye movements
the inability to look to the peripheral field with disturbance In general, the presence of “the four Ds with crossed findings”
of visual attention suggests a brain stem stroke from vertebrobasilar occlusion. The
4. Anton’s syndrome, denial of blindness and confabulation of four Ds are diplopia, dysarthria, dysphagia, and dizziness.
what the patient sees if the lesion extends to both parietal lobes Table 28–1 is a simplified comparison of the major signs and
5. Agitated delirium and memory loss due to bilateral involve- symptoms in internal carotid system and vertebrobasilar system
ment of mesiotemporal territory occlusions.
C. SYNDROMES OF PENETRATING BRANCHES OF POSTERIOR
CEREBRAL ARTERY Lacunar Syndromes
The clinical pictures associated with occlusion of penetrating
Lacunar syndromes result from occlusion of small penetrating
branches of the posterior cerebral artery (thalamogeniculate and
end arteries (variably called lenticulostriate, thalamogeniculate,
thalamoperforating) have been discussed in Chapter 12.
or thalamoperforator) from the proximal anterior cerebral, mid-
Vertebral-Basilar Artery Syndromes dle cerebral, posterior cerebral, and basilar arteries or the
circle of Willis. They occur usually in patients with long-
Occlusion of the vertebral-basilar arterial system usually results standing hypertension and cerebral vessel atherosclero-
in brain stem infarcts. The clinical picture varies according to the sis. Symptomatic lacunae most often involve the following brain
364 / CHAPTER 28
Table 28–1. Major Signs and Symptoms in Internal The red nucleus lesion interrupts the cerebellothalamic
Carotid System and Vertebrobasilar System Occlusions fibers in the brachium conjunctivum (ataxia), and its exten-
sion into the cerebral peduncle explains the hemiparesis.
Symptom of Sign Internal Carotid Vertebrobasilar 4. Dysarthria–clumsy hand syndrome, characterized by central
(supranuclear) facial weakness, dysarthria, dysphagia, and hand
Motor deficit Contralateral Bilateral, crossed
paresis and clumsiness due to a lacuna in the basis pontis.
Sensory deficit Contralateral Bilateral, crossed
Visual deficit Monocular blindness Bilateral, cortical 5. État lacunaire syndrome. This syndrome is associated with bi-
contralateral field blindness lateral numerous lacunae in the frontal lobes. It is character-
defect
ized by progressive dementia, shuffling gait, emotional labil-
ity (abrupt laughing and crying), and pseudobulbar palsy
Speech deficit Present Absent
(hyperactive palate and gag reflex, lingual and pharyngeal
(aphasia)
paralysis, and difficulty swallowing).
Cranial nerve Absent Present
deficit
CEREBRAL HEMORRHAGE SYNDROMES

regions: putamen, caudate nucleus, posterior limb of the internal Intracranial hemorrhage may result from (1) spontaneous rup-
capsule, thalamus, and basis pontis. Several discrete lacunar syn- ture of an arterial wall because of longstanding hyper-
dromes exist. The five well-recognized lacunar syndromes are tension, (2) rupture of a congenital saccular outpouch-
ing of a vessel wall (aneurysm) (Figure 28–5), (3) rupture
1. Pure motor (hemiparesis) syndrome, involving the contralat- of an arteriovenous malformation (Figure 28–6), (4) trauma to the
eral face, arm, trunk, and leg due to a lacuna (small infarct) head, or (5) a bleeding disorder. Hemorrhage may occur (1) within
in the corticospinal tract within the internal capsule or basis the brain parenchyma, (2) into the ventricular system, or (3) into
pontis. There are no sensory, speech, or visual deficits. meningeal spaces (subarachnoid, subdural, epidural). The ensu-
2. Pure sensory syndrome, involving the contralateral face, arm, ing clinical picture varies depending on the location, size, cause,
trunk, and leg with loss or diminution of all sensory modali- and rate of development of the hemorrhage. About 15 to 20 per-
ties (hemianesthesia) due to a lacuna in the sensory thalamic cent of strokes are due to hemorrhage, and roughly half of these
nuclei (ventral posterior lateral, ventral posterior medial). are due to subarachnoid hemorrhage. Subarachnoid hemorrhage
There are no motor, speech, or visual deficits. usually results from leakage or rupture of a congenital aneurysm.
3. Ataxic hemiparesis syndrome, characterized by weakness, pyra- The clinical picture is characterized by sudden onset of severe
midal signs, and cerebellar-like ataxia involving the limbs on headache, neck stiffness, and loss of consciousness. The diagno-
the same side due to a lacuna in one of the following sites: sis is established by computed tomographic (CT) scan, which
(a) contralateral posterior limb of the internal capsule, (b) basis shows blood in the subarachnoid space (Figure 28–7). Paren-
pontis, or (c) red nucleus with extension of the lesion to the chymal hemorrhage is usually due to rupture of an arterial wall
adjacent cerebral peduncle. The internal capsule lesion in hypertensive patients. In some cases, the hemorrhage may
involves the corticospinal (hemiparesis) and corticopontine burst into the ventricular system. Subdural and epidural hemor-
fibers (cerebellar-like ataxia). The basis pontis lesion involves rhages usually are associated with trauma. Subdural hemorrhage
corticospinal (hemiplegia) and pontocerebellar (ataxia) fibers. is due to rupture of bridging veins in the subdural space (Figure
Anterior
Cerebral Artery
Internal Carotid
Artery
Middle Cerebral
Artery
Ventriculostomy
Tube Posterior Communicating
Artery
Posterior Cerebral
Artery Aneurysm
Figure 28–5. Three-dimensional computed tomography (CT) image showing an aneurysm (star).
Internal Carotid Artery
Figure 28–6. Arteriogram show-

ing an arteriovenous malformation
(arrow).
28–8). Epidural hemorrhage, a life-threatening situation, is due TERMINOLOGY

to rupture of the middle meningeal artery in the epidural space.
Bleeding from arteriovenous malformations may occur into the Agraphia (Greek a, “negative”; graphein, “to write”). Inability
cerebral parenchyma, into the subarachnoid or subdural spaces, to express thoughts in writing. The first modern descriptions were
or into the ventricles (Figure 28–9). those of Jean Pitres in 1884 and Dejerine in 1891.
Frontal Lobe
Sylvian Fissure
Temporal Lobe
Lateral Ventricle,
Temporal (Inferior)
Horn
Fourth Ventricle
Figure 28–7. Axial CT image showing blood (arrows) in the sylvian fissure.
366 / CHAPTER 28
Falx Cerebri
Subarachnoid
Space
Subdural Space
Frontal Lobe
Parietal Lobe
Occipital Lobe
Figure 28–8. MRI showing blood in the subdural space, subdural hematoma (stars).
Lateral Ventricle,
Frontal (Anterior)
Horn
Third Ventricle
Perimesencephalic
Cistern
Figure 28–9. CT image showing

blood in the ventricular system
(arrows).
Akinetic mutism (persistent vegetative state). The state in Topographagnosia (Greek topo, “place”; graphein, “to write”;
which patients appear awake and maintain a sleep-wake cycle gnosis, “know”). Failure to localize a point on the body or read
but are unable to communicate in any way. The term was intro- maps.
duced by H. Cairns in 1941.
Alexia (Greek a, “negative”; lexis, “word”). Loss of the power
to grasp the meaning of written or printed words. SUGGESTED READINGS
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42:803–808.
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Anton’s syndrome. Denial of blindness. Described by Gabriel farct topography, causes and outcome. Multicenter results and a review
Anton, an Austrian neurologist, in 1899. Although unable to of the literature. Cerebrovasc Dis 2000; 10:170–182.
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Aphasia (Greek a, “negative”; phasis, “speech”). Impairment Fisher CM: Lacunar strokes and infarcts: A review. Neurology 1982; 32:871–876.
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Apraxia (Greek a, “negative”; pratto, “to do”). Inability to Ghika J et al: Infarcts in the territory of the deep perforators from the carotid
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not paralyzed. Glass JD et al: The dysarthria–clumsy hand syndrome: A distinct clinical en-
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Hemianopia (Greek hemi, “half ”; an, “negative”; opia, “vi- Goodwin JA et al: Symptoms of amaurosis fugax in atherosclerotic carotid
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Homonymous (Greek homo, “same”; onoma, “name”). Loss Helgason C et al: Anterior choroidal artery–territory infarction: Report of
of vision in the same half field in each eye. cases and review. Arch Neurol 1986; 43:681–686.
Infarct (Latin infarcire, “to stuff or fill in”). Regional death of Helweg-Larsen S et al: Ataxic hemiparesis: Three different locations of lesions
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dimensional tactile feeling. Arch Neurol 1990; 47:129–132.
Cerebrospinal Fluid and the 29

Barrier System
Anatomy of the Ventricular System Spinal (Lumbar), Cisternal, and Ventricular Taps
Subarachnoid Cisterns (Punctures)
Choroid Plexus Brain Barrier System
Cerebrospinal Fluid
Classic Concepts
Current Concepts
KEY CONCEPTS
The ventricular system is composed of four intercon- CSF is resorbed primarily through the arachnoid granula-
nected spaces: two lateral ventricles, a third ventricle, and tions into the superior sagittal sinus. Other sites include
a fourth ventricle.The foramen of Monro connects the lat- the leptomeningeal vessels, ependyma lining the ventri-
eral and third ventricles.The aqueduct of Sylvius connects cles, and sheaths of cranial and spinal nerves.
the third and fourth ventricles.
CSF has three functions: buoyancy of the brain, physical
Certain sites within the ventricular system contain buffer between brain and skull, and chemical buffer be-
choroid plexus. These include the body, trigone, and infe- tween the blood and brain.
rior horns of the lateral ventricle, the foramen of Monro,
Access to the CSF via the lumbar subarachnoid space
the roof of the third ventricle, and the posterior part of the
is contraindicated in states of increased intracranial
roof of the fourth ventricle.
pressure.
Subarachnoid cisterns are dilations within the subarachnoid
The brain barrier system has three components: blood-
space. They include the cisterna magna, medullary cistern,
brain barrier, blood-CSF barrier, and blood-nerve barrier.
cisterna pontis, cisterna interpeduncularis, suprasellar cis-
tern,superior cistern,cisterna ambiens,and lumbar cistern. Certain areas of the brain are devoid of brain barrier sys-
tem. They include area postrema, neurohypophysis,
Besides the choroid plexus, the CSF is formed in the
pineal gland, organ vasculosum, median eminence, sub-
ependyma, cerebral pial surface, and cerebral extracellu-
commissural organ, and subfornical organ. Collectively,
lar space.
these areas are known as the circumventricular organs.
CSF is formed by a variety of processes that include diffu-
sion, active transport, and free passage of water.
ANATOMY OF THE VENTRICULAR SYSTEM through the foramen of Monro, named after Alexander Monro,
who described it in 1783 (Figures 29–1 and 29–2), the third and
The brain contains four ependyma-lined cavities known as cere- fourth ventricles through the aqueduct of Sylvius (cerebral aque-
bral ventricles; these are the right and left lateral ventricles, the duct or iter) (Figure 29–2), and the fourth ventricle and the sub-
third ventricle, and the fourth ventricle (Figure 29–1). arachnoid space through the foramina of Magendie and
The four cavities communicate with each other and with Luschka. The term fifth ventricle is sometimes used to refer to the
the subarachnoid space: the lateral and third ventricles cavity (Figures 29–3 and 29–4) that develops within the septum
368
CEREBROSPINAL FLUID AND THE BARRIER SYSTEM / 369
Body of
lateral ventricle Choroid plexus
Anterior horn of Atrium of

lateral ventricle lateral ventricle
Posterior horn of
lateral ventricle
Foramen of Mon
ricle
Third ventricle
Figure 29–1. Schematic diagram Inferior horn

in composite sagittal view show- of lateral ventricle xus
ing the ventricular cavities of the
brain with intraventricular sites of
choroid plexus.
pellucidum (the cavum septum pellucidum). This, however, is a and magnetic resonance imaging (MRI)] in neonates. Its incidence
misnomer because the cavity is lined with astrocytes and does at 6 months of age and beyond falls to about 6 percent.
not have the ependymal lining characteristic of ventricular cavi- Posterior extension of the cavum septum pellucidum (Figures
ties, nor does it contain cerebrospinal fluid (CSF). 29–3 and 29–4) above the fornix and posterior to the foramen of
Cavum septum pellucidum is found in all premature newborns. Monro constitutes the cavum vergae (sixth ventricle), named af-
It begins to close just before birth in full-term newborns and is fre- ter the Italian anatomist Andrea Verga, who described the cavum
quently seen in brain images [computed tomographic (CT) scans in 1851. It communicates with the cavum septi pellucidi.
Pineal recess
Aqueduct of
Sylvius
Midbrain
Fourth ventricle
Foramen of Monro
Medulla oblongata
Lamina terminalis
Pons Third ventricle Infundibular Optic recess

recess
Figure 29–2. Midsagittal view of the brain showing the foramen of Monro, third ventricle, aqueduct of Sylvius, and fourth
ventricle.
370 / CHAPTER 29
Anterior (frontal)
horn of lateral Cavum septum
ventricle pellucidum
Cavum vergae
Atrium (trigone) of
lateral ventricle
Figure 29–3. T2-weighted axial magnetic resonance image (MRI) showing cavum septum pellucidum and cavum vergae.
The cavum veli interpositi (interventricular cavum) is a trian- to be large in infants and becomes small beyond 2 years of age.
gular cavity located rostral to the superior (quadrigeminal) cis- The cavum veli interpositi communicates with the subarachnoid
tern below the fornix and above the thalamus and the roof of the space, in contrast to the cavum vergae, which communicates
third ventricle (Figure 29–4). The cavity develops as a result of with the ventricle. The two cavities also can be differentiated by
abnormal separation of the limbs of the fornix. The cavity tends their relationship to the fornix. The cavum vergae is located
Cavum vergae
Cavum velum
interpositum
Cavum septum
pellucidum
Figure 29–4. Schematic composite diagram showing the location and relationship, in midsagittal view, of the
cavum septum pellucidum (medium gray), cavum vergae (dark gray), and cavum velum interpositum (light gray).
CC, corpus callosum;TH, thalamus; FM, foramen of Monro; P, pineal gland; SC, superior cistern; MB, midbrain; P, pons;
V4, fourth ventricle; CBL, cerebellum.
above the fornix, whereas the cavum interpositi is beneath the ami and hypothalami. It is bounded anteriorly by the lamina ter-
fornix. A composite schema of the cava septum pellucidum, ver- minalis (Figure 29–2) and the anterior commissure, superiorly
gae, and interpositum is shown in Figure 29–4. The lateral ven- by ependyma fused with the overlying leptomeninges of the em-
tricles have an archlike configuration corresponding to the shape bryonic diencephalon (velum interpositum or tela choroidea) in-
of the hemisphere. Each lateral ventricle is subdivided into five corporating numerous blood vessels, posteriorly by the epithala-
segments (Figure 29–1): mus, and inferiorly by hypothalamic structures (infundibular
recess, tuber cinereum, and mamillary body).
1. Frontal (anterior) horn The third ventricle has a number of recesses that are impor-
2. Body tant in localizing lesions in the region of the third ventricle. These
3. Atrium (trigone) recesses include the pineal (suprapineal) recess above the pos-
4. Occipital (posterior) horn terior commissure, the optic recess above the optic chiasma,
5. Temporal (inferior) horn and the infundibular recess into the infundibulum (Figures
29–2 and 29–5).
The frontal (anterior) horn is the part of the lateral ventricle The aqueduct of Sylvius (cerebral aqueduct or iter) is a nar-
rostral to the foramen of Monro (Figures 29–1 and 29–2). In row canal that connects the third and fourth ventricles through
sections, this part of the ventricle has a butterfly configuration, the midbrain (Figure 29–2). It is about 1.5 to 2.0 cm long and
with the corpus callosum forming its roof, the septum pellu- 1 to 2 mm in diameter. Stenosis (narrowing) or complete ob-
cidum and fornix constituting its medial wall, and the caudate struction of the aqueduct, which may occur congenitally or as a
nucleus bulging into the lateral wall. This characteristic bulge of consequence of inflammatory processes, results in accumulation
the caudate nucleus into the lateral wall disappears in degenera- of CSF, an increase in cerebrospinal pressure, and ventricular
tive diseases of the brain involving the caudate nucleus such as in dilatation rostral to the site of obstruction (in the third and lat-
Huntington’s chorea. eral ventricles).
The body of the lateral ventricle (Figure 29–1) extends from The fourth ventricle lies between the anterior surface of the
the foramen of Monro posteriorly to the trigone. The atrium or cerebellum and the posterior (dorsal) surfaces of the pons and
trigone (Figure 29–1) is the area of confluence of the posterior medulla oblongata (Figures 29–1 and 29–2). The fourth ventri-
part of the body with the occipital and temporal horns. The cle boundaries are discussed in the chapter on the medulla ob-
atrium is the most expanded subdivision of the ventricle and the longata (Chapter 5). The fourth ventricle communicates with
site of early ventricular enlargement in degenerative diseases of the subarachnoid space through three foramina in its roof. These
the brain. are a midline foramen of Magendie and two lateral foramina of
The occipital (posterior) horn (Figure 29–1) extends from Luschka.
the atrium backward toward the occipital pole. It is the most Ventricular cavities are lined by ependymal epithelium. In
variable subdivision in shape and size, with the left usually larger some specific sites, the ependymal lining is invaginated by a vas-
than the right, and may be rudimentary or altogether absent. cular pial fold known as the choroid plexus. Such choroid
The calcarine fissure produces an impression in the medial wall plexus sites are encountered in the body, atrium, inferior
of the occipital horn known as the calcar avis. horn of the lateral ventricle, foramen of Monro, roof of
The temporal (inferior) horn (Figure 29–1) extends from the the third ventricle, and posterior part of the roof of the fourth
atrium downward and forward into the temporal lobe and ends ventricle (Figure 29–1). The choroid plexus achieves its largest
approximately 3 cm behind the temporal tip. size in the anterior part of the atrium (trigone), an area referred
The lateral ventricles communicate with the third ventricle to as the glomus. The absence of choroid plexus from the ante-
through the interventricular foramen of Monro (Figure 29–1). rior horn makes it an appropriate site for placement of shunt
The cavity of the third ventricle is enclosed between the two thal- tubes for drainage of CSF in hydrocephalus.
Third ventricle Suprapineal recess
Optic recess
Infundibular reces
gram of the ventricular system
showing recesses of the third
ventricle.
372 / CHAPTER 29
SUBARACHNOID CISTERNS prechiasmatic and postchiasmatic parts. The former is located

anterior to and above the optic chiasma, whereas the latter is
The subarachnoid cisterns are dilatations in the sub- located behind and below the optic chiasma. The suprasellar
arachnoid spaces located principally at the base of the cistern is thus useful in localizing pathologic processes in or
brain. Radiologic visualization of the subarachnoid cis- around the sella turcica and optic chiasma.
terns is important in localization of pathologic processes, espe- 6. The superior (quadrigeminal) cistern (Figure 29–6) is located
cially those due to tumors in the base of the brain. The clinically dorsal to the midbrain. It contains the vein of Galen.
relevant cranial subarachnoid cisterns include the following:
The interpeduncular and superior (quadrigeminal) cisterns
1. The cisterna magna (cisterna cerebellomedullaris), largest of are connected along the lateral surface of the midbrain by the
the subarachnoid cisterns, is located between the medulla ambient cistern (cisterna ambiens).
oblongata, the cerebellum, and the occipital bone (Figure The clinically relevant spinal subarachnoid cistern is the lum-
29–6). CSF from the fourth ventricle reaches the cisterna bar cistern, site of lumbar puncture (spinal tap).
magna via the foramina of Magendie and Luschka. The cis-
terna magna is continuous anteriorly with the cisterna pon-
tis. The cisterna magna is occasionally accessed to obtain CSF CHOROID PLEXUS
(cisternal puncture). A special needle for this purpose is in-
serted suboccipitally through the posterior atlanto-occipital The choroid plexus is one of the sites for production of CSF. It is
membrane to the cisterna magna. composed of villi extending from the ventricular wall into the
2. The medullary cistern lies ventral and lateral to the medulla CSF. It is distributed in the body, trigone, and inferior horn of
oblongata (Figure 29–6). The vertebral arteries are located in the lateral ventricle, foramen of Monro, roof of the third ventri-
this cistern. cle, and posterior part of the roof of the fourth ventricle (Figure
29–1). Each villus is composed of an extensive network of fenes-
3. The cisterna pontis (Figure 29–6) is located between the ba- trated capillaries embedded in connective tissue stroma (Figure
sis pontis and the clivus. It has a midline segment and two 29–7). Villi are lined by a single layer of choroidal cuboidal epi-
lateral extensions. The midline segment is important in lo- thelium in continuity with the ependymal cell lining of the ven-
calizing pathologic processes in the pontine area, whereas the tricular wall (Figure 29–7). The apical surfaces of the choroidal
lateral extensions are useful in localization of pathologic epithelium in contact with CSF are specialized into microvilli
processes in the cerebellopontine angle. The basilar artery that increase their ventricular surface. Choroidal epithelial cells
and sixth (abducens) nerve run in the cisterna pontis. are attached to each other by tight junctions that constitute an
4. The cisterna interpeduncularis (Figure 29–6) extends be- effective barrier to the free passage of substances from the blood
tween the cerebral peduncles and is helpful in localization of vessels in the core of the villus into the CSF (blood-CSF barrier).
pathology in that region. The third (oculomotor) nerve exits Hydrostatic pressure within the fenestrated capillaries of choroid
the midbrain through the interpeduncular cistern. plexus forces water, solutes, and proteins out into the connective
5. The suprasellar cistern (Figure 29–6) is located dorsal to the tissue core of the villus. Macromolecular substances, however,
sella turcica and communicates with the cisterna interpe- are prevented from free passage to the CSF by the tight junctions
duncularis. Some authors divide the suprasellar cistern into between the lining choroidal epithelial cells.
Lateral ventricle
Superior
(quadrigeminal)
cistern
Fourth ventricle
Suprasellar cistern
Cisterna magna
Cisterna
interpeduncularis Cisterna pontis Medullary cistern
Figure 29–6. T2-weighted midsagittal MRI showing the major subarachnoid cisterns.
Figure 29–7. Schematic diagram of the components of the choroid plexus. FC, fenestrated capillary; CT, connective tissue stroma; CE,
choroidal epithelium with tight junctions.
CEREBROSPINAL FLUID space, perineural space, etc). Approximately 60 percent of CSF is

formed in the ventricles. About half the CSF formed in the ven-
The classic concepts of formation, circulation, and absorption of tricles comes from the choroid plexus; the rest comes from the
CSF elaborated early in this century have since undergone major ependymal lining. In humans, CSF is formed at the rate
modifications. of 0.35 ml/min (about 15 to 20 ml/hr, 500 ml/day) by
the choroid plexus and to a much lesser degree by the
Classic Concepts ependyma. Its average volume in the adult is about 140 ml, with
most of the fluid filling the cranial subarachnoid spaces.
According to the classic concepts elaborated between 1914 and Approximately 30 ml of CSF is located in the ventricles and
1918 by Cushing, Weed, and Dandy, the CSF is formed by the about 30 ml is in the spinal subarachnoid space. It is estimated
choroid plexus and circulates by bulk flow in the lateral ventri- that the turnover rate of CSF is four to five times per day.
cles, the foramen of Monro, the third ventricle, the aqueduct of The rate of CSF formation is rather constant and is not gen-
Sylvius, and the fourth ventricle. It flows via the foramina of erally affected by alterations in CSF pressure below 280 mm of
Magendie and Luschka to the cisterna magna and subarachnoid CSF. There is evidence, however, to suggest a decrease in CSF
spaces, where it is finally absorbed through the arachnoid granu- formation rate in chronic, experimentally produced, or human
lations in the superior sagittal sinus into the venous circulation hydrocephalus in which CSF pressure is very high. CSF forma-
(Figure 29–8). tion from the choroid plexus is also decreased with local arterio-
lar vasoconstriction or hypotension. Almost total cessation of
Current Concepts CSF formation from the choroid plexus may result following
vasoconstriction induced by low PCO2 during hyperventilation.
A. FORMATION On the other hand, vasodilatation induced by carbon dioxide in-
Although the choroid plexus remains one of the major sites of halation has been shown to result in a substantial increase in
CSF formation, CSF production can be maintained in the ab- CSF formation. Drugs acting on enzyme systems may influence
sence of the choroid plexus. Sites of CSF production and their CSF formation by interfering with active transport mechanisms.
relative contribution to the overall CSF volume are not yet re- Drugs that inhibit carbonic anhydrase, such as Diamox, can par-
solved. While there is clear evidence for a ventricular source (from tially or completely inhibit CSF formation. Ouabain, an ATPase
the choroid plexus), there is equal evidence for extraventricular inhibitor, can produce effects similar to those of Diamox. Gluco-
sites of production (cerebral pial surface, cerebral extracellular corticoids have been shown to exert an inhibitory effect on the
374 / CHAPTER 29

by arrows the pattern of cerebrospinal fluid
circulation from the lateral ventricles to the
superior sagittal sinus. LV, lateral ventricle; V3,
third ventricle; AS, aqueduct of Sylvius; V4,
fourth ventricle; SC, spinal cord; SAS, sub-
arachnoid space; AG, arachnoid granulations;
SSS, superior sagittal sinus.
rate of CSF formation. Several diuretic agents also have been is the primary mechanism of transport for respiratory gases and
shown to reduce the rate of CSF formation. Although both res- some central nervous system active drugs such as diazepam
piratory and metabolic alkalosis have been shown to depress the (Valium), phenobarbital, and phenytoin. Ethanol is also trans-
rate of CSF formation, the former is more effective than the lat- ported by diffusion. Water enters the CSF readily by diffusion.
ter. CSF formation is known to increase with maturation; this 2. Active Transport. Major cations that pass through the choroid
may reflect the maturation of the enzyme systems involved in the plexus into the CSF are sodium and potassium. The concentra-
secretory process. tion of sodium is higher in CSF than in plasma, whereas that of
B. MECHANISM OF FORMATION potassium is lower. Of all the cations in CSF, sodium is found in
the greatest amount and is used to stabilize the pH and total
CSF was considered to be an ultrafiltrate of plasma. Recent evi- cation concentration in CSF. Most of the sodium in CSF enters
dence seems to suggest, however, that CSF is formed by the fol- via the choroid plexus, and only a very small fraction traverses
lowing mechanisms: the brain capillaries and brain substance. The concentration of
1. Diffusion. The rate of diffusion depends on particle potassium in CSF is very stable and is not affected by fluctua-
size and the lipid solubility of the compound. Diffusion tions in blood or CSF pH. A proper balance between intracellular
and extracellular potassium is critical to nerve cell function. D. RESORPTION

Excess CSF potassium is quickly incorporated by neural tissue, The classic concept of CSF resorption states that the fluid is re-
whereas reduction in CSF potassium is compensated by move- sorbed through the arachnoid granulations into the venous sys-
ment of potassium from neural tissue to CSF. Chloride consti- tem of the superior sagittal sinus (Figure 29–8) and in the lacu-
tutes the major anion in CSF and seems to diffuse passively nae lateralis in the parasagittal dura. Arachnoid granulations are
through the choroid plexus, although this passage is closely regu- not discernible in the newborn. They become evident by the
lated by sodium and potassium transport. eighteenth month and become numerous and widely dissemi-
Certain metabolic substances of low lipid solubility, such as nated by the third or fourth year of life. They are most common
glucose and some amino acids, reach CSF by means of specific along the superior sagittal sinus but occur at or near other si-
carrier-mediated transport systems. The carrier systems for nuses as well.
amino acids are independent of the glucose carriers. Glucose is Although the arachnoid granulations and lacunae lateralis
the major energy substrate for the brain. Entry into the CSF is constitute the major resorption sites for CSF, other alter-
facilitated by an insulin-dependent GLUT-1 glucose transporter. native sites have been described. They are (1) arachnoid
Reduced GLUT-1 transport may be associated with seizures, im- membrane, (2) adventitia of leptomeningeal blood ves-
paired brain development, and mental retardation. sels, (3) cranial and spinal nerve root sleeves, (4) capillary endo-
Large molecules, such as plasma proteins, are almost com- thelium, (5) choroid plexus, (6) leptomeningeal vessels, (7) peri-
pletely blocked by the choroid plexus from entering CSF. Studies neural sheaths of cranial and spinal nerves, and (8) ependyma of
using perfusion techniques have shown that albumin transfer the ventricles.
from blood to CSF is only partially dependent on bulk flow. The The controversy over reconciling the behavior of CSF outflow
major mechanism for protein entry into the CSF is receptor- with its structural basis remains unresolved. Earlier studies suggest
mediated transcytosis. In this mechanism, protein binds to a re- that substances varying widely in molecular weight and lipid solu-
ceptor on the luminal surface of brain capillaries, is then internal- bility pass readily from CSF pathways to the blood. Such studies
ized and forms intracellular vesicles similar to pinocytotic vesicles. are at variance with ultrastructural observations of the arachnoid
The protein then reaches the abluminal surface of the blood-brain granulations, which show the presence of intact endothelium with
barrier. Immunoglobulins enter the CNS by this mechanism. tight junctions effectively separating CSF and blood compart-
ments. More recent studies, however, may have resolved this con-
C. CIRCULATION troversy by suggesting a mechanism for CSF resorption in the
CSF flows from the lateral ventricles through the foramen of arachnoid granulations similar to that described for drainage of
Monro to the third ventricle and then through the aqueduct of ocular fluid in the canal of Schlemm. According to this hypothesis,
Sylvius to the fourth ventricle, where it reaches the subarachnoid exit of CSF via the arachnoid granulations is pressure dependent.
space of the brain and spinal cord through the foramina of Endothelial cells of the arachnoid villus undergo vacuolation on
Magendie and Luschka (Figure 29–8). the CSF side. Vacuoles increase in size because of the differential
Using isotope cisternography, CSF circulation can be followed pressure gradient between CSF (higher) and blood compartments
from the lateral ventricles to the superior sagittal sinus, where it (lower) and ultimately reach the blood side of the endothelial cells,
is resorbed. CSF reaches the basal cisterns in a few minutes, flow- where they rupture and create a patent channel between CSF and
ing from there into the rostral subarachnoid space and sylvian blood. Such a hypothesis has been confirmed by electron micro-
fissure and finally into the convexity of the brain. Isotopes in- scopic observations of the behavior of arachnoid granulations.
jected into the lumbar subarachnoid space can be detected in In addition to this filtration route, it is believed that sub-
basal cisterns within 1 hour. stances are resorbed by the two other routes of diffusion and active
Three factors seem to facilitate CSF circulation. transport.
1. Drift. The drift of CSF from areas of positive balance to areas E. FUNCTION
of negative balance facilitates circulation. Although CSF produc-
tion and absorption are in almost perfect balance when the total CSF serves three principal functions:
CSF space is considered, any one point in the system may be at 1. It supports the weight of the brain within the skull.
positive or negative balance. CSF will therefore drift from areas This buoyancy function is disturbed when CSF is
of positive balance to those of negative balance. This drift will withdrawn, resulting in headache because of more
contribute to CSF flow. traction on vessels and nerves.
2. Oscillation. CSF is also in a continuous state of oscillation, 2. It acts as a buffer or cushion between the brain and adjacent
with a to-and-fro movement the amplitude of which increases as dura and skull; it protects the brain from physical trauma dur-
the fluid approaches the fourth ventricle. This oscillation con- ing injury to the skull by dampening the effects of trauma.
tributes to the flow of CSF, and the increase in amplitude in the 3. It provides a stable chemical environment for the central
fourth ventricle facilitates the flow of CSF into the cisterna nervous system. The chemical composition of CSF is rather
magna. stable even in the presence of major changes in the chemical
composition of plasma.
3. Pulsatile Movement. Rhythmic movements synchronous
with arterial pulse have been described in CSF. These pulsatile F. COMPOSITION
oscillations assume an upward and downward movement in the CSF is a clear, colorless fluid composed of the following sub-
fourth ventricle and basal cisterns. The origin of these oscilla- stances and elements:
tions is believed to be the expansion of the cerebrum and its ar-
teries during systole rather than choroid plexus pulsations, as 1. Water. Water is the major constituent of CSF.
previously assumed. The CSF pulsations occur roughly simulta- 2. Protein. The value of protein in normal CSF is approximately
neously with intracranial arterial pulsations, and both begin about 15 to 45 mg/dl. The lower value (15 mg/dl) reflects protein value
150 ms into the cardiac cycle. in ventricular CSF; the higher value (45 mg/dl) reflects protein
376 / CHAPTER 29
value in the lumbar subarachnoid space. Protein values increase introduced the lumbar puncture. CSF can be obtained from
in various disease states of the nervous system (infection, tumor, three sites: (1) the spinal subarachnoid space (spinal or lumbar
hemorrhage), as well as after obstruction of CSF pathways. Three puncture), (2) the cisterna magna (cisternal puncture), and (3) the
proteins account for the bulk of CSF protein content: albumin lateral ventricles (ventricular puncture). The first route is used
and beta and gamma globulins. The presence of oligoclonal bands most commonly. In this procedure (spinal or lumbar tap), a spe-
(electrophoretic bands in the immunoglobulin G region) and cial needle is introduced using sterile techniques and local anes-
myelin basic proteins in the CSF suggest a demyelinating process thesia in the L-2 and L-3, L-3 and L-4, or L-4 and L-5 vertebral
such as multiple sclerosis. space. The needle is gently eased into the subarachnoid space,
3. Sugar. The amount of glucose in normal CSF is approximately and CSF is withdrawn. Since the conus medullaris of the spinal
two-thirds that of the blood. Glucose value is slightly higher (75 cord ends at the L-1 or L-2 vertebral level and the meninges ex-
mg/dl) in ventricular fluid than in lumbar subarachnoid space tend to the S-1 or S-2 vertebral level, the space between L-2 and
fluid (60 mg/dl). Ratio of CSF glucose to blood glucose is higher L-3 vertebrae constitutes a safe area into which to introduce the
in newborns and premature infants, probably because of the im- lumbar tap needle without the danger of injuring the spinal
maturity of the blood-CSF barrier. The value decreases in menin- cord. The cisterna magna is accessed by a suboccipital route
gitis and after meningeal infiltration by tumors. through the posterior atlanto-occipital membrane. The lateral
ventricles are accessed through the brain substance. Withdrawal
4. Cells. A normal sample of CSF contains up to three lympho-
of CSF from the lumbar subarachnoid space is con-
cytes per cubic millimeter. An increase in the number of white
traindicated in the presence of increased intracranial
cells in CSF occurs in infectious processes. In general, leukocytes
pressure. Spinal taps in such conditions may lead to her-
predominate in bacterial infections (bacterial meningitis) and
niation of the uncus of the temporal lobe through the tentorium
lymphocytes in viral infections (viral meningitis and encepha-
or the cerebellar tonsils through the foramen magnum with re-
litis). Normal CSF contains no red blood cells (RBCs). The pres-
ence of RBCs in CSF occurs as a result of trauma during its col- sulting coma and death. The lumbar subarachnoid space, the cis-
lection or secondary to hemorrhage into the CSF. Traumatic ternal space, and the ventricles are entered not only to obtain
RBCs are usually present in samples of CSF obtained early in the CSF for examination but also to inject air, contrast material, or
process of CSF collection and disappear in samples collected drugs for either diagnosis or treatment of neurologic disorders.
subsequently. RBCs from pathologic bleeding (e.g., subarach-
noid hemorrhage) render the CSF grossly bloody and xantho-
chromic (yellow). The xanthochromia is due to release of biliru- BRAIN BARRIER SYSTEM
bin from the RBCs. Neoplastic cells may occur in some types of The concept of a barrier system between blood and brain dates
central nervous system neoplasms, particularly those associated back to 1885, when it was found that intravenously injected
with leptomeningeal dissemination. acidic dyes stained all organs of the body except the brain. It was
5. Electrolytes. CSF contains sodium, potassium, chloride, mag- later observed that when these acidic dyes were injected
nesium, and calcium. Sodium and potassium constitute the major into the CSF, the brain was stained. Thus a barrier was
cations, whereas chloride constitutes the major anion. The con- assumed to be located at the blood-brain interface that
centration of sodium, chloride, and magnesium ions is higher in prevented entry of acidic dyes into the brain. It has since been
CSF than in plasma, whereas the concentration of potassium and discovered that these acidic dyes bind themselves to serum albu-
calcium ions is lower. min and that the barrier to their entry to the brain is the low per-
6. Peptides. Numerous peptides are also found in the CSF. They meability of brain capillaries to the albumin to which the dyes
include luteinizing hormone–releasing factor, cholecystokinin, an- are bound.
giotensin II, substance P, somatostatin, thyroid hormone–releasing Although earlier studies conceived of only one barrier, at the
hormone, oxytocin, and vasopressin. blood-brain interface, studies dating back to the 1930s have elu-
cidated the existence of other brain barrier sites. Consequently,
G. PHYSICAL PROPERTIES the term blood-brain barrier has been replaced by the more useful
term brain barrier system. Two separate barriers compose this sys-
1. Specific Gravity. The specific gravity of normal CSF varies tem: (1) the blood-brain barrier, located at the interface between
between 1.006 and 1.009. An increase in the protein content of the capillary wall and brain substance, and (2) the blood-CSF
the CSF raises its specific gravity. Mean CSF density is reported barrier, located in the choroid plexus. The blood-brain barrier
to be significantly lower in women than men. This difference in forms a unique anatomic structure very different from other
density may modify subarachnoid distribution of local anesthet- blood-organ barriers (Figure 29–9). The major difference is the
ics and other drugs. impermeable construction of endothelial cells. The fenestrations
2. Pressure. Normal CSF pressure measured in the lumbar sub- in endothelial cells lining capillaries of other organs are absent in
arachnoid space varies between 50 and 200 mm of CSF (up to the brain except in some locations (circumventricular organs).
8 mmHg), measured with the patient in the lateral recumbent po- Additionally, brain endothelial cells adhere to each other by
sition and relaxed. The normal pressure range is higher (200 to 300 means of tight junctions. Brain endothelial cells are coated with
mm of CSF) when measured in the upright seated position. CSF a glycocalyx (P-glycoprotein) that maintains a negative charge on
pressure is increased in central nervous system infections (meningi- the luminal surface and ejects certain undesired substances.
tis), tumors, hemorrhage, thrombosis, and hydrocephalus. Another special feature of the blood-brain barrier is a layer of as-
trocytic foot processes (glia limitans) that cover almost the entire
Spinal (Lumbar), Cisternal, and Ventricular abluminal surface of brain capillaries. A striking feature of the
Taps (Punctures) blood-brain barrier is the high number of mitochondria in en-
dothelial cells. They provide the high level of energy needed to
The examination of CSF is of major value in neurologic diagno- maintain the blood-brain barrier function. The blood-brain bar-
sis. Access to CSF for diagnosis dates back to 1891 when Quinke rier is the more extensive of the barriers. It separates blood within
thus conceivable that other factors are operative in the barrier

system. These factors include the following:
Blood flow. This factor is operative in the entry to the brain
of substances of high lipid solubility. The rate of blood flow
to a brain region will determine the amount of entry of such
substances.
Metabolic requirement. The rate of entry of some substances
into the brain seems to be dependent on the metabolic re-
quirement of that region of the brain for the particular sub-
stance. Cholesterol, for example, is accumulated in the brain
during myelin formation and decreases when myelination is
completed.
The brain barrier system is more permeable in newborn infants
than in adults. As the brain matures with age, the barrier system
becomes less permeable. The brain of the newborn, for example, is
permeable to bilirubin. A rise in bilirubin levels in the blood of a
newborn is detrimental to brain function. In contrast, an excessive
rise in serum bilirubin in the adult does not affect the brain.
Certain areas of the brain are devoid of a barrier system.
These areas, known as circumventricular organs include (1) the
area postrema, a chemoreceptor center in the caudal
medulla oblongata; (2) the neurohypophysis; (3) the or-
gan vasculosum of the lamina terminalis (superior and
Figure 29–9. Schematic diagram of the anatomic substrate of rostral to the optic chiasma), which is sensitive to plasma osmo-
the blood-brain barrier. larity, (4) the median eminence of the hypothalamus; (5) the
subcommissural organ located ventral to the posterior commis-
sure at the junction of the third ventricle and aqueduct of
Sylvius; (6) the subfornical organ (under the fornix), which is
the capillaries from brain substance. The blood-brain barrier im- sensitive to circulating angiotensin II; and (7) the pineal gland.
pedes entry from blood to brain of virtually all molecules except In some circumventricular organs, neurons have specialized re-
those that are small (less than 20 kDa) and are lipophilic. There ceptors for specific proteins. These include the area postrema,
are, however, small and large hydrophilic molecules that cross subfornical organ, and organ vasculosum. Other circumventric-
the barrier. They do so by means of active carrier-mediated trans- ular organs have neurons with secretory properties. These in-
port and receptor-mediated transcytosis. clude the median eminence, neurohypophysis, subcommissural
During inflammation or an immune-mediated pathologic organ, and pineal gland. All these areas are characterized by rich
process the blood-brain barrier breaks down and allows access of vascularity. Unlike vessels elsewhere in the brain, the endothelial
cells and other substances into the brain. The increased perme- lining of vessels in these areas is fenestrated.
ability of the blood-brain barrier during inflammation depends
on several factors: opening of tight junctions, gaps across en-
dothelial cells, increase in receptor-mediated transcytosis, and TERMINOLOGY
increase in pinocytosis.
It was originally believed that the brain is an immune-privi- Aqueduct of Sylvius. Narrow passage linking the third and
leged organ. It has since been shown that T lymphocytes can fourth ventricles. Named after Franciscus de la Boe Sylvius, who
cross the blood-brain barrier in small numbers. Once in the described it in 1650.
brain, lymphocytes that react to neural antigens will remain in Cavum vergae. Intraventricular cystic space in the body of the
the brain and initiate inflammation. T lymphocytes that do not lateral ventricle and continuous with the cavum septum pellu-
react to neural antigens exit quite rapidly. The T lymphocytes cidum. Named after Andrea Verga, the Italian anatomist who de-
that migrate into the brain are the CD4+ variety. scribed it in 1851.
In the blood-CSF barrier, tight junctions that join choroidal Cisternal puncture. Accessing CSF in the cisterna magna by in-
epithelial cells (Figure 29–7) constitute the barrier at this site. serting a needle in the suboccipital region through the atlanto-
The surface area of the blood-CSF barrier is only 0.02 percent of occipital membrane. The procedure was introduced by Oberga
the surface area of the blood-brain barrier. The ependymal cells in 1908.
lining the ventricles are not joined together by tight junctions
(Figure 29–7) and thus do not constitute a barrier between the Foramen of Luschka. Paired openings in the lateral recesses of
CSF and brain. A third barrier, the blood-nerve barrier, com- the arachnoid roof of the fourth ventricle through which CSF
prises the perineurium and capillaries of the endoneurium. Walls from the fourth ventricle reaches the cisterna magna. Named
of capillaries are nonfenestrated, and endothelial cells have tight after Hubert von Luschka, the German anatomist, in 1863.
junctions. This barrier is most effective in dorsal root ganglia and Foramen of Magendie. Median aperture in the roof of the
autonomic ganglia. fourth ventricle connecting it with the cisterna magna. Named
Studies on the mechanisms of the barrier system have shown after François Magendie, the French physiologist, who described
that the anatomic substrates of the barrier (endothelial lining, the foramen in 1842.
basement membrane, glial processes, tight junctions) cannot ac- Foramen of Monro. Site of communication between the lateral
count for all the observed phenomena of the barrier system. It is and third ventricles. First described by Alexander Monro, the
378 / CHAPTER 29
Scottish anatomist, in 1753. Before that time, it was assumed Kempe LG, Busch E: Clinical significance of cisterna veli interpositi. Acta
that the lateral and third ventricles communicated by a hole or Neurochir 1967; 16:241–248.
passage at the upper end of the third ventricle called the vulva or Leech RW: Normal anatomy of ventricles, meninges, subarachnoid space, and
by a place under the fornix called the anus. There had been no venous system. In Leech RW, Brumback RA (eds): Hydrocephalus:
Current Clinical Concepts. St Louis, Mosby–Year Book, 1991:18.
demonstration of these apertures. They were presumed to occur
Leech RW: Normal physiology of cerebrospinal fluid. In Leech RW, Brumback
by necessity. RA (eds): Hydrocephalus: Current Clinical Concepts. St Louis, Mosby–
Lumbar puncture. A method of accessing CSF in the lumbar Year Book, 1991:30.
subarachnoid space by introducing a needle between the lumbar Leslie W: Cyst of the cavum vergae. Can Med Assoc J 1940; 43:433–435.
vertebrae. The procedure was introduced in 1891 by Heinrich Mori K: Subcallosal midline cysts in anomalies of the central nervous system.
Quinke, a German physician who obtained CSF for the first In Nadjmi M (ed): Neuro-radiologic Atlases. New York, Thieme-Stratton,
time from a living patient. William Gowers disapproved of the 1985:69.
procedure and discouraged its use at the National Hospital in Pryse-Phillips W: Companion to Clinical Neurology. Boston: Little, Brown,
London until after his retirement. 1995.
Rubin LL, Staddon JM: The cell biology of the blood-brain barrier. Annu Rev
Neurosci 1999; 22:11–28.
Sage MR, Wilson AJ: The blood-brain barrier: An important concept in neu-
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possible pathway for flow of cerebrospinal fluid. Neurosurgery 1996; 39: Selmaj K: Pathophysiology of the blood-brain barrier. Semin Immunopathol
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Cerebrospinal Fluid and the Barrier 30

System: Clinical Correlates
Cerebrospinal Fluid in Disease Idiopathic Intracranial Hypertension (Pseudotumor

Ventriculomegaly Cerebri) and Benign Intracranial Hypertension
Hydrocephalus Intraventricular Neuroepithelial Cysts
Normal-Pressure Hydrocephalus (Hakim-Adams The Bobble-Head Doll Syndrome
Syndrome) Dandy-Walker Syndrome (Malformation)
Benign External Hydrocephalus
KEY CONCEPTS
Ventriculomegaly is associated with overproduction of CSF, Idiopathic intracranial hypertension is characterized by
brain atrophy, developmental failure of growth of the cere- increased intracranial pressure without hydrocephalus or
bral mantle, and obstruction of CSF flow or absorption. a brain tumor, small ventricular cavities, and a favorable
response to acetazolamide or corticosteroids.
Hydrocephalus refers to an increased amount of CSF in
the ventricle, with or without a concomitant increase in Intraventricular cysts may occur in any of the ventricular
CSF pressure. Hydrocephalus is classified into communi- cavities but are most common in the third ventricle (col-
cating and noncommunicating varieties. loid cysts of the third ventricle).
Normal-pressure hydrocephalus refers to uniform en- Bobble-head doll syndrome is associated with third ven-
largement of the ventricular system without a concomi- tricular cysts and less commonly is associated with aque-
tant increase in CSF or intracranial pressure. ductal stenosis and shunt obstruction.
Benign external hydrocephalus refers to the accumulation Dandy-Walker syndrome is characterized by the triad of
of CSF in the subarachnoid spaces around the brain with- large cystic dilation of the fourth ventricle, agenesis of the
out significant enlargement of the ventricular cavities. cerebellar vermis, and enlargement of the posterior fossa.
CEREBROSPINAL FLUID IN DISEASE (100 to 1000 mg), and low glucose (below 20 mg/dl). Examina-
tion of fluid by Gram stain and culture reveals the organism re-
CSF examination in patients with neurologic disorders can pro- sponsible for the meningitis.
vide valuable information about the nature of the disease process. In viral encephalitis the CSF usually is clear, is under normal
This is particularly true in infections (meningitis, encephalitis), or slightly elevated pressure, and contains either a normal or a
autoimmune disorders (multiple sclerosis, Guillain-Barré poly- slightly increased number of cells (five to several hundred, mostly
neuritis), tumors, and hemorrhage. lymphocytes), normal or slightly increased protein (50 to 200 mg/
Normal CSF obtained from the lumbar subarachnoid space is dl), and normal glucose. Gram staining shows no bacteria. Cul-
clear and colorless, is under 50 to 200 mm of CSF pressure in the ture of the CSF may reveal the viral agent involved.
recumbent relaxed state, and contains three cells (lymphocytes) In multiple sclerosis the CSF is clear, is under normal pres-
or fewer per cubic millimeter, 15 to 45 mg of protein, and 60 to sure, and contains a normal or an increased number (50 to 300)
80 mg/dl of glucose. of cells, predominantly lymphocytes, normal or moderately in-
In bacterial meningitis the CSF is cloudy and turbid, is under creased protein including oligoclonal and myelin basic proteins,
considerably increased pressure (200 to 500 mm of CSF pressure), increased gamma globulins, and normal glucose.
and contains an increased number of cells, almost all polymor- In Guillain-Barré the CSF is characterized by albuminocyto-
phonuclear leukocytes (2000 to 10,000/mm3), increased protein logic dissociation in which protein is moderately to markedly
379
380 / CHAPTER 30
elevated in the presence of normal cells. The fluid is clear, is un- stance. Hence, it is called hydrocephalus ex vacuo. It usually is asso-
der normal pressure, and contains a normal amount of glucose. ciated with concomitant enlargement of the subarachnoid spaces.
In brain tumors the CSF is clear, is under increased pressure, Developmental ventriculomegaly is due to failure of growth
and contains a normal or increased number of cells, an increased of the cerebral mantle. In an 8-week-old embryo, the ventricles
amount of protein, and normal glucose. Spinning of the CSF are large and the cerebral mantle is thin. With normal develop-
may reveal the presence of tumor cells in the sediment. Seeding ment, the cerebral mantle grows faster than do the ventricles, so
of tumor cells along the meninges is associated with an increase that by mid gestation the ventricles become relatively small. If
in cells and protein. Lumbar puncture is contraindicated in the the cerebral mantle fails to grow normally, the ventricles remain
presence of increased intracranial pressure to avoid herniation. relatively large, a condition known as colpocephaly (Figure
In spinal cord tumors the CSF may have a yellowish tinge as 30–3), a term coined by Yakovlev and Wadsworth in 1946 to re-
a result of the marked increase in protein, is under normal pres- fer to disproportionate enlargement of the occipital horns.
sure, and contains a normal or slightly increased number of cells,
a marked increase in protein, and normal glucose. Tumor cells HYDROCEPHALUS
may be found in the sediment.
In subarachnoid hemorrhage the CSF is bloody, is under Hydrocephalus is a condition characterized by an increased
markedly increased pressure, and contains a large number of red amount of CSF in the ventricles (Figure 30–4). Hippocrates was
blood cells, a very high amount of protein (as a result of the pres- one of the first physicians to deal with hydrocephalus, advocating
ence of blood), and low glucose. the use of laxatives and sneeze-inducing substances for its treat-
Table 30–1 summarizes CSF findings in health and disease. ment. The surgical approach to the treatment of hydrocephalus,
though suggested by Hippocrates and others, was not accepted as
VENTRICULOMEGALY the most effective mode of treatment until the nineteenth century.
There are two types of hydrocephalus: communicating and
Enlargement of the ventricles (ventriculomegaly) usually is asso- noncommunicating. In communicating hydrocephalus
ciated with one of the following conditions: (1) overpro- there is free communication between the ventricles and
duction of CSF, as occurs in tumors of the choroid plexus the subarachnoid space. The obstruction to the flow of
(choroid plexus papilloma), (2) atrophy of the brain CSF in this type of hydrocephalus is usually distal to the ventric-
with secondary (compensatory) enlargement of the ventricles ular system, in the subarachnoid spaces (as a result of fibrosis
(hydrocephalus ex vacuo), as in Alzheimer’s disease; (3) develop- from previous infection) or the arachnoid granulations (as a re-
mental failure of growth of the cerebral mantle (the brain be- sult of a lack of or abnormalities in those structures). This results
tween the ventricle and the brain surface), as in the condition in CSF accumulation and enlargement of all the ventricular cav-
known as colpocephaly; or (4) obstruction of CSF flow or ab- ities as well as the subarachnoid spaces.
sorption, as in obstructive hydrocephalus. In noncommunicating hydrocephalus CSF in the ventricular
The mechanism of ventriculomegaly in hypersecreting tu- cavities cannot reach the subarachnoid spaces because of obstruc-
mors of the choroid plexus (Figure 30–1) is not clear. It may be tion of CSF flow in the foramen of Monro (Figure 30–5), the
due to overproduction of CSF in excess of resorption, overpro- aqueduct of Sylvius (Figure 30–6), or the foramina of Magendie
duction of protein, or both. and Luschka. Obstruction of the foramen of Monro—for example,
Ventriculomegaly associated with brain atrophy may be focal (as by tumor—blocks the flow of CSF from the lateral ventricle to
in infarction) (Figure 30–2) or generalized (as in Alzheimer’s dis- the third ventricle, resulting in an accumulation of CSF and en-
ease and hypoxic ischemic encephalopathy) and is a compensatory largement of the lateral ventricle on the side of obstruction
mechanism that fills the space created by the loss of brain sub- (Figure 30–5). Obstruction of the aqueduct of Sylvius by tumor,
Table 30–1. Cerebrospinal Fluid Findings in Health and Disease
Condition Color Pressure Cells/mm3 Protein (mg/dl) Glucose (mg/dl) Other

(mmCSF)
Normal Clear 50–200 0–3 15–45 60–80 —

Bacterial meningitis Cloudy ↑ ↑ (neutrophils) ↑ ↓ Organism by Gram stain
and culture
Viral encephalitis Clear Normal or ↑ Normal or ↑ Normal or ↑ Normal Organism by culture
(lymphocytes)
Multiple sclerosis Clear Normal Normal or ↑ Normal or ↑ (increased Normal Oligoclonal bands, and
gamma globulins) myelin basic proteins
Guillain-Barré Clear Normal Normal ↑ Normal Albuminocytologic
syndrome disassociation
Brain tumor Clear ↑ Normal or ↑ ↑ Normal Tumor cells in sediment
Spinal tumor Yellow Normal Normal or ↑ ↑ Normal Tumor cells in sediment
Subarachnoid Bloody ↑ ↑ (red cells) ↑ ↓ —
hemorrhage
NOTE: ↑, elevated; ↓, decreased.
CEREBROSPINAL FLUID AND THE BARRIER SYSTEM: CLINICAL CORRELATES / 381
Choroid Plexus
Papilloma
Ventriculomegaly
Figure 30–1. Parasagittal gadolinium

enhanced magnetic resonance image
(MRI) showing choroid plexus papil-
loma and ventriculomegaly.
inflammation, or congenital atresia results in accumulation of tricles become rounded and there is an outflow of CSF across
CSF and enlargement of the ventricular cavities draining into the ependyma into the periventricular spaces (transependymal
the aqueduct (third ventricle and both lateral ventricles) (Figure flow) (Figure 30–7). Pressure exerted on the corticospinal fibers
30–6). Obstruction at the foramina of Magendie and Luschka that innervate the lower extremities, which travel in proximity
by tumor, inflammation, or congenital atresia results in CSF ac- to the lateral ventricles, results in lower extremity weakness.
cumulation and enlargement of the fourth, third, and both lat- If hydrocephalus develops in early childhood, before closure of
eral ventricles. the skull sutures, the skull yields to the increased pressure by
In adults in whom the skull sutures have closed, hydro- widening of the sutures and a progressive increase in head cir-
cephalus is associated with a marked increase in intracranial cumference. A rapid increase in intracranial pressure in these chil-
pressure. This is associated with headache, vomiting, dizziness, a dren may result in a decreased level of consciousness and alert-
decrease in the state of consciousness, and edema of the optic ness, vomiting, irritability, and the “setting-sun” sign, in which
disks. In these patients, the lateral margins of the lateral ven- the upper lids are retracted and the globes are directed downward.
Focal Ventriculomegaly
(Hydrocephalus Ex-Vacuo)
Lateral Ventricle,
Anterior (Frontal)
Horn
Caudate Nucleus
(Head)
Infarct
Internal Capsule
(Anterior Limb)
Insula
Putamen
Figure 30–2. Coronal section of the brain showing cerebral infarct and secondary focal ventriculomegaly.
382 / CHAPTER 30
Colpocephaly
Figure 30–3. T1-weighted parasagittal MRI

showing disproportionate enlargement of
the occipital horn in colpocephaly.
Normal-Pressure Hydrocephalus without a concomitant increase in CSF pressure or intracranial

(Hakim-Adams Syndrome) pressure. The pathophysiology of normal-pressure hydrocephalus
is poorly understood. Impaired resorption of CSF is believed to
Normal-pressure hydrocephalus (a type of communicat- be the cause of CSF accumulation and ventricular enlargement.
ing hydrocephalus) is a disorder of the elderly character- Clinically, the condition is characterized by dementia, urinary
ized by uniform enlargement of the ventricular system incontinence, and gait disturbance. These signs sometimes im-
Ventriculomegaly
(Hydrocephalus)
Figure 30–4. T2-weighted axial MRI

showing enlarged ventricular cavities
(ventriculomegaly) due to hydrocephalus.
Ventriculomegaly
Secondary to Atresia
of the Foramen of Monro
Septum
Pellucidum
Figure 30–5. T1-weighted axial MRI showing unilateral enlargement of the lateral ventricle with displacement of
the septum pellucidum across the midline due to obstruction of the foramen of Monro by atresia.
Lateral Ventricle
Fourth Ventricle
Third Ventricle
Figure 30–6. T1-weighted midsagittal MRI showing selective enlargement of the lateral and third ventricles due to aque-
ductal stenosis.The fourth ventricle is normal in size.
384 / CHAPTER 30
Transependymal Flow
Lateral Ventricle
Transependymal Flow
Figure 30–7. T2-weighted axial
MRI showing transependymal flow
of cerebrospinal fluid to the ad-
jacent brain substance in hydro-
cephalus.
prove after shunting of the CSF to extracranial sites. Normal- carbonic anhydrase inhibitor, and to corticosteroids, both of which
pressure hydrocephalus is thus considered a treatable dementing reduce or inhibit the formation of CSF. Studies of CSF hydrody-
disorder. The condition can be diagnosed by radioisotope scans, namics in pseudotumor cerebri differentiate two types: type I
which demonstrate reflux of the radioisotope into the ventricles with normal CSF conductance and type II with very low conduc-
after its injection into the lumbar subarachnoid space. tance and high CSF pressure. Type I is believed to result from ex-
tracellular brain edema, and type II from impaired CSF resorp-
Benign External Hydrocephalus tion through the arachnoid granulations. CSF hydrodynamic
studies suggest that patients with type II IIH share a common
Benign external hydrocephalus is a disorder of childhood charac- physiologic mechanism with patients who have normal-pressure
terized by the accumulation of CSF in the subarachnoid space hydrocephalus.
over the brain surface, particularly over the frontal lobes
and in the interhemispheric fissure, without significant INTRAVENTRICULAR NEUROEPITHELIAL
involvement of the ventricular cavities (Figure 30–8).
The condition was first described in the eighteenth century by CYSTS
Underwood, who also observed its benign nature. The condition Intraventricular cysts are rare developmental cysts lined by neuro-
was rediscovered after the advent of newer imaging techniques. It epithelium. The precise origin of these cysts is controversial. They
is a self-limited condition which usually resolves spontaneously are believed to arise from choroid plexus tissue derived from
without sequelae. primitive neuroepithelium. They have been reported to occur in
all the ventricular cavities, but most commonly in the third ven-
IDIOPATHIC INTRACRANIAL HYPERTENSION tricle (colloid cysts of the third ventricle). A variety of
(PSEUDOTUMOR CEREBRI) AND BENIGN names have been used to describe these cysts, including
INTRACRANIAL HYPERTENSION epithelial cysts, ependymal cysts, choroid plexus cysts,
choroidal epithelial cysts, and subarachnoid ependymal cysts.
Idiopathic intracranial hypertension (IIH), which was described The term neuroepithelial cysts was introduced by Fulton and
by Quincke in 1891, is a disorder characterized by increased in- Bailey in 1929. Intraventricular cysts contain a clear serous liquid
tracranial pressure without hydrocephalus or brain tumor. It is resembling CSF with a mildly elevated protein content. The fluid
more common in adult obese women of childbearing age and in colloid cysts of the third ventricle is usually viscid with a gelati-
affects both sexes equally in childhood. These patients nous or mucinous appearance. Intraventricular cysts are clearly
complain of headache, papilledema, and transient vi- visible on magnetic resonance imaging (Figure 30–9). They usu-
sual obscuration. Imaging studies usually show small ally are asymptomatic and are found accidentally on neuroimag-
ventricles. The condition responds to acetazolamide (Diamox), a ing studies. Some may enlarge and become symptomatic.
Prominent Frontal
Subarachnoid Space
Prominent
Interhemispheric
Subarachnoid Space
Lateral Ventricle
(Antrior Horn)
Third Ventricle
Figure 30–8. Computed tomography scan showing accumulation of cerebrospinal fluid in the subarachnoid space
over the frontal lobe and in the interhemispheric fissure as seen in benign external hydrocephalus.
THE BOBBLE-HEAD DOLL SYNDROME appears in the supine position and during sleep. This disorder was
described by Benton in 1966. In most cases the syndrome is asso-
The bobble-head doll syndrome is a disorder of child- ciated with an intraventricular cyst in the region of the anterior
hood characterized by a to-and-fro, 2- to 3-Hz rhythmic third ventricle (Figure 30–10) or an arachnoid cyst in the suprasel-
nodding of the head similar to that in a doll with a lar region. The phenomenon results from intermittent obstruction
weighted head attached to a coil-spring neck. The movement dis- of the foramen of Monro by the cyst. The head bobbing is be-
Lateral Ventricle
Neuroepithelial
Cyst
Figure 30–9. T1-weighted parasagittal MRI showing a neuroepithelial cyst in the posterior part of the
lateral ventricle.
386 / CHAPTER 30
Lateral Ventricle
(Anterior Horn)
Third Ventricle
Cyst
Lateral Ventricle
(Posterior Horn)
Figure 30–10. T2-weighted axial MRI showing a third ventricle cyst in the bobble-head doll syndrome.
lieved to be a learned behavior which relieves the obstruction by DANDY-WALKER SYNDROME

means of posterior displacement of the cyst away from the fora- (MALFORMATION)
men of Monro. The syndrome has less commonly been described
in association with aqueductal stenosis and shunt obstruction. The The Dandy-Walker malformation (Figure 30–11) consists of
syndrome is treated by shunting or fenestration of the cyst. the triad of (1) large cystic dilatation of the posterior part of the
Lateral Ventricle
Cerebellar
Vermis
Third Ventricle
Dandy-Walker
Cyst
Fourth Ventricle
Figure 30–11. T1-weighted midsagittal MRI showing features of the Dandy-Walker syndrome.
fourth ventricle, (2) complete or partial agenesis of the after François Magendie, a French physiologist who described it
cerebellar vermis, and (3) enlargement of the posterior in 1842.
fossa with upward displacement of the tentorium, tor- Foramen of Monro. The site of communication between the
cula, and transverse sinus. Hydrocephalus, though common, is lateral and third ventricles. Named after Alexander Monro, a
not an essential feature of the syndrome. The syndrome was de- Scottish anatomist who described it in 1753.
scribed by Sutton in 1887 and was recognized as a distinct entity Guillain-Barré syndrome. An acute inflammatory demyelinat-
in 1914 by Dandy and Blackfan, who attributed it to atresia of ing polyneuropathy. Described by George Guillain, Jean Alexander
the foramina of Magendie and Luschka. In 1942 Taggart and Barré, and Andre Strohl, French physicians, in 1916.
Walker documented the entity and supported the proposed eti-
ology of atresia. The term Dandy-Walker syndrome was pro- Hydrocephalus (Greek hydro, “water”; kephalé, “head”).
posed in 1954 by Benda, who recognized that atresia of the Dilatation of the cerebral ventricles. Known to Hippocrates, it
foramina of Magendie and Luschka is not an essential feature of was described accurately by Vesalius in 1550.
the syndrome. The pathogenesis of the syndrome remains con- Hydrocephalus ex vacuo. An increase in the volume of CSF
troversial. The syndrome arises early in gestation, at about 4 weeks, and ventriculomegaly secondary to brain atrophy.
and involves multiple developmental defects of the central ner- Noncommunicating hydrocephalus. A type of hydrocephalus
vous system. Foraminal atresia may be a contributing factor in caused by obstruction of cerebrospinal fluid flow between the
some cases. The cystic dilatation of the fourth ventricle is attrib- sites of its formation and the roof of the fourth ventricle.
uted to the persistence of the anterior membranous area that Pseudotumor cerebri. A condition consisting of a rise in intra-
forms the roof of the fetal fourth ventricle, which ordinarily re- cranial pressure in the absence of an intracranial mass or hydro-
gresses and disappears as the choroid plexus and vermis develop. cephalus. Known by other terms, including idiopathic intracra-
Various treatment modalities have been tried with varying nial hypertension, hydrops, serous meningitis, Julien-Marie-See
success, including ventriculoperitoneal shunting, opening of the syndrome, Dupré’s syndrome, and Symonds syndrome. First de-
fourth ventricle, and excision of the cyst membrane. Current scribed by Quincke in 1891.
treatment consists of shunting of the cyst to the peritoneum Setting-sun sign. Depression of the eyeball with failure of upward
(cystoperitoneal shunt) combined with shunting of the lateral gaze and retraction of upper lid. Seen in children with hydro-
ventricles to the peritoneum (ventriculoperitoneal shunt). cephalus and pressure on the dorsal tectum.
Visual obscuration. Transient dimming of vision caused by in-
TERMINOLOGY creased intracranial pressure.
Alzheimer’s disease. A type of cortical dementia named after
Alois Alzheimer, the German neuropsychiatrist and pathologist
who described the disease in 1906. The term Alzheimer’s disease SUGGESTED READINGS
was coined by Ernst Kraepelin, a German psychiatrist, in 1910. Benda CE: The Dandy-Walker syndrome or the so-called atresia of the fora-
Aqueduct of Sylvius. A narrow passage linking the third and men of Magendie. J Neuropathol Exp Neurol 1954; 13:14–29.
fourth ventricles. Named after Franciscus de la Boe Sylvius, who Benson DF et al: Diagnosis of normal pressure hydrocephalus. N Engl J Med
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Benton JW et al: The bobble-head doll syndrome. Neurology 1966; 16:
Bobble-head doll syndrome. A syndrome of to-and-fro rhyth- 725–729.
mic movement of the head associated with anterior third ventri-
Coker SB: Bobble-head doll syndrome due to trapped fourth ventricle and
cle cysts or tumors. The movement is believed to be a learned be- aqueduct. Pediatr Neurol 1986; 2:115–116.
havior that relieves obstruction of the foramen of Monro. Czervionke LF et al: Neuroepithelial cysts of the lateral ventricle: MR appear-
Colpocephaly. A developmental condition characterized by fail- ance. AJNR 1987; 8:609–613.
ure of development of the cerebral mantle and secondary ven- Dandy WE, Blackfan KD: Internal hydrocephalus: An experimental, clinical,
triculomegaly with disproportionate enlargement of the occipital and pathological study. Am J Dis Child 1914; 8:406–482.
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and Wadsworth in 1946. Neurosurg Psychiatry 1981; 44:1046–1049.
Communicating hydrocephalus. A type of hydrocephalus in Hart MN et al: The Dandy-Walker syndrome: A clinicopathological study
based on 28 cases. Neurology 1972; 22:771–780.
which obstruction to CSF flow occurs between the roof of the
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pects. Neurology 1985; 35:1594–1598.
Dandy-Walker syndrome. A developmental malformation Leech RW, Goldstein E: Hydrocephalus: Classification and mechanisms. In
characterized by large cystic dilatation of the fourth ventricle, Leech RW, Brumback RA (eds): Hydrocephalus: Current Clinical Concepts.
agenesis of the cerebellar vermis, and upward displacement of St. Louis, Mosby 1991:45–70.
the tentorium cerebelli, torcula, and transverse sinus. The condi- New PFJ, Davis KR: Intraventricular noncolloid neuroepithelial cysts. AJNR
tion was first described by J. B. Sutton in 1887 and was recog- 1981; 2:569–576.
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Taggert and Walker in 1942. The term Dandy-Walker syndrome Congenital Malformations of the Brain: Pathological, Embryological,
was proposed by Benda in 1954. Clinical, Radiological, and Genetic Aspects. New York, Oxford University
Press, 1995:343–347.
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the fourth ventricle through which cerebrospinal fluid flows Brain: Pathological, Embryological, Clinical, Radiological, and Genetic
from the fourth ventricle to the cisterna magna. Named after Aspects. New York, Oxford University Press, 1995:333–339.
Hubert von Luschka, a German anatomist, in 1863. Papazian O et al: The history of hydrocephalus. Int Pediatr 1991; 6:233–235.
Foramen of Magendie. The median aperture in the roof of the Pryse-Phillips W: Companion to Clinical Neurology. Boston, Little, Brown,
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Puden RH: The surgical treatment of hydrocephalus: An historical review. cysts and tumors of the cerebellum and to occipital meningocele. Brain
Surg Neurol 1981; 15:15–26. 1887; 9:352–361.
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Sarnat HB: Dandy-Walker malformation. In Norman MG et al (eds): Cerebral Wiese JA et al: Bobble-head doll syndrome: Review of the pathophysiology
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Major Sensory and Motor Pathways 31
Major Sensory Pathways Major Motor Pathways

Pathway for Conscious Proprioception Cortical Origin
Pathways for Nonconscious Proprioception Subcortical Origin
Pathway for Pain and Temperature
Trigeminal Pathways
KEY CONCEPTS
Posterior column fibers ascend ipsilateral to their side of Corticospinal fibers originate principally from the motor
entry into the spinal cord and synapse on the nuclei gra- and premotor areas, descend throughout the neuraxis,
cilis and cuneatus in the medulla oblongata. Second- mostly decussate in the medulla oblongata (motor decus-
order fibers from the nuclei gracilis and cuneatus cross in sation), and terminate on interneurons or alpha motor-
the medulla oblongata (sensory, lemniscal decussation) neurons in the spinal cord.
to form the medial lemniscus. Medial lemniscal fibers ter-
Corticopontocerebellar fibers constitute the largest com-
minate on neurons in the ventral posterior lateral nucleus
ponent of corticofugal fibers. They originate principally
of the thalamus.
from primary sensory and motor cortices and synapse on
The dorsal spinocerebellar tract reaches the cerebellum pontine nuclei. Second-order neurons from the pontine
via the restiform body. The ventral spinocerebellar tract nuclei terminate in the cerebellum.
reaches the cerebellum via the brachium conjunctivum.
Cortically originating (cortifugal) motor pathways include
The spinothalamic fibers are somatotopically organized the corticospinal (pyramidal), corticopontocerebellar, cor-
so that sacral originating fibers are lateral in the tract and ticobulbar, corticothalamic, corticostriate, and corticohy-
cervical originating fibers are medial in the tract. Spino- pothalamic tracts.
thalamic fibers terminate on neurons in the ventral poste-
Subcortically originating fibers include the rubrospinal,
rior lateral nucleus of the thalamus.
vestibulospinal and reticulospinal.
Trigeminal pathways convey exteroceptive and proprio-
ceptive sensations from the face.
MAJOR SENSORY PATHWAYS movement, and pressure and (2) proprioceptive receptors (muscle
spindle, Golgi tendon organ, and joint receptors). Muscle recep-
Pathway for Conscious Proprioception tors (muscle spindles and Golgi tendon organs) are the primary
receptors that convey position sense. Joint receptors may be con-
The pathway for kinesthesia (position and vibration sense) and cerned with signaling joint movement but not joint position.
discriminative touch (well-localized touch and two-point dis- Impulses arising in the receptors travel via the thickly myeli-
crimination) is the posterior column–medial lemniscus system nated large nerve fibers that enter the spinal cord as the dorsolat-
(Figure 31–1). eral division of the posterior (dorsal) root and occupy
Nerve fibers that contribute to this pathway have their cell the posterior funiculus of the spinal cord. Those arising
bodies in the dorsal root ganglia. The receptors for this system are below the sixth thoracic spinal segment form the medial
(1) cutaneous mechanoreceptors (hair follicles and touch pressure part of the posterior funiculus (gracile tract, tract of Goll). Those
receptors) which convey the sensations of touch, vibration, hair arising above the sixth thoracic segment form the lateral part of
389
390 / CHAPTER 31
CEREBRAL CORTEX
Primary sensory cortex
Ventroposterolateral
DIENCEPHALON (VPL) nucleus
MIDBRAIN
Medial lemniscus
PONS
Sensory decussation
MEDULLA
Gracile and cuneate

nuclei
Posterior column
SPINAL CORD Pacinian corpuscle
Figure 31–1. Schematic diagram of the pathway for kinesthesia and discriminative touch.
MAJOR SENSORY AND MOTOR PATHWAYS / 391
the posterior funiculus (cuneate tract, Burdach column). Fibers 5. Inability to maintain a steady standing posture when the eyes
in the gracile and cuneate tracts project on neurons in the pos- are closed and the feet are placed close together (Romberg
terior column nuclei of the medulla oblongata (nuclei gracilis test). These patients begin to sway and may fall when they
and cuneatus). Axons of neurons in the posterior column nuclei close their eyes, eliminating visual compensation.
(second-order neurons, internal arcuate fibers) decussate in the Some of the fibers in the posterior funiculus send collateral
tegmentum of the medulla oblongata (sensory, lemniscal decus- branches that terminate on neurons in the gray matter of the pos-
sation) to form the medial lemniscus, which ascends throughout terior horn. These collaterals give the posterior column system a
the medulla oblongata, pons, and midbrain to terminate on neu- role in modifying sensory activity in the posterior horn. This role
rons of the ventroposterolateral (VPL) nucleus of the thalamus. is inhibitory to pain impulses. Thus, lesions in the posterior fu-
The axons of neurons in this thalamic nucleus (third-order neu- niculus decrease the threshold to painful stimuli. Nonpainful
rons) project on the terminal station of this pathway in the stimuli become painful, and painful stimuli are triggered by lower
somesthetic (primary sensory) cortex of the parietal lobe. stimulation thresholds.
Lesions in the posterior column–medial lemniscus system are In addition to its classical role in sensory transmission, the
manifested clinically by the following signs: dorsal column plays a role in certain types of motor control. The
1. Inability to identify the position of a limb in space with the dorsal column transmits to the motor cortex sensory information
eyes closed. These patients are unable to tell whether a joint from muscle spindles, joint receptors, and cutaneous receptors
is in a position of flexion or one of extension. that is necessary in planning, initiating, programming, and mon-
2. Inability to identify objects placed in the hands, such as keys itoring tasks that involve manipulative movements by the digits.
and coins, from their shape, size, and texture with the eyes
closed.
3. Loss of two-point discrimination. These patients are unable Pathways for Nonconscious Proprioception
to recognize two stimuli simultaneously applied to the skin Nonconscious proprioception is mediated via the two spinocere-
when the stimuli are separated by the minimal necessary dis- bellar tracts (Figures 31–2 and 31–3), the posterior (dorsal) and
tance for their proper identification as two stimuli. the anterior (ventral).
4. Inability to perceive vibration when a vibrating tuning fork The posterior spinocerebellar tract conveys impulses from the
is applied to a bony prominence. muscle spindle and the Golgi tendon organ. Such impulses travel
CEREBELLUM
Accessory cuneate nucleus
Restiform
body
MEDULLA
Posterior
spinocerebellar Dorsal root Muscle
tract ganglion spindle
SPINAL CORD
Figure 31–2. Schematic diagram of Nucleus dorsalis Golgi tendon
the posterior spinocerebellar pathway. (Clarke's column) organ
392 / CHAPTER 31
CEREBELLUM
Brachium
conjunctivum
PONS
MEDULLA
Muscle
Anterior
spinocerebellar
tract

of the anterior spinocerebellar
SPINAL CORD Golgi tendon organ pathway.
via groups Ia, Ib, and II nerve fibers; enter the spinal cord in the The anterior spinocerebellar tract conveys impulses from the
dorsolateral, thickly myelinated, large-diameter fiber portion of Golgi tendon organ via Ib afferents. Incoming fibers project on
the posterior root; and project on the ipsilateral nucleus dorsalis neurons in the posterior horn of the spinal cord (laminae V to
(Clarke’s nucleus, Stilling column, Stilling nucleus, nucleus tho- VII). Axons of neurons in these laminae decussate to the contra-
racicus) and the accessory cuneate nucleus. Axons of neurons in lateral lateral funiculus to form the anterior spinocerebellar tract,
the nucleus dorsalis (second-order neurons) form the posterior which ascends throughout the spinal cord, medulla ob-
spinocerebellar tract, which ascends in the lateral funiculus of longata, and pons; loops backward to join the superior
the spinal cord and the medulla oblongata to reach the cerebel- cerebellar peduncle (brachium conjunctivum); and en-
lum via the inferior cerebellar peduncle (restiform body). Axons ters the cerebellum. The anterior spinocerebellar tract conveys to
of neurons in the accessory cuneate nucleus form the cuneocere- the cerebellum information related to interneuronal activity and
bellar tract, which reaches the cerebellum via the restiform the effectiveness of descending pathways.
body. Information relayed to the cerebellum via the posterior Lesions in the spinocerebellar pathways (such as those which
spinocerebellar tract and the cuneocerebellar tract relates to occur in hereditary spinocerebellar degeneration) result in inco-
muscle contraction, including the phase, rate, and strength of ordinate movement. These patients tend to walk with a wide base,
contraction. stagger, and frequently fall.
Pathway for Pain and Temperature Within the spinal cord they ascend for one or two segments and
project on neurons in several laminae (I to VI) in the posterior
Small-diameter, unmyelinated, or thinly myelinated fibers (C horn. From tract neurons in laminae I and V to VII, axons cross
fibers and A delta fibers) that convey pain and thermal in the anterior white commissure and form the lateral spinotha-
sensations (Figure 31–4) enter the spinal cord via the lamic tract in the lateral funiculus. Sacral fibers are laterally
ventrolateral division of the dorsal (posterior) root. placed in the tract, and cervical fibers are more medially placed.
The spinothalamic tract ascends throughout the spinal cord and
brain stem to project on neurons in the VPL of the thalamus.
CEREBRAL CORTEX Axons of VPL neurons project, via the posterior limb of the in-
ternal capsule, to the somesthetic cortex.
Lesions of the spinothalamic tract result in diminution or loss
of pain and thermal sense contralateral to the lesion. When the
tract is affected in the spinal cord, the sensory deficit begins one
or two segments below the level of the lesion.
The spinothalamic tract may be sectioned surgically (cor-
dotomy) to relieve intractable pain.
Trigeminal Pathways
The trigeminal pathways convey exteroceptive and propriocep-
tive sensations from the face to the thalamus. They thus
correspond to the spinothalamic and posterior col-
umn–medial lemniscus pathways, which convey similar
DIENCEPHALON
Ventroposterolateral sensations from the rest of the body.
(VPL) nucleus Exteroceptive fibers are general somatic sensory fibers that con-
vey pain, temperature, and touch sensations from the face and
the anterior aspect of the head. Neurons of origin of these fibers
are located in the semilunar (gasserian) ganglion (see Figure 7–18).
Peripheral processes of neurons in the ganglion are distributed in
the three divisions of the trigeminal nerve: ophthalmic, maxil-
lary, and mandibular. Central processes of these unipolar neu-
rons enter the lateral aspect of the pons and distribute themselves
MIDBRAIN as follows.
Some of these fibers descend in the pons and the medulla and
down to the level of the second or third cervical spinal segment
as the descending (spinal) tract of the trigeminal nerve. They
convey pain and temperature sensations. Throughout their cau-
dal course these fibers project on neurons in the adjacent nu-
cleus of the descending tract of the trigeminal nerve (spinal
trigeminal nucleus). Axons of neurons in the spinal trigeminal
nucleus cross the midline and form the ventral secondary as-
cending trigeminal (ventral trigeminothalamic) tract, which
PONS Lateral
courses rostrally to terminate in the ventral posterior medial nu-
spinothalamic cleus of the thalamus.
tract Other incoming fibers of the trigeminal nerve bifurcate on
entry into the pons into ascending and descending branches.
These fibers convey touch sensation. The descending branches
join the spinal tract of the trigeminal nerve and follow the course
that was outlined above. The shorter ascending branches project
on the main (principal) sensory nucleus of the trigeminal nerve
(see Figure 7–18). From the main sensory nucleus, second-order
fibers ascend ipsilaterally and contralaterally as the dorsal ascend-
ing trigeminal (dorsal trigeminothalamic) tract to the ventral pos-
MEDULLA
terior medial nucleus of the thalamus. Some crossed fibers also
travel in the ventral ascending trigeminal tract. Once formed,
both secondary trigeminal tracts (dorsal and ventral) lie lateral to
the medial lemniscus between it and the spinothalamic tract. A
Thermal and
schematic summary of the afferent and efferent trigeminal roots
pain receptors and their nuclei is shown in Figure 7–19. Recent studies of tri-
geminothalamic fibers have revealed that the bulk of these fibers
SPINAL CORD
arise from the main sensory nucleus and the interpolaris segment
of the spinal nucleus.
Figure 31–4. Schematic diagram of the pathway for specific Proprioceptive fibers from deep structures of the face are
pain and temperature sensations. peripheral processes of unipolar neurons in the mesencephalic
394 / CHAPTER 31
nucleus of the trigeminal located at the rostral pontine and cau- midal decussation to form the lateral corticospinal tract in the
dal mesencephalic levels. Proprioceptive fibers to the mesen- lateral funiculus of the spinal cord. About 8 percent of pyramidal
cephalic nucleus convey pressure and kinesthesia from the teeth, fibers remain uncrossed and form the anterior corticospinal tract
periodontium, hard palate, and joint capsules as well as impulses (Türck’s bundle) in the anterior funiculus of the spinal cord.
from stretch receptors in the muscles of mastication. The output Fibers in the anterior corticospinal tract decussate at segmental
from the mesencephalic nucleus is destined for the cerebellum, spinal levels. In the final analysis, therefore, roughly about 98 per-
the thalamus, the motor nuclei of the brain stem, and the reticu- cent of fibers in the pyramidal tract are crossed. The remaining
lar formation. The mesencephalic nucleus is concerned with 2 percent remain ipsilateral and form the tract of Barnes. Pyra-
mechanisms that control the force of the bite. midal tract fibers influence alpha motor neurons directly or via
interneurons. They facilitate flexor motor neurons and inhibit
MAJOR MOTOR PATHWAYS extensor motor neurons. Lateral corticospinal tract fibers termi-
nate on motor neurons in the lateral part of the ventral horn that
Cortical Origin supply the distal limb musculature. Anterior corticospinal tract
fibers terminate on motor neurons in the medial part of the ven-
A. CORTICOSPINAL (PYRAMIDAL) TRACT tral horn that supply the neck, the trunk, and the proximal limb
The corticospinal tract (Figure 31–5) is the most important de- musculature.
scending tract. From its origin in the cerebral cortex it The corticospinal tract is essential for skill and precision in
descends through all levels of the neuraxis except the movement and the execution of discrete fine finger movements.
cerebellum. It arises primarily from the motor (area 4) However, it cannot initiate these movements by itself; other cor-
and premotor (area 6) cortices and passes through the internal ticofugal (cortically originating) fibers are needed for this. The
capsule, the cerebral peduncle, the basis pontis, and the pyra- corticospinal tract also regulates sensory relay processes and the
mids of the medulla oblongata. In the caudal medulla, about 75 selection of the sensory modality that reaches the cortex. The se-
to 90 percent of the fibers decussate through the motor or pyra- lection function is achieved via terminations of corticospinal
tract fibers on primary afferent fibers and sensory relay neurons
in the posterior (dorsal) horn of the spinal cord.
Lesions in this tract result in paralysis. If the lesion is above
the level of the motor decussation, the paralysis is contralateral
to the site of the lesion. In lesions of the pyramidal tract below
the decussation, the paralysis is ipsilateral to the site of the lesion.
In addition to paralysis, lesions in the corticospinal tract result
in a conglomerate of neurologic signs, including (1) spasticity,
(2) hyperactive myotatic reflexes (hyperreflexia), (3) Babinski’s
sign, and (4) clonus. Collectively, this conglomerate of signs is
referred to as upper motor neuron signs.
B. CORTICOPONTOCEREBELLAR TRACT
The corticopontocerebellar tract (Figure 31–6) constitutes by far
the largest component of the cortically originating de-
scending fiber system. It has been estimated to contain
approximately 19 million fibers, in contrast to the pyra-
midal tract, which contains approximately 1 million. The tract
originates from wide areas of the cerebral cortex, but primarily
from the primary sensory and motor cortices, and descends in
the internal capsule, cerebral peduncle, and basis pontis, from
which its fibers project on pontine nuclei. Second-order neurons
from pontine nuclei cross to the contralateral side of the basis
pontis, enter the middle cerebellar peduncle (brachium pontis),
and project on the cerebellum.
Although the pontocerebellar projection is primarily crossed,
it has been estimated that 30 percent of the pontine projection to
the cerebellar vermis and 10 percent of the projection to the cere-
bellar hemisphere are ipsilateral. The density of projection to the
cerebellar hemisphere is three times that to the vermis. The cor-
ticopontocerebellar tract is somatotopically organized. The pri-
mary motor cortex projects to the medial pontine nuclei, the pri-
mary sensory cortex projects to the lateral pontine nuclei, the arm
area of the sensory motor cortex projects to the dorsal pontine
nuclei and the leg area projects to the ventral pontine nuclei, the
caudal pontine nuclei project to the anterior lobe of the cerebel-
lum, and the rostral pontine nuclei project to the posterior lobe of
the cerebellum. The corticopontocerebellar tract is one of several
pathways by which the cerebral cortex influences the cerebellum;
Figure 31–5. Schematic diagram of corticospinal pathway. it plays a role in the rapid correction of movement. Lesions of the
F, face; A, arm; L, leg. corticopontocerebellar pathway result in ataxia. The ataxia that
Figure 31–6. Schematic diagram of

corticopontocerebellar tract. p
occurs contralateral to frontal or temporal lobe pathology is ex- Corticohypothalamic fibers arise from the prefrontal cortex,
plained by interruption of the corticopontine pathway. cingulate gyrus, olfactory cortex, hippocampus, and septal area.
They reach the hypothalamus via the internal capsule.
C. CORTICOBULBAR TRACT
Corticobulbar fibers (Figure 31–7) originate from the face areas Subcortical Origin
of the cerebral cortex. They descend in the genu of the internal
capsule, the cerebral peduncle (where they occupy a dorsolateral Tracts of subcortical origin arise from the midbrain, pons,
corner of the corticospinal segment of the peduncle as well as a and medulla oblongata.
small area in the medial part of the base of the peduncle), and
the basis pontis (where they intermix with corticospinal fibers) A. MIDBRAIN
and pyramid but do not reach the spinal cord. At different levels
of the neuraxis, they project on cranial nerve nuclei. Some corti- The major motor pathway from the midbrain is the rubrospinal
cobulbar fibers project directly on cranial nerve nuclei (trigemi- tract (see Figure 3–20). This tract originates from neurons in the
nal, facial, and hypoglossal); the majority, however, project on caudal (magnicellular) part of the red nucleus, crosses in the ven-
reticular nuclei before reaching the cranial nerve nuclei. This sys- tral tegmental decussation of the midbrain, and descends in the
tem is known as the corticoreticulobulbar tract. The majority of midbrain, pons, medulla, and spinal cord, where it occupies a po-
cranial nerve nuclei receive bilateral cortical input. Bilateral in- sition in the lateral funiculus in close proximity to the lateral cor-
terruption of the corticobulbar or corticoreticulobulbar fiber sys- ticospinal tract. The rubrospinal tract is considered an indirect
tem results in paresis (weakness) of the muscles supplied by the corticospinal tract. Like the corticospinal tract, the rubrospinal
corresponding cranial nerve nucleus. This condition is known as tract facilitates flexor motor neurons and inhibits extensor motor
pseudobulbar palsy. neurons. In most mammals the rubrospinal tract is the major out-
put of the red nucleus. With evolution the output of the red nu-
D. OTHER CORTICOFUGAL TRACTS cleus to the spinal cord decreased, and in humans the red nucleus
Other corticofugal tracts include the corticothalamic, cortico- sends its major output to the inferior olive, which in turn projects
striate, and corticohypothalamic tracts, which serve as feedback to the cerebellum.
mechanisms from the cortex to these sites. B. PONS
Corticothalamic fibers arise from cortical areas that receive
thalamic projections. They descend in the internal cap- The major motor pathways emanating from the pons are the
sule and enter the thalamus via the thalamic radiation, lateral and medial vestibulospinal and pontine reticulospinal
which also includes reciprocal thalamocortical fibers. tracts.
Corticostriate fibers can be direct or indirect. Direct cortico- 1. Lateral Vestibulospinal Tract. The lateral vestibulospinal
striate projections reach the neostriatum via the internal and ex- tract (see Figure 3–21) originates from the lateral vestibular nu-
ternal capsules. Indirect corticostriate pathways include the cor- cleus and descends ipsilaterally in the pons, medulla, and spinal
ticothalamostriate and the collaterals of the corticoolivary and cord, where it occupies a position in the lateral funiculus. The
corticopontine pathways. Almost all cortical areas contribute to lateral vestibulospinal tract terminates on interneurons in lami-
the corticostriate projections. Corticostriate pathways are soma- nae VII and VIII, with some direct terminations on alpha motor-
totopically organized so that cortical association areas project neuron dendrites in the same laminae. The lateral vestibulospinal
preferentially to the caudate nucleus, whereas sensorimotor cor- tract facilitates extensor motor neurons and inhibits flexor motor
tical areas preferentially project to the putamen. neurons.
396 / CHAPTER 31
CORTEX C. MEDULLA OBLONGATA

The major descending pathway from the medulla oblongata is the
medullary reticulospinal tract (see Figure 3–23). It arises mainly
from the medial (central) group of medullary reticular nuclei
(nucleus reticularis gigantocellularis), descends primarily ipsilat-
eral to its site of origin, and occupies a position in the lateral fu-
niculus of the spinal cord. It facilitates flexor motor neurons and
inhibits extensor motor neurons.
TERMINOLOGY
Ataxia (Greek taxis, “order”). Lack of order. Lack of coordina-
tion with unsteadiness of movement.
Burdach, Karl Friedrich (1776–1847). German anatomist and
physiologist. Described many of the tracts of the brain and
spinal cord and especially the posterior column of the spinal cord
which he designated as fasciculus cuneatus. Although the tract
was previously described by Rosenthal, the description of Burdach
was more accurate.
Clarke, Jacob Augustus Lockhart (1817–1880). English anat-
omist who described the nucleus dorsalis in 1851 in a memoir to
the Royal Society, published in the Philosophical Transactions.
DBRAIN Corticofugal (cortex; Latin, fugere, “to flee”). Moving away
from the cortex.
Cuneatus (Latin, “wedge”). The fasciculus cuneatus is so named
Abducens nucleus because of its wedge shape.
Decussation (Latin decussare, “to cross like an X”). X-shaped
crossing of nerve fiber tracts in the midline, as in the motor
(pyramidal) and sensory (lemniscal) decussations.
Exteroceptive (Latin, “to take outside”). Received from outside.
Exteroceptive receptors receive impulses from the outside.
Corticoreticulobulbar Funiculus (Latin funis, “cord”). A bundle of white matter con-
tract PO
ONS
taining one or more tracts.
Ganglion (Greek, “swelling, knot”). A collection of nerve cells
outside the central nervous system, as in the gasserian (trigeminal)
ganglion.
Hypoglossal nucleus Golgi tendon organ. Specialized stretch receptors in the tendons.
Named after Camillo Golgi, an Italian anatomist.
Goll, Friedrich (1829–1903). Swiss anatomist. Described the
Corticobulbar tract fasciculus gracilis in the posterior column in 1862.
Gracilis (Latin, “slender, thin”). The fasciculus or tractus gra-
Pyramid MEDULLA cilis is so named because it is slender.
Kinesthesia (Greek kinesis, “motion”; aisthesis, “sensation”).
Figure 31–7. Schematic diagram of the corticobulbar pathway. The sense of perception of movement.
Nucleus dorsalis (Clarke’s nucleus). A nucleus in the inter-
mediate zone of the spinal cord gray matter that gives rise to
2. Medial Vestibulospinal Tract (see Figure 3–22). The neu- the dorsal spinocerebellar tract. Named after Jacob Augustus
rons of origin of the medial vestibulospinal tract are located in Lockhart Clarke, an English anatomist who described this nucleus
the medial vestibular nucleus. From their neurons of origin, in 1851.
fibers join the ipsilateral and contralateral medial longitudinal
fasciculus, descend in the anterior funiculus of the cervical cord Paralysis (Greek para, “beside”; lyein, “to loosen”). Loss of
segments, and terminate on neurons in laminae VII and VIII. voluntary movement.
They exert a facilitatory effect on flexor motor neurons. This tract Paresis (Greek parienai, “to relax, to let go”). Slight or incom-
plays a role in controlling head position. plete paralysis.
3. Pontine Reticulospinal Tract (see Figure 3–23). The pon- Proprioception (Latin propius, “one’s own”; perceptio, “per-
tine reticulospinal tract arises mainly from the medial group of ception”). The sense of position and movement.
pontine reticular nuclei (nuclei reticularis pontis caudalis and Receptor (Latin recipere, “to receive”). A sensory nerve ending
oralis), descends primarily ipsilaterally through the pons and or sensory organ that receives sensory stimuli.
medulla oblongata, and occupies a position in the anterior funicu- Restiform body (Latin restis, “a rope”; forma, “form” or
lus of the spinal cord. It facilitates extensor motor neurons and “shape”). The restiform body (inferior cerebellar peduncle) is a
inhibits flexor motor neurons. compact bundle of nerve fibers connecting the medulla oblongata
and the cerebellum. It was described and named by Humphrey Cherubini E et al: Caudate neuronal responses evoked by cortical stimulation:
Ridley, an English anatomist, in 1695. Contribution of an indirect corticothalamic pathway. Brain Res 1979;
173:331–336.
Romberg test. A test for conscious proprioception. The inability Davidoff RA: The dorsal column. Neurology 1989; 39:1377–1385.
to maintain a steady standing posture when the eyes are closed and
Davidoff RA: The pyramidal tract. Neurology 1990; 40:332–339.
the feet are placed close together. Named after Moritz Heinrich
Iwatsubo T et al: Corticofugal projections to the motor nuclei of the brainstem
Romberg, a German physician who described the test in 1840. and spinal cord in humans. Neurology 1990; 40:309–312.
Rubro (Latin, ruber, “red”). The rubrospinal tract originates Matsushita M et al: Anatomical organization of the spinocerebellar system in the
from the red nucleus. cat as studied by retrograde transport of horseradish peroxidase. J Comp
Somatotopic (Greek soma, “body”; topos, “place”). Representa- Neurol 1979; 184:81–106.
tion of parts of the body in corresponding parts of the brain or Nathan PW et al: The corticospinal tract in man: Course and location of fibers
spinal cord. at different segmental levels. Brain 1990; 113:303–324.
Smith MC, Deacon P: Topographical anatomy of the posterior column of
Stilling, Benedikt (1810–1879). German anatomist and surgeon. the spinal cord in man: The long ascending fibers. Brain 1984; 107:
Described nucleus dorsalis of the spinal cord and reported that it 671–698.
extended from C8–L3–4. Wiesendanger R et al: An anatomical investigation of the corticopontine pro-
Türck’s Bundle. Anterior corticospinal tract. Described by Ludwig jection in the primate (Macaca fascicularis and Saimiri sciureus): II. The
Türck, an Austrian anatomist and neurologist, in 1849. projection from frontal and parietal association areas. Neuroscience 1979;
4:747–765.
Willis WD: Studies of the spinothalamic tract. Tex Rep Biol Med 1979; 38:
SUGGESTED READINGS 1–45.
Brodal P: The corticopontine projection in the Rhesus monkey: Origin and Yeterian EH, VanHoesen GW: Cortico-striate projections in the Rhesus mon-
principles of organization. Brain 1978; 101:251–283. key: The organization of certain cortico-caudate connections. Brain Res
1978; 139:43–63.
Brodal P: The pontocerebellar projection in the Rhesus monkey: An experi-
mental study with retrograde axonal transport of horseradish peroxidase.
Neuroscience 1979; 4:193–208.
Reticular Formation,Wakefulness, 32
and Sleep
Nomenclature Functions
Organization Somatic Motor Function
Connections Somatic Sensory Function
Raphe Nuclei Visceral Motor Function
Medial Group Arousal and Alertness
Paramedian Group Ascending Reticular Activating System (ARAS)
Lateral Group Sleep
Reticular Nucleus of Thalamus Phases and Stages of Sleep
Chemically Specified Systems Sleep and Arousal Mechanisms
Cholinergic System
Monoaminergic System
KEY CONCEPTS
The reticular formation of the brain stem is organized into Two chemically specified systems have been identified
four nuclear groups: median raphe, paramedian, medial, within the reticular formation: cholinergic and monoamin-
and lateral. ergic. The latter includes dopaminergic, noradrenergic,
adrenergic, and serotonergic subsystems.
The caudal raphe nuclei are concerned with pain mecha-
nism while the rostral raphe nuclei relate to wakefulness, The reticular formation plays important roles in somatic
alertness and sleep. motor and visceral motor functions, somatic sensory
functions, and in arousal and alertness.
The medial group of reticular nuclei have descending
(caudal) and ascending (rostral) connections. The former There are two phases of sleep: slow wave (non-REM) sleep,
play a role in motor control, whereas the latter relate to and REM (rapid eye movement) sleep. Slow sleep is divisi-
consciousness and alertness. ble into four stages ranging from light to deep sleep.
The paramedian reticular nuclei have reciprocal connec- The sleep-promoting, ventrolateral preoptic nucleus and
tions with the cerebellum; hence they are designated as the aminergic arousal system nuclei are reciprocally in-
precerebellar nuclei. hibitory to each other.
The lateral group of reticular nuclei is related to locomo- Orexin (hypocretin) neurons in the hypothalamus facili-
tion and autonomic regulation. They also relay inputs tate the aminergic arousal system. They are active during
from several sites to the medial group of reticular nuclei. wakefulness. Narcolepsy is associated with orexin (hypo-
cretin) neuron lesions.
The reticular nucleus of thalamus plays a role in integrat-
ing and gating activities of other thalamic nuclei.
The term reticular formation refers to a mass of neurons and Although older accounts of the reticular formation described it
nerve fibers extending from the caudal medulla to the rostral mid- as a mass of intermeshed, poorly organized neurons and nerve
brain and continuous with the zona incerta of the subthalamus fibers, it has now been established that the reticular formation is
and midline, intralaminar and reticular nuclei of the thalamus. organized into definite nuclear groups with known afferent and
398
RETICULAR FORMATION, WAKEFULNESS, AND SLEEP / 399
efferent connections. As a whole, the reticular formation com- ORGANIZATION (Figure 32–1)
prises a neural system with multiple inputs and multisynaptic
system of impulse conduction. Current methodologies such as Several different systems for naming nuclei of the brain stem
histo- and immunofluorescent techniques, orthograde and retro- reticular formation have been used, resulting in confusion and
grade fiber tracing methods, and intra- as well as extracellular controversy. In general, the reticular formation of the brain stem
microphysiology have enriched our knowledge of the organiza- is divided into the following nuclear groups (Table 32–1):
tional precision and complexity of this system. 1. Median raphe
2. Paramedian reticular
NOMENCLATURE 3. Medial reticular
There is no entirely satisfactory term to designate the complex of 4. Lateral reticular
cell pools, neuropil fields and associated fiber systems which The median raphe nuclear group includes the following mid-
make up the reticular core of the brain stem. The term reticular line nuclei: raphe obscurus and raphe pallidus in the medulla ob-
formation was used by early neuroscientists to describe the retic- longata; raphe magnus in the caudal pons and rostral medulla;
ulated appearance of the core formed by a nonpatterned mixture raphe pontis in the pons; and the dorsal raphe and superior cen-
of neurons and myelinated fibers. Another designation, the non- tral (Bekhterev) nuclei in the midbrain. The neurotransmitter of
specific system, differentiates it from the specific system repre- most raphe nuclei is serotonin.
sented by the medial lemniscus and the spinothalamic tracts. A The paramedian reticular nuclei are located lateral to the me-
term that gained popularity in the fifties and sixties is the as- dial longitudinal fasciculus and the medial lemniscus. They in-
cending reticular activating system, which focused attention on clude the paramedian reticular nucleus in the rostral medulla
the core’s role in wakeful and alert states. It is now known that and caudal pons, and the reticulotegmental nucleus in the rostral
the functions of this system transcend this behavioral role. In the pons and caudal midbrain.
absence of a fully satisfactory term, the term “brain stem reticu- The medial reticular nuclear group includes the nucleus retic-
lar core” remains in common use. ularis gigantocellularis in the medulla oblongata, and the nucleus
Figure 32–1. Schematic representation of the different groups of reticular nuclei.

400 / CHAPTER 32
Table 32–1. Reticular Nuclei.
Median Raphe Paramedian Medial Lateral
Medulla Raphe obscurus Reticularis giganto cellularis Reticularis parvocellularis

Raphe pallidus Reticularis lateralis
Rostral medulla– Raphe magnus Paramedian reticular
caudal pons
Pons Raphe pontis Reticularis pontis caudalis Reticularis parvocellularis
Reticularis pontis oralis
Rostral pons– Reticulotegmental Parabrachial
caudal midbrain Pedunculopontine
Midbrain Dorsal Raphe (nucleus Cuneiform
supratrochlearis) Subcuneiform
Superior central (Bekhterev)
reticularis pontis caudalis and nucleus reticularis pontis oralis in systems (spinothalamic and second-order axons from trigeminal
the pons. and auditory nuclei), superior colliculus (tectoreticular), cerebel-
The lateral reticular nuclear group includes the following nu- lum (vestibulocerebellum) hypothalamus, and cerebral cortex.
clei: nucleus reticularis parvocellularis and nucleus reticularis lat- Descending projections from the medial group of reticular nu-
eralis in the medulla oblongata; the nucleus reticularis parvocel- clei project to the spinal cord (pontine and medullary reticu-
lularis in the pons; parabrachial and pedunculopontine nuclei in lospinal tracts located in the ventral and lateral funiculi of the
the rostral pons and caudal midbrain; and the cuneiform and spinal cord respectively). Ascending projections are destined to
subcuneiform reticular nuclei in the midbrain. the intralaminar nuclei of the thalamus (centromedian and para-
The reticular formation of the brain stem continues into the fascicular), and to the basal cholinergic nuclei (nucleus basalis of
diencephalon. The reticular nucleus of thalamus, located lateral Meynert, nucleus of the diagonal band).
to the internal capsule, is a continuation of the brain stem retic- The descending projections of this group of reticular nuclei
ular formation. suggest a role in motor control, whereas the ascending projec-
tions relate these nuclei to consciousness and alertness.
CONNECTIONS The nucleus reticularis pontis caudalis has been associ-
ated with paradoxical sleep. Bilateral lesions in the nu-
Raphe Nuclei cleus result in complete elimination of paradoxical sleep.
Raphe nuclei of the medulla oblongata (raphe magnus, obscu-
rus, pallidus) receive inputs from the spinal cord, trigeminal sen- Paramedian Group
sory nuclei (second-order sensory input), and the periaqueductal The paramedian group of reticular nuclei (paramedian reticular
gray matter of midbrain. and reticulotegmental) receives inputs from the spinal
Raphe nuclei of the medulla oblongata project to the cerebel- cord (spinoreticular), cerebral cortex, and vestibular nu-
lum, dorsal horn of spinal cord (spinothalamic neurons), and clei and project to the cerebellum. They are designated,
trigeminal nuclei. by some, as precerebellar nuclei.
The facilitatory input from the periaqueductal gray matter to
the medullary raphe nuclei, and the inhibitory projections of the Lateral Group
latter on spinothalamic neurons in the dorsal horn of spinal cord
constitute the anatomic substrate for the analgesic effect of elec- The lateral group of reticular nuclei in the medulla and pons
trical stimulation of the midbrain periaqueductal gray. (parvocellularis and lateralis) constitute the receptive component
Raphe nuclei of the rostral pons and midbrain (raphe pontis, of reticular nuclei. They receive inputs from the contralateral red
dorsal raphe, superior central) receive inputs from the prefrontal nucleus, spinal cord (spinothalamic and spinoreticular tracts)
cortex, the limbic system, and hypothalamus and project widely and second-order neurons of trigeminal, auditory and
to the forebrain, cerebellum, and brain stem. vestibular sensory systems. They, in turn, project to both
It becomes evident from their connections that the caudal cerebellar hemispheres (mostly homolateral) and to the
raphe nuclei are involved in pain mechanisms while the medial group of reticular nuclei.
rostral raphe nuclei are part of the reticular activating An expiratory center has been located experimentally within
system concerned with wakefulness, alertness, and sleep. the parvocellular reticular area of the medulla oblongata.
The pedunculopontine nucleus (rostral pons-caudal midbrain)
Medial Group receives inputs from the cerebral cortex, the medial segment of
globus pallidus, and substantia nigra (pars reticulata). It projects
In addition to the medial group of nuclei in the medulla oblon- to the thalamus and pars compacta of the substantia nigra. The
gata and pons (nuclei reticularis gigantocellularis, pontis caudalis nucleus lies in a region from which walking movements can be
and oralis), two nuclei of the lateral group of reticular nuclei in elicited on stimulation (locomotor center).
the midbrain (cuneiform and subcuneiform) are included here The parabrachial nucleus (rostral pons-caudal midbrain) receives
because of similar connectivity pattern. input from the amygdala, and the nucleus solitarius and projects
Input to this group of reticular nuclei originates from the to the hypothalamus, preoptic area, amygdala and intralaminar
spinal cord (spinoreticular), collaterals from ascending sensory thalamic nuclei. It is believed that the nucleus plays a role in auto-
nomic regulation. The involvement of the parabrachial nucleus in Noradrenergic neurons of the brain stem are divided into two
Parkinson’s disease may explain the autonomic disturbances that major components. The first is the norepinephrine system of the
occur in that disease. locus ceruleus (catecholamine neuron cell group A6). The sec-
As stated previously, the cuneiform and subcuneiform reticu- ond is the lateral tegmental norepinephrine system, comprising
lar nuclei have similar connections to the medial group of reticu- another series of noradrenergic cell groups scattered in the pons
lar nuclei. and medulla (groups A1 to A7). Axons of these neurons are di-
rected to the spinal cord, brain stem, cerebellum, diencephalon,
and telencephalon. The ascending noradrenergic system is in-
Reticular Nucleus of Thalamus volved in modulation of attention, sleep-wake state and mood.
The reticular nucleus of thalamus is a continuation of the retic- Noradrenergic enhancing drugs are used in treatment of attention
ular formation of the brain stem into the diencephalon. It receives deficit disorder and in sleep disorders such as narcolepsy. Nor-
inputs from the cerebral cortex and other thalamic nu- adrenergic projections to the brain stem, cerebellum, and spinal
clei. The former are collaterals of corticothalamic pro- cord are involved in modulation of autonomic (sympathetic)
jections, and the latter are collaterals of thalamocortical functions as in regulation of blood pressure.
projections. The reticular nucleus projects to other thalamic nu- Adrenergic neurons are located in the same regions of the
clei. The inhibitory neurotransmitter in this projection is caudal medulla as the noradrenergic neurons. They project to
GABA. The reticular nucleus is unique among thalamic nuclei the spinal cord, brain stem, thalamus, and hypothalamus. This
in that its axons do not leave the thalamus. Based on its connec- system is small in comparison with the dopaminergic and nor-
tions, the reticular nucleus plays a role in integrating and gating adrenergic systems and represents a minor component of the
activities of thalamic nuclei. monoaminergic system.
Serotonergic neurons comprise nine cell groups designated B1
to B9. The vast majority of serotonergic neurons lie within the
CHEMICALLY SPECIFIED SYSTEMS raphe nuclei of the midbrain, pons and medulla oblongata. The
rostral pontine and mesencephalic serotonergic raphe neurons
Two chemically specified systems have been identified project to the entire forebrain, whereas the caudal pontine and
among the rich ensemble of reticular neurons; these are medullary serotonergic raphe neurons project to the cerebellum,
the cholinergic and monoaminergic systems. medulla, and spinal cord. The rostral raphe serotonergic system
plays a role in psychiatric disorders (depression, obsession-compul-
Cholinergic System sion, aggression, anxiety). The projection from the nucleus raphe
magnus of the medulla oblongata to the spinal cord has received
Cholinergic neurons are found in two locations: (1) rostral pons- much attention. This projection has been shown to inhibit dorsal
caudal midbrain, and (2) basal forebrain. horn neurons that give rise to the spinothalamic tract. Serotonin
The pedunculopontine reticular nucleus and the adjacent lat- containing neurons (as noradrenergic neurons) play a role in sleep.
eral dorsal tegmental nucleus lie within the tegmentum of the Inhibition of serotonin synthesis or destruction of serotonin con-
pontomesencephalic junction, dorsolateral to and overlapping the taining neurons in the raphe system leads to insomnia.
lateral margin of the superior cerebellar peduncle, between it and The dopaminergic system neurons have a discrete topogra-
the lateral lemniscus. They play roles in arousal and movement. phy and restricted area of terminal distribution, whereas the
The two nuclei belong to a region (locomotor center) from which noradrenergic, adrenergic, and serotonergic neuron systems have
electrical stimulation causes coordinated walking movements. a more diffuse and wide-spread projection.
Neurons of the pedunculopontine nucleus are affected in patients
with progressive supranuclear palsy, a degenerative central nervous
disease. FUNCTIONS
The nucleus basalis of Meynert, located in the basal forebrain,
sends axons to almost the entire cerebral cortex. Degeneration of The reticular formation has somatic motor, somatic sen-
cholinergic neurons in this area is associated with memory de- sory, visceral motor, and arousal and sleep functions.
cline in Alzheimer’s disease.
Somatic Motor Function
Monoaminergic System
Somatic motor function is mediated via reticular connections
Four types of monoamine neurons have been identified within the to motor neurons of the spinal cord and cranial nerve nuclei.
brain stem reticular core: dopaminergic, noradrenergic, adrener- These effects are triggered by activities in the cerebral cortex
gic, and serotonergic. and cerebellum.
Dopaminergic neurons form small clusters at several brain The role of the reticulospinal tracts in control of somatic mo-
loci. Many of these neurons are found in the ventral tegmentum tor activity has been outlined in the chapters on spinal cord and
of the midbrain (ventral tegmental area of Tsai) and the adjacent major motor and sensory pathways. Descending reticulospinal
substantia nigra (pars compacta). Projections of this area follow pathways modify both alpha and gamma motor neuron activity,
three pathways: (1) mesostriatal (nigrostriatal), from the substan- exerting facilitatory as well as inhibitory effects on both reflex and
tia nigra to the striatum (caudate and putamen). Interruption of cortically induced motor activity. In general, the pontine reticu-
this system is associated with Parkinson’s disease. (2) mesolimbic, lar formation exerts facilitatory influences, whereas the medullary
from the ventral tegmental area to limbic nuclei. Overactivity reticular formation exerts inhibitory influences.
of this system is associated with schizophrenic hallucinations. The paramedian pontine reticular formation (PPRF) inte-
(3) mesocortical, from the ventral tegmental area to the prefrontal grates horizontal eye movements through its connections to the
cortex. Lesions in this system are associated with cognitive deficits ipsilateral abducens nucleus and from there via the medial longi-
in Parkinson’s disease. tudinal fasciculus to the contralateral medial rectus subnucleus
402 / CHAPTER 32
of the oculomotor nucleus. A similar group of neurons in the have shown that learning is greatly enhanced during stimulation
rostral midbrain control vertical eye movements. of the reticular activating system. Destruction of this system, on
the other hand, produces a state of somnolence or coma.
Somatic Sensory Function Activity in the ascending reticular activating system is a tonic
one maintained by incoming afferent stimuli. Although the retic-
The reticular formation exerts an effect on the transmission of ular activating system responds in a nonspecific fashion to all
sensory impulses. As in the case of somatic motor function, the incoming sensory stimuli, some stimuli are more effective than
effect of the reticular formation on sensory transmission is trig- others. Auditory stimuli are more effective than visual stimuli.
gered by cortical activity. This effect is both facilitatory and in- Impulses from pain receptors are more effective than those from
hibitory and is exerted on sensory nuclei of the spinal cord and other receptors. Trigeminal stimuli are particularly effective. Ani-
brain stem, including cranial nerve nuclei. Modulation of activ- mals in which the brain stem has been sectioned below the level of
ity in the posterior column nuclei by the reticular formation is the trigeminal nerve in the pons retain the arousal response. How-
one such example. The role of the nucleus raphe magnus of the ever, if a cut is made at the level of the trigeminal nerve, such ani-
medulla oblongata in the inhibition of pain transmission is well mals lose the arousal response and become stuporous.
established. Fibers from the nucleus raphe magnus descend in The convergence of various sensory inputs on the reticular
the brain stem and spinal cord to terminate on the spinal trigem- formation, its multisynaptic connections, and the divergence of
inal nucleus and substantia gelatinosa neurons. Axon terminals its projections to wide areas of the cerebral cortex, make this sys-
liberate serotonin which facilitates enkephalinergic interneurons tem best suited for arousal.
which in turn exerts pre- and postsynaptic inhibition of the no- It should be emphasized, however, that the reticular activa-
ciceptive neurons in these sites. Electrical stimulation of the nu- tion system receives constant feedback from the cerebral cortex
cleus raphe magnus, in animals, produces analgesia. The analge- and the peripheral receptors. These feedback mechanisms help
sia produced by stimulation of the periaqueductal gray is mediated maintain the state of arousal. The depression in the state of
by facilitatory input from the periaqueductal gray to the nucleus consciousness seen in degenerative brain disease is due in part
raphe magnus. to interruption of the feedback from the cortex to the reticular
formation.
Visceral Motor Function The reticular activating system is particularly sensitive to gen-
eral anesthetics and tranquilizing drugs. These drugs may either
Physiologic data suggest the presence of centers in the reticular for- suppress or attenuate transmission in this system, thus produc-
mation for the control and regulation of several visceral functions. ing sleep or tranquilization. They do not, however, suppress trans-
Stimulation of the medial group of reticular nuclei in the mission along the specific lemniscal system.
medulla oblongata elicits an inspiratory response and depressor Interest in the reticular activating system has focused on the
effect on the circulatory system (slowing of the heart rate and re- substrate for selective awareness (how attention is selectively
duction in blood pressure). focused toward one sensory stream to the exclusion of other in-
Stimulation of the lateral group of reticular nuclei elicits the puts). Anatomic and physiologic evidence suggests that the retic-
opposite effect, namely an expiratory response and pressor circu- ular nucleus plays a central role in selective awareness. The retic-
latory effect (acceleration of the heart rate and elevation in blood ular nucleus of the thalamus, activated by volleys ascending
pressure). along thalamocortical axons, in turn projects back upon tha-
A pontine reticular center (pneumotaxic center) which regu- lamic nuclei and the mesencephalic tegmentum, exerting tonic
lates respiratory rhythm has been identified in the area of and/or phasic inhibition of cell groups in the thalamus and mes-
parabrachial–Kölliker-Fuse nuclei located dorsal to the motor encephalic tegmentum. Physiologic studies have demonstrated
nucleus of the trigeminal nerve. Direct connections from the facilitatory influences of the frontal cortex upon units in the
pontine respiratory center to the medullary respiratory centers reticular nucleus of thalamus. Thus, a concept has emerged of a
have been demonstrated. reticularis complex selectively gating interactions between the
specific thalamic nuclei and the cerebral cortex under the control
Arousal and Alertness of the brain stem reticular formation and frontal cortex. This
gating mechanism seems highly selective: depending on the na-
The reticular formation plays a role in arousal and alertness
ture of the alerting stimulus or locus of central stimulation, only
through the ascending reticular activating system (ARAS) which
that portion of the reticular nucleus of thalamus which controls
was originally described in the late 1940s by Morruzi in Italy and
the appropriate thalamic sensory field will open.
Magoun in the USA.
ASCENDING RETICULAR ACTIVATING SLEEP

SYSTEM (ARAS)
Sleep is an altered state of consciousness necessary for the well-
This multisynaptic pathway from the reticular formation to being of the organism. Humans deprived of sleep for long periods
the diencephalon (intralaminar nuclei of thalamus) and subse- of time become emotionally disturbed and may even manifest
quently to the cortex plays a major role in cortical arousal and in psychotic behavior. It is estimated that humans spend approxi-
sharpening the attentiveness of the cortex to incoming sensory mately one-third of their lives asleep.
stimuli. This phenomenon of cortical arousal is associated with a
characteristic electroencephalographic (EEG) pattern consisting Phases and Stages of Sleep
of low voltage, high frequency waves known as a desynchroniza-
tion pattern. There are two recognized phases of sleep: (1) slow wave
Stimulation of the ascending reticular activating system pro- sleep and (2) rapid eye movement (REM) or paradoxical
duces a state of arousal, alertness, and attentiveness. Experiments sleep.
A. SLOW WAVE SLEEP The various phases of sleep (stages I to IV of slow wave sleep
Slow wave sleep is also known as synchronized sleep, light sleep, and REM sleep) follow each other with the same order through-
slow sleep, and non-REM sleep. It constitutes 75% of the sleep- out sleep. The first REM phase occurs about 90 minutes after
ing period in adults and is characterized by the following somatic, sleep onset and lasts about 10 to 15 minutes. Subsequent REM
behavioral, and EEG manifestations: phases recur every 1 to 2 hours.
In general, there is more REM sleep toward the morning and
1. Reduced muscle tone. more of the slow wave sleep early at night. REM sleep consti-
2. Drop in blood pressure, heart rate, and respiratory rate. tutes almost all sleeping time in the fetus and about 50% of
3. Synchronized slow EEG activity of high voltage; hence the sleeping time in the infant. As the brain matures, slow wave sleep
name slow wave sleep. increases, constituting 75% of sleeping time in the adult.
Drugs affect the stages of sleep differentially. Barbiturates and
Slow wave sleep is divided into four stages: alcohol suppress REM sleep but have little effect on stage IV of
Stage I (drowsiness). This stage lasts from one to seven min- non-REM (slow wave) sleep. On the other hand, benzodiazepines
utes. The individual is easily aroused in this stage. (Valium, Librium) suppress stage IV non-REM sleep and have
less effect on REM sleep.
Stage II (light sleep). Arousal in this stage needs more in-
tense stimuli than in Stage I.
Stage III (moderately deep sleep). The EEG in this stage is Sleep and Arousal Mechanisms
characterized by the appearance of slow, high voltage waves.
Sleep is an active process triggered by known brain stem struc-
Stage IV (deep sleep). Arousal from this stage requires strong tures and through known chemical transmitters.
stimuli. Slow activity in the EEG in this stage comprises more The sleep-waking cycle follows a circadian rhythm and is
than 50% of the EEG record. During this stage, blood pres- controlled by a circadian rhythm generator in the suprachias-
sure, pulse rate, respiratory rate and oxygen consumption of matic nucleus of the hypothalamus.
the brain are very low. Over seventy years ago, a Viennese neurologist and neuro-
Sleep walking, bed wetting, night terrors, and seizures are pathologist, von Economo, predicted, based on studies of patients
known to occur in slow wave sleep. suffering of encephalitis lethargica (a viral encephalitis
that caused a profound and prolonged state of sleepi-
B. REM (PARADOXICAL) SLEEP ness), the existence of a sleep-promoting region in the
rostral midbrain and caudal hypothalamus, and a wake-promot-
REM (paradoxical) sleep is also known as desynchronized sleep,
ing area in the posterior hypothalamus.
active sleep, dreaming sleep, fast wave sleep, and deep sleep. It
In the years following the second World War, Moruzzi, in
constitutes 25% of sleeping time in adults and is characterized
Italy, and Magoun (in the USA) described the ascending reticu-
by the following manifestations:
lar activating system (ARAS) that regulates wakefulness. The ba-
1. Marked hypotonia, especially in neck muscles, hence head sic neuronal circuitry of this system was, however, only defined
drop in people entering this state while sitting up in a chair. in the 1980s and early 1990s. Subsequent research on the mech-
2. Increase in blood pressure and heart rate; irregular and rapid anisms of sleep and wakefulness, especially in the last 5 to 7
respiration. years, has confirmed and elaborated on earlier observations made
3. Erection in males. by von Economa and Moruzzi-Magoun as follows:
4. Teeth grinding. 1. It is now established that the ascending reticular activating
5. Dreaming, hence the name dreaming sleep. system and cortical arousal are mediated via two systems
6. Rapid eye movements (50 to 60 movements per min), hence (Figure 32–2)
the name REM sleep. a. A cholinergic system from the pedunculopontine and
7. High voltage potentials in the pons, lateral geniculate nu- laterodorsal tegmental reticular nuclei to several thalam-
cleus, and occipital cortex (PGO for pontogeniculooccipital ic nuclei (intralaminar, relay, reticular) and from there,
spikes). PGO spikes are generated in the pons, propagate via thalamocortical projections, to the cerebral cortex.
rostrally through the lateral geniculate nucleus and other This system is active during wakefulness and REM sleep.
thalamic nuclei to reach the cortex. b. An aminergic system from locus ceruleus (norepineph-
rine), raphe nuclei (serotonin), tuberomammillary nu-
8. Rapid, low voltage, irregular electroencephalographic (EEG) cleus (histamine) directly (without passing through the
activity resembling the waking pattern (desynchronization thalamus) to the cerebral cortex. This system is active
pattern) during wakefulness but not during REM sleep.
9. Increased threshold of arousal, hence deep sleep 2. It has been shown that sleep is induced by activity in the ven-
It is easier to awaken a person from REM sleep than from trolateral preoptic nucleus (of hypothalamus). GABAergic
stage IV slow wave (non-REM) sleep. Anginal pain and cluster (inhibitory) connections have been demonstrated from this
headache (type of vascular headache) are known to occur during hypothalamic nucleus to the arousal system (pedunculopon-
REM sleep. tine, laterodorsal tegmental, locus ceruleus, raphe, and tubero-
The coexistence of rapid, low voltage cortical activity (active mammillary nuclei). It has also been demonstrated that the
EEG state) and increased autonomic activity (heart rate, blood ventrolateral preoptic nucleus receives reciprocal inhibitory
pressure, respiration) in an otherwise motionless individual in input from aminergic arousal system nuclei (tuberomammil-
deep sleep justifies calling this stage the paradoxical stage of sleep. lary, locus ceruleus, raphe) (Figure 32–3).
During sleep, one alternates between slow wave sleep lasting 3. Aminergic nuclei (tuberomammillary, locus ceruleus, raphe)
90 to 100 minutes and 10 to 30 minutes of REM sleep. can thus promote wakefulness via direct excitation of cortex
404 / CHAPTER 32
CEREBRAL CORTEX
Thalamocortical Pathways
THALAMUS
Intralaminar Relay Reticular

Nuclei Nuclei Nucleus
Histamine
Tuberomamillary
Nucleus
Acetylcholine
Pathway
Locus Norepinephrine
Ceruleus
Serotonin Laterodorsal Tegmental Nucleus
Raphe
Nuclei
Direct Arousal System Indirect Arousal System Figure 32–2. Schematic diagram of the
Active Only During Active During Both direct (aminergic) and indirect (cholinergic)
Wakefulness Wakefulness and REM Sleep cortical arousal system.
(1b above) and inhibition of sleep-promoting neurons in the sleep via inhibition of locus ceruleus, raphe, pedunculopon-
ventrolateral preoptic nucleus (Figure 32–4). tine and laterodorsal tegmental nuclei (Figure 32–5).
4. REM and non-REM sleep are regulated by two different 5. In 1998, two groups of investigators identified a family of
populations of neurons in the ventrolateral preoptic nucleus. peptide neurotransmitters in the lateral hypothalamus. These
Core neurons within the nucleus regulate non-REM sleep are now known as orexins or hypocretins. Neurons con-
via inhibition of the tuberomammillary nucleus. Extended taining orexins (hypocretins) were found to increase ac-
neurons of the ventrolateral preoptic nucleus regulate REM tivity of aminergic neurons of the ascending arousal sys-
SLEEP PROMOTING WAKEFULNESS

REGION PROMOTING
SYSTEM
Aminergic
Tuberomamillary Nucleus
GABA/GALANINE Raphe Nuclei
Locus Ceruleus
–
Ventrolateral Preoptic
Nucleus
HISTAMINE/SEROTONIN/NOREPINEPHRINE
–
Cholinergic
GABA Pedunculopontine nucleus

Laterodorsal Tegmental Nucleus
GALANINE –
Figure 32–3. Schematic diagram of the connections between the sleep promoting ventrolateral preoptic nucleus
and the nuclei (aminergic and cholinergic) of the ascending arousal system. , inhibition.
CORTICAL AROUSAL
Cerebral Cortex
––
SLEEP-PROMOTING
REGION
Ventrolateral Preoptic
Nucleus
–
Tuberomamillary Nucleus
Figure 32–4. Schematic diagram showing how Locus Ceruleus
aminergic brain stem nuclei promote wakeful- Raphe Nuclei
ness via facilitation of the cerebral cortex and in-
hibition of sleep-promoting neurons. , facilita- AMINERGIC AROUSAL
tion; , inhibition. NUCLEI
tem. Orexin (hypocretin) neurons are predominantly wake- Recent imaging studies have shed more light on sleep mecha-
active, although some fire also during REM sleep. Destruction nisms. Positron emission tomography (PET) scans have shown
of orexin (hypocretin) neurons is associated with narcolepsy. that during slow wave sleep, the most deactivated areas are the
upper brain stem, thalamic nuclei, basal forebrain, and the basal
In retrospect, the hypersomnolence described by von Economo ganglia. In the cortex, the least active areas are the association
in encephalitis lethargica is now believed to be due to lesion in cortices of the frontal and parietal lobes. In REM sleep, in com-
the ascending arousal system at the midbrain-diencephalic junc- parison, there is significant activation of the ponto-mesencephalic
tion. The insomnia of von Economo is now believed to be due to area and thalamic nuclei. The cortical areas activated are the lim-
lesion in the ventrolateral preoptic nucleus. Von Economo’s pre- bic cortex (amygdala, hippocampus, orbitofrontal cortex, and
diction that narcolepsy is caused by lesion of the posterior dien- anterior cingulate cortex). These imaging studies confirm the ex-
cephalon is now believed to be related to loss of orexin (hypocre- istence of different patterns of neuronal activities in slow wave
tin) neurons in that area. and REM sleep.
VENTROLATERAL PREOPTIC
NUCLEUS
Cluster (Core) Extended

Subnucleus Subnucleus
Tuberomamillary Locus Ceruleus

Nucleus Raphe Nuclei
Laterodorsal Tegmental Nucleus

two neuronal systems that regulate REM and NON-REM REM SLEEP
non-REM sleep. SLEEP
406 / CHAPTER 32
TERMINOLOGY von Economo, Baron Konstantin (1876–1931). Austrian neu-

rologist and neuropathologist who, among other contributions,
Alzheimer’s disease. A degenerative disease of the brain formerly published on May 10, 1917, a paper about encephalitis lethargica.
known as senile dementia. Characterized by memory loss, corti- Jean-Rene Cruchet, French pathologist and pediatrician had re-
cal atrophy, senile plaques, and neurofibrillary tangles. Described ported 13 days earlier (April 27, 1917) 40 cases of the same dis-
by Alois Alzheimer, a German neuropsychiatrist, in 1907. ease. Cruchet claimed precedence but van Bogaert, Belgian neu-
Cuneiform nucleus (Latin cuneus, “wedge”). The cuneiform rologist, adjudicated in favor of von Economo on the basis that
nucleus is wedge shaped. he had defined the condition as a single disease which Cruchet
Encephalitis lethargica (von Economo’s disease). An epidemic had not.
encephalitis that followed the influenza pandemic of 1915–1924.
Although described by Jean-Rene Cruchet two weeks before von SUGGESTED READINGS
Economo, the latter got credit because he had defined the condi-
tion as a single disease which Cruchet had not. Autret A et al: Sleep and brain lesions: A critical review of the literature and ad-
ditional new cases. Neurophysiol Clin 2001; 31:356–375.
Locus ceruleus (Latin, “place, dark blue”). The pigmented Bystrzycka EK: Afferent projections to the dorsal and ventral respiratory nuclei
noradrenergic nucleus in the rostral pons is dark blue in sections. in the medulla oblongata of the cat studied by the horseradish peroxidase
Meynert, Theodor Hermann (1833–1892). Austrian psychia- technique. Brain Res 1980; 185:59–66.
trist and neurologist. Son of a historian father and an opera singer Corvaja N: The lateral reticular nucleus in the cat. I. An experimental anatom-
mother. He studied the anatomy of the cortex and brain stem in ical study of its spinal and supraspinal afferent connections. Neuroscience
detail. Among others, he described the Meynert’s decussation 1977; 2:537–553.
(dorsal tegmental decussation of midbrain) and Meynert’s fasci- Evans BM: What does brain damage tell us about the mechanisms of sleep?
J Roy Soc Med 2002; 95:591–597.
culus (habenulo-interpeduncular tract). He described the nucleus
Gottesmann C: GABA mechanisms and sleep. Neuroscience 2002; 111:231–
basalis in the 1872 book, Handbook of Human and Animal 239.
Histology. The term nucleus basalis of Meynert was coined by
Hobson JA, Scheibel AB: The brain stem core: Sensorimotor integration and
Albert Kölliker in 1896. behavioral state control. Neurosci Res Program Bull 1980; 18, No. 1.
Narcolepsy (Greek, “numbness, seizure”). A syndrome of ex- Hobson, JA, Pace-Schott EF: The cognitive neuroscience of sleep: Neuronal
cessive and irresistible urge of day sleeping. The condition was so systems, consciousness and learning. Nat Rev Neurosci 2002; 3:679–693.
named by Gélineau, who gave the first modern account of the Jessop EG: Sleep. J Public Health Med 2001; 23:89–90.
disorder in 1880. The American general “Stonewall” Jackson is Kastin AJ et al: DSIP—More than a sleep peptide? Trends Neurosci 1980; 3:
believed to have had narcolepsy. 163–165.
Parabrachial nucleus (Greek para, “beside”). The parabrachial Künzle M: Autoradiographic tracing of the cerebellar projections from the
nucleus is beside the brachium conjunctivum (superior cerebel- lateral reticular nucleus in the cat. Exp Brain Res 1975; 22:255–266.
lar peduncle). LeBon E et al: Correlations using NREM-REM sleep cycle frequency support
distinct regulation mechanisms for REM and NREM sleep. J Appl Physiol
Paradoxical sleep. Rapid eye movement sleep. So named because 2002; 93:141–146.
electroencephalography shows a wakefulness pattern when the Maquet P: Brain mechanisms of sleep: Contribution of neuroimaging tech-
person is asleep. niques. J Psychopharmacol 1999; 13:S25–S28.
Parkinson’s disease. A degenerative disease of the brain charac- Mendelson WB: Neurotransmitters and sleep. J Clin Psychiatry 2001; 62
terized by postural tremor and rigidity from loss of dopaminergic (Suppl 10):5–8.
neurons in the substantia nigra. Described by James Parkinson, Moore RY: The reticular formation: Monoamine neuron systems. In: Hobson
an English physician, in 1817 under the name of shaking palsy. JA, Brazier MAB (eds): The reticular formation revisited: Specifying func-
tion for a nonspecific system. International Brain Research Organization
Parvocellular nucleus (Latin parvus, “small”; cellula, “cell”). Monograph Series, Vol. 6, pp. 67–81, Raven Press, 1980.
So named because it is composed of small cells. Salin-Pascual R et al: Hypothalamic regulation of sleep. Neuropsychopharmacol-
Raphe (Greek raphe, “a seam or suture”). This word was used ogy 2001; 25 (Suppl 5):S21–S27.
by Homer in the Odyssey in connection with the sewing of har- Saper CB et al: The sleep switch: Hypothalamic control of sleep and wakeful-
nesses for horses. The term is used in anatomy to refer to a seam- ness. Trends Neurosci 2001; 24:726–731.
like formation that suggests that adjacent structures have been Scheibel AB: Anatomical and physiological substrates of arousal: A view from
sewn together. The midline reticular nuclei are called the raphe the bridge. In: Hobson JA, Brazier MAB (eds): The reticular formation
nuclei. revisited: Specifying function for a nonspecific system. International Brain
Research Organization Monograph Series, Vol. 6, pp. 55–66, Raven Press,
von Bekhterev, Vladimir Mikhailovich (1857–1927). Russian 1980.
neuropathologist and psychiatrist. He published many papers on Zemlan FP, Pfaff DW: Topographical organization in medullary reticulospinal
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Reticular Formation,Wakefulness, 33
and Sleep: Clinical Correlates
Parasomnias (Dyssomnias) Central Sleep Apnea

Sleep Walking (Somnambulism) Ondine’s Curse
Night Terror (Pavor Nocturnus) Fatal Familial Insomnia
Nocturnal Groaning (Catathrenia) Coma
REM Intrusion Akinetic Mutism (Cairn’s Syndrome)
Narcolepsy (Gélineau’s Syndrome) Locked-In Syndrome
Kleine-Levin Syndrome (Kleine-Levin-Critchley Brain Death
Syndrome, Hypersomnia-Bulimia)
KEY CONCEPTS
Parasomnias are a group of sleep disorders that include Ondine’s curse is a sleep disorder characterized by cessa-
sleep walking, night terror, nocturnal groaning, and REM tion of respiration in sleep due to failure of automatic
intrusions. The first three are slow wave (non-REM) sleep respiration.
disorders and the fourth (REM intrusions) is a REM sleep
Fatal familial insomnia is an inherited fatal sleep disorder
disorder.
due to point mutation in the prion protein gene.
Narcolepsy is a sleep disorder characterized by recurrent
Coma is a state of loss of consciousness in which motor
brief attacks of irresistible daytime sleep. It is due to loss of
and sensory responses of the individual are impaired.
orexin (hypocretin) neurons in the hypothalamus.
Akinetic mutism is an altered state of consciousness in
Kleine-Levin syndrome is a sleep disorder characterized
which the patient appears awake but is unable to com-
by recurrent attacks of excessive somnolence alternating
municate.
with voracious appetite and sexual disinhibition when
awake. Locked-in syndrome is an altered state of consciousness
in which consciousness is preserved but is inexpressible.
Central sleep apnea is a sleep disorder characterized by
Patients communicate by eye blinking.
apneic spells in sleep. The congenital form is evident dur-
ing the first few days of life, the acquired form is associ- Brain death is a state of irreversible brain damage in which
ated usually with bilateral medullary infarcts. normal cortical and brain stem functions are absent.
PARASOMNIAS (DYSSOMNIAS) Sleep Walking (Somnambulism)

Parasomnias are a group of sleep disorders characterized by un- This parasomnia occurs in the first one to three hours after going
usual motor behaviors, autonomic behaviors, or both, occurring to sleep. The walking is not recalled. Patients may sit or stand in
in slow wave (non-REM) sleep. They include sleep walking, bed, fumble with clothing without walking, or get up from bed
night terror, and nocturnal groaning, among others. and walk, open doors, or descend stairs. They usually follow in-
These disorders are thought to be due to impaired abil- structions to return to bed. Behaviors associated with sleep walk-
ity to arouse fully from slow wave sleep. They usually oc- ing include eating, leaving the house through a door or window,
cur in the first third of the sleep cycle. violent behavior, and homicide. Sleep walking is more common
407
408 / CHAPTER 33
in children than adults. In children, it may be associated with KLEINE-LEVIN SYNDROME

enuresis or night terrors. (KLEINE-LEVIN-CRITCHLEY SYNDROME,
HYPERSOMNIA-BULIMIA)
Night Terror (Pavor Nocturnus)
This is a rare syndrome that presents a fascinating complexity of
As in sleep walking, this parasomnia occurs in the first third neurologic and psychiatric symptoms. Although a syndrome of
of nocturnal sleep [stages 3 to 4 of slow wave (non-REM) episodic hypersomnolence and morbid hunger was de-
sleep], and is more common in children. Episodes consist of scribed by Antimoff in 1898, credit for describing this
agitation, apparent fear, screaming, a number of autonomic syndrome is given to Willi Kleine, a German psychiatrist
behaviors (tachycardia, dilated pupil, sweating), attempts to who described the complete clinical picture in 1925 and to Max
leave the bed or room, and inconsolability. The episode lasts a Levin, an American psychiatrist who, in 1929, described a pa-
few (2 to 10) minutes at the end of which patients become tient with extreme hunger and sleep attacks. The syndrome,
quiet and return to deep sleep. The patient has no recall for as currently defined, refers to a recurrent constellation of symp-
the episode. toms, lasting days to weeks, which includes episodes of excessive
somnolence, voracious appetite, and sexual disinhibition. When
awake, affected patients may exhibit irritability, lack of energy,
Nocturnal Groaning (Catathrenia) and apathy and may appear confused or exhibit manic depressive
This is an uncommon parasomnia characterized by expiratory symptoms. Although adolescent males are more frequently af-
groaning during slow wave (non-REM) sleep as well as REM fected, reports of the syndrome in females are available. Etiology
sleep. Patients are unaware of the behavior which causes concern is uncertain, but is believed to be due to a hypothalamic-pitu-
to bed partners. itary dysfunction.
CENTRAL SLEEP APNEA

REM Intrusion
Central sleep apnea refers to dysfunction of central control of
A more serious parasomnia in REM sleep in which the person breathing. Normal breathing requires the normal functioning of
will enact a dream. Affected individuals can hurt their bed part- a number of central and peripheral nervous system
ner or themselves as they are enacting the dream content. structures. Lesions in any of these structures (chemo-
receptors, sensory pathways, brain stem centers, motor
pathways, or effector muscles) may lead to respiratory abnormal-
NARCOLEPSY (GÉLINEAU’S SYNDROME) ity during sleep.
The term narcolepsy was coined by Jean Baptiste Gélineau, a Central sleep apnea may be congenital or acquired. Congenital
French neuropsychiatrist, in 1880 to describe a condition char- central sleep apnea is usually seen in the first few days of life and
acterized by recurrent, brief attacks of irresistible daytime sleep. is manifested by apnea at onset of sleep. Acquired central sleep
He recognized the association of narcolepsy with loss of muscle apnea is usually associated with bilateral vascular lesions in the
tone subsequently called cataplexy. posterolateral medulla.
The combination of excessive daytime sleepiness (narcolepsy) Sleep related apneic events have also been reported in en-
and spells of sudden loss of muscle tone (cataplexy) provoked cephalitis, neuromuscular junction disorders (myasthenia gravis),
by emotional triggers (laughter, surprise, fright, excite- primary muscle disorders (muscular dystrophy), and in patients
ment, and rage) has puzzled neuroscientists for more who undergo bilateral cervical cordotomy for relief of intractable
than a century. In 1960, it was recognized that narco- cancer pain.
lepsy was associated with premature onset of REM sleep. In
1999, a major breakthrough occurred relating narcolepsy to a ONDINE’S CURSE
decrease in a peptide, orexin (hypocretin), elaborated in the
perifornical area of the lateral hypothalamus. It is now believed This is a rare neurologic syndrome characterized by ces-
that the sleepiness of narcolepsy reflects lack of hypocretin ex- sations of respiration in sleep due to failure of the auto-
citatory effects on histaminergic (tuberomamillary nucleus), matic respiratory center in the medulla oblongata.
dopaminergic (ventral tegmental area and substantia nigra), and Failure of automatic respiration results from the loss of vagal and
cholinergic (pedunculopontine and laterodorsal tegmental nu- chemotactic inputs to the carbon dioxide receptors in the
clei) components of the ascending reticular activating system medulla removing the drive to breathe. The first distinct case was
(ARAS) which promote arousal. According to this hypothesis, reported in 1955 by Ratto et al. in a patient with a stroke. The
cataplexy results from loss of hypocretin excitation of serotoner- syndrome was misnamed Ondine’s curse by Severinghaus and
gic (raphe nuclei) and noradrenergic (locus ceruleus) pathways Mitchell in 1962 in reference to a water nymph in a 1939 novel
responsible for REM sleep inhibition. In addition to excessive (Ondine) by the French playwright Jean Giraudoux who intro-
daytime sleepiness and spells of loss of muscle tone, narcoleptics duced the loss of all automatic functions (not just breathing) as
characteristically show vivid perceptual (auditory or visual) ex- the manner of the nymph’s human lover’s death. The word
periences at sleep onset (hypnagogic hallucinations) or upon “ondine” is the French word for mermaid and not the name of
awakening from sleep (hypnopompic hallucinations), and tran- any specific person. The legend that gave rise to the name
sient (few seconds), generalized inability to move or speak dur- “Ondine’s curse” is an old Germanic myth of a water nymph
ing transition between sleep and wakefulness (sleep paralysis). (“undine” in German) that falls in love with and marries a human
Hypnagogic hallucinations and sleep paralysis were added to and makes a pact with the mermaid king that if her lover were
the clinical picture of narcolepsy-cataplexy by Yoss and Daly ever unfaithful, he would forfeit his life and she would return to
in 1957. the sea. The term Ondine’s curse is thus a misnomer. Mermaids
RETICULAR FORMATION, WAKEFULNESS, AND SLEEP: CLINICAL CORRELATES / 409
loved their human lovers; there was never a curse. The prevalent inexpressible. Patients are able to communicate by eye
narrative of a nymph punishing her unfaithful mortal husband blinking signifying yes or no. The patients are otherwise
by depriving him of the ability to breathe while asleep is unlikely. mute and akinetic. Only eye opening, vertical eye move-
ments and convergence remain. The syndrome was first de-
scribed by Darelles in 1875 in a patient with occlusion of the
FATAL FAMILIAL INSOMNIA basilar artery. The syndrome has been described most frequently
This is a rare disorder, inherited as an autosomal domi- with bilateral infarcts in the basis pontis but also in infarcts in
nant trait genetically linked to a point mutation at both cerebral peduncles. Structures usually involved when the le-
codon 178 of the prion protein gene. Affected patients sion is in the basis pontis include corticospinal tracts (immobil-
display intractable insomnia, alterations in the sleep-wake cycle, ity) corticobulbar fibers (loss of facial movements and speech
attention deficit, sympathetic hyperactivity and gait abnormal- articulation) and abducens nerve (loss of horizontal eye move-
ity. Non-REM sleep is characteristically absent. The disease pro- ments). Synonyms include pseudocoma, de-efferented state, ven-
gresses rapidly to stupor, coma, and death within two years. tral pontine syndrome, Monte Cristo syndrome (Alexandre
Impairment of sleep and autonomic functions has been attrib- Dumas’ novel, The Count of Monte Cristo, in which M. Noirtier
uted to damage of the dorsomedial and anterior thalamic nuclei, communicated only by eye blinks), ponto-pseudo-coma, and
cingulate gyrus, and orbitofrontal gyrus leading to interruption pontine disconnection syndrome.
of thalamocortical limbic circuits involved in the sleep-wake cy-
cle. Enhanced serotonergic neurotransmission has been impli- BRAIN DEATH
cated in some symptoms of this disorder.
Brain death is a state of irreversible brain damage so severe that
normal respiration and cardiovascular function can no longer be
COMA maintained. Such patients are in deep coma, remain unrespon-
Coma is a state of loss of consciousness characterized by impair- sive to external stimuli, and their respiration and cardio-
ment in the motor and sensory responses of the individual. A pa- vascular functions are maintained by external means
tient in coma cannot vocalize, has no spontaneous eye (respirators, pressor drugs, etc.). In modern clinical
movements, and responds reflexly or not at all to painful medicine, cessation of life is equated with brain death rather
stimuli. The electroencephalogram is characterized by than with cessation of heart beat.
slow activity in the delta range (about 3 cycles per second). Several criteria have to be present before a state of brain death
There are grades of loss of consciousness. These vary from a is declared. These criteria include the following.
state of lethargy (also called obtundation) in which wakefulness 1. Unresponsiveness to external stimuli
is barely maintained (drowsiness), responses to stimuli are slug- 2. Absence of spontaneous breathing
gish or delayed, and vocalization is slow, slurred, and sponta- 3. Dilated fixed pupils
neous, to a state of stupor (semicoma) in which there are some
spontaneous eye movements, motor responses only to painful 4. Absence of brain stem reflexes (corneal, gag, vestibuloocular)
stimuli, and no spontaneous vocalization. 5. No recognizable reversible cause for the coma
Coma can result from different causes. These include diseases of 6. Flat electroencephalogram (absence of electrical activity)
the central nervous system (infection, tumor, trauma, hemorrhage, 7. Nonfilling of cerebral vessels in arteriography or radioiso-
thrombosis, etc.), metabolic disorders (acidosis, hypoglycemia, tope imaging
etc.), and drug overdosage (barbiturates, tranquilizers, etc.).
In coma secondary to central nervous system affection, in- Comatose patients who fulfill the above criteria are consid-
volvement of the brain stem reticular formation (ascending retic- ered dead; heroic measures to save life are futile.
ular activating system) is pivotal in the genesis of coma. Coma,
however, can result from extensive cortical disease without sig- TERMINOLOGY
nificant involvement of the brain stem reticular formation. Cairns, Sir Hugh William Bell (1896–1952). Australian neu-
rosurgeon who described the persistent vegetative state (akinetic
AKINETIC MUTISM (CAIRN’S SYNDROME) mutism) in 1941. Cairns suggested that the syndrome reflects
cortical dysfunction secondary to a diencephalic lesion.
This is an altered state of consciousness, first described by Cairns Cataplexy (Greek, “to strike down”). A REM sleep disorder in
in 1941, in which the patient appears awake and main- which the patient loses muscle power suddenly in response to emo-
tains a sleep-wake cycle, but does not react to environ- tional triggers. The term was first applied by Henneberg in 1916.
mental stimuli and is unable to communicate in any way.
Synonyms include persistent vegetative state and coma vigil. The Gélineau, Jean-Baptiste-Edouard (1828–1906). French sur-
condition is characterized by hypersomnolence or coma, some geon and neuropsychiatrist who described narcolepsy (Gélineau
retention of eye movements, and loss of REM sleep and of syndrome) in 1880. He invented and marketed his own pills for
arousal mechanisms. Lesions producing akinetic mutism have epilepsy.
been reported in the pons, basal ganglia, thalamus, anterior cin- Kleine, Willi. German neuropsychiatrist who, in 1925, pub-
gulate gyrus, and septal area. lished a series of cases of periodic somnolence and morbid
hunger, the Kleine-Levin syndrome.
LOCKED-IN SYNDROME Levin, Max. American neurologist who, in 1929, reported one
case of periodic somnolence and extreme hunger, and in 1936
This term was introduced by Plum and Posner to describe pa- described the features of the Kleine-Levin syndrome.
tients who are completely immobile, unable to speak, and inca- Ondine. French for mermaid or water nymph. The title of a
pable of facial movements. Consciousness is preserved though novel written in 1939 by the French playwright Jean Giraudoux.
410 / CHAPTER 33
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Control of Posture and Movement 34
Major Players in Control of Posture and Movement Neuromuscular Junction (Motor End Plate) Syndrome
Sequence of Events in Control of Posture Primary Muscle Disorders
and Movement Suprasegmental Motor Control
Functional Anatomy of Motor Control Brain Stem
Segmental Motor Control Cerebellum
Stretch (Myotatic) Reflex Basal Ganglia
Segmental Motor Disorders Cerebral Cortex
Lower Motor Neuron Syndrome Locomotion
Peripheral Nerve Syndrome Overview of Control of Posture and Movement
KEY CONCEPTS
Neural control of posture and movement is the result of Decorticate states are associated with lesions rostral to
an orderly sequence of events involving the cerebral cor- the midbrain that disconnect the whole brain stem from
tex, basal ganglia, cerebellum, brain stem, spinal cord, the cerebral cortex.
peripheral nerves, neuromuscular junction, and skeletal
Disorders of the cerebellum are associated with volitional
muscle.
tremor, ataxia, dyssynergia, dysmetria, and difficulty per-
Segmental control of movement and posture is based on forming alternate motion rate.
a number of spinal reflexes, the myotatic (stretch) reflex
Disorders of basal ganglia are associated with hyperki-
being one of them.
netic (e.g., chorea) and hypokinetic (e.g., Parkinson’s dis-
Disorders of segmental motor control include: (1) the ease) syndromes.
lower motor neuron syndrome exemplified by motor neu-
Lesions in the cerebral cortex or in its output (cortico-
ron disease (Werdnig-Hoffmann, amyotrophic lateral
spinal tract) are associated with the upper motor neuron
sclerosis) and poliomyelitis; (2) peripheral nerve disorders
syndrome characterized by paresis or paralysis, spasticity,
(acquired and inherited peripheral neuropathies); (3) neu-
hyperactive reflexes, Babinski sign, and clonus.
romuscular junction disorders (myasthenia gravis); and
(4) primary muscle disorders (muscular dystrophy and Locomotion is the outcome of a series of events involving
various myopathies). segmental and suprasegmental areas.
Decerebrate states in human are associated with lesions
in the midbrain caudal to the red nucleus.
411
412 / CHAPTER 34
The story of the neural control of posture and movement is one 12. Neuromuscular junction
of the most fascinating chapters in the study of the nervous sys- 13. Skeletal muscle
tem. A proper understanding of neural control is essential not
only to the comprehension of the mechanisms underlying nor- Lesions in one or more of these areas result in characteristic clin-
mal posture and movement but also to an appreciation of func- ical syndromes.
tional disturbances in those who have developed a disease of the
system of control and who therefore have lost the ability either to SEQUENCE OF EVENTS IN CONTROL OF
execute or to coordinate movement. POSTURE AND MOVEMENT (Figure 34–1)
MAJOR PLAYERS IN CONTROL OF POSTURE The process of control of posture and movement is initiated in
AND MOVEMENT the sensory association cortices of the parietal, temporal, and oc-
cipital lobes. These areas project to the frontal association cortex
Several areas in the central and peripheral nervous sys- by means of the long association fiber bundles (1 in Figure 34–
tems participate in the planning and execution of pos- 1). The frontal association cortex [areas of the frontal lobe rostral
ture and movement. These are: to the premotor cortex (Brodmann area 6) and frontal eye field
(Brodmann area 8)] is the seat of thought processes and internal
1. The frontal association cortex commands that culminate in a motor act. The command to
2. Primary motor cortex (precentral gyrus) move is transmitted from the frontal association cortex to the
cerebellum via the corticopontocerebellar pathway (2 in Figure
3. Premotor cortex
34–1) and to the basal ganglia via corticostriate pathways (3 in
4. Basal ganglia Figure 34–1). The cerebellum and basal ganglia exert a modulat-
5. Cerebellum ing effect on the motor command. The cerebellum and basal
6. Thalamus (primarily ventrolateral and ventral anterior nuclei) ganglia project to the thalamus. Cerebellar output to the thala-
7. Red nucleus mus (4 in Figure 34–1) targets primarily the ventrolateral tha-
8. Reticular formation lamic nucleus and reaches there via the dentatothalamic path-
way, in the brachium conjunctivum. Basal ganglia output to the
9. Vestibular nuclei thalamus (5 in Figure 34–1) targets primarily the ventral anterior
10. Alpha and gamma spinal motor neurons thalamic nucleus and reaches there via the ansa lenticularis, the
11. Peripheral nerves lenticular fasciculus, and the thalamic fasciculus. The internal
Sensory Association Frontal Association Cortex Motor and Premotor

1
Cortices Thought Processes Cortex
Parietal, Temporal, Occipital Internal Command Executor
3
2 Basal Ganglia 6 7
Modulator 5
8
Thalamus
Cerebellum
4
Modulator
1. Long Association Fibers Brain Stem
2. Corticopontocerebellar Fibers Vestibular
3. Corticostriate Fibers Reticular
4. Dentatothalamic Fibers Rubral
5. Ansa Lenticularis, Lenticular
Fasciculus, Thalamic Fasciculus 9
6. Thalamocortical Fibers
7. Corticobulbar, Corticorubral, Spinal Cord
Corticoreticular Fibers Motor Neurons
8. Corticospinal Fibers
10
9. Rubrospinal, Reticulospinal,
Vestibulospinal Fibers
10. Peripheral Nerve Muscle
Figure 34–1. Schematic diagram showing the sequence of events in the control of posture and movement.
CONTROL OF POSTURE AND MOVEMENT / 413
command to movement generated in the frontal association

cortex—now modulated by input from the cerebellum, basal
ganglia, and thalamus—finally reaches the primary motor cortex
(area 4 of Brodmann) and premotor cortex (area 6 of Brodmann)
via thalamocortical projections (6 in Figure 34–1) in the internal
capsule. The command for movement is now transmitted to the
spinal cord motor neurons (alpha and gamma), indirectly via
brain stem motor centers (7 and 9 in Figure 34–1) or directly via
the corticospinal (pyramidal) system (8 in Figure 34–1). Motor
signals from the spinal cord reach skeletal muscles via peripheral
nerves (10 in Figure 34–1) and the neuromuscular junction to
effect the command to move.
Positron emission tomography scans in humans have shown
that the dorsolateral prefrontal cortex (frontal association cor-
tex), as well as the caudate nucleus and anterior putamen, is ac-
tivated during learning of new movement. During the selection
of movement, activation is noted in the premotor cortex (area 6
of Brodmann), and midputamen. During automatic (over-
learned) movement, activation is noted in the sensory motor
cortex and posterior putamen. Movement under sensory guid-
ance activates the cerebellum. These activations suggest that the
basal ganglia are concerned with selection of movement or the
selection of the appropriate muscles to perform a movement se-
lected by cortical areas, whereas the cerebellum (neocerebellum)
is involved in monitoring and optimizing movement using sen-
sory feedback.
FUNCTIONAL ANATOMY
OF MOTOR CONTROL
In studying the motor system, one is inclined to overemphasize
the role of one component of the system, the corticospinal
tract. Although no one denies the importance of this tract, one
should not understate the roles of less voluminous but other-
wise important tracts, such as the reticulospinal, vestibulo-
spinal, and rubrospinal. In the same vein, one should not un- Figure 34–2. Schematic diagram showing the segmental re-
derestimate the role of modifying inputs from the cerebellum flex arc at the spinal cord level and suprasegmental structures
and basal ganglia. Last but not least, one should add to the that are involved in posture and movement.
schema the input into this system from peripheral organs, the
muscle fibers without which movement could not be executed
(Figure 34–2).
It is obvious from the above that neural control of posture The reflexes elicited in a spinal animal include the following:
and movement is multifaceted. In the final analysis, all levels of
control work in unison to produce coordinated and integrated 1. Stretch (myotatic) reflex
movement. For didactic purposes, however, the individual con- 2. Inverse myotatic reflex
tributions of each of the different levels of control of posture and 3. Flexor reflex
movement will be dealt with separately. 4. Crossed extension reflex
SEGMENTAL MOTOR CONTROL Stretch (Myotatic) Reflex (see Figure 3–25)

The spinal cord contains, in its anterior horn, motor neurons Stretching a muscle (by tapping its tendon) activates the muscle
with axons that supply somatic body musculature. Activation of spindle of the intrafusal muscle fiber (primary annulospiral end-
groups of motor neurons gives rise to contraction of ings). Impulses from the activated muscle spindle activate mono-
groups of skeletal muscle and hence movement. Motor synaptically via Ia fibers the homonymous (corresponding, ipsi-
neurons of the spinal cord are activated by (1) impulses lateral) alpha motor neurons in the anterior horn of the spinal
from the periphery as part of reflex mechanisms and (2) impulses cord. This type of excitation is known as autogenic. Impulses
from higher levels (suprasegmental), with descending fibers that traveling via the axons of such alpha motor neurons then reach
exert a modifying influence on reflex mechanisms. the stretched skeletal muscle and result in contraction of the
To study the role of spinal reflex mechanisms in posture and muscle. Ia afferents also make direct monosynaptic excitatory
movement, experimentalists resorted to artificial preparations connections with alpha motor neurons, which innervate muscles
in which the spinal cord was disconnected from higher levels that are synergistic in action to the muscle from which the Ia
by transection. Such an animal preparation is known as a spinal fiber originated. In addition, the activity in the Ia fibers disynap-
animal. tically inhibits the motor neurons that supply the antagonistic
414 / CHAPTER 34
muscle (reciprocal inhibition). This obviously facilitates contrac-

tion of the homonymous muscle.
In humans, myotatic stretch reflexes can be elicited in the fol-
lowing sites and are part of a neurologic examination.
Biceps jerk: This reflex is elicited by tapping the tendon of
(1)
the biceps muscle. The biceps muscle will contract, resulting
in flexion at the elbow.
Triceps jerk: This reflex is elicited by tapping the tendon of I
the triceps muscle. As a result, the triceps will contract and
extend the elbow joint.
Radial jerk: Tapping the tendon of the brachioradialis mus-
cle at the wrist will contract the brachioradialis muscle and
flex the wrist joint.
Knee jerk (quadriceps myotatic reflex): This reflex is elicited
by tapping the tendon of the quadriceps femoris muscle at
the patella. The quadriceps muscle contraction will extend
the knee joint.
Ankle jerk: Tapping the tendon of the gastrocnemius muscle Figure 34–3. Schematic diagram of the components of the
at the Achilles tendon will contract the gastrocnemius and gamma loop. Activation of gamma motor neurons (1) results in
plantar flex the ankle. contraction of the poles of the muscle spindle and activation
of the annulospiral ending. Impulses travel via the Ia afferents
Pathology anywhere in the path of the reflex arc from the
(2) and activate alpha motor neurons. Axons (3) of the alpha mo-
receptor to the effector site will interfere with these reflexes.
Reduction or absence of myotatic reflexes reflects pathology in tor neurons contract the skeletal muscle fiber.
the receptor site (the muscle spindle), the afferent or efferent
nerve fibers (peripheral neuropathy), or the central neurons (an-
terior horn cells), as in poliomyelitis.
Myotatic reflexes may be exaggerated (hyperactive) in diseases and maintains the tension of the spindle necessary for posture.
that interfere with the descending modifying influences. Such a The gamma neuron is activated by descending influences from
condition occurs in upper motor neuron disorders (e.g., stroke, the cortex, cerebellum, etc. This maintains activity in the muscle
multiple sclerosis, spinal cord tumors). spindle and secures constant firing of Ia nerve fibers and the al-
The described technique of eliciting a muscle contraction, pha motor neuron. As a result, the muscle contraction necessary
namely stretching the muscle by tapping its tendon, is the clini- for standing posture is maintained.
cal method. There is, however, another way by which a muscle The inverse myotatic reflex, the flexor reflex, and the crossed
can be made to contract; this is by eliciting a contraction of the extension reflexes are discussed in Chapter 3.
muscle spindle without stretching the muscle. Activity in gamma
neurons within the anterior horn of the spinal cord sends im-
pulses via the gamma efferent fibers to both poles of the muscle SEGMENTAL MOTOR DISORDERS
spindle. Contraction of the poles of the muscle spindle activates
the primary (annulospiral) endings. Consequently, impulses Lower Motor Neuron Syndrome
travel via the Ia nerve fibers to activate monosynaptically alpha
motor neurons, resulting in contraction of the extrafusal muscle This syndrome is characterized by loss or diminution of muscle
fibers. This type of muscle contraction is elicited through activity movement (paralysis or paresis of muscle), absence or
in the gamma loop system (Figure 34–3). marked decrease in myotatic (stretch) reflexes (areflexia
Thus, under normal conditions, the cerebral cortex can trig- or hyporeflexia), decrease in muscle tone (hypotonia),
ger muscle contraction and initiate postural changes and move- muscle atrophy, and spontaneous muscle activity at rest (fibrilla-
ment through two mechanisms: by activating the alpha motor tions, fasciculations). The conglomerate of these signs consti-
neuron directly or by activating the alpha motor neuron indi- tutes the lower motor neuron syndrome and is the result of loss
rectly via the gamma system loop. of spinal and cranial nerve motor neurons. The lower motor
Voluntary, precise, and sensitive movements are executed by neuron syndrome is seen in motor neuron disease (Werdnig-
the simultaneous activation of both systems. In general, activa- Hoffmann disease, amyotrophic lateral sclerosis, Lou Gehrig dis-
tion of the alpha system predominates when a quick response is ease) and in poliomyelitis.
desired, whereas activation of the gamma system predominates
when a smooth and precise movement is desired. The two sys- Peripheral Nerve Syndrome
tems are complementary.
The importance of, and rationale for, the described role of the Peripheral nerve disorders may be acquired (inflammatory de-
gamma loop can be illustrated in the mechanism of standing myelinating polyneuropathy, Guillain-Barré-Strohl syndrome) or
posture. When one stands, the stretch of the quadriceps tendon inherited (hereditary sensory motor neuropathies). The classical
activates the muscle spindle and the alpha motor neuron, thus syndrome consists of muscle paresis or paralysis (more marked in
producing muscle contraction. As soon as muscle contraction distal muscles), hyporeflexia or areflexia, muscle hypotonia, and
occurs, tension on the muscle spindle ceases, the rate of dis- muscle atrophy—all signs of lower motor neuron syndrome. In
charge on the alpha motor neuron diminishes, and subsequently contrast to the lower motor neuron syndrome, peripheral nerve
the muscle relaxes. The gamma system corrects this, however, syndrome is associated with sensory deficit.
Neuromuscular Junction (Motor End Plate)

Syndrome
Neuromuscular junction syndromes are characterized by fluctuat-
ing muscle weakness. Muscle weakness usually appears with use
of muscle and disappears with rest. The fluctuating muscle weak-
ness may be regional (extraocular or facial muscles) or general-
ized. Muscle tone and myotatic reflexes are usually normal. There
is no muscle atrophy or sensory deficit. Neuromuscular junction
syndrome is seen in myasthenia gravis, a disorder due to abnor-
malities in the acetylcholine receptor on the muscle membrane.
Primary Muscle Disorders

Primary muscle disorders are characterized by muscle weakness
and hypotonia. Muscle weakness is more marked in proximal
muscles (shoulder and hip girdles) than distal muscles. Myotatic
reflexes remain intact until late in the disease, when there is mus-
cle atrophy. There is no sensory deficit. Primary muscle disorders
may be acquired (myositis) or hereditary (muscular dystrophy,
congenital myopathy).
SUPRASEGMENTAL MOTOR CONTROL

Brain Stem
Several descending tracts from the brain stem contribute to pos-
ture and movement. The most important of these are the rubro-
spinal, vestibulospinal, and reticulospinal tracts. Collectively, Figure 34–4. Schematic diagram showing the mechanism of
they contribute to the recovery of stereotyped movements in decerebrate rigidity.
proximal muscle groups and to the spasticity noted following a
cerebral stroke.
The contribution of brain stem structures to posture and an extensor posture of the neck, trunk, and limbs, with hyper-
movement can be studied in two types of experimental prepara- pronation of the arms. The decerebrate state was first described
tions, the decerebrate state and the midbrain animal. These two in 1898 by Sherrington.
experimental states resemble those in humans with similar lesions.
B. DECORTICATE STATE
A. DECEREBRATE STATE In decorticate states, the lesion is rostral to the midbrain, thus dis-
In the decerebrate state, the disconnection between lower and connecting the whole brain stem from the cerebral cor-
upper levels for control of posture and movement is made at the tex, basal ganglia, and the diencephalon (Figure 34–5).
midcollicular level, between the superior and inferior In the decorticate state, the head, trunk and lower ex-
colliculi. In addition to the spinal cord, the medulla ob- tremities are extended while the upper extremities are flexed at
longata and pons are intact. The facilitatory part of the the elbow. The lesion in decorticate states leaves the rubrospinal
reticular formation at the level of the pons is released from the tract intact. The rubrospinal tract primarily facilitates flexor mus-
inhibitory effect of the caudate nucleus and cerebral cortex. The cles, mostly in the upper extremities, hence the flexion of the up-
reticular formation thus released tonically activates gamma mo- per extremities. The extensor hypertonus in the lower extremities
tor neurons in the spinal cord (Figure 34–4). The activated is explained on the same basis as that in the decerebrate state.
gamma motor neurons stimulate the annulospiral endings of the
intrafusal muscle fibers through the gamma loop. Activation of Cerebellum
the latter generates impulses via the Ia nerve fibers, which dis-
charge the alpha motor neurons monosynaptically (myotatic re- The cerebellum is intimately related to all regions involved in
flex). As a result, skeletal muscles are tonically activated and motor activity. Thus, it is related to the peripheral organ (mus-
rigidity sets in. Decerebrate rigidity involves predominantly anti- cle) as well as to all the central levels concerned with movement
gravity (extensor) muscles. Animals in which the extensor mus- (spinal cord, brain stem, thalamus, cerebral cortex). It is perfectly
cles are the antigravity muscles maintain a rigid posture, holding suited, therefore, to play the role of coordinator and integrator of
all four extremities in the extended position while the head and motor activity. The cerebellum plays this role in both voluntary
tail are maximally extended backward. Although the reticu- and involuntary motor activities. Although it is generally ac-
lospinal system plays the major role in decerebrate rigidity, the knowledged that the cerebellum exerts its effect on movement
vestibulospinal system is also important. The lateral vestibular that has already been initiated elsewhere (i.e., cerebral cortex),
nucleus has a powerful descending excitatory influence on alpha evidence suggests that the cerebellum is also involved in the
and gamma extensor motor neurons. Ablation of the lateral planning and initiation of movement as well as in the moment-
vestibular nucleus in a decerebrate preparation greatly reduces to-moment control of movement. Electrophysiologic recordings
the rigidity. In humans, lesions in the midbrain caudal to the red from the cerebellum have shown that the Purkinje neurons dis-
nucleus result in a decerebrate state in which the patient assumes charge prior to the start of movement. It is generally agreed that
416 / CHAPTER 34
Also important in the smooth execution of movement is the

force of movement. In diseases of the cerebellum, the normal
steady increase and decrease in the force of movement are af-
fected. Such patients, therefore, execute movement in a jerky, ir-
regular manner. This phenomenon is known as dyssynergia. In
clinical situations, dyssynergia can be manifested in the irregular,
jerky movements of the patient’s finger as it is moving toward the
finger of the examiner.
The defective feedback mechanisms for the control of the
force and timing of movement in cerebellar disease are responsi-
ble for volitional tremor. This type of tremor is characteristically
absent when the limb is at rest but becomes manifest when the
patient attempts to move the limb.
In addition to its role in control of movement, the cerebellum
plays an equally important role in maintenance of body equilib-
rium. Lesions in the flocculonodular lobe of the cerebellum
(archicerebellum) are associated with disturbances in body equi-
librium. Such patients manifest unsteadiness of gait (ataxia).
This unsteadiness results from the inability of the diseased cere-
bellum to detect changes in direction of motion as signaled by
the semicircular canals and to institute corrective action to main-
tain a steady gait.
Basal Ganglia
Although the key role of the basal ganglia in motor control is
undisputed, the exact mechanism by which the basal ganglia exert
this control remains incompletely explored despite the volumi-
nous experimental work and published literature on the subject.
Like the cerebellum, the basal ganglia exert a modifying and
coordinating effect on already initiated movement. As for the
cerebellum, evidence suggests that the basal ganglia may play a
role in the initiation of motor activity. Recordings of unit activ-
Figure 34–5. Schematic diagram showing the site of lesions in

the decerebrate (1) and decorticate (2) states.
Cerebral cortex
the cerebellum plays a role in regulating the following parame-

ters of voluntary movement: rate, range, force, and direction.
The cerebellum is able to execute this role via the multitude of
feedback mechanisms that exist between it and the vari-
ous motor centers (Figure 34–6). Through these feedback
circuits, the cerebellum can detect errors in movement Thalamus
and institute corrective measures. If a moving limb appears to be
moving too fast (rate), to the degree of overshooting the intended
target, the cerebellum will detect this and institute inhibitory im-
Cerebellum
pulses through the cerebral cortex to slow down the movement
and prevent the overshoot (range). In cerebellar disease, this ability
to control the rate and range of movement is defective. As a result,
the patient tends to move the limb farther than intended. This is Brain stem
referred to as dysmetria. In clinical practice, this phenomenon can
be shown by asking the patient to touch a fingertip to the tip of
the nose. A patient with cerebellar disease tends to overshoot the
nose and reach the cheek or ear (“past pointing”).
In the smooth execution of movement, proper timing of the
initiation and termination of sequential steps in movement is ex-
tremely important. A delay in the initiation of each successive
movement will lead to a failure of proper progression. In clinical Spinal cord Muscle
medicine, this is demonstrated by asking the patient to perform
repetitive movements with the hand or tongue. Failure to do this Figure 34–6. Schematic diagram showing the feedback mech-
in orderly succession is referred to as dysdiadochokinesia. anisms between the cerebellum and other motor centers.
Disorders of movement in basal ganglia dysfunction are gen-

Cerebral cortex
erally of two types, hyperkinetic and hypokinetic. The hyper-
kinetic variety includes such involuntary movements as
chorea, athetosis, hemiballismus, and the rhythmic
tremor of Parkinson’s disease. The hypokinetic variety is
exemplified by the akinesia of Parkinson’s disease. The descrip-
tion of each of these involuntary movements is detailed Chapter
13. In contrast to cerebellar tremor, the involuntary movements
Thalamus Basal ganglia
of basal ganglia disorders are manifest in repose or in the absence
of motion; hence, they are known as rest tremor or postural
tremor.
Although complete correlation of the type of involuntary
movement with a specific nucleus of the basal ganglia has not
been achieved, it is generally accepted that hemiballism is associ-
ated with lesions in the subthalamic nucleus, parkinsonism with
lesions of the nigrostriatal axis, and chorea with caudate nucleus
Brain stem lesions.
Cerebral Cortex
The role of the cerebral cortex in control of movement assumes
more importance as one ascends in the phylogenetic tree. The
areas of the cerebral cortex that are involved in the control of
movement and posture have been described previously in this
Spinal cord
chapter and in the chapter on the cerebral cortex. They include
Figure 34–7. Schematic diagram showing the feedback mech- the primary motor cortex, the premotor area, the supplementary
anisms between the basal ganglia and other motor centers. motor cortex, the frontal association cortex, and part of the pri-
mary sensory cortex.
The cerebral cortex exerts its effects on movement and pos-
ture by two pathways (Figure 34–8): (1) the direct, oligosynaptic
pathway (direct corticospinal), and (2) the indirect, multisynap-
ity in the globus pallidus and putamen have revealed activity in tic pathway (indirect corticospinal).
their neurons prior to the onset of movement.
Both anatomic and physiologic data suggest that the basal
ganglia exert their modifying effect on movement through two
systems (Figure 34–7):
Cerebral cortex
1. A feedback circuit from the motor cortex to the basal gan-
glia, thalamus, and back to the motor cortex and spinal
cord
2. A descending pathway from the basal ganglia to motor cen- Indirect pathway
ters of the brain stem and from there to the spinal cord
It is evident that the basal ganglia do not exert direct influ-
ence on motor activity in the spinal cord. Direct pathway
The thalamus is the central meeting place for inputs from the
cerebellum and basal ganglia. The significance of this in the co-
ordination of cerebellar and basal ganglia roles in motor activity
is obvious. The relief of basal ganglia and cerebellar involuntary
movement by lesions in the thalamus attests to this important
Brain stem
focal role of the thalamus.
Most knowledge about the role of basal ganglia in motor
control has been derived from clinical material. Unfortunately,
most of the clinical syndromes of basal ganglia diseases cannot
be reproduced in experimental animals, a fact that is at the core
of the scarcity of information about the exact pathophysiologic
mechanisms.
In humans, disturbances in basal ganglia function are mani-
fested as disturbances in muscle tone and involuntary movements.
Different nuclei of the basal ganglia may have varying effects
on muscle tone, whereas the sum total effect of the basal ganglia
is inhibitory on muscle tone. This effect is mediated via the retic- Spinal cord
ular formation of the brain stem. Thus, in lesions of basal gan-
glia, the tone of muscle is increased, leading to a state of rigidity, Figure 34–8. Schematic diagram showing the direct and indi-
as in Parkinson’s disease. rect corticospinal pathways.
418 / CHAPTER 34
The role of the direct pathway is mainly in the control of

rapid, voluntary, and fine skilled movements. The role of the in- Cerebral cortex
direct pathway is in the control of slow postural type move-
ments. The two pathways have been referred to as the pyramidal
and extrapyramidal pathways, respectively. The pyramidal path-
way exerts a facilitatory effect on motor neurons, whereas the
sum total effect of the extrapyramidal pathway is inhibitory.
In the execution of voluntary motor activity, the descending
influences from the cortex and subcortical structures via these Basal ganglia Cerebellum
two pathways most likely act simultaneously on alpha and gamma
motor neurons of the spinal cord. Alpha activation predominates
in the case of rapid movements, however, whereas gamma activa-
tion predominates in the case of slow, graduated movements.
Selective lesions in the two pathways in humans are difficult
to produce, and both pathways are usually affected together to
varying degrees. Lesions of the motor areas of the cortex or of
their axons along the neuraxis give rise generally to a clinical pic-
Spinal cord
ture known collectively as upper motor neuron syn-
drome. It is usually seen in stroke patients and is charac-
terized by the following signs: Figure 34–9. Schematic diagram showing the feedback cir-
cuits between the cortex, cerebellum, and basal ganglia.
1. Paresis (weakness) or paralysis (loss of movement), particu-
larly affecting distal muscles controlling fine skilled move-
ments
2. Hyperactive deep tendon reflexes (hyperreflexia) The present concept suggests that locomotion is not re-
3. Babinski sign flexive in nature but is generated by neurons located ex-
clusively in the spinal cord. Although, according to this
4. Spasticity concept, afferent inputs are not essential, they are nevertheless
5. Clonus important in grading the individual component movements.
Careful observation and analysis of these different signs, how- The spinal cord neurons concerned with programming loco-
ever, allow their division into two groups. motion not only produce alternate flexor and extensor activa-
Immediately after onset of the lesion, there is paresis or paral- tion, they also correctly time the contraction of appropriate mus-
ysis, hypotonia, and reduction or absence of deep tendon reflexes cles for normal locomotion. Such neurons have been termed
(hyporeflexia or areflexia). These early signs are attributable to pattern generators or neural oscillators. It has been shown that
the affection of the pyramidal pathway. there are individual pattern generators for each limb; when all
Later on the following signs appear: (1) spasticity, (2) hyper- limbs are active, however, as in normal walking, the pattern gen-
active deep tendon reflexes (hyperreflexia), (3) Babinski sign, erators of the different limbs are coupled to one another.
and (4) clonus. These later signs are attributed to the affection of As in posture and movement, spinal mechanisms for locomo-
the extrapyramidal pathway. The mechanism of the Babinski tion are under the influence of modulatory descending inputs
sign, however, remains uncertain. It is believed to be due to in- from supraspinal centers. Rubrospinal, vestibulospinal, and retic-
volvement of the supplementary motor area or its outflow fibers. ulospinal tracts are rhythmically active in phase with locomotor
The further course of this clinical picture is characterized by movements. In addition, locomotion can be triggered by stimu-
the reappearance of gross postural movements, usually in proxi- lation of the pedunculopontine nucleus in rostral pons and cau-
mal muscles. This return of postural function is attributed to the dal mesencephalon (locomotor center). The pedunculopontine
part of the extrapyramidal areas or pathways not involved in the nucleus receives facilitatory input from the cerebral cortex and
lesion. inhibitory input from the basal ganglia. It projects to the med-
The cerebral cortex has long been recognized as the initiator ullary reticular formation concerned with locomotion. It is be-
and planner of movement. Electrophysiologic studies confirm lieved that the pedunculopontine nucleus serves a relay function
this concept and show that the motor neurons in the cerebral between the cerebral cortex and spinal cord for interlimb coordi-
cortex begin to discharge prior to the onset of movement. The nation in locomotion.
cerebral cortex also plays a central role in the execution of appro- Both dorsal and ventral spinocerebellar tract neurons in the
priate movement. It can accomplish this by virtue of the feed- spinal cord are active during locomotion. The two tracts convey
back it receives from the cerebellum and basal ganglia, which different information to the cerebellum: the dorsal tract ordinar-
supply the cerebral cortex with continuous information about ily informs the cerebellum about the state of muscle activity in
the progress of movement so that corrective action can be taken. the periphery, whereas the ventral tract conveys information
In turn, the cerebral cortex, by virtue of collaterals to the cere- about the active processes within the spinal cord and pattern
bellum and basal ganglia, keeps these two structures informed of generation for locomotion.
ongoing activity (Figure 34–9).
OVERVIEW OF CONTROL OF POSTURE
LOCOMOTION AND MOVEMENT
The older concept of locomotion as a set of chain reflexes in Clearly, normal posture and movement are the products of inter-
which the sensory input from a given part of a step cycle triggers action among a number of neural structures. In the final analysis,
the next part of the cycle by reflex action has been challenged. spinal motor neurons have to be activated to move the muscles.
The spinal motor neurons are in turn controlled by supraseg- spinal cord (as in stroke, hemorrhage, tumor, trauma)—pro-
mental influences that originate from cortical and subcortical duce the upper motor neuron syndrome characterized by
motor centers. The latter are also under cortical control. Super- paresis, spasticity, hyperactive myotatic reflexes, abnormal
imposed on this vertical axis (represented by the direct and indi- reflexes (Babinski reflex), and clonus.
rect corticospinal pathways) are modifying influences from the 2. Lesions of the cerebellum produce a disorganized and erratic
basal ganglia and the cerebellum (Figure 34–10). type of movement characterized by volitional tremor on
Lesions along the vertical axis (whether in the cerebral cortex, movement, ataxia of gait, dysmetria, disturbances in alter-
corticospinal tract, or spinal cord) will produce a partial or total nate motion rate (dysdiadochokinesia), and dyssynergia.
loss of movement. Lesions of the modifying motor centers (basal 3. Lesions of the basal ganglia produce involuntary movements
ganglia, cerebellum), on the other hand, will result in disor- in repose, as seen in the tremor of Parkinson’s disease,
ganized, abnormal movement. The disorganized movement of chorea, athetosis, and hemiballismus. Such lesions also pro-
cerebellar lesions is manifest on volition, whereas that of basal duce rigidity of muscles and, in some cases, reduction in
ganglia lesions is manifest in repose. movement (hypokinesia).
Figure 34–10 is a simplified schematic diagram showing the
loci of pathology commonly encountered in clinical practice and 4. Lesions of the motor neurons in the spinal cord (as in po-
listing the major motor deficits accruing from such lesions. liomyelitis and motor neuron disease) produce paresis or
paralysis of all muscles supplied by the affected spinal cord
1. Lesions of the corticospinal tract anywhere along its path— segments. Because of the interruption of the reflex arc, the
from its origin in the cerebral cortex to its termination in the muscles are hypotonic and myotatic reflexes are either re-
duced or lost. Loss of the trophic influence of motor neu-
rons on the muscle fibers leads to atrophy of these fibers,
which also exhibit spontaneous movements at rest (fibrilla-
tion) attributed to denervation hypersensitivity at the mo-
tor end plate.
5. Lesions interrupting the axons of motor neurons to the mus-
cle (as in peripheral neuropathy) produce weakness (paresis)
or paralysis in the group of muscles supplied by the affected
nerve or nerves. Because such a lesion will interrupt the re-
flex arc of myotatic reflexes, such reflexes will be depressed
(hyporeflexia) or lost (areflexia) and the muscles will be hy-
potonic. Because most peripheral nerves are mixed (contain-
ing both motor and sensory fibers), such lesions will also be
manifested by sensory loss.
6. Lesions in the neuromuscular junction, as in myasthenia
gravis, result in fluctuating muscle weakness precipitated by
use of muscle and reversed by rest.
7. Lesions in the muscle, as occur in muscular dystrophy, result
in muscle weakness and hypotonia.
TERMINOLOGY
Barré, J. A. (1880–1967). French physician who, with George
Guillain and Andre Strohl, described the Guillain-Barré-Strohl
syndrome.
Gehrig, Lou. Renowned first base player for the New York
Yankees from 1923–1939. Had a lifetime batting average of .340
with a record 23 grand slams. Died of amyotrophic lateral scle-
rosis. Other famous personalities afflicted with the disease in-
clude actor David Niven, senator Jacob Javits, heavyweight boxer
Ezzard Charles, physicist Stephen Hawking, photographer Eliot
Porter, and composer Dmitri Shostakovich.
Guillain, George (1876–1961). French physician who, in col-
laboration with J. A. Barré and Andre Strohl, described acute in-
flammatory demyelinating polyneuropathy (the Guillain-Barré-
Strohl syndrome, later called Guillain-Barré syndrome) in World
War I soldiers.
Hoffmann, Johann (1857–1919). German neurologist who
described Werdnig-Hoffmann disease in articles published in
1893, 1897, and 1900 and acknowledged the previous descrip-
Figure 34–10. Simplified diagram showing the motor deficits tion of the disease.
that result from lesions in different loci concerned with move- Sherrington, Sir Charles (1857–1952). English physician and
ment and posture. physiologist. Nobel laureate for medicine in 1932. Coined the
420 / CHAPTER 34
term synapse in 1897 and introduced the terms exteroception, Grillner S, Shik ML: On the descending control of the lumbosacral spinal cord
interoception, and nociception. He described the decerebrate from the “mesencephalic locomotor region.” Acta Physiol Scand 1973;
87:320–333.
state and contributed significantly to knowledge of neuro-
physiology. Henneman E: Motor functions of the brain stem and basal ganglia. In
Mountcastle VB (ed): Medical Physiology, 14th ed, vol 1. Mosby, 1980:
Strohl, Andre (b. 1887). French physician who contributed to 787–812.
the original description of Guillain-Barré-Strohl syndrome but Henneman E: Organization of the spinal cord and its reflexes. In Mountcastle
whose name was dropped from subsequent publications. VB (ed): Medical Physiology, 14th ed, vol 1. Mosby, 1980:762–786.
Werdnig, Guido (1844–1919). Austrian neurologist who de- Jueptner M, Weiller C: A review of differences between basal ganglia and cere-
scribed motor neuron disease (Werdnig-Hoffmann) in a series of bellar control of movements as revealed by functional imaging studies.
articles between 1891 and 1894. Brain 1998; 121:1437–1449.
Lance JW: The control of muscle tone, reflexes, and movement. Robert
Wartenberg Lecture. Neurology 1980; 30:1303–1313.
Mettler FA et al: The extrapyramidal system: An experimental demonstration
SUGGESTED READINGS of function. Arch Neurol Psychiatry 1939; 41:984–995.
Nutt JG et al: Human walking and higher-level gait disorders, particularly in
Arshavsky YI et al: Recordings of neurons of the dorsal spinocerebellar tract the elderly. Neurology 1993; 43:268–279.
during evoked locomotion. Brain Res 1972; 43:272–275.
Pryse-Phillips W: Companion to Clinical Neurology. Oxford University Press,
Asanuma H: Cerebral cortical control of movement. Physiologist 1973; 16: 2003.
143–166. Reeves AG: The initiation, elaborations and maintenance of movement: An
Evarts EV et al: Central control of movements. Neurosci Res Progr Bull 1971; overview. In Mosenthal WT (ed): Textbook of Neuroanatomy. Parthenon,
9:1–170. 1995:329–334.
Approach to a Patient with 35

a Neurologic Disorder
The Where and What Tempo of Disease

The Art and Challenges of History Taking Duration of Symptoms
The Neurologic Examination Past Medical History
The Equipment Identification of Site of Disorder
The Examination Cerebral Cortex
Neurologic Examination of Infants and Small Children Brain Stem
Developmental Reflexes Cerebellum
The Neurologic Diagnosis, The First Impression Basal Ganglia
Considerations That Influence Diagnosis Spinal Cord
Age Peripheral Nerve
Gender Neuromuscular Junction
Ethnicity Muscle
Socioeconomic Status
KEY CONCEPTS
The approach to a patient with a neurologic disorder Certain developmental reflexes are elicited only in
aims to define the site (where) and the type (what) of the infancy.
lesion.
Careful observation of the behavior of the patient in the
History taking in neurology is both an art and a chal- waiting room, of his/her gait and facial features may yield
lenge; 90% of diagnosis relies on accurate history taking. important information for the diagnosis.
Neurologic examination should be comprehensive with In making a diagnosis, consideration should be given to
tests for cortical function, cranial nerves, motor function, the age, gender, ethnicity, socioeconomic status, tempo of
coordination, sensory function and reflexes. the disease, duration of symptoms, and medical history.
Neurologic examination of infants and small children re- Familiarity with symptoms and signs associated with spe-
quires patience, persistence, and familiarity with develop- cific regions of the central and peripheral nervous system
mental milestones. are useful at defining the site of the lesion.
A major objective in learning functional neuroanatomy is the lo- THE WHERE AND WHAT
calization of neurological disorders. Among the different medical
subspecialties, neurology lends itself best to correlation of symp- Whatever approach the healthcare professional uses should an-
toms and signs with structure and function. swer two questions:
The approach to a patient with a neurological problem varies 1. Where is the lesion?
from one healthcare professional to the other. With experience,
each healthcare professional develops his or her own personal ap- 2. What is the lesion?
proach. All, however, adhere to a standard format by which all es- Neurological disorders may be localized to one or more of the
sential information is obtained to arrive at the proper diagnosis. following sites: cerebral hemisphere, cerebellum, basal ganglia,
421
422 / CHAPTER 35
brain stem, spinal cord, peripheral nerve, neuromuscular junc- suffers from episodes of loss of consciousness, in patients with
tion, or skeletal muscle. Each of these sites has characteristic memory defect or mental change, and when there is a need to
symptoms and signs that help answer the question of “where is obtain information about other family members.
the lesion?” As important as eliciting a reliable history is the accurate
In attempting to answer the question of “what is the lesion?”, recording of the history. The record should be clear, complete,
consideration is given to the following etiologies of disease: con- and reflect the patient’s own narrative.
genital, traumatic, infectious, metabolic, toxic, vascular, neoplas-
tic, degenerative, and idiopathic. THE NEUROLOGIC EXAMINATION
In addressing the questions of “where is the lesion?” and
“what is the lesion?” the “where,” in general, precedes the “what.” The Equipment
In some instances, however, the sequence is reversed as occurs in
a patient presenting with sudden onset of loss of speech (aphasia) Besides the patient, the following items are needed for a thor-
and hemiplegia. In such a patient, the diagnosis of stroke (the ough neurological examination:
what) is presumed. The location (the where) is then induced from 1. Examination couch
findings on the neurologic examination. 2. Stethoscope
3. Penlight
THE ART AND CHALLENGES 4. Tuning fork
OF HISTORY TAKING 5. Safety pin
History taking in medicine in general, and in neurology in par- 6. Soft tissue paper
ticular, is extremely important. It is estimated that 90% of neu- 7. Test tubes with hot and cold water for thermal testing
rologic diagnosis depends on the patient’s medical his- 8. Test tube with coffee for testing of smell
tory. The remaining 10% is derived from the neurologic 9. Two point discriminator
examination and laboratory tests. A doctor who does 10. Percussion hammer
not know how to take a history, and a patient who cannot give
one are in danger of giving and receiving bad treatment. 11. Ophthalmoscope
The use of modern technology is no substitute for a good his- 12. Visual acuity card
tory. History taking is a dynamic process in which the seasoned 13. Tongue blades
health professional frequently alters the direction and depth of 14. Measuring tape
questioning to elicit specific information useful in arriving at the
proper diagnosis. The Examination
History taking is an art and a challenge. Seasoned historians
master the art of subtle direction of a conversation with the The purpose of the neurologic examination is to test the struc-
patient, and succeed in the challenging task of eliciting history ture and function of different regions of the nervous system. It
from a poor observer, an uneducated person, or from a person includes assessment of the level of consciousness, exami-
who enjoys twisting the meaning of things. nation of higher cortical functions, cranial nerves, motor
In attempting to obtain a history, the healthcare professional function, coordination, sensory function, and reflexes.
follows a plan of inquiry about symptoms that includes the fol- There are as many ways of performing a neurologic examination
lowing features: as there are physicians performing it.
1. Date of onset A. CORTICAL FUNCTION
2. Character and severity
1. Level of consciousness. The level of alertness of the patient
3. Location and extension (alert and oriented, hyperalert, sleepy, lethargic, stuporous,
4. Time relationship comatose, etc.) should be assessed.
5. Associated complaints 2. Higher cortical function. Examination of higher brain func-
6. Aggravating and alleviating factors tion should include assessment of the following:
7. Previous treatments and their effect a. General information. This refers to general knowledge
8. Progress, remissions, and exacerbations possessed by most people such as the name of the
President, famous people, capitals of countries, current
In eliciting a history, it is important for the healthcare profes- events, etc.
sionals to exclude irrelevant information, and to arrive at their b. Orientation to time (day, month, year), place, and
own opinion. Some patients delight in providing inaccurate in- person.
formation about hospitals they have been to, doctors they have
seen, and treatment ordered. c. Memory for recent and remote events such as birth and
In eliciting a history, it is important to clarify the intended wedding dates, names and ages of children and close rel-
meaning of terms used by the patient. The term “giddiness” or atives, and details of recent events.
“dizziness” used by a patient may refer to lightheadedness, ver- d. Language. This includes assessment of expression, com-
tigo, postural instability, ataxia, disturbance of vision, nausea, or prehension, fluency, and prosody of spoken language,
epileptic convulsion. Similarly, the term “blackout” may refer to repetition, ability to read, write, recognize, and name fa-
loss of consciousness, loss of vision, loss of memory, or loss of miliar objects.
confidence. e. Calculation. This is assessed by ability of the patient to
Interviewing patient’s relatives is a desirable exercise and be- count from 1–20 forward and backward, serial sevens
comes obligatory when the patient is a child, when the patient (counting from 100 backwards in increments of seven),
APPROACH TO A PATIENT WITH A NEUROLOGIC DISORDER / 423
multiplication and division of single numbers. The ex- Table 35–1. Symptoms and Signs of Cranial Nerve Lesions
tent of these tests varies with the educational level of the
patient. Cranial nerve Symptoms and signs
f. Retention and repetition of digits in natural or reverse
I. Olfactory Anosmia
order (usually seven forward and five backward).
II. Optic Decreased visual acuity
g. Judgment. This is tested by asking the patient to inter- Abnormal pupillary light response
pret the meaning of simple proverbs or the meaning of a III. Oculomotor Diplopia
story. Dilated, unresponsive pupil
h. Mood. The degree of anxiety, apathy, elation, depres- Ptosis
sion, etc. Eye deviation down and out
i. Sensory interpretation. Stereognosis, spatial orientation, IV. Trochlear Diplopia
graphesthesia. V. Trigeminal Decreased facial sensations
Decreased corneal reflex
Weak masseter muscle
B. CRANIAL NERVES VI. Abducens Diplopia
A thorough examination of cranial nerve function should in- Decreased eye abduction
clude evaluation of the following functions. The order of testing VII. Facial Decrease strength in muscles of facial
of these functions varies between examiners. expression
Decrease in taste sensation
1. Smell (CN I). Tested by using nonirritating familiar odors
VIII. Auditory-vestibular Deafness
such as coffee, peppermint, menthol, etc. Vertigo
2. Visual acuity (CN II). Tested by use of Snellen chart or vi- IX. Glossopharyngeal Dysarthria
sual acuity card. Dysphagia
3. Visual Field (CN II). Tested by the confrontation technique Decreased gag reflex
or perimetry. X. Vagus Dysarthria
4. Pupillary response to light and accommodation (CN II, III). Dysphagia
Tested by flashing light on one pupil and observing the Decreased gag reflex
Decreased palatal elevation
response of both pupils (light response); and by looking at a
XI. Accessory Decreased strength in neck turning
near object (accommodation response). and shoulder shrug
5. Extraocular movements in the horizontal and vertical planes XII. Hypoglossal Dysarthria
(CN III, IV, VI). The patient is asked to move his eyes later- Dysphagia
ally, upward and downward. Tongue atrophy
6. Facial sensations (sensory root CN V). Tested by using a pin Decreased tongue movement
or a piece of cotton on the face and anterior scalp. Deviation of protruded tongue
7. Corneal reflex (CN V, VII). Tested by gently touching the
cornea with a wisp of cotton.
8. Forceful jaw deviation to one side (motor root CN V),
pterygoid muscle.
9. Teeth clenching (motor root, CN V), masseter muscle.
10. Facial symmetry (CN VII). Tested by asking the patient to 2. Muscle tone. Resistance of the limb to passive movement.
smile, whistle, pucker lips, show teeth, close eyes, and wrin- 3. Muscle bulk.
kle forehead. 4. Muscle strength (hopping, squatting, walking on heels and
11. Taste (CN VII, IX, X). Tested by applying solutions of sugar, tiptoes, testing of individual muscle groups). Muscle strength
vinegar, saline, and quinine to tongue. is graded on a scale of 0 to 5 where 5 denotes normal strength;
12. Hearing (CN VIII). Tested by use of vibrating tuning fork in 4, movement against gravity and resistance; 3, movement
front and on a bony prominence behind the ear. against gravity but not resistance; 2, movement only with
13. Palatal elevation (CN IX, X). gravity eliminated; 1, flicker or trace of contraction; and 0,
no contraction.
14. Gag reflex (CN IX, X). Tested by touching the pharynx by a
tongue blade. D. MOTOR COORDINATION
15. Shoulder shrug against resistance (CN XI). Examination of motor coordination consists primarily of evalua-
16. Head and neck turning against resistance (CN XI). tion of cerebellar and basal ganglia functions. It includes:
17. Tongue mass and movement (CN XII) 1. Steadiness of gait and posture.
Common symptoms and signs noted in lesions of each of the 2. Tandem gait. Walking heel-to-toe down a line on the floor.
cranial nerves are listed in Table 35–1. 3. Rapid alternate movement.
4. Finger to nose to finger test. Patient to rapidly touch nose
C. MOTOR FUNCTION with the point of forefinger and then the examiner’s finger.
Examination of motor function should include evaluation of the 5. Heel to knee to shin test. Running the heel carefully up and
following: down the opposite shin.
1. Gait and stance (posture, balance, arm swing, and leg move- 6. Finger tapping. Approximating the pulp of the thumb to the
ment). pad of each finger in succession rapidly and accurately.
424 / CHAPTER 35
E. SENSORY FUNCTION Thirteen different methods of eliciting the Babinski sign have
Examination of sensory function is the most subjective and been described with varying degrees of positive response:
requires patience, determination, and a thorough knowledge of 1. Gonda-Allen sign, elicited by forceful downward stretching
sensory patterns to perform adequately. It requires utmost coop- or snapping of the distal phalanx of the second or fourth toe.
eration from the patient, and hence is least reliable in children. It 2. Allen-Cleckley sign, elicited by sharp upward flick and sud-
should include evaluation of the following sensory modalities: den release of the second toe or pressure over the ball of
1. Vibration sense, by placing the vibrating tuning fork over that toe.
bony prominences in the upper and lower extremities. 3. Chaddock reflex (lateral malleolar sign) elicited by scratch-
2. Joint position sense, by asking the patient to determine the ing the skin below the lateral malleolus from behind for-
position of toes and fingers when moved passively by the ward. Described in 1911 by Charles Gilbert Chaddock who
examiner. claimed that it has greater sensitivity than the original
3. Pain, by applying the tip of a pin to the tested body part. Babinski sign. The reversed Chaddock sign is elicited by
scratching the skin from the front backward.
4. Temperature, by applying tubes containing cold and warm
water to the tested body parts. 4. Cornell sign, elicited by scratching the inner side of the dor-
sum of foot.
5. Light touch, by touching the tested part of the body by a
piece of cotton. 5. Oppenheim reflex, elicited by heavy pressure with thumb
and index finger to the anterior surface of the tibia, over the
6. Two point discrimination, by the ability of the patient to
shin, from knee to ankle.
recognize two stimuli applied simultaneously to the tested
body parts. The distance between the two stimuli varies in 6. Bing sign, elicited by pricking the dorsum of foot with a pin.
different body parts (0.3 to 0.6 cm over finger tips, 1.5 to 7. Schaffer sign, elicited by pinching the Achilles tendon. This
2 cm over the soles of feet and palms of hands. method was described by Babinski one year before Schaffer’s
report of 1899.
The Romberg test is particularly useful in evaluating poste-
rior column disorders but not cerebellar disorders. The test as- 8. Moniz sign, elicited by passive plantar flexion of the ankle.
sesses the ability of the patient to maintain upright posture while 9. Strümpell sign, elicited by forceful pressure by the finger and
standing on a narrow base with eyes closed. A patient with pos- thumb down the anterior tibial spine.
terior column disease will sway and may fall. 10. Throckmorton sign, elicited by tapping over the dorsum of
the first metatarsophalangeal joint just medial to the exten-
sor hallucis longus tendon.
F. REFLEXES 11. Gordon sign, elicited by squeezing the calf muscles.
1. Deep tendon (myotatic) reflexes. These include the follow- 12. Thomas reflex, elicited by rubbing the sole of the foot with
ing deep tendon (myotatic) reflexes: the back of the knuckles two or three times.
a. Biceps (C-5 and C-6). 13. Stransky sign, elicited by pulling the little toe laterally and
b. Triceps (C-7 and C-8). suddenly releasing it.
c. Brachioradialis (C-5 and C-6). The comparative yield of twelve methods used to elicit the
d. Quadriceps (knee, patellar reflex) (L-3 and L-4). extensor plantar reflex (Babinski sign) in eighty-one children
e. Achilles (ankle) (S-1 and S-2). with spastic cerebral palsy is shown in Table 35–2.
Clonus is the repetitive, rhythmic, involuntary contraction of
All are elicited by tapping the appropriate tendon. agonist and antagonist muscles induced by sudden passive dorsi-
2. Superficial reflexes. These include the following reflexes: flexion of the ankle.
a. Plantar (S-1). Firmly stroking the outer border of the Frontal release, encountered with frontal lobe damage, con-
sole of the foot will result in flexion of toes. sists of grasping or curling of fingers in response to stimulation
b. Abdominal (T-8 and T-12). Gentle stroking of abdomen of the palmar surface of the hand and finger tips.
in each quadrant will pull the umbilicus in that direction.
c. Cremasteric (L-1 and L--2). Stroking of inner aspect of
thigh lightly results in retraction of ipsilateral testis. Table 35–2. Extensor Plantar Reflex
3. Pathological reflexes appear with upper motor neuron dis-
orders. These include the following reflexes: Method of elicitation of reflex Yield
a. Babinski.
Classic Babinski 75%
b. Clonus. Gonda-Allen 90%
c. Frontal release. Allen-Cleckley 82%
d. Crossed adductor. Chaddock 74%
e. Finger flexor. Cornell 54%
Oppenheim 30%
f. Trommer. Bing 28%
g. Jaw jerk. Schaffer 22%
In the Babinski reflex, stroking the lateral aspect of the sole Moniz 20%
results in dorsiflexion of the big toe and fanning out of the other Strümpell 18%
Throckmorton 14%
toes. The reflex was described in 1896 by Josef-François-Felix
Gordon 8%
Babinski as the “phenomenon of the toes.”
Crossed adductor reflex consists of adduction of both thighs flex is present at birth and usually disappears by two to three
in response to tapping or striking (with a reflex hammer) the ten- or four months of age. Integrity of the trigeminal system (CN
don of the adductor tendon of one thigh. V) is important for the reflex. Persistence of the reflex beyond
Finger flexor reflex consists of adduction and flexion of the four months suggests abnormal brain function.
thumb and exaggerated flexion of fingers in response to snapping Sucking reflex. Stimulation of the circumoral area results in
the nail of the middle finger. involuntary tongue and lip movement (sucking). The reflex is
Trommer reflex, a variant of the finger flexor reflex, consists present at birth and disappears by ten to twelve months.
of flexion of fingers in response to a tap on the volar surface of
Moro reflex (startle reflex, embrace reflex). This reflex is
the tip of the patient’s second or third fingers.
elicited by holding the infant supine at 45 degrees and allow-
Jaw jerk reflex consists of exaggerated contraction of the mas-
ing the head to gently but abruptly drop. In response, the
seter muscle in response to tapping the relaxed chin.
arms briskly abduct, circumduct, and extend, with extension
of the fingers except the thumb and index finger which flex to
NEUROLOGIC EXAMINATION OF INFANTS form a “C.” The legs either flex or extend slightly, and the
AND SMALL CHILDREN hips abduct to a lesser degree than the arms. This is followed
by adduction of the arms. The reflex is present at birth and
Neurologic examination of small children can be a challenging disappears between four and six months of age. The reflex
task, especially for the beginner. The orderly sequence of was described by E. Moro in 1918.
neurologic examination described earlier is not possible
in infants and young children. Much information can be Tonic neck (fencing) reflex. The reflex is elicited by rotating
gained by the principle of “watch before you touch.” Observing to one side the head of the infant who is in supine position.
the infant or young child, while asleep, for posture, spontaneous In response, the extremities on the side to which the head has
movement, symmetry of limb movement, facial symmetry or been turned extend. The extremities of the other side flex.
asymmetry, and birth marks will yield valuable information. The The reflex appears one month after birth or in the first month
full-term infant assumes, when asleep, a posture of semiflexion of life and disappears by six months of life.
of all four limbs with the thighs tucked under the lower ab- Palmar grasp reflex. In response to gentle stroking of the
domen. Muscle tone can be assessed by passive movements of palmar surface of the hand toward the fingers, the infant will
limbs and by vertical suspension. Pulling the forearms toward forcefully grip the examiner’s fingers. The reflex is present at
the opposite shoulder can provide information about muscle birth and disappears by three to six months.
tone. In motor neuron disease (Werdnig-Hoffman disease), it is Plantar grasp reflex. In response to pressing a thumb against
possible to wrap the arm around the neck, as if it were a scarf the sole just behind the toes in the foot, or stroking the outer
(scarf sign). Observation of the awake child provides informa- surface of the sole from the heel to the toes, the toes will flex.
tion about the degree of alertness and interest and the status of The reflex is present at birth and persists for six to twelve
extraocular eye movements. The infant at birth blinks to bright months.
light and conjugate eye movements develop rapidly after birth. Crossed adductor reflex. Contraction of contralateral ad-
The eyes may not follow objects, however, for a few weeks after ductor muscles in response to a tap on the quadriceps tendon.
birth. Attention should be paid to the vigor of the infant’s cry, It is basically a spread of the quadriceps reflex (knee jerk) to
and the ability and vigor of sucking. Those aspects of the exami- the contralateral side. The reflex is present at birth and per-
nation that require restraint or discomfort should be done last. sists for seven to eight months.
Specifics about developmental milestones are found in pediatric
Parachute reflex. This reflex consists of extension of the arms
and child neurology texts.
of an infant suspended prone and dropped while still in the
The neurologic examination is incomplete without evaluat-
examiner’s hand. The reflex appears between eight and nine
ing the skeletal structures enclosing the central nervous system,
months and persists.
the extracranial blood vessels, and the skin. The shape and size of
the skull (especially in infants and young children) should be ob- Galant reflex (truncal incurvation reflex). In response to
served. The skull should be palpated for bony defects or lumps. scratching the skin of the infant back from the shoulder
Auscultation of the head and both eyes for bruits should be downward, 2 to 3 cm lateral to the spine, there will be incur-
done. The carotid artery in the neck should be palpated and aus- vation of the trunk with the concavity on the stimulated side.
cultated for bruits or murmurs. The head and neck should be The reflex is present at birth and persists for two to four
flexed for signs of meningismus. If a spinal cord lesion is sus- months.
pected, the spine should be examined for local tenderness or de- Landau (ventral suspension) reflex. When held prone in a
formity such as spina bifida. The skin should be observed for vas- horizontal position, the body of the infant forms a convex arc
cular malformations, neurofibromas, nevi, café-au-lait spots, or upward with head, neck, and hips extended, with shoulders
other stigmata of neurocutaneous syndromes. drawn back, and legs slightly flexed. The reflex appears at
about three months and persists to the age of two years.
DEVELOPMENTAL REFLEXES Finger extension reflex. The reflex is elicited by gentle but
firm pressure applied to the ulnar surface of the small finger,
These are a group of reflexes that are present at birth or in the starting at the second phalanx and proceeding to the lateral
early neonatal period and disappear later. They include: surface of the hypothenar eminence. This results in extension
Rooting reflex (search reflex, points cardineaux). of the fingers starting from the small finger and continuing to
Exploration of the mother’s skin by the newborn mouth the index finger.
in search for the nipple. It can be elicited also by gently Glabellar reflex. When the glabellar area (space between the
rubbing the infant’s cheek. As a result, the head turns toward brows) is tapped, the infant blinks. The reflex is present at
the stimulus, the mouth opens, and sucking begins. The re- birth and usually persists.
426 / CHAPTER 35
Stepping (automatic walk, dance) reflex. When the infant Gender

is held under the arms in a vertical position, and the feet con-
tact a smooth surface, the neonate simulates walking by a rec- Certain neurological disorders are gender prevalent or specific.
iprocal flexion and extension of the legs. The reflex is present X-linked Duchenne muscular dystrophy occurs in males. Auto-
at birth and disappears by four months. immune disorders such as myasthenia gravis and lupus erythe-
matosus are more common in females.
Placing reflex. When the infant is held vertically and the
dorsum of the foot is placed under the edge of a table, the in-
fant responds by raising the foot and placing it on the table Ethnicity
top. The reflex is present at birth and disappears between ten Certain disorders are more prevalent or are specific to certain
months and one year of age. ethnic groups. Sickle cell disease and sarcoidosis are more preva-
Crossed extension reflex. With the infant in supine posi- lent in blacks; Tay-Sachs disease is more prevalent in Ashkenazi
tion, one leg is firmly held with the knee pressed down. The Jews; moyamoya disease and thyrotoxic periodic paralysis are
sole of the fixed foot is stimulated and the free leg will flex, more prevalent in the Japanese; and the Marchiafava-Bignami
adduct, and extend. The reflex is present at birth and disap- disease is more prevalent among Italians.
pears by one month of age.
Socioeconomic Status
THE NEUROLOGIC DIAGNOSIS, Certain disorders are more prevalent among those of low socio-
THE FIRST IMPRESSION economic status. Such disorders include alcoholism, drug addic-
Arriving at the correct neurologic diagnosis is a time-consuming tion, trauma, malnutrition, and infections.
task that begins by careful observation of the patient in the wait-
ing room or as the patient enters the clinic. Tempo of Disease
The loud but relaxed conversation of a patient in the The tempo of the disease process is characteristic of certain eti-
waiting room reflects a patient very familiar with doc- ologies. An abrupt onset is characteristic of seizures, syncope,
tors’ waiting rooms. In contrast, the loud but labored and stroke. Onset over hours is characteristic of infection, intox-
conversation of a patient reflects a nervous patient not accus- ication, and subdural hematoma. Protracted onset is characteris-
tomed to the milieu of doctors’ waiting rooms. tic of brain and cord tumors. Very slow onset is characteristic of
Observing the gait of the approaching patient can clinch the Parkinson’s and Alzheimer’s disease. Remissions and exacerba-
diagnosis. Certain gaits are characteristic of the underlying neu- tions are characteristic of myasthenia gravis and multiple sclero-
rological conditions. Examples include the hemiplegic gait of sis. Diurnal variations and fluctuation in symptoms is character-
stroke; the shuffling short-stepped gait of Parkinsonism; the istic of myasthenia gravis and dystonia. Episodic occurrence of
spastic paraplegic (scissoring) gait of multiple sclerosis; the step- symptoms is characteristic of periodic paralysis and migraine.
page and scraping toe gait of foot drop; the wide-based ataxic
gait of cerebellar disease; the waddling gait of hip girdle weakness Duration of Symptoms
(as in muscular dystrophy); and the dancing gait of chorea.
Similar to characteristic gaits, there are characteristic facial Long lasting (years) daily headache is characteristic of tension
features that suggest the underlying diagnosis. These include the headache. Recent onset headache associated with change in per-
plethoric and hairy facies of Cushing syndrome; the exophthal- sonality, on the other hand, is consistent with brain tumor.
mus and lid retraction of hyperthyroidism; the baldness, ptosis,
and myopathic facies of myotonic dystrophy; and the ptotic lids Past Medical History
of myasthenia gravis and ocular dystrophy.
Elements in the past medical history are useful in arriving at the
correct diagnosis. Past medical history of hypertension and/or
CONSIDERATIONS THAT diabetes are usual preludes to stroke. History of carcinoma is a
INFLUENCE DIAGNOSIS prelude to metastatic brain disease or the remote effects of can-
cer. History of drug intake is a prelude to intoxication.
In arriving at the diagnosis of a neurological problem, considera-
tion should be given to the following factors: age, gen-
der, ethnicity, socioeconomic status, tempo of disease, IDENTIFICATION OF SITE OF DISORDER
duration of symptoms, and past medical history. In identifying the site of the neurological disorder
(where is the lesion?), the following neurological signs
Age are helpful:
Age of the patient is an important determinant in the etiology of
a neurological condition. Cerebral Cortex
The etiology of strokes in adults and children is different. In Disorders of the cerebral cortex are usually associated with one
adults, atherosclerosis, hypertension, and aneurysm rupture are or more of the following symptoms and signs: seizures; focal
common etiologies for stroke. In contrast, etiologies for stroke in cerebral signs such as aphasia, hemianopia, hemiplegia; non-
children commonly include cyanotic heart disease, arteriovenous focal cerebral signs such as dementia, headache, and delirium.
malformation, moyamoya, fibromuscular dysplasia, coagulopathies,
congenital vascular hypoplasia, and developmental brain anomalies. Brain Stem
The etiology of progressive paraparesis in adults is commonly
multiple sclerosis, whereas in children it is commonly spinal Disorders of the brain stem are commonly associated with cra-
cord tumor. nial nerve palsies which are localizing, ocular signs (gaze palsies),
involuntary movements, and crossed syndromes (cranial nerve Moniz, Antonio Caetano de Egas (1874–1955). Portuguese
palsy on one side and hemiparesis on the contralateral side). neurosurgeon who introduced prefrontal leucotomy in 1936 and
cerebral angiography in 1927. Also known for the less significant
Cerebellum description of an alternative method to elicit the Babinski reflex.
He received the Nobel prize for his prefrontal leucotomy work.
Cerebellar disorders characteristically present with ataxia and vo- Moro, E. (1874–1951). Austrian pediatrician. Described the
litional tremor. Ataxia is primarily truncal in midline cerebellar Moro reflex in 1918.
(vermis) disorders, and appendicular or generalized in cerebellar
hemisphere disorders. Nystagmus is also characteristic of midline Oppenheim, Hermann (1859–1919). German neuropsychia-
cerebellar disorders. trist. Described an alternative method to elicit the Babinski re-
flex in 1902.
Basal Ganglia Romberg, Moritz Heinrich (1795–1873). German physician
who described the Romberg sign between 1840 and 1846 as a
Basal ganglia disorders manifest with dyskinesia. Two types of diagnostic sign of tabes dorsalis.
basal ganglia disorder are the hyperkinetic (chorea, ballism, Schaffer, Karoly (1864–1939). Austrian neurologist and neu-
athetosis) and the hypokinetic (Parkinson’s disease). ropathologist who was a pioneer in the study of hereditary dis-
eases of the nervous system. Also, in 1899, described an alterna-
Spinal Cord tive method to elicit the Babinski reflex, although Babinski had
mentioned the method one year earlier.
Spinal cord disorders usually manifest with spastic gait, bladder
and bowel symptoms, sensory level and possible sacral sparing. Strümpell, Ernst Adolf Gustav Gottfried von (1853–1925).
Russian physician. Published extensively on many topics in
neurology. Described an alternative method to elicit the Babinski
Peripheral Nerve reflex.
Peripheral nerve disorders (neuropathies) manifest characteristi- Throckmorton, T.B. (b. 1885). American neurologist who de-
cally with both motor and sensory deficits. Distal (“glove and scribed an alternative method to elicit the Babinski sign.
sock”) distribution of sensory deficit, distal more than proximal
muscle weakness, and early loss of myotatic reflexes are charac-
teristic features. SUGGESTED READINGS
DeMyer WE: Technique of the Neurologic Examination. A Programmed Text,
5th ed. New York, McGraw-Hill, 2004.
Neuromuscular Junction
Futagi Y et al: Asymmetry in plantar grasp response during infancy. Pediatr
Neuromuscular junction disorders manifest with purely motor Neurol 1995; 12:54–57.
deficits that characteristically fluctuate during the day, are trig- Ghosh D, Pradhan S: “Extensor toe sign” by various methods in spastic chil-
gered by use of muscle and relieved with rest, with predomi- dren with cerebral palsy. J Child Neurol 1998; 13:216–220.
nance of weakness in facial and ocular muscles. Greenberg DA et al: Clinical Neurology, 5th ed, New York, Lange Medical
Books/McGraw-Hill, 2002.
Hoekelman RA: The Physical Examination of Infants and Children. In: Bates
Muscle B, ed. Guide to Physical Examination, Philadelphia, J.B. Lippincott Co.,
1983.
Primary disorders of muscle (myopathies, dystrophies) are also
purely motor and involve primarily proximal muscles. There are Jaffe M et al: The parachute reaction in normal and late walkers. Pediatr
Neurol 1996; 14:46–48.
no associated sensory deficits. Myotatic reflexes are normal early
and are decreased or lost late in the disease. Marcus JC: Flexor plantar responses in children with upper motor neuron dis-
ease. Arch Neurol 1992; 49:1198–1199.
Mondanlou HD: Extension reflex of fingers in the newborn. Pediatr Neurol
1988; 4:66–67.
TERMINOLOGY
Myers GJ et al: Clinical neurologic examination of the preterm and term
Bing, Robert Paul (1878–1956). Swiss neurologist who de- neonate. Sem Neurol 1993; 13:1–9.
scribed an alternative method to elicit the Babinski sign in 1939. Pryse-Phillips W: Companion to Clinical Neurology, 2d ed. Oxford, Oxford
University Press, 2003.
Chaddock, Charles Gilbert (1861–1936). American neurolo-
gist who trained with Babinski and who introduced an alterna- Rodnitzky RL: Van Allen’s Pictorial Manual of Neurologic Tests, 3d ed. Chicago,
Year Book Medical Publishers, 1988.
tive method (the malleolar way) to elicit the Babinski sign. The
same method had been described five years earlier, in 1906, by Rowland LP: Signs and Symptoms in Neurologic Diagnosis. In: Rowland
LP, ed. Merritt’s Textbook of Neurology, 8th ed. Philadelphia, Lea &
the Japanese physician Kisaku Yoshimura. Febiger, 1989, pp 58–60.
Gordon, A.M. (1874–1953). French-American neurologist and Zafeiriou DI et al: Prospective follow-up of primitive reflex profiles in high-
psychiatrist whose main interest was the study of reflexes. He de- risk infants: Clues to an early diagnosis of cerebral palsy. Pediatr Neurol
scribed an alternative method to elicit the Babinski reflex in 1904. 1995; 13:148–152.
ch36_Atlas_6082_Afifi_MGH 12/10/04 1:11 PM Page 429
PART II
atlas
Sectional Anatomy 1
Superior Superior sagittal

frontal gyrus sinus
Superior frontal
sulcus
Scalp
Precentral Calvarium
gyrus
Central (Rolandic) Dura mater

sulcus Precentral gyrus
Postcentral Central (Rolandic)
gyrus sulcus
Subarachnoid Postcentral
space gyrus
Marginal
sulcus
Falx cerebri Superior parietal

lobule
Figure A1–1. Superficial axial section through the pre- and postcentral gyri.
Falx cerebri Superior frontal

gyrus
Anterior cerebral artery Superior sagittal Superior frontal
(pericallosal branch) sinus sulcus Anterior cerebral
artery
Corpus callosum (callosomarginal
(Forceps minor) branch)
Cingulate gyrus
Middle frontal
gyrus
Precentral sulcus
Caudate nucleus Precentral
(head) gyrus
Central (Rolandic)
sulcus
Thalamostriate Postcentral gyrus
(terminal) vein
Postcentral sulcus
Scalp
Lateral ventricle Supramarginal
(body) gyrus
Lateral
Precuneus (sylvian) fissure
gyrus
Corpus callosum
Parieto-occipital (Forceps major)
sulcus
Cuneus gyrus Galea

aponeurotica
Angular
gyrus
Figure A1–2. Axial section through the body of the lateral ventricles and the forceps minor and major.
431
432 / SECTION 1
Cingulate Superior sagittal Anterior cerebral artery

Corpus callosum gyrus sinus (pericallosal branch)
Septum pellucidum
Lateral ventricle
(frontal, anterior Fornix
horn)
Caudate nucleus
Internal capsule (head)
(anterior limb) Stria medullaris
thalami
Anterior thalamic
nucleus Central (Rolandic)
sulcus
Internal capsule
Putamen
(genu)
Internal capsule Dorsomedial nucleus
(posterior limb) of thalamus
Insula
Lateral (Sylvian) (island of Reil)
fissure
Transverse
Ventral lateral gyri of Heschl
nucleus of thalamus Superior temporal
gyrus
Pulvinar nucleus Fimbria fornix
of thalamus
Alveus
Lateral ventricle
Hippocampus
(trigone)
Internal
cerebral vein
Straight sinus
Striate (primary
visual) cortex
Figure A1–3. Axial section through the thalamus and basal ganglia.
Lateral ventricle Anterior cerebral

(frontal, anterior horn) artery Third ventricle
Caudate nucleus
(head)
Internal capsule Anterior
(anterior limb) commissure
Putamen
External capsule
Claustrum
Insula (island
Extreme capsule of Reil)
Lateral (sylvian) Middle cerebral
fissure artery branches
Optic tract Mamillary body
Cerebral peduncle Superior temporal
Substantia nigra gyrus
Red nucleus
Fimbria fornix Hippocampus
Parahippocampal Posterior
gyrus cerebral artery
Tentorium Aqueduct of
cerebelli Sylvius
Vermis of
cerebellum
Cerebellar
hemisphere
Figure A1–4. Axial section through the basal ganglia, midbrain, and cerebellum.
SECTIONAL ANATOMY / 433
Optic Frontal Frontal air Falx Superior rectus

chiasma lobe sinus cerebri muscle Orbital fat
Middle cerebral
artery branches
Internal carotid
artery
Amygdala
Basilar artery Temporal lobe
Hippocampus Superficial
temporal artery
and vein
Basis pontis
Mastoid air
Superior cerebellar cells
peduncle (brachium
Locus
conjunctivum)
ceruleus
Fourth ventricle
Vermis of Confluence of Cerebellar

cerebellum sinuses hemisphere
Figure A1–5. Axial section through the pons and cerebellum.
Frontal lobe Frontal air Falx cerebri Frontal lobe

(orbital gyrus) sinus (gyrus rectus) Optic nerve
Internal
carotid artery Basilar artery
Abducens nerve
Oculomotor
nerve
Temporal lobe
Middle cerebral
artery branches Basis pontis
Anterior
petroclinoid
ligament Trigeminal
Posterior nerve
petroclinoid Petrous portion
ligament of temporal bone
Tentorium cerebelli
Auricle
Middle cerebellar
peduncle (brachium
pontis) Mastoid air
cells
Cerebellar
hemisphere
Sigmoid
Fourth sinus
ventricle
Vermis of Tegmentum of
cerebellum pons
Figure A1–6. Axial section through the middle cerebellar peduncle (brachium pontis).
434 / SECTION 1
Internal carotid artery Sphenoid sinus Nasal concha Medial rectus muscle
Lateral rectus muscle
Basilar Trigeminal
artery (gasserian)
ganglion
Temporal lobe
Vertebral
artery
Abducens nerve
Mastoid air Internal auditory

cells meatus
Facial nerve
Auricle
Cochleovestibular
nerve
Ventral cochlear
nucleus
Pyramid
Tegmentum of
medulla
oblongata
Cerebellar hemisphere Vermis of cerebellum Corpus medullare of cerebellum
Figure A1–7. Axial section through the temporal lobe, medulla oblongata, and cerebellum.
Internal
carotid artery
Trigeminal
(gasserian)
ganglion
Temporal lobe
Cochlea
Pyramid
Vestibular nerve
Cochlear nerve
Medulla
oblongata
Vagus and
glossopharyngeal
nerves
Fourth ventricle Cerebellum
Figure A1–8. Axial section through the temporal lobe, medulla oblongata, and cerebellum.
Sagittal Yakovlev 2
Frontal Parietal
lobe lobe
Lateral (sylvian) Occipital

fissure lobe
Temporal
lobe
Cerebellum
Figure A2–1. Parasagittal brain section just superficial to the insula.
Central
Centrum Precentral (rolandic) Postcentral
semiovale gyrus sulcus gyrus
Insula
(island of
Reil)
Lateral (sylvian)
fissure
Cerebellum
Middle cerebral Lateral ventricle,

artery branches inferior (temporal)
horn
Figure A2–2. Parasagittal brain section through the insula.
435
436 / SECTION 2
Centrum
Putamen semiovale
External
capsule
Internal
Claustrum capsule
Extreme capsule
Anterior
commissure
Cerebellum
Middle cerebral
artery branch
Amygdala Lateral ventricle, Caudate Hippocampal

inferior (temporal) nucleus formation
horn (tail)
Figure A2–3. Parasagittal brain section through the lenticular nucleus.
Centrum Internal Pulvinar

Putamen semiovale capsule nucleus
Lateral ventricle
(atrium)
Fimbria fornix
Lateral ventricle,
posterior
(occipital)
Globus horn
pallidus
(external
segment)
Parahippocampal
gyrus
Anterior
commissure
Cerebellum
Middle
cerebral
artery
branch Globus pallidus Amygdala Hippocampus Fimbria Lateral geniculate
(internal segment) fornix nucleus
Figure A2–4. Parasagittal brain section through the lateral geniculate nucleus, amygdala, and hippocampus.
SAGITTAL YAKOVLEV / 437
Caudate nucleus Centrum Lateral posterior

(head) semiovale nucleus of thalamus
Internal Ventral posterior

capsule lateral nucleus
(anterior of thalamus
limb)
Parietooccipital
sulcus
Putamen Fimbria fornix
Globus Calcarine
pallidus sulcus
(external
segment)
Anterior Pulvinar
commissure nucleus
Band of Gennari
Middle in primary
cerebral visual cortex
artery
branch
Dentate gyrus
Substantia innominata Globus pallidus Hippocampal Internal capsule Choroidal Cerebellum

(nucleus basalis of Meynert) (internal segment) formation (posterior limb) fissure
Figure A2–5. Parasagittal brain section through the corpus striatum.
Internal capsule Globus pallidus Globus pallidus Lateral ventricle External medullary lamina and Centromedian nucleus
(anterior limb) (external segment) (internal segment) (body) reticular nucleus of thalamus of thalamus
Lateral
ventricle
(anterior
horn)
Fimbria
fornix
Caudate
nucleus
(head) Pulvinar
Putamen Medial
geniculate
nucleus
Anterior
commissure
Cerebellar
folia
Substantia
innominata
(nucleus
basalis
of Meynert)
Optic tract Substantia Cerebral Pons Middle cerebellar Dentate nucleus
nigra peduncle peduncle (brachium pontis)
Figure A2–6. Parasagittal brain section through the centromedian nucleus of the thalamus.
438 / SECTION 2
Internal capsule Corpus callosum Ventral anterior Ventral lateral nucleus Ventral posterior lateral Lateral dorsal
(genu) (body) nucleus of thalamus of thalamus nucleus of thalamus thalamic nucleus
Fimbria
fornix
Corpus
callosum
Caudate
(splenium)
nucleus
(head)
Pulvinar
Corpus
callosum Centromedian
(genu) nucleus of
thalamus
Globus
pallidus Medial
geniculate
nucleus
Brachium
of inferior
Putamen colliculus
Dentate
nucleus
Ventral
Anterior Optic Subthalamic Pons Substantia Inferior cerebellar posterior medial
commissure tract nucleus nigra peduncle (restiform body) nucleus of
thalamus
Figure A2–7. Parasagittal brain section through the centromedian nucleus of thalamus and subthalamic nucleus.
Ventral anterior Ventral lateral Dorsomedial Lateral dorsal Centromedian

Corpus callosum Stria Terminal nucleus of nucleus of nucleus of nucleus of nucleus
(body) terminalis vein thalamus thalamus thalamus thalamus of thalamus Fornix
Parieto-
occipital
sulcus
Corpus
callosum
(splenium)
Pulvinar
Corpus Band of
callosum Gennari
(genu) (visual cortex)
Caudate Calcarine
nucleus sulcus
(head)
Internal
capsule
(genu)
Anterior
commissure
Optic
Cerebellar
tract
folia
Optic Dentate
nerve nucleus
Oculomotor Subthalamic Basis Substantia Inferior cerebellar peduncle
nerve nucleus pontis nigra (restiform body)
Figure A2–8. Parasagittal brain section through the medial thalamus.

SAGITTAL YAKOVLEV / 439
Ventral anterior Anterior nucleus Mamillothalamic Dorsomedial nucleus Centromedian and parafascicular
nucleus of thalamus of thalamus tract of thalamus nuclei of thalamus
Pulvinar
Red
nucleus
Superior
Stria terminalis colliculus
Inferior
colliculus
Stria medullaris
thalami Superior
cerebellar
peduncle
Septal (brachium
area conjunctivum)
Fourth
ventricle
Preoptic area
(hypothalamus) Medial
lemniscus
Basis
pontis
Central
tegmental
Optic chiasm tract
Hypothalamus Fornix Mamillary Oculomotor Inferior Dorsal column nuclei

(column) body nerve rootlets olive (gracilis and cuneatus)
Figure A2–9. Parasagittal brain section through the red nucleus and optic chiasma.
Axial Yakovlev 3
Frontal pole
Gyrus
Interhemispheric
fissure
Centrum semiovale
Sulcus
Occipital
pole
Figure A3–1. Axial section of the brain through the centrum semiovale.
Frontal pole
Cingulate gyrus
Cingulate
sulcus
Lateral ventricle Corpus callosum
(anterior horn)
Caudate nucleus (head)
Stria terminalis
Lateral ventricle
(body) Caudate nucleus (body)
Virchow-Robin
space Corpus callosum (body)
Internal capsule (anterior limb)

Corpus callosum
(splenium)
Insular cortex (island of Reil)
Visual (calcarine) cortex with

Occipital stria of Gennari
pole
Figure A3–2. Axial section of the brain through the body of the corpus callosum.
440
AXIAL YAKOVLEV / 441
Cingulate gyrus
Corpus callosum
(genu) Lateral ventricle
(anterior horn)
Caudate nucleus
Septum pellucidum (head)
Putamen
Lateral ventricle
(body) Insula (island of Reil)
Internal capsule
Caudate nucleus
(body) (anterior limb)
Corpus callosum Choroid plexus

(splenium)
Band of Gennari
Visual (calcarine)
cortex Occipital pole
Figure A3–3. Axial section of the brain through the genu and splenium of the corpus callosum.
Interhemispheric
fissure Cingulate gyrus
Lateral ventricle,
anterior (frontal) horn Corpus callosum (genu)
Caudate nucleus
(head)
Septum pellucidum
Internal capsule (anterior limb)
Putamen Internal capsule (genu)
Internal capsule (post limb)

Terminal
(thalamostriate)
vein Anterior nucleus of thalamus
Internal medullary Ventral lateral nucleus of
lamina thalamus
Lateral dorsal nucleus of
thalamus
Fornix (crus)
Pulvinar
Caudate nucleus (tail)
Corpus callosum
(splenium)
Lateral ventricle, posterior
(occipital) horn
Band of Gennari
Visual (calcarine)
cortex
Figure A3–4. Axial section of the brain through the crus of the fornix and dorsal thalamus.
442 / SECTION 3
Corpus callosum (genu)

Lateral ventricle,
frontal (anterior)
horn
Internal capsule
(anterior limb) Putamen
Internal capsule
External capsule
(genu)
Extreme capsule Claustrum
Internal capsule Insula (island of Reil)

(posterior limb) Thalamostriate (terminal)
Anterior nucleus of vein
thalamus Ventral anterior nucleus
of thalamus
External medullary
lamina Ventral lateral nucleus
of thalamus
Pulvinar-lateral
posterior complex Dorsomedial nucleus
of thalamus
Caudate nucleus Corpus callosum
(tail) (splenium)
Choroid plexus
Lateral ventricle,
posterior (occipital)
horn
Fornix, crus
Figure A3–5. Axial section of the brain through the frontal and occipital horns of the lateral ventricle.

Putamen
Massa intermedia Fornix, column
Ventral lateral nucleus Globus pallidus (lateral segment)

of thalamus
Dorsomedial nucleus
of thalamus Globus pallidus (medial segment)
Centromedian nucleus Mamillothalamic tract

of thalamus
Ventral posterior lateral nucleus
Pulvinar of thalamus
Ventral posterior medial nucleus
Caudate nucleus
of thalamus
(tail)
Habenular nucleus
Fimbria fornix
Hippocampus
Stria terminalis
Alveus Corpus callosum, splenium
Lateral ventricle
(trigone)
Figure A3–6. Axial section of the brain through the trigone of the lateral ventricle.
Anterior
commissure
Internal capsule
(anterior limb)
Globus pallidus
(lateral segment)
Claustrum
External capsule
Putamen
Globus pallidus
(internal segment) Fornix (column)
Internal capsule Insular cortex
(posterior limb)
Dorsomedial nucleus Transverse gyrus of Heschl
of thalamus (auditory cortex)
Caudate nucleus Mamillothalamic tract
(tail)
Ventral posterior nucleus
Fimbria fornix of thalamus
Centromedian nucleus
Hippocampal formation of thalamus
Alveus Pulvinar
Lateral ventricle Habenular nucleus

(trigone)
Figure A3–7. Axial section of the brain through the anterior commissure and habenular nucleus.
Interhemispheric fissure Frontal pole

Anterior cerebral
artery branches
Lamina terminalis
Caudate nucleus
(head)
Fornix (column)
Putamen
Ansa lenticularis
Anterior commissure
Internal capsule
(posterior limb)
Globus pallidus
(lateral segment) Medial geniculate nucleus
Dorsomedial nucleus Posterior commissure

of thalamus Habenular commissure
Caudate nucleus (tail) Superior colliculus
Fimbria fornix Pineal gland
Pulvinar
Occipital pole
Figure A3–8. Axial section of the brain through the habenular and posterior commissures.
444 / SECTION 3
Interhemispheric
fissure Gyrus rectus
Lamina terminalis
Anterior cerebral artery
Third ventricle
Middle cerebral artery

Amygdala
Hypothalamus
Anterior commissure
Optic tract
Putamen
Fornix (column)
Lateral geniculate Mamillothalamic tract
nucleus Cerebral peduncle
Medial geniculate Substantia nigra
nucleus Red nucleus
Medial lemniscus
Aqueduct of Sylvius Periaqueductal gray
Superior colliculus
Cerebellum (vermis)
Figure A3–9. Axial section of the brain through the dorsal midbrain.
Olfactory sulcus Optic chiasm
Hypothalamus
Third ventricle
Amygdala
Mamillary body
Substantia
nigra Cerebral peduncle
Hippocampus
Lateral ventricle (temporal, Red nucleus
inferior horn)
Parahippocampal Superior colliculus
gyrus
Periaqueductal Cerebellum, vermis

gray
Figure A3–10. Axial section of the brain through the mamillary body and optic chiasma.
Temporal lobe
Pons
Superior medullary Superior cerebellar peduncle

velum (brachium conjunctivum)
Dentate nucleus
Cerebellar
hemisphere
Cerebellar vermis
Figure A3–11. Axial section of the brain through the pons.
Basis pontis
Basilar groove
Fourth ventricle
Middle cerebellar peduncle

(brachium pontis)
Dentate nucleus
Pontine tegmentum
Cerebellar hemisphere
Cerebellar vermis
Figure A3–12. Axial section of the brain stem through the middle cerebellar peduncle.
446 / SECTION 3
Inferior Inferior cerebellar peduncle

Pyramid olive (restiform body)
Facial nerve
Facial nerve
rootlets
Middle cerebellar peduncle
(brachium pontis) Cerebellar
hemisphere
Superior cerebellar peduncle

(brachium conjunctive) Dentate nucleus
Facial colliculus Cerebellar Fourth ventricle

vermis
Figure A3–13. Axial section of the brain through the pontomedullary junction.
Coronal Yakovlev 4
Interhemispheric
fissure
Cortical Centrum semiovale

gyri
Figure A4–1. Coronal section of the frontal lobe rostral to the genu of the
corpus callosum.
Cingulate
gyrus
Body of
corpus
callosum
Genu of
corpus
callosum
Rostrum of
corpus
callosum
Subcallosal Lateral ventricle
gyrus (frontal horn)
Head of
caudate
nucleus
Figure A4–2. Coronal section of the brain through the genu and rostrum
of the corpus callosum.
447
448 / SECTION 4
Cingulate Interhemispheric
gyrus fissure Corpus callosum
Lateral ventricle
Head of (frontal horn)
caudate
nucleus
Internal capsule Putamen

(anterior limb)
External
capsule Septum pellucidum
Extreme
capsule
Figure A4–3. Coronal section of the brain through the rostral striatum (neostriatum).
Corpus
callosum Cingulate Interhemispheric
(body) gyrus fissure Cingulum
Lateral
ventricle
Centrum
semiovale
Caudate
nucleus
(head)
Putamen
Internal
capsule
(anterior
limb)
Globus
External
pallidus
capsule
Claustrum
Extreme Nucleus accumbens Subcallosal Fornix

capsule septi gyrus
Figure A4–4. Coronal section of the brain through the corpus striatum.
CORONAL YAKOVLEV / 449
Corpus Cingulate
callosum gyrus Lateral ventricle
Fornix
Caudate
Internal capsule nucleus
(posterior limb)
Putamen Anterior nucleus

of thalamus
External capsule
Ventral anterior
Claustrum nucleus of thalamus
Extreme Fornix
capsule
Globus
pallidus
Anterior
commissure
Nucleus
accumbens
septi
Figure A4–5. Coronal section of the brain through the anterior commissure.
Body of Corpus Centrum

caudate nucleus Fornix callosum semiovale
Anterior nucleus Putamen

of thalamus
Ventral anterior
nucleus of
thalamus External
capsule
Internal
capsule
(posterior Extreme
limb) capsule
Claustrum
Anterior Nucleus accumbens Fornix Globus pallidus Globus pallidus

commissure septi Mamillothalamic (internal segment) (external segment)
tract
Figure A4–6. Coronal section of the brain through the rostral thalamus.
450 / SECTION 4
Caudate nucleus Corpus Cingulate Lateral

(body) callosum gyrus Fornix ventricle
Dorsolateral nucleus
of thalamus
Dorsomedial nucleus
External of thalamus
medullary
lamina
Ventrolateral nucleus
Reticular of thalamus
nucleus of
thalamus
Internal medullary
Internal capsule lamina
(posterior limb)
Massa intermedia
Putamen Third ventricle
Globus pallidus
Optic tract
Amygdala Fornix
Hypothalamus
Thalamic Lenticular Infundibular
fasciculus fasciculus stalk
(H1 field of (H2 field of
Forel) Forel)
Figure A4–7. Coronal section of the brain through the fields of Forel.
Corpus Cingulate Lateral

Fornix callosum gyrus Cingulum ventricle
Stria
Stria medullaris
terminalis
thalami
Caudate nucleus
(body)
Dorsomedial
nucleus of
thalamus Lateral dorsal
Ventrolateral thalamic nucleus
nucleus of Internal capsule
thalamus (posterior limb)
Ventral posterior lateral
Zona nucleus of thalamus
incerta
Ventral posterior medial
nucleus of thalamus
Lenticular
fasciculus Thalamic fasciculus
(H2 field of (H1 field of Forel)
Forel)
Optic tract
Subthalamic
nucleus
Stria terminalis Mamillary body
Figure A4–8. Coronal section of the brain through the mamillary body and subthalamus.
CORONAL YAKOVLEV / 451
Fornix Corpus callosum
Lateral ventricle
(body)
Caudate nucleus
(body) Stria medullaris
thalami
Stria terminalis
Dorsomedial Reticular nucleus

nucleus of of thalamus
thalamus
Third Centromedian
ventricle nucleus of
thalamus
Ventral posterior lateral
nucleus of thalamus
Thalamic
fasciculus
Internal capsule
(posterior limb)
Lateral ventricle Internal

(temporal horn) capsule
(sublenticular part)
Mamillary Cerebral Substantia Subthalamic

body peduncle nigra nucleus
Figure A4–9. Coronal section of the brain through the subthalamic region.
Habenulo-interpeduncular
tract (fasciculus retroflexus Habenular Transverse Pulvinar nucleus
of Meynert) nucleus fissure of thalamus
Centromedian nucleus
of thalamus
Medial geniculate Caudate nucleus

nucleus (body)
Stria terminalis
Lateral geniculate Red nucleus

nucleus
Caudate nucleus
(tail)
Substantia Fimbria
nigra
Hippocampal
formation
Alveus
Cerebral
peduncle
Figure A4–10. Coronal section of the brain through the habenula and lateral geniculate nucleus.
452 / SECTION 4
Habenular Posterior
Fornix commissure commissure Pretectal area
Cerebral
aqueduct
Red nucleus
Pulvinar nucleus of
thalamus
Substantia
nigra Medial geniculate
nucleus
Alveus
Lateral geniculate
nucleus
Fimbria
Hippocampus
Dentate gyrus
Cerebral
peduncle
Subiculum
Basis pontis Basilar Occipitotemporal Parahippocampal

artery gyrus gyrus
Figure A4–11. Coronal section of the brain through the pretectal area.
Cerebellum (hemisphere) Cerebellum (vermis)
Emboliform
nucleus
Dentate
nucleus
Cerebellar
folium
Cerebellum (white
matter core)
Figure A4–12. Coronal section of the brain through the dentate nucleus of the cerebellum.
Brain Stem 5
Cuneate Cuneate Gracile Gracile

nucleus fasciculus nucleus fasciculus
Spinal trigeminal
tract
Spinal trigeminal
nucleus
Dorsal spinocerebellar
Pyramidal
tract
decussation
Lateral corticospinal tract
Spinothalamic Ventral spinocerebellar

tract tract
Spinal root of
accessory nerve
Medial longitudinal
fasciculus Spinal accessory
nucleus
Figure A5–1. Coronal section of the brain stem through the medulla oblongata at the level of the motor (pyramidal)
decussation.
Cuneate Cuneate Dorsal median Gracile Gracile

fasciculus nucleus sulcus nucleus fasciculus Hypoglossal nucleus
Spinal trigeminal tract
Accessory cuneate Spinal trigeminal

nucleus nucleus
Dorsal motor nucleus
of vagus Dorsal spinocerebellar
tract
Medial longitudinal Internal arcuate
fasciculus fibers
Spinothalamic tract
Medial
lemniscus Ventral spinocerebellar
tract
External arcuate
fibers Sensory (lemniscal)
Lateral reticular decussation
nucleus
Inferior olive
Pyramid Arcuate nucleus
Anterior spinal
artery
Anterior median fissure
Figure A5–2. Coronal section of the brain stem through the medulla oblongata at the level of the sensory
(lemniscal) decussation.
453
454 / SECTION 5
Nucleus Hypoglossal Fourth Dorsal motor nucleus Gracile Cuneate Cuneate

solitarius nucleus ventricle of vagus nucleus nucleus tract
Cuneocerebellar
tract Lateral (accessory)
cuneate nucleus
Inferior cerebellar
peduncle
(restiform body)
Spinal trigeminal
Medial longitudinal tract
fasciculus
Spinal trigeminal
nucleus
Ventral spinocerebellar
tract
Internal arcuate
fibers
Medial
Spinothalamic
lemniscus
tract
Amiculum
Principal inferior olivae
olive
Medial accessory
olive
Hypoglossal Preolivary Arcuate Pyramid
nerve sulcus nucleus
Figure A5–3. Coronal section of the brain stem through the medulla oblongata at the level of the obex.
Inferior vestibular Hypoglossal Inferior (posterior) Choroid Fourth Medial vestibular Tractus
nucleus nucleus medullary velum plexus ventricle nucleus solitarius
Inferior
cerebellar
peduncle
(restiform Nucleus
body) solitarius
Spinal
Medial trigeminal
longitudinal nucleus
fasciculus
Medial
Ventral
lemniscus
spinocerebellar
Superior tract
accessory
olive
Spinothalamic
Principal tract
olive
Nucleus
ambiguus
Amiculum
olivae
Pyramid Anterior Medial Olivocerebellar

spinal artery accessory olive fibers
Figure A5–4. Coronal section of the brain stem through the medulla oblongata at the level of the middle
inferior olivary complex.
BRAIN STEM / 455
Dorsal cochlear Dorsal external arcuate Choroid Fourth Inferior Foramen of

nucleus fibers (stria medullaris) plexus ventricle medullary velum Luschka
Inferior vestibular
nucleus
Inferior cerebellar
Solitary nucleus peduncle
(restiform body)
Ventral cochlear Medial vestibular
nucleus nucleus
Medial Dorsal motor
lemniscus nucleus of vagus
Nucleus Hypoglossal
ambiguus nucleus
Medial
Cochlear nerve longitudinal
fasciculus
Inferior olive
(dorsal Glossopharyngeal
accessory nerve
nucleus)
Olivocerebellar
Amiculum tract
olivae
Inferior olive
Inferior olive (principal nucleus)
(medial
accessory Pyramid
nucleus)
Arcuate
nucleus
Figure A5–5. Coronal section of the brain stem through the medulla oblongata at the level of the cochlear nuclei and the
glossopharyngeal nerve.
Emboliform Globose Nodulus Nucleus Superior cerebellar peduncle

nucleus nucleus of cerebellum fastigii (brachium conjunctivum)
Nucleus prepositus
Dentate nucleus
Inferior cerebellar
peduncle
Fourth ventricle (restiform body)
Medial longitudinal Juxtarestiform body

fasciculus
Middle cerebellar
peduncle Spinal trigeminal tract
(brachium pontis)
Flocculus of cerebellum
Facial nerve
Inferior olive
Arcuate nucleus Pyramid
Basis pontis
Figure A5–6. Coronal section of the brain stem through the pontomedullary junction.
456 / SECTION 5
Facial nerve Fourth Superior cerebellar Dentate Facial Superior

genu ventricle peduncle nucleus colliculus vestibular nucleus
(brachium conjunctivum)
Medial longitudinal
fasciculus
Inferior cerebellar
peduncle (restiform
Spinal trigeminal body)
nucleus
Lateral vestibular
tract
Abducens nucleus
Facial nucleus
Facial nerve
Central tegmental
tract
Abducens nerve
Medial lemniscus
Superior olivary
Middle cerebellar nucleus
peduncle (brachium Flocculus of
pontis) cerebellum
Cochleovestibular nerve Trapezoid body

fascicles
Facial nerve
Corticofugal fibers
Pontocerebellar fibers
Pontine nuclei
Figure A5–7. Coronal section of the brain stem through the pons at the level of the abducens and facial nerves.
Superior cerebellar Fourth Superior medullary Cerebellar Cerebellar

peduncle (brachium ventricle velum vermis hemisphere
conjunctivum)
Mesencephalic
trigeminal nucleus Medial longitudinal
and tract fasciculus
Main sensory
trigeminal nucleus
Motor trigeminal
Nucleus of lateral nucleus
lemniscus
Central tegmental
Lateral lemniscus tract
Trigeminal nerve Middle cerebellar

peduncle (brachium
Spinal lemniscus pontis)
(spinothalamic tract)
Pontocerebellar
fibers
Medial lemniscus
Corticofugal fibers
Pontine nuclei
Figure A5–8. Coronal section of the brain stem through the midpons at the level of sensory and motor nuclei of the trigeminal
nerve.
BRAIN STEM / 457
Mesencephalic Cerebellar Cerebellar

trigeminal tract and nucleus Fourth ventricle vermis hemisphere
Superior cerebellar
Nucleus peduncle (brachium
ceruleus conjunctivum)
Ventral Lateral lemniscus

trigeminothalamic
tract
Medial longitudinal
Spinal lemniscus fasciculus
Central tegmental
Medial lemniscus
tract
Middle cerebellar
Pontocerebellar peduncle (brachium
fibers pontis)
Trigeminal
nerve
Corticofugal
fibers
Pontine nuclei
Figure A5–9. Coronal section of the brain stem through the rostral pons at the level of the isthmus.
Trochlear Decussation of
Cerebellum nerve trochlear nerve Fourth ventricle
Trochlear nerve
rootlets
Medial longitudinal
Locus ceruleus
fasciculus
Lateral lemniscus
Spinal lemniscus
(spinothalamic tract) Superior cerebellar
peduncle (brachium
conjunctivum)
Ventral
trigeminothalamic Central tegmental
tract tract
medial lemniscus
Pontocerebellar
fibers
Corticofugal
fibers Pontine nuclei
Figure A5–10. Coronal section of the brain stem through the rostral pons at the level of the trochlear nerve.
458 / SECTION 5
Trochlear Periaqueductal Aqueduct of Inferior Medial longitudinal

nucleus gray matter Sylvius colliculus fasciculus
Central
tegmental
tract Medial
lemniscus
Pontocerebellar
fibers
Middle
cerebellar
peduncle
(brachium
pontis)
Corticofugal
fibers
Superior cerebellar peduncle
(brachium conjunctivum) decussation
Figure A5–11. Coronal section of the brain stem through the midbrain at the level of the caudal in-
ferior colliculus and trochlear nucleus.
Periaqueductal Cerebral aqueduct Nucleus of

gray matter (of Sylvius) inferior colliculus
Trochlear
Mesencephalic nucleus
trigeminal nucleus
and tract
Lateral lemniscus
Medial longitudinal Spinal lemniscus

fasciculus (spinothalamic tract)
Medial lemniscus
Decussation of
superior cerebellar
peduncle (brachium
conjunctivum)
Pontocerebellar
fibers
Pontine nuclei
Corticofugal
fibers
Figure A5–12. Coronal section of the brain stem through the midbrain at the level of the inferior colliculus.
BRAIN STEM / 459
Aqueduct of Periaqueductal Superior Brachium of

Sylvius gray matter colliculus superior colliculus
Brachium of
inferior collliculus
Medial geniculate
Spinal lemniscus nucleus
Brachium of
inferior colliculus
Medial lemniscus
Edinger Westphal
nucleus of oculomotor
nucleus
Medial longitudinal
fasciculus Oculomotor nucleus
(somatic motor part)
Substantia
nigra Medial lemniscus
Cerebral Red nucleus and

peduncle dentatothalamic
fibers
Oculomotor Ventral tegmental

nerve decussation
Basis pontis Interpeduncular
nucleus
Figure A5–13. Coronal section of the brain stem through the midbrain at the level of the superior colliculus.
Brachium of Periaqueductal Superior Pineal Aqueduct of Pulvinar

superior colliculus gray matter colliculus gland Sylvius nucleus
Brachium of
inferior colliculus
Medial geniculate
nucleus Medial geniculate
nucleus
Oculomotor
nucleus Lateral geniculate
nucleus
Cerebral peduncle
Red nucleus
Substantia nigra
Oculomotor nerve
rootlets
Interpeduncular nucleus
Figure A5–14. Coronal section of the brain stem through the midbrain at the level of the rostral superior colliculus.
460 / SECTION 5
Auditory Medial geniculate Habenular Pineal Posterior Pretectal Medial geniculate

radiation nucleus nucleus gland commissure area Pulvinar nucleus
Lateral geniculate
nucleus
Geniculocalcarine
(visual)
radiation
Red nucleus
Centromedian thalamic
nucleus Optic tract
Ventral posteromedial
thalamic nucleus
Medial lemniscus Cerebral peduncle
and spinal lemniscus
Subthalamic Substantia nigra

nucleus
Dentatothalamic Mamillary body

fibers
Fornix Optic Third Hypothalamus Mamillothalamic tract

chiasma ventricle
Figure A5–15. Coronal section of the brain stem through the midbrain-diencephalic junction.
Corpus callosum
Habenular
nucleus
Pulvinar
External medullary
lamina
Centromedian Third ventricle

nucleus of
thalamus
Ventral posterior Optic radiation
lateral nucleus
of thalamus
Ventral posterior Lateral geniculate
medial nucleus nucleus
of thalamus Thalamic fasciculus
Habenulo-
interpeduncular Optic tract
tract
Subthalamic
nucleus Red nucleus
Mamillary Substantia nigra

body
Amygdala Cerebral peduncle
Figure A5–16. Coronal section of the brain stem through the caudal diencephalon at the level of the habenular nuclei and mamillary
bodies.
BRAIN STEM / 461
Stria medullaris Fornix

thalami
Ventral lateral External medullary lamina
nucleus of
thalamus Dorsomedial nucleus
Internal medullary of thalamus
lamina Reticular nucleus
Internal capsule of thalamus
(posterior limb)
Zona incerta Globus pallidus
(external segment)
Thalamic fasciculus Globus pallidus
(internal segment)
Lenticular fasciculus
Mamillothalamic
tract Subthalamic nucleus
Optic tract
Fornix
Amygdala
Third ventricle Massa intermedia

Hypothalamus
Figure A5–17. Coronal section of the brain stem through the mid-diencephalon at the level of the ventral lateral nucleus of the
thalamus.
Cingulum
Corpus callosum Cingulate gyrus
Lateral ventricle
(anterior horn)
Caudate nucleus
Terminal vein (head)
Choroid plexus Fornix
Anterior nucleus Reticular nucleus

of thalamus
Internal medullary
Ventral anterior
lamina
nucleus of thalamus
External medullary
lamina
Mamillothalamic Internal capsule
tract (posterior limb)
Fornix
Putamen
Globus pallidus
Anterior
commissure
Choroid plexus
Figure A5–18. Coronal section of the brain stem through the rostral diencephalon at the level of the ventral anterior thalamic
nucleus.
462 / SECTION 5
Anterior cerebral Corpus callosum

artery Cingulate gyrus (body)
Lateral ventricle
(anterior horn)
Caudate nucleus
External capsule
Internal capsule
(anterior limb)
Septum pellucidum
Putamen
Cavum septum
Corpus callosum pellucidum
(rostrum)
Figure A5–19. Coronal section of the brain stem through the basal ganglia at the level of the head of the caudate nucleus and the
putamen.
Spinal Cord 6
Upper Lower
cervical Vertebral cervical Thoracic
cord artery cord cord
Dorsal root
Rib
Vertebral
artery
Ventral root Vertebral
body
Odontoid
process
Skin
Vertebral
spine
Nerve roots
Cauda equina
Subarachnoid
space
Lumbar Sacral Nerve Intervertebral

cord cord roots disk
Figure A6–1. Composite coronal sections of spinal cord at different levels.
Posterior Posterior
Posteromarginal Cuneate Gracile median intermediate
nucleus tract tract sulcus sulcus Lissauer tract
Substantia
gelatinosa
Nucleus Lateral
proprius corticospinal
tract
Dorsal
spinocerebellar
tract
Ventral
spinocerebellar
tract
Spinal accessory
nerve rootlets
Central canal
Pyramidal
decussation
Anterior Anterior Ventral

median fissure corticospinal horn
tract
Figure A6–2. Coronal section of the spinal cord at the upper cervical (C1–C2) level.
463
464 / SECTION 6
Posterior
median
Cuneate Gracile sulcus Posterior
Dorsal fasciculus fasciculus intermediate
root (tract) (tract) sulcus
Substantia Lissauer tract

gelatinosa
Dorsal
spinocerebellar Posteromarginal
nucleus
tract
Nucleus
Lateral
proprius
corticospinal
tract
Ventral
spinocerebellar Reticular process
tract
Spinothalamic
tract
Ventral horn
Anterior Anterior Anterior Anterior

white commissure median corticospinal gray
fissure tract commissure
Figure A6–3. Coronal section of the spinal cord at the lower cervical (C8) level.
Posterior Posterior
Posterolateral median Gracile intermediate Cuneate
sulcus sulcus fasciculus sulcus fasciculus
Lissauer
tract
Dorsal
spinocerebellar
Substantia tract
galatinosa
Lateral
Nucleus corticospinal
proprius tract
Ventral
spinocerebellar
tract
Lateral
spinothalamic Intermediolateral
tract cell column
Anterior Anterior Anterior Ventral horn

corticospinal median white
tract fissure commissure
Figure A6–4. Coronal section of the spinal cord at the upper thoracic level.
SPINAL CORD / 465
Posterior
median
sulcus Gracile fasciculus Lissauer tract
Substantia
Lateral gelatinosa
corticospinal
tract
Dorsal Nucleus proprius

spinocerebellar
tract
Intermediolateral
cell column
Ventral
spinocerebellar
tract
Lateral Dorsal nucleus

spinothalamic of Clarke
tract
Anterior Anterior Anterior Ventral horn

corticospinal median white
tract fissure commissure
Figure A6–5. Coronal section of the spinal cord at the lower thoracic level.
Posterior
Dorsal root Gracile median
fiber bundles fasciculus sulcus Lissauer tract
Lateral
corticospinal
tract Substantia
gelatinosa
Nucleus
proprius
Ventral
spinocerebellar
tract
Lateral Ventral horn

spinothalamic
tract
Ventral root
fiber bundles
Anterior Anterior
median corticospinal
fissure tract
Figure A6–6. Coronal section of the spinal cord at the lower lumbar level.
466 / SECTION 6
Posterior
Gracile medial Dorsal root
fasciculus sulcus fiber bundles Lissauer tract
Posteromarginal
nucleus
Substantia gelatinosa
Lateral
corticospinal
tract
Nucleus proprius
Autonomic
parasympathetic Central canal
cell column
Lateral
spinothalamic Ventral
tract spinocerebellar
tract
Ventral root
Ventral horn
fiber bundles
Anterior Anterior
median corticospinal
fissure tract
Figure A6–7. Coronal section of the spinal cord at the level of the third sacral segment.
Gracile Cauda equina

fasciculus fiber bundles
Substantia
gelatinosa
Lateral
corticospinal tract
(poorly myelinated)
Posterior gray
commissure
Central
canal
Anterior gray
commissure Ventral spinocerebellar
tract
Lateral
spinothalamic
tract
Ventral horn
Anterior Anterior Anterior

white median corticospinal tract
commissure fissure (poorly myelinated)
Figure A6–8. Coronal section of the spinal cord of a term stillborn infant at the lower lumbar level showing variation in
degree of myelination of different tracts.
Sagittal MRI 7
Scalp
Parietal lobe
Frontal lobe
Insular cortex
Occipital lobe
Middle cerebral
artery
Semicircular canals
Temporal lobe Cerebellum
Figure A7–1. T2-weighted parasagittal section of the brain through the insular cortex.
Central (rolandic)
Frontal lobe Precentral gyrus sulcus Postcentral gyrus Parietal lobe
Lateral ventricle
Caudate nucleus (atrium)
Putamen
Occipital lobe
Middle cerebral
artery
Tentorium cerebelli
Temporal lobe Cerebellum
Globus pallidus
Figure A7–2. T2-weighted parasagittal section of the brain through the basal ganglia.
467
468 / SECTION 7
Superior cerebral Central (rolandic) Postcentral

Precentral gyrus vein sulcus gyrus Lateral ventricle
Precuneus gyrus
Corpus callosum
(body)
Occipitoparietal
sulcus
Caudate nucleus
Occipital lobe
Pons
Cerebellum
Middle cerebellar
peduncle (brachium
pontis)
Vertebral artery
Figure A7–3. T2-weighted parasagittal section of the brain close to the midline through the brain stem.
Callosomarginal Paracentral
artery artery Internal cerebral vein Tectum
Great cerebral
vein (of Galen)
Pericallosal Cerebellum
artery (anterior lobe)
Septal vein
Straight sinus
Frontopolar artery
Thalamus Primary fissure

Anterior
commissure
Confluence of
Anterior sinuses
cerebral artery
Mamillary body Fourth ventricle
Suprasellar Cerebellum
cistern (posterior lobe)
Basilar
artery
Basis pontis Vertebral Medulla Cisterna

artery oblongata magna
Figure A7–4. T2-weighted midsagittal section of the brain through the corpus callosum and brain stem.
SAGITTAL MRI / 469
Cingulate gyrus Corpus callosum (body)
Corpus callosum
(splenium)
Superior colliculus
Corpus callosum Inferior colliculus

(genu)
Corpus callosum
(rostrum) Cerebellum
(anterior lobe)
Suprasellar (chiasmatic)
cistern
Primary fissure
Pituitary gland
Cerebellum
(posterior lobe)
Basilar artery
Basis pontis Fourth ventricle
Vertebral artery Medulla oblongata
Figure A7–5. T2-weighted midsagittal section of the brain through the corpus callosum and brain stem.
Axial MRI 8
Superior frontal
gyrus
Precentral sulcus
Superior frontal
sulcus
Middle frontal
gyrus
Precentral gyrus
Virchow-Robin
spaces Postcentral gyrus
Centrum Postcentral sulcus

semiovale
Parietooccipital
sulcus
Virchow-Robin
spaces
Figure A8–1. T2-weighted axial section of the upper part of the brain through the centrum semiovale of
the frontal and parietal lobes.
Superior sagittal
sinus
Superior frontal
gyrus Cingulate gyrus
Anterior cerebral artery Corpus callosum

(pericallosal branch) (forceps minor)
Lateral ventricle Septum pellucidum

[anterior (frontal) horn]
Lateral ventricle (body)

Caudate nucleus (body)

Corpus callosum
(forceps major)
Choroid plexus
Anterior cerebral artery Precuneus gyrus

(pericallosal branch)
Cuneus gyrus
Superior sagittal
sinus
Figure A8–2. T2-weighted axial section of the brain through the body of the lateral ventricle.
470
AXIAL MRI / 471
Internal capsule Anterior cerebral artery Lateral ventricle

(anterior limb) (pericallosal branch) (anterior horn)
Frontal lobe
External
Putamen
capsule
Internal capsule branches
(posterior limb) Fornix (column)
Mamillothalamic tract
Third ventricle
Thalamus
Basal vein
Internal cerebral Lateral ventricle (trigone)
vein
Straight sinus
Optic radiation
Occipital lobe
Superior sagittal
sinus
Figure A8–3. T2-weighted axial section of the brain through the thalamus.
Internal carotid
artery
Gyrus rectus
Middle cerebral Orbital gyrus

artery
Mamillary body
Temporal lobe
Interpeduncular
cistern
Cerebral peduncle
Posterior cerebral artery
Substantia nigra
Quadrigeminal (superior) Red nucleus
cistern
Cerebral aqueduct
Cerebellum (superior
vermis) Superior colliculus
Straight sinus Calcarine artery
Superior sagittal
sinus
Figure A8–4. T2-weighted axial section of the brain through the rostral midbrain.
472 / SECTION 8
Eyeball (anterior chamber)

Sphenoid bone
(greater wing) Lens
Eyeball (vitreous body)

Temporalis
muscle
Optic nerve
Internal carotid
artery
Temporal lobe
Basilar artery
Pontine cistern
Basis pontis
Fourth ventricle
Pontine tegmentum
Cerebellum
(hemisphere) Cerebellum (vermis)
Figure A8–5. T2-weighted axial section of the brain through the pons and cerebellum.
Sphenoid bone Temporalis muscle

(greater wing)
Internal carotid Temporal lobe

artery
Basilar artery
Pontine cistern
Meckel's cavity
Basis pontis
Facial and vestibulocochlear
nerves
Fourth ventricle Middle cerebellar peduncle
(brachium pontis)
Cerebellum (hemisphere)
Cerebellum
(nodulus of vermis)
Cerebellum (vermis)
Figure A8–6. T2-weighted axial section of the brain through the middle cerebellar peduncle and cerebellum.
AXIAL MRI / 473
Vertebral artery
Basiocciput
Internal carotid artery

Medulla (pyramids)
Jugular vein
Medulla (inferior cerebellar
peduncle, restiform body)
Fourth ventricle
Vertebral artery
Cerebellum (tonsil)
Cisterna magna
Figure A8–7. T2-weighted axial section of the brain through the medulla oblongata and cerebellum.
Coronal MRI 9
Superior frontal
gyrus
Middle frontal gyrus
Cingulate gyrus
Cingulum
Corpus callosum
Caudate nucleus
(head) Lateral ventricle
(anterior horn)
Internal capsule
Insular cortex
(anterior limb)
(island of Reil)
Precommissural
fornix Putamen
Anterior cerebral
arteries Temporal lobe
Optic chiasma Internal carotid

arteries
Internal carotid
artery
Hypophysis
Nasopharynx
Figure A9–1. T2-weighted coronal section of the brain at the level of the neostriatum.
Lateral ventricle Superior sagittal Superior frontal Superior frontal

(anterior horn) sinus gyrus sulcus
Middle frontal
Caudate gyrus
nucleus
(head)
Corpus callosum
(body)
Septal vein
Inferior frontal
gyrus
Lateral (sylvian) Putamen

fissure Middle cerebral
artery branch
Superior temporal
Globus gyrus
pallidus
Internal carotid
artery
Middle temporal
Fornix gyrus
Amygdala Optic Third Meckel's Anterior
tract ventricle cavity commissure
Figure A9–2. T2-weighted coronal section of the brain at the level of the amygdaloid nucleus and corpus striatum.
474
CORONAL MRI / 475
Superior sagittal Superior cerebral

sinus vein Cingulum

Cingulate gyrus (pericallosal branch)
Corpus callosum
(body) Lateral ventricle
(body)
Internal cerebral
vein
Lateral (sylvian)
Thalamus fissure
Insular cortex
Middle cerebral (island of Reil)
artery branch
Lateral ventricle
Third ventricle [temporal (inferior)
horn]
Temporal lobe
Interpeduncular
cistern
Pons
Basilar artery
Figure A9–3. T2-weighted coronal section of the brain at the level of the thalamus and third ventricle.
Cingulate Superior sagittal Anterior cerebral

gyrus sinus artery (pericallosal branch)
Lateral ventricle
(body) Corpus callosum
(body)
Internal cerebral Caudate nucleus

vein (body)
Fornix (column)
Third ventricle
Thalamus
Lateral ventricle
[inferior (temporal)
horn] Red nucleus
Interpeduncular
fossa Hippocampus
Cochlea
Parahippocampal
gyrus
Pons Vertebral artery
Figure A9–4. T2-weighted coronal section of the brain at the level of the caudal thalamus.
476 / SECTION 9
Interhemispheric Superior parietal lobule

subarachnoid
space
Cingulate sulcus Corpus callosum (splenium)
Cingulum
Thalamus
Pericallosal
cistern
Third ventricle
Lateral ventricle
(trigone)
Internal cerebral
Inferior temporal gyrus
vein
Tectum
Occipitotemporal gyrus
Pons Tentorium cerebelli
Cerebellum Middle cerebellar peduncle

(brachium pontis)
Medulla
oblongata Inferior cerebellopontine
cistern
Foramen
magnum Spinal cord
Figure A9–5. T2-weighted coronal section of the brain through the cerebral hemispheres and brain stem.
Superior parietal lobule
Falx cerebri
Cingulum
Corpus callosum (splenium)
Lateral ventricle
Internal cerebral vein
(trigone)
Aqueduct of Sylvius
(cerebral aqueduct)
Tectum
Inferior temporal gyrus
Cerebellum
Middle cerebellar
peduncle (brachium
pontis) Tentorium cerebelli
Medulla oblongata
Fourth ventricle (median

sulcus)
Spinal cord Inferior cerebellopontine

cistern
Figure A9–6. T2-weighted coronal section of the brain through the cerebral hemispheres and brain stem.
CORONAL MRI / 477
Superior parietal Superior sagittal sinus

lobule
Intraparietal Falx cerebri

sulcus
Lateral ventricle [posterior

(occipital) horn]
Inferior parietal
lobule
Optic (visual)
radiation Internal cerebral vein
Fourth ventricle
Cerebellum (superior vermis)
Cerebellum (deep
white matter core)
Figure A9–7. T2-weighted coronal section of the brain at the level of the occipital horn of the lateral ventricle.
Great cerebral vein

(of Galen)
Straight sinus
Lateral ventricle [posterior

(occipital) horn]
Lingual gyrus
Superior cerebellar cistern
Transverse sinus
Nucleus fastigii
Cerebellum (vermis)
Dentate nucleus
Cerebellum
(hemisphere)
Cisterna magna
Figure A9–8. T2-weighted coronal section of the brain at the level of the occipital lobe and cerebellum.
ch45_Bib_6082_Afifi_MGH 12/10/04 1:21 PM Page 479
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Index
NOTE: Page numbers followed by f indicate figures; those followed by t indicate tables.
A Amygdalohypothalamic tract, 271 Arteria radicularis magna, 67

Amygdaloid nucleus, T2-weighted coronal section Artery of Adamkiewicz, 67
Abducens nerve (VI), 37 of brain at level of, 474f Ascending reticular activating system (ARAS), 402
assessment of, 423t Amyotrophic lateral sclerosis (ALS), 74, 74f, 414 Ascending tracts, spinal, 51, 51t, 54–59, 56f –59f
pons at level of, coronal section of brain stem Anencephaly, 327, 338, 338f Association fiber system input, to cerebral cortex,
through, 456f Aneurysms, of cerebellar arteries, 37 234f, 234–235
pontine nuclei of, 115f, 115–117, 116f Anhidrosis, in lateral medullary syndrome, 100 Associative memory, 289
Aberrant pyramidal tract, 235 Anisocoria, in Parinaud’s syndrome, 138 Astasia, 216
Acalculia, 251 Ankle jerk reflex, 63, 414 Astrocytes (astroglia), 8, 8f
with thalamic infarcts, 177–178 Anomic aphasia, 261 Asynergia, 216
Accessory cuniate nucleus, 85 Anosmia, 297, 323 Ataxia, 87
Accessory nerve (XI), 37 Anosognosia, 264–265 in cerebellar hemisphere syndrome, 224
assessment of, 423t Anterior cerebral artery syndrome, 360–361, 361f optic, in posterior cerebral artery syndrome,
medullary nucleus of, 89, 89f Anterior choroidal artery syndrome, 362, 362f 363
Accommodation-convergence reflex, 144, 145f Anterior commissure, 33, 38, 39 vestibular, 324, 325
Acetylcholine (ACh), medullary, 94, 94t axial section of brain through, 443f Ataxic hemiparesis syndrome, 364
Acoustic neuromas, 104 coronal section of brain through, 449f Ataxic nystagmus, 111, 112f
Action potentials, auditory, 318–319 Anterior inferior cerebellar artery (AICA), 353 Athetosis, 196
Activity, septal area and, 294 Anterior inferior cerebellar artery (AICA) Atrium, of lateral ventricle, 39
Adiadochokinesia, in cerebellar hemisphere syndrome, 225 Audiometry, 319
syndrome, 224 Anterior spinal artery syndrome, 75, 76f Auditory agnosia, 263
Adie’s pupil, 144 Anterior white commissure signs, 72, 73f verbal, 261
Afferent fibers, of posterior funiculus, 53 Anterograde amnesia, 289 Auditory artery, 353
Aging, of nervous system, 334 Anterolateral system, 59 Auditory association cortex, primary, 245
Agnosia, 251 Antidiuretic hormone (ADH), 269–270, 270f Auditory cortex, primary, 244f, 244–245
cerebral cortex and, 262–263 Anton-Babinski syndrome, 264–265 Auditory end organ, 317f, 317–318, 318f
Agraphia, 251 Anton’s syndrome, 265 Auditory tube, 315
unilateral, 263, 263f in posterior cerebral artery syndrome, 363 Auditory-vestibular nerve (VIII), assessment of, 423t
Agyria, 231 Aphasia, 30, 249 Autism, cerebellum and, 219
Akinesia, 198, 247 anomic, 261 Automatic walk reflex, 426
Akinetic mutism, 153, 361, 409 Broca’s, 259–260, 260t Autonomic dysfunction syndrome, 77
Akinetopsia, 244 cerebral cortex and, 259–261, 260t Autonomic fibers, descending, from hypothalamus,
Alar plate development, 330, 330f in cerebrovascular occlusion syndromes, 360 272, 272f, 273t
Alertness, reticular mediation of, 402 conduction, 260, 260t Autonomic functions, septal area and, 294
Alexia, 262, 262f crossed, 261 Autonomic ganglia, 4f, 9
pure, in posterior cerebral artery syndrome, 362 global, 260, 260t Autonomic neuron signs, 71, 71f
Alien hand (limb) syndrome, 177, 265 subcortical, 261 Autonomic pathway, descending, 52t, 62
Allen-Checkley sign, 424 transcortical, 260t, 260–261 Autonomic regulation, hypothalamic, 273–274
Allocortex, 229 Wernicke’s, 260, 260t Autonomic syndromes, 76–77
Alveus, 288 Apraxia, 247, 259 Autoregulation
Alzheimer’s disease, 380 cerebral cortex and, 261–262 cerebral circulation and, 356
cerebral cortex and, 264 in cerebrovascular occlusion syndromes, 360 hypertension and, 357
limbic system and, 301, 301f Aqueduct of Sylvius, 142, 368, 369f, 371 Axis cylinders. See Axon(s)
locus ceruleus in, 106 Arachnoid mater, of brain, 25, 26f, 27f Axon(s), 4, 6f, 6–7, 7f
occipital lobe in, 31, 32f Archicerebellar signs, 217 myelinated, 6–7, 7f, 11
Amacrine cells, retinal, 309, 312, 313 Archicerebellar syndrome, 224 reaction to injury, 19
Amaurosis fugax, 361 Archicerebellum, 203 of ventral horn, 49
Amnesia, 299 nonmotor functions of, 219t Axonal transport, 12, 12f
anterograde, 289 Archicortex, 229 Axon hillocks, 6, 6f
global, transient, 299 Arcuate fasciculus, 250
retrograde, 299 Arcuate nuclei, 85, 85f B
Amygdala, 289–292, 290f Area postrema, 85
functions of, 292 Argyll Robertson pupil, 144 Babinski-Fröhlich syndrome, 277
inputs to, 290f, 290–291 Arnold-Chiari malformation, 339 Babinski-Nageotte syndrome, 101
intra-amygdaloid connections of, 292 Arousal Babinski reflex, assessment of, 424, 424t
output of, 291, 291f amygdala and, 292 Babinski’s sign, 60, 71
parasagittal brain section through, 436f reticular mediation of, 402 in medial medullary syndrome, 98
Amygdalofugal pathway, ventral, 291 with thalamic infarcts, 177 Bacterial meningitis, cerebrospinal fluid in, 379, 380t
481
482 / INDEX
Balint-Holmes syndrome, 244 Blindness Brain stem, 39, 41, 41f, 42f
Balint’s syndrome, 153, 264 color, 314 coronal section through basal ganglia, at level
in posterior cerebral artery syndrome, 363 cortical, in posterior cerebral artery syndrome, of head of caudate nucleus and putamen,
Ballism, 196 363 462f
Barns, tract of, 52t, 59 Blood, viscosity of, cerebral circulation and, 356 coronal section through caudal diencephalon,
Basal cells Blood-brain barrier, 376–377, 377f at level of habenular nuclei and mamillary
of olfactory epithelium, 306 Blood pressure, cerebral circulation and, 356 bodies, 460f
in taste buds, 308 Bobble-head doll syndrome, 385–386, 386f coronal section through medulla oblongata
Basal ganglia, 34, 35f, 39, 40f, 180–194, 181f Boutons terminaux, 12 at level of cochlear nuclei and
axial section through, 432f Bowel function, in spinal shock, 76 glossopharyngeal nerve, 455f
blood supply of, 193, 193t Bowman’s glands, 306 at level of middle inferior olivary complex,
clinical correlates of, 195–199 Brachium conjunctivum, 80, 80f, 87, 106, 132, 454f
hyperkinetic disorders, 195–197, 196f, 132f as level of motor decussation, 453f
197f Brachium pontis, 87 at level of obex, 454f
hypokinetic disorders, 198, 198f axial section through, 433f at level of sensory decussation, 453f
complementarity with cerebellum in motor Bradykinesia, 195 coronal section through midbrain
function, 193, 193f, 217–218, 218f Brain, 25–41. See also Central nervous system at level of caudal inferior colliculus and
corticostriatothalamocortical loops and, (CNS) trochlear nucleus, 458f
189–191, 190f, 191f cerebral dural venous sinuses and, 27, 28f at level of inferior colliculus, 458f
definitions related to, 181 external topography of, 27, 29–37 at level of rostral superior colliculus, 459f
development of, 331 of cerebellum and brain stem, 34, 36f, 37, at level of superior colliculus, 459f
disorders of, 427 37f coronal section through midbrain-diencephalic
facial nerve and, 114 of lateral surface, 29f, 29–31, 30f junction, 460f
function of, 191–193 of medial surface, 31, 33f –35f, 33–34 coronal section through mid-diencephalon, at
cognitive, 192 of ventral surface, 34, 36f level of ventral lateral nucleus of thalamus,
emotion and motivation, 192–193 internal topography of, 38–41 461f
gating, 192 of axial sections, 38–41, 40f – 42f coronal section through pons
motor, 191–192, 192f, 193, 193f of coronal sections, 38, 38f at level of abducens and facial nerves, 456f
spatial neglect and, 193 meninges and, 25, 26f, 27f at level of isthmus, 457f
globus pallidus of, 185 postnatal performance of, 333–334, 334t at level of sensory and motor nuclei of
at level of head of caudate nucleus and prenatal performance of, 332–333 trigeminal nerve, 456f
putamen, coronal section of brain stem sectional anatomy of, 431f – 434f at level of trochlear nerve, 457f
through, 462f spaces around, 25, 27 coronal section through pontomedullary
neostriatum of, 181–184, 183f, 184f, 185t T2-weighted axial section of junction, 455f
input to, 185f, 185–186, 186f through body of lateral ventricle, 470f coronal section through rostral diencephalon,
output of, 186, 187f, 187t through centrum semiovale of frontal and at level of ventral anterior thalamic nucleus,
nigral outputs and, 187f –189f, 187–188 parietal lobes, 470f 461f
nigral projections to, 187 through medulla oblongata and cerebellum, posture/motor control and, 415, 415f, 416f
nomenclature for, 181, 183t 473f T2-weighted coronal section of brain through,
pallidal outputs and, 187f –189f, 187–188 through middle cerebellar peduncle and 476f
pallidal projections to, 187 cerebellum, 472f T2-weighted midsagittal section of brain
posture/motor control and, 416–417, 417f through pons and cerebellum, 472f through, 468f, 469f
split pathways and, 191, 192f through rostral midbrain, 471f T2-weighted parasagittal section of brain close
substantia nigra pars reticulata of, 185 through thalamus, 471f to midline through, 468f
subthalamic nucleus of, 188, 189f T2-weighted coronal section of Brain stem disorders, 426–427
T2-weighted parasagittal section of brain at level of amygdaloid nucleus and corpus Brain tumors, cerebrospinal fluid and, 380, 380t
through, 467f striatum, 474f Bratz sector, 286
ventral striatum of, 188–189 at level of caudal thalamus, 475f Brissaud-Sicard syndrome, 124
Basal plate development, 330, 330f at level of neostriatum, 474f Broca’s aphasia, 259–260, 260t
Basal pontine syndromes, 124f, 124–125, 125f at level of occipital horn of lateral ventricle, Broca’s area, 249f, 249–250
Basal vein of Rosenthal, 355 477f Brodmann’s area, 29
Basilar artery, 352–354 at level of occipital lobe and cerebellum, Brown-Séquard syndrome, 73–74, 74f
Basilar membrane, vibrations of, 318 477f Bulimia, 278
Basis pedunculi, 131 at level of thalamus and third ventricle, Bundle of Türck, 52t, 59, 60f
Basis pontis, 105, 105f 475f Bundles of Probst, 344, 345f, 346
Basket cells, 204–205, 205t through cerebral hemispheres and brain Burdach column, 52, 391
Batten-Russell-Collier disease, 277 stem, 476f
Bechterew’s nucleus, 110 T2-weighted midsagittal section of, through C
Benedikt’s syndrome, 151, 151t, 152f corpus callosum and brain stem, 468f, 469f
Bernard-Horner syndrome, 62, 71 T2-weighted parasagittal section of Cairn’s syndrome, 153, 361, 409
Biceps jerk reflex, 63, 414 close to midline through brain stem, 468f Calcarine sulcus, 324
Bielschowsky-Lutz-Cogan syndrome, 111, 112f through basal ganglia, 467f Callosal syndrome, 263
Bing sign, 424 through insular cortex, 467f Callosomarginal artery, 350, 350f
Bipolar cells, retinal, 311, 312, 313 ventricles. See Ventricular system Caloric balance, disorders of, hypothalamic, 277, 278t
Bladder function weight of, 25, 25t Carbon dioxide, cerebral circulation and, 356
control of, 64–66, 65t, 66f Brain barrier system, 376–377, 377f Cardiovascular control, medulla and, 92
in spinal shock, 76 Brain death, 409 Carotid arteries
INDEX / 483
internal, 193, 193t, 349f, 349–351 posterior inferior cerebellar artery syndrome posture/motor control and, 415–416, 416f
internal carotid artery syndrome and, 361 and, 99f, 99–101, 100f, 101t, 225, 225f sensory systems and, 220
lumen of, cerebral circulation and, 356 superior, 220, 220f, 353 T2-weighted axial section of brain through,
Catathrenia, 408 superior cerebellar artery syndrome and, 472f, 473f
Cauda equina syndrome, 76 224f, 224–225 T2-weighted coronal section of brain at level
Caudal inferior colliculus, midbrain at level of, Cerebellar body, inferior. See Restiform body of, 477f
coronal section of brain stem through, 458f Cerebellar cortex, physiology of, 215f, 215–216 venous drainage of, 220
Caudate nucleus, 34, 35f, 183t Cerebellar disorders, 427 Cerebral arteries
basal ganglia at level of head of, coronal section Cerebellar hemisphere syndrome, 224 anterior, 193, 193t, 340–351, 350f
of brain stem through, 462f Cerebellar hypoplasia, 225 anterior cerebral artery syndrome and,
Cavum septum pellucidum, 369, 370f Cerebellar nuclei, deep, of thalamus, 161 360–361, 361f
Cavum veli interpositi, 370, 370f Cerebellar peduncle middle, 193, 193t
Cavum vergae, 369, 370f, 370–371 inferior, input to cerebellum from, 206–207 middle cerebral artery syndrome and, 359–360,
Cell body, of neurons, 5f, 5–6, 6f middle 360f
reaction to injury, 18–19 axial section of brain through, 445f midline, 351, 351f
Cells of Hensen, 317–318, 318f input to cerebellum from, 207 posterior, 353f, 353–354
Cells of Martinotti, 230f, 231 T2-weighted axial section of brain through, posterior cerebral artery syndrome and,
Central gray region, of mesencephalon, 142 472f 362–363, 363f
Central nervous system (CNS), 25, 326–335. See superior, input to cerebellum from, 207–209, Cerebral blood flow, 333
also Brain; Spinal cord 209f, 209t in coma, 357
aging and, 334 Cerebellocerebral pathways, 214, 214f in epilepsy, 357
congenital malformations of, 337–346 Cerebellohypothalamic fibers, 272, 273t mean, 357
midline defects, 344–346 Cerebellopontine angle, 104 regional, 357
neuroblast migration defects, 340–344 Cerebellum, 34, 36f, 162, 162f, 200–221 Cerebral circulation, 348–357
neuronal and glial proliferation defects, arterial supply of, 219f, 220, 220f cerebral dural venous sinuses and, 355
340 axial section through, 432f, 433f, 434f circle of Willis and, 354
neurulation defects, 337–340 cerebrocerebellar and cerebellocerebral collateral, 354
embryogenesis of, 326–329 circuitries and, 214, 214f conducting and penetrating vessels and, 354
of choroid plexus, 329 clinical correlates of, 223–227 factors regulating, 355–356
induction and, 326–327 cerebellar syndromes, 224 histology of cerebral vessels and, 354
neurulation and, 327, 327f clinical manifestations of, 223 mean cerebral blood flow and, 357
of ventricular system, 328f, 328–329, 329t developmental syndromes, 225, 226f, 227f regional cerebral blood flow and, 357
vesicle formation and, 327–328, 328t, 329f terminology for, 226–227 sources of blood supply and, 349–354
functional maturation of, 333 vascular syndromes, 224f, 224–225, 225f basilar artery, 352–354, 353f
histogenesis of, 329–330 complementarity with basal ganglia in motor internal carotid artery, 349f –352f, 349–351
cellular differentiation and, 329, 329f function, 193, 193f, 217–218, 218f vertebral artery, 352
cellular maturation and, 329–330 cortex of, physiology of, 215f, 215–216 venous drainage and, 354f, 354–355, 355f
myelination and, 332 deep nuclei of, 212–214 Cerebral commissures, development of, 332
myths and facts about, 334 physiology of, 216 Cerebral cortex, 228–256
postnatal, 333 dentate nucleus of, coronal section of brain blood supply to, 253f, 253–254, 254f
postnatal brain performance and, 333–334, through, 452f clinical correlates of, 258–266
334t development of, 331 agnosia, 262–263
prenatal brain performance and, 332–333 functions of, 216–219 alexia, 262, 262f
regional development of, 330–332 autism and, 219 alien hand (limb) syndrome, 265
of alar and basal plates, 330, 330f historical background of, 216 Alzheimer’s disease, 264
of basal ganglia, 331 motor, 216–218 anosognosia, 264–265
of cerebellum, 331 nonmotor, 218–219, 219t Anton’s syndrome, 265
of cerebral commissures, 332 gross features of, 201f –203f, 201–203 aphasia, 259–261, 260t
of cerebral hemispheres, 331f, 331–332, of lobes and subdivisions, 201–203, 203t, apraxia, 261–262
332t 204f Balint’s syndrome, 264
of diencephalon, 331 somatotopic representation and, 203, 204f callosal syndrome, 263
of medulla oblongata and pons, 330f, input to, 205–206, 207f, 208f epileptic seizures, 258–259
330–331 from inferior cerebellar peduncle, 206–207 forced collectionism, 264
of mesencephalon, 331 from middle cerebellar peduncle, 207 Gerstmann’s syndrome, 264
of spinal cord, 330 from superior cerebellar peduncle, grasp reflex, 264
Central tegmental tract, 132, 132f 207–209, 209f, 209t hemisphere specialization, 259
Centrum semiovale internal circuitry of, 209, 210f, 211, 211f Kluver-Bucy syndrome, 265
axial section of brain through, 440f microscopic structure of, 203–205 prefrontal lobe syndrome, 263–264
of frontal and parietal lobes, T2-weighted axial of cerebellar cortex, 203, 205t simultanagnosia, 265
section of brain through, 470f of cerebellar glomerulus, 205, 206f cytoarchitectonic areas of, 239–240, 240t
Cerebellar arteries of intrinsic neurons, 204–205, 205t disorders of, 426
aneurysms of, 37 of Purkinje neuron, 204, 205t electroencephalography of, 252f, 253
inferior neurotransmitters of, 214–215 electrophysiology of, 252–253
anterior, 118, 119f, 120, 219f, 220, 353 output from, 211–212, 212f –214f input to, 232f, 232–235
anterior inferior cerebellar artery syndrome physiology of, 215–216 from association fiber system, 234f,
and, 225 cortical, 215f, 215–216 234–235
posterior, 219f, 220, 352 of deep nuclei, 216 from commissural fiber system, 235
484 / INDEX
Cerebral cortex (cont.) Cerebro-oculomotor fibers, 140f, 140–142, 141f Cogwheel rigidity, 198
extrathalamic, 232–234 Cerebrospinal fluid (CSF), 373–376 Collateral circulation, cerebral, 354
thalamocortical, 232, 233f brain barrier system and, 376–377, 377f Collectionism, forced, cerebral cortex and, 264
insula of, 252 circulation of, 375 Collet-Sicard syndrome, 101
intracortical circuitry of, 238–239, 239f cisternal puncture and, 376 Collier’s sign, in Parinaud’s syndrome, 138, 152
language areas of, 249–250 classic concepts of, 373, 374f Color blindness, 314, 324
arcuate fasciculus, 250 composition of, 375–376 Color vision, 313–314
Broca’s area, 249f, 249–250 in disease, 379–380, 380t Colpocephaly, 380
right hemisphere, 250 formation of, 373–375 Coma, 409
sequence of cortical activities during function of, 375 cerebral blood flow in, 357
language processing and, 2 hydrocephalus and, 380–382, 382f–384f, 384 Combined system degeneration syndrome, 75,
Wernicke’s area, 249, 249f intracranial hypertension and, 384 75f
major association cortex of, 251, 251f intraventricular neuroepithelial cysts and, 384, Commissural fiber system input, to cerebral cortex,
microscopic structure of, 229–232 385f 235
cell types and, 229–230, 230f lumbar puncture and, 376 Communicating artery, posterior, 351, 352f
of interneurons, 230f, 230–231 physical properties of, 376 Conducting arteries, 354
of layers, 231t, 231–232 resorption of, 375 Conduction aphasia, 260, 260t
of principal neurons, 230, 230f ventricular puncture and, 376 Conductive hearing loss, 324
motor areas of, 246–249 ventriculomegaly and, 380, 381f, 382f Cones, retinal, 310, 310f, 312–313
cortical eye fields, 247–249, 248f Cerebrovascular syndromes, 359–367 Conjugate eye movements, 111
premotor area, 247 hemorrhage syndromes, 364f–366f, 364–365 Conjugate gaze paralysis, in cerebrovascular
primary, 246, 246f occlusion syndromes, 359–364 occlusion syndromes, 359–360
supplementary, 246–247 Cervical flexure, 328, 328f Conus medullaris syndrome, 76
music localization in, 250 Chaddock reflex, 424 Cordotomy, 56
output of, 235f, 235–238 Cheiro-Oral syndrome, 177 Corneal reflex, 118
aberrant pyramidal tract and, 235 Chiari malformation, 225, 226f Cornell sign, 424
corticohypothalamic pathway and, 238 Cholecystokinin, medullary, 94, 94t Cornu ammonis, 286, 286t
corticopontine pathway and, 237f, Cholinergic system, reticular, 401 Corpora quadrigemina, 130
237–238 Chorea, 195–196, 196f Corpus callosum, 31, 33f, 39, 40f
corticoreticular pathway and, 235–236 Choroidal artery agenesis of, 344, 345f, 346
corticospinal pathway and, 235, 236f anterior, 167t, 174t, 193, 193t, 349–350 axial section of brain through body of, 440f
corticostriate pathway and, 238 anterior choroidal artery syndrome and, 362, genu of
corticothalamic pathway and, 238, 238f 362f axial section of brain through, 441f
through corticobulbar pathway and, posterior, 167t, 174t coronal section of brain through, 447f
236–237, 237f Choroid plexus, 372, 373f rostrum of, coronal section of brain through,
posture/motor control and, 417f, 417–418, development of, 329 447f
418f Cingulate gyrus, 31, 33 splenium of, axial section of brain through,
prefrontal cortex of, 250–251, 251f Cingulum, 234 441f
projection to intralaminar nuclei from, 162f, Circadian rhythm, hypothalamus and, 274 T2-weighted midsagittal section of brain
163 Circle of Willis, 37, 37f, 354 through, 468f, 469f
sensory areas of, 240–245 Circumferential arteries Corpus striatum, 181, 183t
primary auditory association cortex, 245 long, 353 coronal section of brain through, 448f
primary auditory cortex, 244f, 244–245 short, 352 parasagittal brain section through, 437f
primary gustatory cortex, 245 Circumlocution, 260 T2-weighted coronal section of brain at level
primary olfactory cortex, 245 Circumvallate papillae, 307 of, 474f
primary somatosensory association areas, Cisterna cerebellomedullaris, 372, 372f Cortical function, assessment of, 422–423
242 Cisterna interpeduncularis, 372, 372f Cortical plate, 331
primary somesthetic area, 240–241, 241f Cisterna magna, 372, 372f Corticobulbar pathway, 236–237, 237f, 395, 396f
primary vestibular cortex, 245 Cisterna pontis, 372, 372f Corticocollicular fibers, 136
primary visual association areas, 244 Cisternal puncture, 372, 376 Corticofacial fibers, 113f, 113–114
primary visual cortex, 242f, 242–244, 243f Clarke’s column, 54, 56f Corticohypothalamic pathway, 238
secondary somesthetic area, 241–242 Clarke’s nucleus, 392 Corticonigral projection, 135
supplementary sensory area, 242 Claude’s syndrome, 151, 151t Corticopontine pathway, 237f, 237–238
types of, 229 Clava, 80, 80f Corticopontocerebellar tract, 394–395, 395f
Cerebral dural venous sinuses, 27, 28f, 355 Climbing fiber input, to cerebellum, 207–208, Corticoreticular pathway, 235–236
Cerebral glucose metabolism, 333 209f, 209t, 211, 211f Corticoreticulobulbar fibers, 140
Cerebral hemispheres Clonus, 71, 424 Corticorubral fibers, 138–139
development of, 331f, 331–332, 332t in medial medullary syndrome, 98 Corticospinal tract, 59–60, 235, 236f, 394, 394f
T2-weighted coronal section of brain through, Cochlea, 107, 316–317, 317f anterior, 52t, 59, 60f
476f Cochlear implants, 324 lateral, 52t, 59, 60f
Cerebral oxygen consumption, 333 Cochlear nuclei, medulla oblongata at level, lesions of, 60
Cerebral peduncle, 131, 134, 134f coronal section of brain stem through, 455f Corticostriate pathway, 238
Cerebral vein Cochleovestibular nerve (VIII), 37, 37f Corticostriate projections, 185, 185f
great (of Galen), 355 pontine nuclei of, 107–112 Corticostriatothalamocortical loops, 189–191,
internal, 355 of cochlear division, 107–109, 108f, 109f 190f, 191f
Cerebrocerebellar pathways, 214, 214f of vestibular division, 109–112, 110f–112f Corticosubthalamic projection, 188
Cerebrocerebellum, 203 Cognitive function, of basal ganglia, 192 Corticothalamic pathway, 238, 238f
INDEX / 485
Cranial nerves, 34, 36f, 37, 37f, 130, 314, 314f Descending tracts, spinal, 52t, 59f–62f, 59–62 Dystonia, 197, 197f
assessment of, 423, 423t Deuteranopia, 314 Dystrophia-adiposogenitalis, 277
medullary nuclei of, 87–94 Diabetes insipidus, 269, 277
of accessory nerve, 89, 89f Diabetes mellitus, 269 E
cardiovascular control and, 92 Diastematomyelia, 339–340
of glossopharyngeal nerve, 91f, 91–92 Diencephalic syndrome of infancy, 277 Ear
of hypoglossal nerve, 87–89, 88f Diencephalon, 155–171, 328f external, 315
neurogenic pulmonary edema and, 93 caudal, at level of habenular nuclei and inner, 315–316
neurotransmitters and neuropeptides and, mamillary bodies, coronal section of brain middle, 315
94, 94t stem through, 460f vestibular sensation and, 319f, 319–320, 320f
nucleus solitarius and, 92, 92f clinical correlates of, 172–178 Edinger-Westphal nucleus, 141
respiratory function and, 92–93 of subthalamic anatomy, 178 Efferent bundle of Rasmussen, 109, 109f
sneezing and, 93 of thalamic anatomy, 172–173, 174t Electroencephalography (EEG), cortical, 252f,
swallowing and, 93, 94f thalamic infarcts, 173, 173f, 175f–177f, 253
of vagus nerve, 89–91, 90f 175–178 Emboliform nucleus, 138
of vestibulocochlear nerve, 92 development of, 331 Embrace reflex, 425
vomiting and, 94 divisions of, 156–170 Embryogenesis. See Central nervous system (CNS),
pontine nuclei of, 107–120 epithalamus, 156f, 156–157 embryogenesis of
abducens, 115f, 115–117, 116f internal capsule, 165–168, 166f Emotional behavior
cochleovestibular, 107–112, 108f–112f metathalamus, 163 amygdala and, 292
facial, 112f–114f, 112–115 subthalamus, 168–170 basal ganglia and, 192–193
trigeminal, 117f–119f, 117–120 thalamus; Thalamic nuclei. See Thalamus hypothalamus and, 274
Craniospinal ganglia, 4f, 9 gross topography of, 156f, 156–157, 157f septal area and, 294
Cribriform plate, 297, 305, 306, 323 at level of ventral lateral nucleus of thalamus, Emotional disorders, hypothalamic, 277, 278t
Crista ampullaris, 320, 320f coronal section of brain stem through, Encephalitis, viral
Crossed adductor reflex, 425 461f cerebrospinal fluid in, 379, 380t
Crossed aphasia, 261 rostral, at level of ventral anterior nucleus of herpes simplex, 301, 302f
Crossed extension reflex, 64, 65f, 426 thalamus, coronal section of brain stem Encephalitis lethargica, 403
Crus, of fornix, 288 through, 461f Encephalocele (encephalomeningocele), 327, 338,
Crus cerebri, 131 Diocele, 328, 328f 339f
Crying, pons and, 125 Diplomyelia, 340 End bulbs of Krause, 15f, 16–17
Cuneate tract, 51t Diplopia, 133 Endoneurium, 10f, 10–11
Cuneate tubercles, 80, 80f Discriminative touch, pathway for, 389, 390f, 391 Endoplasmic reticulum, smooth, 6
Cuneatus, 391 Dopaminergic cell groups, mesencephalic, 136, 136t Enkephalin
Cuneus gyrus, 33 Dorsal column nuclei, 81–83, 83f, 83t medullary, 94, 94t
Cupula, 320 Dorsal horn, 49, 49f, 50f striatal, 187t
Cytoarchitectonic areas, of cerebral cortex, spinal, 66 Entorhinal area, 287, 287f
239–240, 240t Dorsal longitudinal fasciculus, 142, 271, 272, 273t Entorhinal hippocampal circuitry, 288, 289f
Dorsal medullary syndrome, 101 Ependymal cells, 8f, 9
D Dorsal raphe nucleus, 134 Epidural anesthesia, 47
Dorsal root ganglia, 52 Epidural space, 25, 27
Dance reflex, 426 Dorsal root signs, 72, 73f Epilepsy
Dandy-Walker syndrome, 225, 227f, 386f, Dorsal tegmental nucleus, 133 cerebellum and, 217
386–387 Dorsolateral prefrontal loop pathway, cerebral blood flow in, 357
Dark adaptation, 313 corticostriatothalamocortical, 190f, 191 cerebral cortex and, 258–259
Darkschewitsch’s nucleus, 142 Dorsolateral sulcus, 48, 48f photosensitive, mesoneocortical system and,
Deafness, 319 Down syndrome, locus ceruleus in, 106 136
word, pure, 261 Drinking, hypothalamus and, 274 temporal lobe, 299–300, 300f
Decerebrate rigidity, 153 Dural venous sinuses, cerebral, 27, 28f, 355 Epineurium, 10, 10f, 11
Decerebrate state, 415, 415f Dura mater Episodic memory, 298
Declarative memory, 289, 298 of brain, 25, 26f Epithalamus, 156f, 156–157
Decorticate state, 415, 416f spinal, 47 État lacunaire syndrome, 364
Decussation, 391 Dynorphin, striatal, 187t Eustachian tube, 315
Deep tendon reflexes, assessment of, 424 Dysarthria-clumsy hand syndrome, 124–125, 364 Evoked potentials, cortical, 252–253
Deiters’ cells, 317, 318f Dysdiadochokinesia, in cerebellar hemisphere Excitatory postsynaptic potentials (EPSPs),
Deiter’s nucleus, 110 syndrome, 224 cerebellar, 215
Déjà vu experiences, 259 Dyslexia, 262, 262f Explicit memory, 289, 298
Dejerine’s anterior bulbar syndrome, 98, 99f Dysmetria, in cerebellar hemisphere syndrome, External ear, 315
DeMorsier syndrome, 346 224 External limiting membrane, retinal, 310, 310f
Dendrites, 4, 7, 18–19, 51 Dysphagia, 91 Exteroception, 49
Denial syndrome, 264–265 Dysphasia, 249, 249f, 259 pathways for, 393–394
Dentate gyrus, 285, 286, 286f Dyspnea, 91 in thalamic pain syndromes, 176, 177t
Dentate nucleus, 138, 212–213 Dysprosody, 259 Extrapyramidal system, 181
coronal section of brain through, 452f Dysraphic defects, 327 Extrathalamic input, to cerebral cortex, 232–234
Dermatomes, 47, 47f Dyssomnias, 407–408 Eye movements
Descending autonomic pathway, 52t, 62 Dyssynergia, in cerebellar hemisphere syndrome, conjugate, 111
Descending monoaminergic pathways, 52t, 62 224 pons and, 127
486 / INDEX
Eye movements (cont.) Frontal horn, of lateral ventricle, axial section of Golgi-Mazzoni complexes, 16
saccadic brain through, 442f Golgi tendon organ, 389
control of, 145f, 145–146 Frontal lobe Goll, tract of, 52, 389
cortical areas preparing, 248 lateral surface of, 29–30, 30f Gonda-Allen sign, 424
cortical eye fields and, 247–248, 248f rostral to genu of corpus callosum, coronal Gordon sign, 424
smooth-pursuit section of, 447f Gracile tract, 51t
control of, 146–147 ventral surface of, 34 Granule cells, 205, 205t
cortical eye fields and, 248–249 Frontal release, 424 of cerebral cortex, 230f, 230–231
Frontopolar artery, 350, 350f Granule layer, of olfactory bulb, 306
F Fungiform papillae, 307 Grasp reflex, cerebral cortex and, 264
Funiculi, 389 Gray matter, 49–51
Facial expression, amygdala and, 292 anterior, spinal, 54 older terminology for, 49, 50f
Facial nerve (VII), 36f, 37 lateral, spinal, 54 Rexed terminology for, 49–51, 50f, 50t, 51f
assessment of, 423t posterior, spinal, 51–54, 53f–55f, 54t Great cerebral vein (of Galen), 355
pons at level of, coronal section of brain stem spinal, 48, 48f Grenet syndrome, 126
through, 456f Fusiform gyrus, 34 Groaning, nocturnal, 408
pontine nuclei of, 112f, 112–115 Fusiform neurons, of cerebral cortex, 230, 230f Guillain-Barré syndrome, 414
lesions of, 114f, 114–115 cerebrospinal fluid in, 379–380, 380t
motor components of, 112–114 G Gustation. See Taste sense
sensory components of, 112 Gustatory cortex, 323
Facial palsy, 113 Galant reflex, 425 primary, 245
Falx cerebelli, 25, 26f Galen’s vein, 355 Gyri of Heschl, 31, 108
Fascial colliculi, 104 Gamma-aminobutyric acid (GABA), striatal, 186,
Fasciculations, as lower motor neuron sign, 71 187t H
Fasciculus, 49 Ganglia, 4f, 9
arcuate, 250 autonomic, 4f, 9 Habenula, coronal section of brain through, 451f
longitudinal craniospinal, 4f, 9 Habenular commissure, axial section of brain
dorsal, 142, 271, 272, 273t Ganglion cells, retinal, 310f, 311, 312, 313 through, 443f
medial, 84–85, 111, 112f, 132, 132f, 140, Ganglionic eminence, 331 Habenular nuclei, 33, 156
142 Gasserian ganglion, 117 axial section of brain through, 443f
Fasciculus of Schütz, 142 Gating function, of basal ganglia, 192 caudal diencephalon at level of, coronal section
Fasciculus retroflexus of Meynert, 156 Gélineau’s syndrome, 408 of brain stem through, 460f
Fastigial nucleus, 213–214 Gellé syndrome, 124 Hair cells, 317, 318, 318f, 320, 320f
Fatal familial insomnia, 409 Geniculocalcarine fibers, 314–315 Hakim-Adams syndrome, 382, 384
Feeding behavior, hypothalamus and, 274 Geniculostriate visual pathway, 315 Hallucinations, hypnopompic, 408
Fencing reflex, 425 Geniculothalamic artery, 167t, 174t Hallucinosis, musical, 126
Fibrillations Genu, of corpus callosum Hearing, 315–319
as lower motor neuron sign, 71 axial section of brain through, 441f audiometry and, 319
in medial medullary syndrome, 98 coronal section of brain through, 447f auditory end organ and, 317f, 317–318, 318f
Fibrous astrocytes, 8, 8f Gerstmann’s syndrome, 251, 264 auditory physiology and, 318–319
Fields of Forel, 169, 170f in cerebrovascular occlusion syndromes, 360 cochlea and, 316–317, 317f
coronal section of brain through, 450f Glabellar reflex, 425 deafness and, 319
Fifth ventricle, 368–369, 370f Glia. See Neuroglia disorders of, 324
Fimbria, 288 Glial proliferation defects, 340 ear and, 315–316
Finger extension reflex, 425 Global amnesia, transient, 299 otoacoustic emissions and, 319
Finger flexor reflex, 425 Global aphasia, 260, 260t sound transmission and, 316, 316f
Flechig’s loop, 314 Globose nucleus, 138 Helicotrema, 317
Flexor reflex, 64, 64f Globus pallidus, 34, 35f, 135, 160, 161, 181, 183t, Hemiachromatopsia, 244
Flocculus, 34, 37f 185 Hemialexia, 263
Food intake, amygdala and, 292 outputs of, 187f–189f, 187–188 Hemianesthesia, in medullary tegmental paralysis,
Foramen of Luschka, 368 projection to intralaminar nuclei from, 162f, 163 101
Foramen of Magendie, 368 striatopallidal projections and, 187 Hemianopia, 33, 314, 314f, 315f
Foramen of Monro, 368, 369f Glomerular layer, of olfactory bulb, 306 homonymous, 314, 314f, 315, 324
Forced collectionism, cerebral cortex and, 264 Glomerulus, cerebellar, 205, 206f in cerebrovascular occlusion syndromes,
Forceps major, axial section through, 431f Glomus, of lateral ventricle, 39, 40f 360
Forceps minor, axial section through, 431f Glossopharyngeal nerve (IX), 37 quadrantic, 324
Forel, fields of, 169, 170f assessment of, 423t Hemianopsia, with thalamic infarcts, 173
coronal section of brain through, 450f medulla oblongata at level, coronal section of Hemiataxia, with thalamic infarcts, 173
Fornix, 33, 271, 272, 273t, 287–288, 288f brain stem through, 455f Hemiballismus, 169
crus of, 288 medullary nuclei of, 91f, 91–92 subthalamic lesions and, 178
axial section of brain through, 441f inferior salivatory, 91–92 Hemimegalencephaly, 340, 341f
Fourth ventricle, surface landmarks of, 80, 80f nucleus ambiguus, 91 Hemiparesis
Fovea centralis, 311 Glucose metabolism, cerebral, 333 ataxic, 124
Foville’s syndrome, 126 Golgi apparatus, 5f, 6 in cerebrovascular occlusion syndromes,
Friedreich’s ataxia, 75 Golgi cells, 203, 205t 359–360
Fröhlich syndrome, 277 type II, 205, 205t in medullary tegmental paralysis, 101
INDEX / 487
motor, pure, 124 Hypothalamoamygdaloid fibers, 272 Inner ear, 315–316

Hemiplegia, in cerebrovascular occlusion Hypothalamocerebellar fibers, 272, 272f, 273t Inner nuclear layer, retinal, 310f, 311
syndromes, 359–360 Hypothalamohypophyseal tract, 271, 273t Inner plexiform layer, retinal, 310f, 311
Hemiplegia cruciata, 81, 82f Hypothalamoprefrontal fibers, 272, 272f, 273t synaptic organization in, 312, 312f
Hemisphere specialization, 259 Hypothalamothalamic fibers, 272, 272f Insomnia, familial, fatal, 409
Herpes simplex encephalitis, 301, 302f Hypothalamus, 33, 156, 268–275 Insula, 39, 40f, 252
Heschl’s gyri, 31, 108 blood supply of, 274–275 parasagittal brain section superficial to, 435f
Heterogenetic cortex, 229 boundaries and divisions of, 269f, 269–271 parasagittal brain section through, 435f
Heterotopias, 231, 331 mamillary region, 271 Insular cortex, T2-weighted parasagittal section of
cortical, 343, 343f preoptic region, 269, 270f brain through, 467f
Heterotypical cortex, 229 suprachiasmatic (supraoptic) region, Intention tremor, in cerebellar hemisphere
Hippocampal formation, 284, 285f, 286f 269–270, 270f syndrome, 224
inputs to, 287, 287f tuberal region, 270–271 Intermediate zone, 49, 50f
output from, 287, 288f clinical correlates of, 276–278 spinal, 66
Hippocampus, 284, 285f, 286f disorders of caloric balance, 277, 278t Intermediolateral horn, 49, 49f, 50f
divisions of, 285, 286 disorders of water balance, 277, 278t Internal capsule
functions of, 289 emotional disorders, 277, 278t anterior limb of, 38, 38f
lamination of, 285, 286 memory disorders, 278, 278t blood supply of, 166, 168f
neuronal population of, 285–286, 287f sleep disorders, 277–278, 278t Internal carotid artery, 193, 193t, 349f, 349–351
parasagittal brain section through, 436f thermoregulatory disorders, 277, 278t Internal carotid artery syndrome, 361
terminology for, 284–285, 286t connections of, 270f, 271–272 Internal limiting membrane, retinal, 310f, 311
Histogenesis, of central nervous system, 329–330 extrinsic, 271–272, 273t Internal optic artery
cellular differentiation and, 329, 329f local, 271 anterior, 167t, 174t
cellular maturation and, 329–330 functions of, 272–274 posterior, 167t, 174t
History taking, 422 anterior pituitary control, 273 Interneurons, of cerebral cortex, 230f, 230–231
Holoprosencephaly, 344, 344f autonomic regulation, 273–274 Internuclear ophthalmoplegia, 111, 112f
Homogenetic cortex, 229 circadian rhythm, 274 Interpeduncular nucleus, 133
Homonymous hemianopia, 314, 314f, 315, 324 drinking and thirst, 274 Interpeduncular profunda artery, deep, 167t, 174t
in cerebrovascular occlusion syndromes, 360 emotional behavior, 274 Interposed nuclei, cerebellar, 213
Homotypical cortex, 229 feeding behavior, 274 Interstitial nucleus of Cajal, 142
Horizontal cells memory, 274 Intorsion, 133
of Cajal, 230f, 231 posterior pituitary control, 272 Intracranial hemorrhage, 364f–366f, 364–365
retinal, 312 sexual arousal, 274 Intracranial hypertension
Hormones, peptide, as neurotransmitters, 13 sleep and wakefulness, 274 benign, 384
Horner’s syndrome, 62, 71, 151, 151t temperature regulation, 274 idiopathic, 384
in lateral medullary syndrome, 100 Hypothermia, 277 Intraparietal sulcus, 30, 31f
Huntington’s chorea, 196, 196f, 371 Hypotonia, muscular, in cerebellar hemisphere Intraventricular neuroepithelial cysts, 384, 385f
nigrostriatal system and, 136 syndrome, 224 Inverse myotatic reflex, 63f, 63–64
Hydrocephalus, 380–382, 382f–384f, 384 Island of Reil, 39, 40f, 252
communicating, 380 I Isocortex, 229
external, benign, 384, 385f Isthmus, 106
noncommunicating, 380–381, 383f Ideational apraxia, 261 rostral pons at level of, coronal section of brain
normal-pressure, 382, 384 Ideomotor apraxia, 261, 262f stem through, 457f
obstructive, 380 unilateral, 263
Hydrocephalus ex vacuo, 380 Idiographic language, 259 J
Hyperkinetic disorders, 195–197, 196f, 197f Immediate memory, 298
Hyperopia, 324 Implicit memory, 298 Jacksonian seizures, 259
Hyperpathic zone, 76 Inattention, in cerebrovascular occlusion Jaw jerk reflex, 118, 425
Hypersomnia-bulimia, 408 syndromes, 359–360 Juxtarestiform body, 110, 111f
Hypertension Incus, 315
K
autoregulation and, 357 Induction, in embryogenesis, 326–327
intracranial, 384 Infarcts Kinesthesia
Hyperthermia, 277 cerebral, 359 pathway for, 389, 390f, 391
Hyperventilation, neurogenic, central, 127 thalamic. See Thalamic infarcts posterior funiculus and, 51
Hypnopompic hallucinations, 408 Inferior cerebellar body. See Restiform body Kleine-Levin-Critchley syndrome, 408
Hypoglossal nerve (XII), 37 Inferior colliculus, 108 Kleine-Levin syndrome, 278, 408
assessment of, 423t input to superior colliculus, 137 Klüver-Bucy syndrome, 265, 299
medullary nucleus of, 87–89, 88f Inferior mamillary peduncle, 271, 273t Knee jerk reflex, 63, 414
Hypoglossal trigone, 80 Inferior olivary complex, middle, coronal section of Koerber-Salus-Elschnig syndrome, 138, 152
Hypokinesia, 198 brain stem through medulla oblongata at level Koniocortex, 229
Hypokinetic disorders, 195, 198, 198f of, 454f
Hypophysis, hypothalamic control of Inferior olive, 85–86, 86f L
of anterior pituitary, 273 Infundibular stalk, 269
of posterior pituitary, 272 Inhibition, by Renshaw cells, 50 Labbé’s vein, 355
Hypoplasia, cerebellar, 225 Inhibitory postsynaptic potentials (IPSPs), Labyrinth
Hypothalamic sulcus, 33 cerebellar, 215 bony, 315
488 / INDEX
Labyrinth (cont.) structures of, 283 at level of motor decussation, 453f

membranous, 315–316 Lingual gyrus, 33 at level of obex, 454f
Labyrinthine artery, 353 Lipochrome pigment granules, in neurons, 5f, 6 at level of sensory decussation, 453f
Lacunar syndromes, 363–364 Lissencephaly, 331, 341, 342f cranial nerve nuclei of. See Cranial nerves,
Laminae, spinal, 49–50, 50f, 51f Locked-in syndrome, 125, 151t, 152–153, 409 medullary nuclei of
Lamina terminalis, 33 Locomotion, control of, 418 development of, 330f, 330–331
Landau reflex, 425 Locus ceruleus, 106, 134, 401 gross topography of, 79–80
Language areas, of cerebral cortex, 249–250. See Long-term memory, 298 of dorsal surface, 79–80, 80f
Cerebral cortex, language areas of Lou Gehrig’s disease, 74, 74f, 414 of fourth ventricle, 80, 80f
arcuate fasciculus, 250 Lower motor neuron signs, 71, 71f of ventral surface, 79, 79f
Broca’s area, 249f, 249–250 Lower motor neuron syndrome inferior cerebellar peduncle of, 87, 87f
right hemisphere, 250 posture/motor control and, 414 internal structure of, 80–86
sequence of cortical activities during language segmental, 72–73, 73f of area postrema, 85
processing and, 250, 250f Lumbar puncture, 47, 376 of dorsal column nuclei, 81–83, 83f, 83t
Wernicke’s area, 249, 249f Luschka, foramen of, 368 of inferior olive, 85–86, 86f
Language deficits, with thalamic infarcts, 178 Lyra, 288 of pyramidal decussation, 81, 82f
Lateral dorsal tegmental nucleus, 133–134 Lysosomes, 6 of sensory decussation, 84f, 84–85, 85f
Lateral geniculate nucleus, 314 of spinal trigeminal nucleus, 83–84
coronal section of brain through, 451f M of spinocerebellar tracts, 81f, 84
parasagittal brain section through, 436f of spinothalamic tracts, 84
Lateral lemniscus, 108, 132, 132f Macrocephaly, 340 motor pathways arising from, 396
Lateral medullary syndrome, 99f, 99–101, 100f, 101t Macrogyria, 341, 342f projections to oculomotor nucleus, 140
Lateral orbitofrontal prefrontal loop pathway, Macula lutea, 311 reticular formation of, 86
corticostriatothalamocortical, 190f, 191 Magendie, foramen of, 368 T2-weighted axial section of brain through, 473f
Lateral reticular nuclear group, 400t, 400–401 Major association cortex, 251, 251f Medullary cistern, 372, 372f
Lateral ventricles Malleus, 315 Medullary tegmental paralysis, 101
axial section through, 431f Mamillary bodies, 38 Megalencephaly, 340
body of, T2-weighted axial section of brain axial section of brain through, 444f Meissner’s corpuscles, 15f, 16
through, 470f caudal diencephalon at level of, coronal section Memory, 297–299
frontal horn of of brain stem through, 460f anatomic correlates of, 298–299
axial section of brain through, 442f coronal section of brain through, 450f associative, 289
occipital section of brain through, 442f Mamillotegmental tract, 272, 273t declarative, 289, 298
occipital horn of Mamillothalamic tract, 272, 273t episodic, 298
axial section of brain through, 442f Marcus Gunn phenomenon, 143–144, 144f explicit, 289, 298
T2-weighted coronal section of brain at Marie-Foix syndrome, 127 hypothalamus and, 274
level of, 477f Massa intermedia, 156 implicit, 298
trigone of, axial section of brain through, 442f Matrix-forming precursors (MFPs), 19 procedural, 298, 299
Lateropulsion, in lateral medullary syndrome, 100 Mean cerebral blood flow, 357 semantic, 298
Laughter, pons and, 125 Medial forebrain bundle, 271, 272, 273t short-term, 298–299
Learning, septal area and, 294 Medial lemniscus, 84, 84f, 132, 132f Memory deficits, 289
Left ear extinction, 263 Medial longitudinal fasciculus (MLF), 84–85, 132, hypothalamic, 278, 278t
Lenticular nucleus, parasagittal brain section 132f with thalamic infarcts, 176
through, 436f rostral interstitial nucleus of, 140, 142 types of, 299
Lenticulostriate artery syndrome, 360 Medial longitudinal fasciculus (MLF) syndrome, Meninges
Lentiform nucleus, 181, 183t 111, 112f of brain, 25, 26f, 27f
Lhermitte syndrome, 111, 112f Medial medullary syndrome, 98, 99f spinal, 47
Light adaptation, 313 Medial reticular nuclear group, 399–400, 400t Meningitis, 25
Light reflex, 143f, 143–144 Medial striate artery, 350, 350f bacterial, cerebrospinal fluid in, 379, 380t
afferent pathway and, 143 Medial tegmental syndrome, 125, 125f Merckel’s corpuscles, 16
efferent pathway and, 143f, 143–144, 144f Median raphe nuclear group, 399, 400t Mesencephalic dopaminergic cell groups, 136, 136t
Limbic lobe, 33–34, 34, 34f, 283, 284f Medulla oblongata, 34, 34f, 78–96 Mesencephalic nucleus, 132
Limbic loop pathway, corticostriatothalamocortical, axial section through, 434f Mesencephalic reticular formation, 144
190f, 191, 191f blood supply of, 94–95, 95f Mesencephalon, 34, 34f, 129–148, 328f
Limbic system, 280–295 clinical correlates of, 98–102 accommodation-convergence reflex and, 144,
clinical correlates of, 297–303 Babinski-Nageotte syndrome, 101 145f
Alzheimer’s disease, 301, 301f Collet-Sicard syndrome, 101 axial section through, 432f
herpes simplex encephalitis, 301, 302f dorsal medullary syndrome, 101 blood supply of, 146f, 147
memory and, 297–299 lateral medullary syndrome, 99f, 99–101, clinical correlates of, 150–153
olfactory abnormalities, 297 100f, 101t akinetic mutism, 153
schizophrenia, 300–301 medial medullary syndrome, 98, 99f decerebrate rigidity, 153
temporal lobe epilepsy, 299–300, 300f pseudobulbar palsy, 101 vascular syndromes, 150–153, 151t
transient global amnesia, 299 coronal section of brain stem through coronal section of brain stem through
Wernicke-Korsakoff syndrome, 299 at level of cochlear nuclei and at level of caudal inferior colliculus and
definition of, 281 glossopharyngeal nerve, 455f trochlear nucleus, 458f
functions of, 284 at level of middle inferior olivary complex, at level of rostral superior colliculus, 459f
overview of, 295, 295f 454f at level of superior colliculus, 459f
INDEX / 489
development of, 331 Motor end plate syndrome, 415 T2-weighted coronal section of brain at level
dorsal, axial section of brain through, 444f Motor fibers, somatic, facial, 112–114, 113f of, 474f
eye movements and Motor function Nerve cells. See Neuron(s)
saccadic, 145f, 145–146 amygdala and, 292 Nerve fibers, 9–12, 10f, 10t
smooth pursuit, 146–147 assessment of, 423 myelinated, 11
gross topography of, 130 of basal ganglia, 191–192, 192f, 193, 193f in taste buds, 308
dorsal, 130 complementarity with cerebellum in, 193, unmyelinated, 11
ventral, 130, 130f 193f, 217–218, 218f Nerve growth factors, following nerve injury, 19
light reflex and, 143f, 143–144, 144f of cerebellum, 216–218 Nerve impulse conduction, 11–12
microscopic structure of, 130–142 archicerebellar and paleocerebellar signs Nerve injury
general organization, 130–131, 131f and, 217 classification of, 19, 20f, 20t, 21
of inferior colliculus, 131f–135f, 131–136, complementarity of basal ganglia and, in reaction to, 18f, 18–21
134t, 136t motor function, 217–218, 218f Nervus intermedius, 112
of superior colliculus, 136–142, 137f, epilepsy and, 217 Neural crest, 327
139f–141f neurocerebellar signs and, 216–217 Neural oscillators, 418
motor pathways arising from, 395 ocular motor signs and, 217 Neurapraxia, 21
reticular formation of, 144 control of. See Posture/motor control Neurite-promoting factors (NPFs), 19
rostral, T2-weighted axial section of brain somatic, reticular mediation of, 401–402 Neuroblast migration defects, 340–344, 342f, 343f
through, 471f visceral, reticular mediation of, 402 Neuroepithelial cysts, intraventricular, 384, 385f
vertical gaze and, 144–145 Motor homunculus, 29 Neurofibrils, 5f, 6
Mesencephalostriate projections, 185–186, 186f Motor loop pathway, corticostriatothalamocortical, Neurofilaments, 6
Mesocele, 328, 328f 189–191, 190f Neurogenic hyperventilation, central, 127
Mesocortex, 229 Motor neuron disease, 74, 74f Neuroglia, 4, 8f, 8–9
Metacele, 328, 328f Motor pathways Neurologic examination, 422–425
Metathalamus, 163 corticofugal, 394–395 cortical function in, 422–423
Metencephalon, 327, 328f, 328t of subcortical origin, 395–396 cranial nerve function in, 423, 423t
Meyer’s loop, 314, 324 Multilayered fiber system, input to cerebellum equipment for, 422
Microcephaly (micrencephaly), 340 from, 208–209 motor coordination in, 423
Microglia, 8f, 9 Multiple sclerosis, cerebrospinal fluid in, 379, 380t motor function in, 423
Micropolygyria, 231 Muscle disorders, 427 of pediatric patients, 425
Micturition pathway, 64–66, 65t, 66f primary, posture/motor control and, 415 reflexes in, 424t, 424–426
Midbrain. See Mesencephalon Music, localization in cerebral cortex, 250 sensory function and, 424
Midbrain-diencephalic junction, midbrain at level Musical hallucinosis, 126 Neuromuscular junction, 14f, 14–15
of, 460f Mutism, akinetic, 153, 361, 409 disorders of, 427
Midbrain flexure, 328, 328f Myelencephalon, 327, 328f, 328t Neuromuscular junction syndrome, posture/motor
Middle cerebellar peduncle, axial section through, Myelination, 332 control and, 415
433f Myelin sheath, 6–7, 7f, 11 Neuromuscular spindles, 17, 17f
Middle cerebral artery syndrome, 359–360, 360f Myelocele, 328, 328f Neuron(s), 4–7
Middle ear, 315 Myelodysplasias, 327 axons of. See Axon(s)
Midline cerebral artery, 351, 351f Myelomeningocele, 338–339, 339f dendrites of, 4, 7, 18–19, 51
Midline defects, 344f, 344–346, 345f Myoneural junction. See Neuromuscular junction injury of, reaction to, 18f, 18–21
Midline syndrome, 224 Myopia, 324 neostriatal, 181–183
Milkmaid’s grip, 196 Myotatic reflexes, 63, 63f perikaryon of, 5f, 5–6, 6f
Millard-Gubler syndrome, 124, 124f assessment of, 424 reaction to injury, 18–19
Miller-Dieker syndrome, 341 hyperactive, corticospinal tract lesions and, 60 sensory, receptor organs of, 15–18
Mitochondria, 6 inverse, 63f, 63–64 shapes of, 4, 4f
Mitral cell layer, of olfactory bulb, 306 posture/motor control and, 413–414, 414f in spinal gray matter, 51
Modiolus, 316 Myotomes, 47, 47t of thalamic nuclei, 165, 165f
of inner ear, 107 types of, 4
Moniz sign, 424 N Neuronal plasticity, 21
Monoaminergic pathways, descending, 52t, 62 Neuronal proliferation defects, 340, 341f
Monoaminergic system, reticular, 401 Narcolepsy, 408 Neuropeptides
Monro, foramen of, 368, 369f Neglect, in cerebrovascular occlusion syndromes, cerebral circulation and, 356
Monte Cristo syndrome, 409 359–360 medullary, 94, 94t
Morin’s tract, 51t, 55–56 Neocerebellar signs, 216–217 thalamic, 165
Moritz Benedikt syndrome, 141f Neocerebellar syndrome, 224 Neuropeptide Y, medullary, 94, 94t
Moro reflex, 425 Neocerebellum, nonmotor functions of, 219t Neurotensin, striatal, 187t
Mossy fiber system, input to cerebellum from, 208, Neocortex, 229 Neurotmesis, 21
209, 211 Neologism, 260 Neurotransmitters
Motivation, basal ganglia and, 192–193 Neostriatum, 135, 181–184, 183f, 183t, 184f, 185t cerebellar, 214–215
Motor areas, of cerebral cortex. See Cerebral cortex, coronal section of brain through, 448f in chemical synapses, 13
motor areas of corticostriate projections to, 185, 185f medullary, 94, 94t
Motor association cortex, 251, 251f mesencephalostriate projections to, 185–186, striatal, 186, 187t
Motor coordination, assessment of, 423 186f thalamic, 165
Motor decussation, coronal section of brain stem projections from, 186, 187f, 187t Neurulation, 327, 327f
through medulla oblongata at level of, 453f thalamostriate projections to, 186 defects of, 337–340
490 / INDEX
Neurulation (cont.) olfactory mechanisms and, 307 Parahippocampal gyrus, 33–34, 34f
primary, 338f, 338–339, 339f olfactory nerve and, 306 Paralysis, corticospinal tract lesions and, 60
secondary, 339–340, 340f olfactory striae and, 306–307 Paramedian artery, 167t, 174t
Night blindness, 313, 324 olfactory tract and, 306 Paramedian penetrating arteries, 352
Night terrors, 408 primary olfactory cortex and, 307 Paramedian reticular nuclei, 399, 400, 400t
Nigroamygdaloid tract, 136 Olfactory bulb, 281f, 281–282, 282f Paraphasia, 260
Nigrocollicular tract, 135–136 cell types of, 282 Paraplegia-in-flexion, 76
Nigrocortical tract, 135 lamination of, 282, 282f Parasomnias, 407–408
Nigropallidal tract, 135 Olfactory cortex, 283 Parasympathetic innervation, cerebral circulation
Nigrorubral tract, 135 primary, 245 and, 356
Nigrostriate fibers, 135 Olfactory nerve (I), assessment of, 423t Paresthesia, with thalamic infarcts, 173
Nigrosubthalamic projection, 188 Olfactory nerve layer, of olfactory bulb, 306 Parietal lobe, lateral surface of, 30–31, 31f
Nigrotegmental tract, 135–136 Olfactory nerve rootlets, 281 Parinaud’s syndrome, 138, 151t, 152
Nigrothalamic tract, 135 Olfactory striae, 282–283 Parkinsonism, 198, 198f
Nissl bodies, 5, 5f Olfactory tract, 36f, 37, 37f, 282 Parkinson’s disease, 198
Nocturnal groaning, 408 Olfactory tubercle, 183t locus ceruleus in, 106
Norepinephrine, medullary, 94, 94t Oligodendroglia, 8f, 8–9 mesoneocortical system and, 136
Normal-pressure hydrocephalus, 382, 384 Olivocerebellar tract, 207 Parvocellularis, 400
Nothnagel’s syndrome, 151t, 152 Olivocochlear bundle, 109, 109f Pathological reflexes, assessment of, 424
Nucleus accumbens, 183t Ondine’s curse, 93, 408–409 Patient approach, 421–427
Nucleus ambiguus, in lateral medullary syndrome, One-and-a-half syndrome, 125–126, 126f, 127f diagnosis of lesion and, 422
99 Onuf ’s nucleus, 64, 65 factors influencing, 426
Nucleus basalis of Meynert, 301 Opercular gyrus, 30, 249 first impression and, 426
Nucleus dorsalis, 392 Ophthalmic artery, 349 history taking and, 422
of Clarke, 54, 56f Oppenheim reflex, 424 localization of lesions and, 421–422
Nucleus gracilis, 81–82 Optic chiasma, 36f, 37, 37f, 314, 314f signs helpful for, 426–427
Nucleus parabrachialis pigmentosus, 133 axial section of brain through, 444f neurologic examination and, 422–425
Nucleus pigmentosus, 134 parasagittal brain section through, 439f to pediatric patients, 425–426
Nucleus prepositus hypoglossi, 115 Optic nerve (II), 314, 314f Pattern generators, 418
Nucleus solitarius, 92, 92f assessment of, 423t Pavor nocturnus, 408
Nucleus supratrochlearis, 134 Optic nerve layer, retinal, 310f, 311 Pediatric patients, neurologic examination of,
Nucleus tegmenti pedunculopontis, 133–134 Optic tract, 38, 39f 425–426
Nucleus thoracicus, 54, 56f Orbitofrontal artery, 350, 350f Peduncular hallucinosis syndrome, 151t, 153
Nyctalopia, 313, 324 Organ of Corti, 107, 317f, 317–318, 318f Pedunculopontine nucleus, 107, 107f, 400
Nystagmus, 87, 216 Orienting response, amygdala and, 292 Pedunculopontine tegmental nucleus, 133–134
ataxic, 111, 112f Ossicles, auditory, 315 Penetrating arteries, 354
in cerebellar hemisphere syndrome, 224 Otoacoustic emissions, 319 paramedian, 352
in lateral medullary syndrome, 100 Otolithic membrane, 320, 320f Peptide hormones, as neurotransmitters, 13
vestibular lesions and, 324, 325 Otosclerosis, 324 Periallocortex, 229
Outer nuclear layer, retinal, 310, 310f Periaqueductal gray, of mesencephalon, 142
O Outer plexiform layer, retinal, 310f, 311 Periarchicortex, 229
synaptic organization in, 311–312, 312f Pericallosal artery, 350f, 350–351
Obex, coronal section of brain stem through Oxygen, cerebral circulation and, 356 Perikaryon
medulla oblongata at level of, 454f of neurons, 5f, 5–6, 6f
Occipital horn, of lateral ventricle P reaction to injury, 18–19
axial section of brain through, 442f Perineurium, 10, 10f
T2-weighted coronal section of brain at level Pachygyria, 231, 341, 342f Peripheral nerve disorders, 427
of, 477f Pacinian corpuscles, 15f, 16 Peripheral nerve syndrome, posture/motor control
Occipital lobe Pain and, 414
lateral surface of, 31, 32f pathway for, 393, 393f Perlia’s nucleus, 141
T2-weighted coronal section of brain at level thalamus and, 168 pH, cerebral circulation and, 356
of, 477f Pain syndromes, thalamic, 176, 177t Phalangeal cells, 317, 318f
Ocular bobbing, 127 Paleocerebellar signs, 217 Phrenology, 216
Ocular dipping, 127 Paleocerebellar syndrome, 224 Pia mater
Ocular motor signs, 217 Paleocerebellum, 203 of brain, 25, 27f
Oculomotor loop pathway, Paleocortex, 229 spinal, 47
corticostriatothalamocortical, 190f, 191 Paleostriatum, 181, 183t Pigment epithelium, retinal, 309, 310f
Oculomotor nerve (III), 36f, 37, 37f, 130 Pallidohypothalamic fibers, 272, 273t Pillar cells, 317, 318f
assessment of, 423t Pallidosubthalamic projection, 188 Pineal gland, 157
lesions of, 141f, 141–142 Pallidum, 181, 183t Pinna, 315
Oculomotor nerve palsy, 141f Palmar grasp reflex, 425 Piriform cortex, 245
Oculomotor nuclei, 140–142 Pancerebellar syndrome, 224 Pituitary, hypothalamic control of
accessory, 142 Papez circuit, 283 of anterior pituitary, 273
Olfaction, 305–307 Parabigeminal area, 134 of posterior pituitary, 272
disorders of, 297, 323 Parabrachial nucleus, 106–107, 400–401 Placing reflex, 426
olfactory bulb and, 306 Parachute reflex, 425 Plantar grasp reflex, 425
olfactory epithelium and, 305f, 305–306 Paradoxical sleep, 403 Plexiform layer, of olfactory bulb, 306
INDEX / 491
Plus-minus lid syndrome, 151t, 152 Prefrontal cortex, 250–251, 251f free nerve endings, 15f, 15–16
Poikilothermia, 277 Prefrontal-hypothalamic fibers, 272, 273t Recurrent artery of Heubner, 350, 350f
Points cardineaux, 425 Prefrontal lobe syndrome, 263–264 Recurrent artery of Heubner syndrome, 361
Polar artery, 167t, 174t Premotor cortex, 247 Red nucleus, 138–140
Polydipsia, 269, 277 Pretectal area, 138 parasagittal brain section through, 439f
Polymicrogyria, 342–343 coronal section of brain through, 452f Reflexes, 118, 143f –145f, 143–144
Polyuria, 269, 277 Priming, 298, 299 assessment of, 424t, 424–426
Pons, 34, 34f, 103–121 Probst bundles, 344, 345f, 346 myotatic, 60, 63f, 63–64, 64f, 413–414, 414f,
axial section of brain through, 433f, 445f Procedural memory, 298, 299 424
clinical correlates of, 123–128 Proprioception, 49 in neurologic examination, 424–426
basal pontine syndromes, 124f, 124–125, conscious, pathway for, 389, 390f, 391 spinal, 63
125f nonconscious, pathway for, 391f, 391–392, trigeminal, 118
tegmental pontine syndromes, 125f–127f, 392f Regional cerebral blood flow, 357
125–127 pathways for, 393–394 Reissner’s membrane, 317
coronal section of brain stem through in thalamic pain syndromes, 176, 177t Remak’s band. See Axon(s)
at level of abducens and facial nerve, 456f Prosencephalon, 328f, 328t REM intrusion, 408
at level of trigeminal nerve, 456f Prosocele, 328, 328f Remote memory, 298
cranial nerve nuclei of. See Cranial nerves, Prosopagnosia, 244, 262 Renshaw cells, 50
pontine nuclei of in posterior cerebral artery syndrome, 363 Respiratory function
development of, 330f, 330–331 Protanopia, 314 medulla and, 92–93
gross topography of, 104 Protoplasmic astrocytes, 8, 8f pons and, 127
of dorsal surface, 104 Psalterium, 288 Respiratory insufficiency, in autonomic syndromes,
of ventral surface, 104, 104f Pseudobulbar palsy, 101 76–77
microscopic structure of, 105–106 Pseudotumor cerebri, 384 Restiform body, 80, 80f, 87, 87f, 107, 392
of basis pontis, 105, 105f Pulmonary edema, neurogenic, 93 Reticular formation, 398–406
of tegmentum, 105–106, 106f Pulvinar-lateral posterior complex, 159, 159f ascending, 402
motor pathways arising from, 395–396 Pulvinar nucleus, 159–160 of brain stem, projection to intralaminar nuclei
parabrachial nucleus of, 106–107 Pure motor hemiparesis syndrome, 364 from, 162, 162f
pedunculopontine nucleus of, 107, 107f Pure sensory syndrome, lacunar, 364 chemically specified systems of, 401
projections to oculomotor nucleus, 140 Pure word deafness, 261 clinical correlates of, 407–409
reticular formation of, 106 Purkinje cells, 204, 205t connections of, 400–401
rostral Putamen, 34, 35f, 181, 183t, 184f functions of, 401–402
at level of isthmus, coronal section of brain basal ganglia at level of head of, coronal section medullary, 86
stem through, 457f of brain stem through, 462f nomenclature for, 399
at level of trochlear nerve, coronal section Pyramidal decussation, 59, 81, 82f organization of, 399f, 399–400, 400t
of brain stem through, 457f Pyramidal neurons, of cerebral cortex, 230, 230f pontine, 106
T2-weighted axial section of brain through, Pyramidal tract, 394, 394f sleep and, 402–405
472f aberrant, 235 Reticular nucleus, thalamic, 401
Pontine flexure, 328, 328f Reticulospinal tracts, 52t, 61–62, 62f
Pontine reticulospinal tract, 396 Q Reticulosubthalamic projection, 188
Pontomedullary junction Retina, 309–313
axial section of brain through, 446 Quadrantic hemianopia, 324 anatomy of, 309–311, 310f
coronal section of brain stem through, 455f Quadriceps myotatic reflex, 63, 414 photochemistry and physiology of, 312–313
Postcentral gyri, axial section through, 431f Quadrigeminal cistern, 372, 372f projections to superior colliculus, 136–137
Posterior cerebral artery syndrome, 362–363, 363f Quadrigeminal plate, 130 synaptic organization of, 311–312, 312f
Posterior column-medial lemniscus system, 389, Retinohypothalamic tract, 271, 273t
390f, 391 R Reward, septal area and, 294
Posterior commissure Rexed terminology, for spinal gray matter, 49–51,
axial section of brain through, 443f Radial jerk reflex, 63, 414 50f, 50t, 51f
nucleus of, 142 Raphe nuclei, 399–400, 400t Rhinencephalon, 281f, 281–282, 282f, 297
Posterior inferior cerebellar artery (PICA), 352 connections of, 400–401 Rhombencephalon, 328f, 328t
Posterior inferior cerebellar artery (PICA) Rapid eye movement (REM) sleep, 403 Rhombic lip, 331
syndrome, 99f, 99–101, 100f, 101t, 225, 225f pons and, 127 Rhombocele, 328, 328f
Posterior median fissure, 80 Raymond-Cestan-Chenais syndrome, 126–127 Right hemisphere, language and, 250
Posteromedial artery, 167t, 174t Raymond-Foville syndrome, 126 Rinne test, 324
Posture/motor control, 411–420 Receptor cells Rods, retinal, 309–310, 310f, 312–313
functional anatomy of, 413, 413f auditory, 317, 318f Rolandic sulcus, 29, 29f
locomotion and, 418 olfactory, 305–306 Rooting reflex, 425
overview of, 418–419, 419f retinal, interactions with bipolar and horizontal Rostral interstitial nucleus of the medial
peripheral nervous system areas involved in, cells, 311–312 longitudinal fasciculus (RiMLF), 140, 142
412 in taste buds, 307f, 307–308 Rostrum, of corpus callosum, coronal section of
segmental motor control, 413–414, 414f Receptors brain through, 447f
segmental motor disorders and, 414–415 for posterior column-medial lemniscus system, Rubrocerebellar fibers, 140
sequence of events in, 412f, 412–413 389 Rubro-olivary tract, 140
suprasegmental motor control, 415f–418f, of posterior funiculus, 52 Rubroreticular fibers, 140
415–418 sensory, 15–18 Rubrospinal fibers, 139–140
Precentral gyri, axial section through, 431f encapsulated nerve endings, 15f, 16–18, 17f Rubrospinal tract, 52t, 60–61, 61f, 132, 132f
492 / INDEX
Ruffini’s corpuscles, 15f, 16 reticular activating system and, 402–405 of white matter, 51t, 51–62, 52t
Russell syndrome, 277 phases and stages of sleep and, 402–403 myotomes and, 47, 47t
sleep and arousal mechanisms and, regional development of, 330
S 403–405, 404f, 405f transection of, 75–76
slow wave, 403 tumors of, cerebrospinal fluid and, 380, 380t
Saccadic eye movements Sleep apnea, central, 408 Spinal reflexes, 63
control of, 145f, 145–146 Sleep walking, 407–408 Spinal shock, 75–76
cortical areas preparing, 248 Smooth endoplasmic reticulum (SER), 6 Spinal tap, 47
cortical eye fields and, 247–248, 248f Smooth-pursuit eye movements Spindle neurons, of cerebral cortex, 230, 230f
Saccule, 109 control of, 146–147 Spinocerebellar tract
Sacral sparing, 56, 72 cortical eye fields and, 248–249 dorsal, 51t, 54, 56f, 57f
Saddle anesthesia, 76 Sneezing, medulla and, 93 ventral, 51t, 54–55
Scarpa’s ganglion, 109–110, 110f Sneezing reflex, 118 Spinocerebellar tracts, 81f, 84, 391f, 391–392,
Schaffer sign, 424 Somatic motor fibers, facial, 112–114 392f
Schizencephaly, 331, 343f, 343–344 Somatosensory area, primary, of cerebral cortex, Spinocerebellum, 203
Schizophrenia, 300–301 240–241, 241f Spinocervical thalamic tract, 51t, 55–56
Schmidt-Lanterman clefts, 11 Somatosensory association areas, primary, of Spinotectal fibers, 137
Schwalbe’s nucleus, 110 cerebral cortex, 242 Spinothalamic lemniscus, projection to
Schwann cells, 6 Somatostatin, medullary, 94, 94t intralaminar nuclei from, 162, 162f
Search reflex, 425 Somesthetic area, of cerebral cortex Spinothalamic tracts, 84, 132, 132f
Secretomotor fibers, facial, 114 primary, 240–241, 241f anterior, 51t, 58–59
Seizures, epileptic. See Epilepsy secondary, 241–242 lateral, 51t, 56–58, 58f, 59f
Semantic memory, 298 Somesthetic association areas, primary, of cerebral lesions affecting, signs of, 72, 72f
Semilunar ganglion, 117 cortex, 242 Spiral ganglion, 107
Sensorineural hearing loss, 324 Sommer’s sector, 286 Splenium, of corpus callosum, axial section of brain
Sensory areas Somnambulism, 407–408 through, 441f
of cerebral cortex. See Cerebral cortex, sensory Sound, transmission of, 316, 316f Split pathways, corticostriatothalamocortical, 191,
areas of Sound waves, conduction of, 318 192f
general, of cerebral cortex, 240–241, 241f Spatial neglect, basal ganglia and, 193 Stapes, 315
supplementary, of cerebral cortex, 242 Spatial perception disorders, in cerebrovascular Startle reflex, 425
Sensory decussation, 84–85 occlusion syndromes, 359–360 Steal syndrome, 357
coronal section of brain stem through medulla Spinal arteries Stellate cells, 205, 205t
oblongata at level of, 453f anterior, 67, 67f, 352 of cerebral cortex, 230f, 230–231
Sensory function anterior spinal artery syndrome and, 75, 76f Stepping reflex, 426
assessment of, 424 posterior, 67, 67f, 352 Stereognosis, in cerebrovascular occlusion
of cerebellum, 220 Spinal cord, 45–77. See also Central nervous system syndromes, 360
somatic, reticular mediation of, 402 (CNS) Stilling column (nucleus), 54, 56f, 392
Sensory neurons, receptor organs of, 15–18 asymmetry of, 48 Stransky sign, 424
encapsulated nerve endings, 15f, 16–18, 17f blood supply of, 67, 67f Stretch reflexes. See Myotatic reflexes
free nerve endings, 15f, 15–16 clinically important structures of, 70–71, 71f Stria medullaris thalami, 33, 156
Sensory pathways, 389–394 coronal sections of Stria terminalis, 291, 291f
for conscious proprioception, 389, 390f, 391 at different levels, 463f Striatonigral projections, 187
for nonconscious proprioception, 391f, at level of third sacral segment, 466 Striatopallidal projections, 187
391–392, 392f at lower cervical (C8) level, 464f Striatum, 181–184, 183f, 183t, 184f, 185t
for pain and temperature, 393, 393f at lower lumbar level, 465f intralaminar nuclear projections to, 163
trigeminal, 393–394 at lower thoracic level, 465f rostral, coronal section of brain through, 448f
Septal area, 292, 293f, 294–295 of term stillborn infant at lower lumbar ventral, 188–189
connections of, 294, 294f level, showing variation in myelination Stroke, 359–367
functions of, 294–295 of different tracts, 466 hemorrhage syndromes, 364f–366f, 364–365
Septal syndrome, 295 at upper cervical (C1-C2) level, 463f occlusion syndromes, 359–364
Septal vein, 355 at upper thoracic level, 464f Strümpell sign, 424
Septo-optic dysplasia, 346 cross-sectional topography of, 47–48, 48f Stylomastoid foramen, lesions of, 115
Septum pellucidum, 33 dermatomes and, 47, 47f Subarachnoid cisterns, 372, 372f
Serotonin, medullary, 94, 94t disorders of, 427 Subarachnoid hemorrhage, cerebrospinal fluid and,
“Setting-sun sign,” 381 clinicopathologic syndromes, 72–77, 380, 380t
Sexual activity, amygdala and, 292 73f–76f Subarachnoid space, 27
Sexual arousal, hypothalamus and, 274 motor signs of, 71 Subclavian artery, 67
Sexual function, in spinal shock, 76 sensory signs of, 71–72, 72f, 73f Subcortical aphasia, 261
Shapiro syndrome, 277 external topography of, 45–46, 46f, 46t Subdural hematoma, spinal, 47
Shock, spinal, 75–76 functional overview of, 66 Subdural space, 27
Short-term memory, 298–299 hemisection of, 73–74, 74f Subiculum, 285, 286
Simultanagnosia, 262, 265 meninges of, 47 Substance P
Sleep microscopic anatomy of, 48–66, 49f medullary, 94, 94t
disorders of, 407–409 of gray matter, 49–51, 50f, 50t, 51f striatal, 187t
hypothalamic, 277–278, 278t neurotransmitters and neuropeptides and, Substantia nigra, 134–136, 135t
hypothalamus and, 274 62–63 Substantia nigra pars reticulata, 185
REM (paradoxical), 403 spinal reflexes and, 63f–66f, 63–64, 65t outputs of, 187f–189f, 187–188
INDEX / 493
striatonigral projections and, 187 at superior colliculus level, 136–138, 137f axial section through, 432f
Subthalamic nuclei, 135 Tegmental pontine syndromes, 125f–127f, blood supply of, 166, 167t, 174t
of basal ganglia, 185 125–127 caudal, T2-weighted coronal section of brain at
inputs to, 188, 189f caudal, 126 level of, 475f
of Luys, 168–169, 169f dorsolateral, 126 centromedial nucleus of, parasagittal brain
parasagittal brain section through, 438f extreme lateral, 127 section through, 437f, 438f
Subthalamic region, coronal section of brain medial, 125, 125f clinical correlates of thalamic anatomy and,
through, 451f mid-tegmental, 126 172–173, 174t
Subthalamus rostral, 126–127 dorsal, axial section of brain through, 441f
clinical correlates of, 178 Tegmentonigral tracts, 135 functions of, 166, 168
coronal section of brain through, 450f Tegmentum, 105–106, 106f, 131 medial, parasagittal brain section through, 438f
Sucking reflex, 425 at inferior colliculus level, 132, 132f neuropeptides of, 165
Sulcus limitans, 330, 330f at superior colliculus level, 138–142 neurotransmitters of, 165
Superficial reflexes, assessment of, 424 Tela choroidea, 330 in pain, 168
Superior cerebellar artery (SCA) syndrome, 224f, Telencephalon, 327, 328f, 328t reticular nucleus of, 401
224–225, 353 Teloceles, 328, 328f rostral, coronal section of brain through, 449f
Superior cerebellar peduncle, 132, 132f Temperature, pathway for, 393, 393f T2-weighted axial section of brain through,
Superior cistern, 372, 372f Temperature regulation, hypothalamic, 274 471f
Superior colliculus Temporal lobe T2-weighted coronal section of brain at level
facial nerve and, 114 axial section through, 434f of, 475f
midbrain at level of, coronal section of brain lateral surface of, 31, 32f ventral anterior nucleus of, rostral
stem through, 459f ventral surface of, 34 diencephalon at level of, coronal section of
rostral, midbrain at level of, coronal section of Temporal lobe epilepsy, 299–300, 300f brain stem through, 461f
brain stem through, 459f Tendon organs of Golgi, 17f, 17–18 ventral lateral nucleus of, diencephalon at level
Superior olive, facial nerve and, 114 Tentorium cerebelli, 25 of, coronal section of brain stem through,
Supporting cells Teratogens, 337 461f
auditory, 317–318, 318f Terminal vein, 355 Thermoregulatory disorders, hypothalamic, 277,
of olfactory epithelium, 306 Tethered cord syndrome, 327, 340, 340f 278t
in taste buds, 308 Thalamic infarcts, 173, 175–178 Third ventricle, T2-weighted coronal section of
Supraoptic-hypophyseal tract, 270f, 271, 273t acalculia and, 177–178 brain at level of, 475f
Suprasellar cistern, 372, 372f alien hand syndrome and, 177 Thirst, hypothalamus and, 274
Survival factors (NTFs), 19 anterolateral, 173, 175 Thomas reflex, 424
Sustentacular cells, of olfactory epithelium, 306 arousal and, 177 Thoracic nucleus, 54, 56f
Swallowing, medulla and, 93, 94f Cheiro-Oral syndrome and, 177 Throckmorton sign, 424
Sydenham’s chorea, 196 clinical manifestations of, 167t, 174t Tic(s), 197, 198, 198f
Sylvian fissure, 29, 29f, 249 language deficits and, 178 Tic douloureux, 117, 118
Sympathetic nervous system, 49 lateral, 175–176, 176f Tinnitus, 324
cerebral circulation and, 356 medial, 175, 175f Tongue, trombone, 196
Synapses, 12–15, 13f, 51 memory deficits with, 176 Tonic neck reflex, 425
electric, 13 pain syndromes and, 176, 177t Tonsils (cerebellar), 34, 36f
excitatory, 13 posterior, 176, 177f Top of the basilar syndrome, 153
inhibitory, 13 posterolateral, 173, 173f Topographagnosia, in cerebrovascular occlusion
Syndrome of inappropriate antidiuretic hormone, Thalamic nuclei, 157–165, 158f syndromes, 360
277 anterior, 158, 158f Torcular Herophili, 355
Syringobulbia, 75 intralaminar, 162f, 162–163 Torticollis, 197
Syringohydromyelia, 339 intralaminar nuclear projections to, 163 Tourette syndrome, 197, 197f
Syringomyelia, 56, 74–75, 75f lateral, 159–162 Tract of Barns, 52t, 59
Syrinx, 75 dorsal subgroup of, 159f, 159–160 Tract of Goll, 52, 389
geniculate, 163, 164f Tract of Vicq d’Azyr, 272
T medial, 158–159, 159f Transcortical aphasia, 260t, 260–261
geniculate, 163 Transient global amnesia, 299
Tactile agnosia, 263 midline, projections to, 163 Trapezoid body, 107–108
Tactile anomia, unilateral, 263 neuronal circuitry of, 165, 165f Tremor, intention, in cerebellar hemisphere
Taste sense, 307–309 nomenclature for, 163–165, 165t syndrome, 224
abnormalities in, 323–324 posterior, 163 Triceps jerk reflex, 63, 414
central transmission of taste sensations and, reticular, projections to, 163 Trigeminal lemniscus, 132, 132f
308f, 308–309 Thalamocortical input, to cerebral cortex, 232, projection to intralaminar nuclei from, 162,
physiology of, 308 233f 162f
taste buds and, 307f, 307–308 Thalamogeniculate artery, posterolateral, 167t, Trigeminal nerve (V), 36f, 37, 37f
Tearing reflex, 118 174t assessment of, 423t
Tectopontocerebellar tract, 138 Thalamohypothalamic fibers, 271, 273t pons at level of, coronal section of brain stem
Tectoreticular tract, 138 Thalamoperforating artery, 167t, 174t through, 456f
Tectorial membrane, 318 Thalamostriate projections, 186 pontine nuclei of, 117–120
Tectospinal tract, 52t, 62, 62f, 138 Thalamostriate vein, 355 afferent root, 117f, 117–118
Tectothalamic tract, 138 Thalamosubthalamic projection, 188 blood supply and, 118, 119f, 120
Tectum, 130 Thalamus, 33, 39, 40f, 156. See also Thalamic efferent root, 117
at inferior colliculus level, 131 infarcts reflexes and, 118
494 / INDEX
Trigeminal nerve (cont.) Ventral anterior nucleus, of thalamus, 160, 160f retina and, 309–313
spinal nucleus of, 83–84 Ventral horn, 49, 49f, 50f anatomy of, 309–311, 310f
Trigeminal neuralgia, 117, 118 spinal, 66 photochemistry and physiology of,
Trigeminal pathways, 393–394 Ventral lateral nucleus, of thalamus, 160–161, 312–313
Trigeminal reflexes, 118 161f, 161t synaptic organization of, 311–312, 312f
Trigeminal system, facial nerve and, 114 Ventral posterior inferior (VPI) nucleus, of visual pathways and, 314f, 314–315, 315f
Trigeminal tractotomy, 117–118 thalamus, 162 Visual agnosia, 262
Trigone, of lateral ventricle, axial section of brain Ventral posterior nucleus, of thalamus, 161–162, Visual association areas, primary, of cerebral cortex,
through, 442f 162f 244
Tritanopia, 314 Ventral striatum, 188–189 Visual cortex, primary, of cerebral cortex, 242f,
Trochlear nerve (IV), 37, 130 Ventral suspension reflex, 425 242–244, 243f
assessment of, 423t Ventral tegmental nucleus, 133 Visual field deficits, in cerebrovascular occlusion
nucleus of, 132–133, 133f Ventricles syndromes, 359–360
rostral pons at level of, coronal section of brain fifth, 368–369, 370f Visual obscuration, in idiopathic intracranial
stem through, 457f fourth, surface landmarks of, 80, 80f hypertension, 384
Trochlear nucleus, midbrain at level of, coronal lateral. See Lateral ventricles Visual pathways, 314f, 314–315, 315f
section of brain stem through, 458f third, T2-weighted coronal section of brain at Visuoconstructive apraxia, 261–262
Trombone tongue, 196 level of, 475f Vomiting, neuroanatomy of, 94
Trommer reflex, 425 Ventricular puncture, 376 Vomiting reflex, 118
Truncal incurvation reflex, 425 Ventricular system
Tuberohypophyseal tract, 271, 273t anatomy of, 360f–371f, 368–371 W
Tuberoinfundibular tract, 271 embryogenesis of, 328f, 328–329, 329t
Tuberothalamic artery, 167t, 174t Ventriculomegaly, 380, 381f, 382f Wakefulness, hypothalamus and, 274
Türck’s bundle, 394 Ventrobasal complex, 162 Walker-Warburg syndrome, 341
Tympanic cavity, 315 Ventrolateral sulcus, 48, 48f Wallenberg’s syndrome, 99f, 99–101, 100f, 101t
Tympanic membrane, 315 Verbal auditory agnosia, 261 Wallerian degeneration, 19, 20f, 20t, 21
Tympanic reflex, 316 Vermis, 34, 37f Walleyed syndrome, 151t, 152
cerebellar, 201, 201f Water balance, disorders of, hypothalamic, 277,
U Vertebral arteries, 67, 352 278t
lumen of, cerebral circulation and, 356 Water consumption, septal area and, 294
Uncinate fits, 259, 297, 323 Vertebral-basilar artery syndrome, 363, 364t Weber’s syndrome, 141f, 151, 151t
Uncus, 34 Vertical gaze, 144–145 Weber test, 324
Upper motor neuron signs, 60, 71, 71f Vertical one-and-a-half syndrome, 151t, 152 Werdnig-Hoffmann disease, 414, 425
Utricle, 109 Vertigo, 324–325 Wernicke-Korsakoff syndrome, 299
Vesicles, neural tube development into, 327–328, Wernicke’s area, 31, 249, 249f
V 328f, 328t White matter, spinal, 51t, 51–62, 52t
Vestibular cortex, primary, 245 anterior funiculus of, 54
Vagal trigone, 80 Vestibular sensation, 319f, 319–320, 320f ascending tracts of, 51, 51t, 54–59, 56f–59f
Vagus nerve (X), 37 Vestibular sense, disorders of, 324–325 descending tracts of, 52t, 59f–62f, 59–62
assessment of, 423t Vestibulocerebellum, 203 lateral funiculus of, 54
medullary nuclei of, 89–91, 90f Vestibulocochlear nerve (VIII), medullary nucleus posterior funiculus of, 51–54, 53f–55f, 54t
dorsolateral, 89–90 of, 92 Word deafness, pure, 261
nucleus ambiguus, 90–91 Vestibulospinal tracts Working memory, 298–299
Vascular syndromes lateral, 52t, 61, 61f, 395 Wrisberg’s nerve, 112
cerebral, 359–367 medial, 52t, 61, 61f, 396 Writer’s cramp, 197
hemorrhage syndromes, 364f–366f, 364–365 Vibration sense, spinal cord disorders and, 71
occlusion syndromes, 359–364 Vicq d’Azyr, tract of, 272 Y
mesencephalic, 150–153, 151t Viral encephalitis, cerebrospinal fluid in, 379, 380t
Vater-Pacini corpuscles, 15f, 16 Visceral motor fibers, facial, 114 Yawning, neuroanatomy of, 94
Vein of Galen, 355 Vision, 309–315
Vein of Labbé, 355 color, 313–314 Z
Velum, medullary, 80, 80f dark and light adaptation and, 313
Ventral amygdalofugal pathway, 291 disorders of, 324 Zona incerta, 169–170

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FM_6082_Afifi_MGH 12/10/04 10:22 AM Page vi

FM_6082_Afifi_MGH 12/10/04 10:22 AM Page i

Adel K. Afifi, M.D., M.S.

Ronald A. Bergman, Ph.D.

Lange Medical Books/McGraw-Hill

FUNCTIONAL NEUROANATOMY: Text and Atlas, Second Edition

1234567890 QPD QPD 098765

Quebecor Dubuque was printer and binder.

This book is printed on acid-free paper.

Chapter 33 Reticular Formation, Wakefulness, and Sleep: Clinical Correlates . . . . . . . . . . . . . . . . . . . . . . . . . . .407

Adel K. Afifi, M.D., M.S.

The Cells and Their Unique Characteristics Synapse

(continued on next page)

THE CELLS AND THEIR UNIQUE B Ax

root] ganglion cells) have a spherical cell body with single E

one axon and many dendritic processes (Figure 1–1 A–G ).

Small Nucleus Schwann cell Axon

Axon space c midt-

Figure 1–6. Schematic diagram of the structure of a myelin-

type of impulse conduction is known as saltatory conduction; it

Table 1–1. Some Properties of Mammalian Peripheral Nerve Fibers.

A alpha () Ia Proprioception, stretch (muscle, spindle, 12–22 70–120

A Axodendritic B Postsynaptic membrane Synaptic cleft

Flower spray endings

Nucleolus Myelin Axon

Eccentric Synaptic degeneration

Chromatolysis Proximal and distal

Table 1–2. Nerve Injury.

Degree of Wallerian Endoneurium Perineurium Epineurium Nerve Nerve

Figure 1–15. Schematic diagram of the five types of nerve injury.

Central Nervous System Internal Topography of the Brain

CEREBRAL DURAL VENOUS SINUSES EXTERNAL TOPOGRAPHY OF THE BRAIN

Superior Sagittal Sinus Transverse Sinus

(A) Occipital Sinus

Superior Sagittal Inferior Sagittal

Lesions in this area result in an inability to express oneself in spo-

Precentral Central Postcentral

Lateral (Sylvian) Superior Temporal

Parieto-Occipital Marginal Central Cingulate

Medulla Pons Mesencephalon Diencephalon

Centrum Internal Capsule

Olfactory Bulb Olfactory Sulcus

Cerebral Peduncle Optic Chiasma

Facial Nerve Trigeminal Nerve

Septum Internal Capsule

Lateral Medial Internal Medullary

Corpus Callosum Internal Capsule

White Matter Core

Septum Pellucidum Insula

Lateral Ventricle, Putamen

Lateral Ventricle Choroid Plexus

Corpus Callosum Frontal Internal Cerebral Arachnoid Parietal

Pons Medullary Vertebral

Anterior Cerebral Artery

Corpus Callosum Frontal Lobe

Internal Capsule Fornix, Column

Parietal Lobe Lateral Ventricle (Trigone,

Superior Sagittal Occipital Lobe

Figure 2–23. T2-weighted axial MRI through the thalamus.