The inferior colliculus (IC) plays a key role in modulating audiogenic seizures (AS) in rats. We ... more The inferior colliculus (IC) plays a key role in modulating audiogenic seizures (AS) in rats. We investigated whether acoustic brainstem nuclei express Fos-like immunoreactivity (FLI) after flurothyl-induced generalized seizures in rats. Compared to controls, experimental animals showed significantly (P<0.05) more FLI in the dorsal and external cortex of the IC, as well as in the medial part of the medial geniculate body (MGB), perigeniculate area, and dorsal cochlear nucleus. No significant increase of FLI was observed in the central nucleus of the IC, ventral and dorsal parts of the MGB, dorsal nucleus of the lateral lemniscus, or ventral cochlear nucleus. Because this pattern of FLI closely resembles that observed after AS in previous studies, these results suggest that Fos expression in acoustic brainstem nuclei is not specific for AS.
Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference, 2005
Ambulatory EEG recorders are commercially available. The majority of these recorders are only cap... more Ambulatory EEG recorders are commercially available. The majority of these recorders are only capable of capturing and storing EEG for later review by clinicians. A few models are equipped with real-time seizure event detectors, but these detectors make no guarantees on when during a seizure a detection is made. This renders current ambulatory EEG recorders unsuitable for activating alarms or initiating therapies to acutely impact seizure progression in the ambulatory setting. Integrating seizure onset detectors into existing ambulatory recorders will make these applications feasible. Successful integration requires that these detectors be executable on the resource-limited digital signal processors found within ambulatory recorders. In this paper we describe the integration of a patient-specific seizure onset detector with a commercially available ambulatory EEG recorder, and demonstrate how such integration could enable the detection of seizure onset in the ambulatory setting.
... Information , a , c , Corresponding Author Contact Information , Anthony Bolton e , Dara Mano... more ... Information , a , c , Corresponding Author Contact Information , Anthony Bolton e , Dara Manoach d , a , Margaret O'Connor d , a , Sandra Weintraub f , Howard Blume c , b and Donald L. Schomer c , a. a From the Department of Neurology, Beth Israel Hospital and Harvard ...
Electroencephalography and clinical neurophysiology, 1993
The recording of an EEG while the patient is undergoing magnetic resonance imaging (MRI) data acq... more The recording of an EEG while the patient is undergoing magnetic resonance imaging (MRI) data acquisition, as far as we are aware, has not been previously accomplished. By careful selection and arrangement of analog multiplexed cable-telemetry equipment to eliminate both ferrous and RF sources, a stable, readable EEG can be obtained without interfering with the diagnostic quality of the MRI. This arrangement does not cause localized heating or burning at the electrode sites. This technical capability permits more accurate neurophysiological control during the acquisition of echo planar functional MRI studies as well as providing indications of anatomical localization of electrical sources.
Electroencephalography and clinical neurophysiology, 1988
A multi-channel switched-capacitor 6-pole filter for significantly reducing the EMG artifact pres... more A multi-channel switched-capacitor 6-pole filter for significantly reducing the EMG artifact present during seizures recorded by long-term monitoring procedures has been implemented for routine use. This permits repeated replay of the seizures with different filter settings. All of the channels can be simultaneously dialed to any cut-off frequency (3 dB down) between 8 Hz and 70 Hz and the event replayed for filtering and write-out onto any standard EEG machine. The advantage of the 6-pole switched-capacitor filter is that it does not require a complex design with high precision RC components. The cut-off frequency is determined by the frequency of a simple clock that is used to select the same cut-off point for all 16 channels. By changing the clock frequency, the operator moves the cut-off point linearly. The dramatic improvement obtained by off-line digital filtering that was recently reported (Gotman et al. 1981) indicates that more efficient filtering of EMG contaminated seizur...
We previously observed tht low oral doses of melatonin given at noon increase blood melatonin con... more We previously observed tht low oral doses of melatonin given at noon increase blood melatonin concentrations to those normally occurring nocturnally and facilitate sleep onset, as assessed using and involuntary muscle relaxation test. In this study we examined the induction of polysomnographically recorded sleep by similar doses given later in the evening, close to the times of endogenous melatonin release and habitual sleep onset. Volunteers received the hormone (oral doses of 0.3 or 1.0 mg) or placebo at 6, 8, or 9 PM. Latencies to sleep onset, to stage 2 sleep, and to rapid eye movement (REM) sleep were measured polysomnographically. Either dose given at any of the three time points decreased sleep onset latency and latency to stage 2 sleep. Melatonin did not suppress REM sleep or delay its onset. Most volunteers could clearly distinguish between the effects of melatonin and those of placebo when the hormone was tested at 6 or 8 PM. Neither melatonin dose induced "hangover" effects, as assessed with mood and performance tests administered on the morning after treatment. These data provide new evidence that nocturnal melatonin secretion may be involved in physiologic sleep onset and that exogenous melatonin may be useful in treating insomnia.
We previously observed that low oral doses of melatonin given at noon increase blood melatonin co... more We previously observed that low oral doses of melatonin given at noon increase blood melatonin con- centrations to those normally occurring nocturnally and facilitate sleep onset, as assessed using an invol- untary muscle relaxation test. In this study we examined the induction of polysomnographically re- corded sleep by similar doses given later in the evening, dose to the times of
Regulatory toxicology and pharmacology : RTP, 2002
Over 20 years have elapsed since aspartame was approved by regulatory agencies as a sweetener and... more Over 20 years have elapsed since aspartame was approved by regulatory agencies as a sweetener and flavor enhancer. The safety of aspartame and its metabolic constituents was established through extensive toxicology studies in laboratory animals, using much greater doses than people could possibly consume. Its safety was further confirmed through studies in several human subpopulations, including healthy infants, children, adolescents, and adults; obese individuals; diabetics; lactating women; and individuals heterozygous (PKUH) for the genetic disease phenylketonuria (PKU) who have a decreased ability to metabolize the essential amino acid, phenylalanine. Several scientific issues continued to be raised after approval, largely as a concern for theoretical toxicity from its metabolic components--the amino acids, aspartate and phenylalanine, and methanol--even though dietary exposure to these components is much greater than from aspartame. Nonetheless, additional research, including e...
Ophthalmic Plastic and Reconstructive Surgery, 2014
To determine the viability of lacrimal sinus diversion by using a novel Sinopsys Surgical Lacrima... more To determine the viability of lacrimal sinus diversion by using a novel Sinopsys Surgical Lacrimal Stent. Two disarticulated cadaveric heads were used in the laboratory. First, bilateral conjunctivodacryocystorhinostomies (CDCR) were performed by using a traditional Pyrex Jones tube and the Sinopsys Surgical Lacrimal Stent. The fluiditics were then evaluated by using contrast agent and fluroscopy. Subsequently, conjunctivoethmoidectomies (CE) and conjunctivomaxillectomies (CM) were performed by using the Sinopsys Surgical Lacrimal Stent, of which the fluiditics were also studied. The conjunctivodacryocystorhinostomy (CDCR) placement experience of the Jones tube and the Sinopsys Surgical Lacrimal Stent were similar. The CDCR fluiditics as measured by using contrast agent and fluoroscopy were identical with each draining 0.5 mL over 5 to 10 seconds. Placement of the Sinopsys Surgical Lacrimal Stent in the 4 ethmoid (CE) and 4 maxillary (CM) sinuses was similar to the CDCR experience. Fluiditics of lacrimal sinus diversion were similar to CDCR with drainage of 0.5 mL over 5 seconds. The Sinopsys Surgical Lacrimal Stent has flow characteristics that are similar to a Pyrex Jones tube. Drainage in the nose via a CDCR procedure is similar to drainage in the ethmoid and maxillary sinuses via a CE and CM, respectively.
It is still generally believed that complex visual analysis is not carried out within the first 1... more It is still generally believed that complex visual analysis is not carried out within the first 100 ms. Here we show that intra- and extracranial visual evoked potentials (VEPs) differentiate previously seen faces from novel faces as early as 50 ms after stimulus onset. EEG was recorded from scalp electrodes in 12 male healthy volunteers (group I) and intracranially from implanted depth electrodes in the temporal and frontal cortex of seven epilepsy patients (group II). Both groups were engaged in a face recognition task. All subjects showed significant differential responses which occurred very early (50-90 ms) and later (190-600 ms). In group II, the early responses were recorded more frequently in the right hemisphere, whereas the late differential VEPs were found in both hemispheres. Both types of VEPs were more frequent in the temporal neocortex, underlining its role as a major contributor to these fast recognition processes.
Kainic acid-triggered seizures (KATS) induce Fos-like immunoreactivity (FLI) in limbic structures... more Kainic acid-triggered seizures (KATS) induce Fos-like immunoreactivity (FLI) in limbic structures, which send efferents to the locus coeruleus (LC). Following KATS, brain stem sections were stained for Fos immunocytochemistry and double immunostained for Fos and dopamine beta-hydroxylase (DBH). KA-treated animals showed significantly greater numbers of FLI neurons in the LC than control animals (p < 0.05). Co-localization of DBH/Fos was observed in 89.7% of the LC neurons in KA-treated animals and in 1.4% of LC neurons in control animals. Thus, KATS heavily induce Fos in DBH-containing neurons in the LC, which are known to project to the hippocampus. However, the role of activation of the LC noradrenergic neurons during KATS is not well understood at this present time.
We investigated whether: (1) EEG recordings could be successfully performed in an MRI imager, (2)... more We investigated whether: (1) EEG recordings could be successfully performed in an MRI imager, (2) subclinical epileptic discharges could be used to trigger ultrafast functional MRI images, (3) artifact-free functional MRI images could be obtained while the patient was having the EEG monitored, and (4) the functional MRI images so obtained would show focal signal increases in relation to epileptic discharges. We report our results in two patients who showed focally higher signal intensity, reflective of increased local blood flow, in ultrafast functional MRI timed to epileptic discharges recorded while the patients were in the imager and compared with images not associated with discharges. One patient showed a focal increase despite a clinical and EEG history of generalized discharges. This approach may have the potential to identify brain regions activated during brief focal epileptic discharges.
Medications are the most common treatment for epilepsy. Regimens vary from once per day dosing to... more Medications are the most common treatment for epilepsy. Regimens vary from once per day dosing to several pills several times per day. More complex regimens have been associated with lower adherence rates. To date, medication complexity has been measured by the number of pills and the number of times per day the pills are taken. However, complexity also includes special instructions (e.g., take at a separate time than other medications) and the specific administration actions (e.g., take 1/2 pill). This article describes the development of an instrument designed to measure the complexity associated with epilepsy treatment regimens. The medication complexity tool (MCI) was modified to create the Epilepsy Medication and Treatment Complexity Index (EMTCI). The EMTCI comprises four sections: (a) general medication information, (b) frequency of administration, (c) special instructions, and (d) administration actions. Points are given for dosing schedules, special instructions, and administration actions. A total complexity score is calculated by adding points for each section. One form is completed for each medication prescribed for each person. The initial development of the EMTCI included revising the MCI to make it applicable to epilepsy medication. Interrater and intrarater reliability assessments were conducted. The EMTCI was administered to adults with epilepsy as part of a larger study of self-management in people with epilepsy. Data from that study were used for further assessments of the EMTCI including test-retest reliability, criterion validity, and construct validity. The EMTCI shows evidence of both reliability and validity. Information from the tool can be used to describe the medication complexity of epilepsy medication regimens in much greater detail than has been done previously for this population. This information is useful in describing the treatment and adherence issues for persons with epilepsy.
The purpose of this study was to document seizure events associated with the use of a computer-ba... more The purpose of this study was to document seizure events associated with the use of a computer-based assessment and to describe the contextual factors surrounding these seizure episodes. Study participants were adults with epilepsy who were enrolled at research sites in Atlanta and Boston. Subjects were asked to complete a computer-based assessment at 3 time points. Fourteen seizure events were documented; they occurred during 1.6% of all completed assessments (896) and affected 4.4% of the participants (320). The mean age of participants who experienced seizure events was 41.4 years; about 70% were female, and 70% were white. A variety of possible precipitating factors for seizure events included hunger, fatigue, stress, and medication changes. Participants indicated computer use could have triggered their seizures in 2 instances. These findings suggest use of computer-based assessments may pose minimal risks for adults with epilepsy, particularly those without a history of photosensitivity epilepsy.
The inferior colliculus (IC) plays a key role in modulating audiogenic seizures (AS) in rats. We ... more The inferior colliculus (IC) plays a key role in modulating audiogenic seizures (AS) in rats. We investigated whether acoustic brainstem nuclei express Fos-like immunoreactivity (FLI) after flurothyl-induced generalized seizures in rats. Compared to controls, experimental animals showed significantly (P<0.05) more FLI in the dorsal and external cortex of the IC, as well as in the medial part of the medial geniculate body (MGB), perigeniculate area, and dorsal cochlear nucleus. No significant increase of FLI was observed in the central nucleus of the IC, ventral and dorsal parts of the MGB, dorsal nucleus of the lateral lemniscus, or ventral cochlear nucleus. Because this pattern of FLI closely resembles that observed after AS in previous studies, these results suggest that Fos expression in acoustic brainstem nuclei is not specific for AS.
Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference, 2005
Ambulatory EEG recorders are commercially available. The majority of these recorders are only cap... more Ambulatory EEG recorders are commercially available. The majority of these recorders are only capable of capturing and storing EEG for later review by clinicians. A few models are equipped with real-time seizure event detectors, but these detectors make no guarantees on when during a seizure a detection is made. This renders current ambulatory EEG recorders unsuitable for activating alarms or initiating therapies to acutely impact seizure progression in the ambulatory setting. Integrating seizure onset detectors into existing ambulatory recorders will make these applications feasible. Successful integration requires that these detectors be executable on the resource-limited digital signal processors found within ambulatory recorders. In this paper we describe the integration of a patient-specific seizure onset detector with a commercially available ambulatory EEG recorder, and demonstrate how such integration could enable the detection of seizure onset in the ambulatory setting.
... Information , a , c , Corresponding Author Contact Information , Anthony Bolton e , Dara Mano... more ... Information , a , c , Corresponding Author Contact Information , Anthony Bolton e , Dara Manoach d , a , Margaret O'Connor d , a , Sandra Weintraub f , Howard Blume c , b and Donald L. Schomer c , a. a From the Department of Neurology, Beth Israel Hospital and Harvard ...
Electroencephalography and clinical neurophysiology, 1993
The recording of an EEG while the patient is undergoing magnetic resonance imaging (MRI) data acq... more The recording of an EEG while the patient is undergoing magnetic resonance imaging (MRI) data acquisition, as far as we are aware, has not been previously accomplished. By careful selection and arrangement of analog multiplexed cable-telemetry equipment to eliminate both ferrous and RF sources, a stable, readable EEG can be obtained without interfering with the diagnostic quality of the MRI. This arrangement does not cause localized heating or burning at the electrode sites. This technical capability permits more accurate neurophysiological control during the acquisition of echo planar functional MRI studies as well as providing indications of anatomical localization of electrical sources.
Electroencephalography and clinical neurophysiology, 1988
A multi-channel switched-capacitor 6-pole filter for significantly reducing the EMG artifact pres... more A multi-channel switched-capacitor 6-pole filter for significantly reducing the EMG artifact present during seizures recorded by long-term monitoring procedures has been implemented for routine use. This permits repeated replay of the seizures with different filter settings. All of the channels can be simultaneously dialed to any cut-off frequency (3 dB down) between 8 Hz and 70 Hz and the event replayed for filtering and write-out onto any standard EEG machine. The advantage of the 6-pole switched-capacitor filter is that it does not require a complex design with high precision RC components. The cut-off frequency is determined by the frequency of a simple clock that is used to select the same cut-off point for all 16 channels. By changing the clock frequency, the operator moves the cut-off point linearly. The dramatic improvement obtained by off-line digital filtering that was recently reported (Gotman et al. 1981) indicates that more efficient filtering of EMG contaminated seizur...
We previously observed tht low oral doses of melatonin given at noon increase blood melatonin con... more We previously observed tht low oral doses of melatonin given at noon increase blood melatonin concentrations to those normally occurring nocturnally and facilitate sleep onset, as assessed using and involuntary muscle relaxation test. In this study we examined the induction of polysomnographically recorded sleep by similar doses given later in the evening, close to the times of endogenous melatonin release and habitual sleep onset. Volunteers received the hormone (oral doses of 0.3 or 1.0 mg) or placebo at 6, 8, or 9 PM. Latencies to sleep onset, to stage 2 sleep, and to rapid eye movement (REM) sleep were measured polysomnographically. Either dose given at any of the three time points decreased sleep onset latency and latency to stage 2 sleep. Melatonin did not suppress REM sleep or delay its onset. Most volunteers could clearly distinguish between the effects of melatonin and those of placebo when the hormone was tested at 6 or 8 PM. Neither melatonin dose induced "hangover" effects, as assessed with mood and performance tests administered on the morning after treatment. These data provide new evidence that nocturnal melatonin secretion may be involved in physiologic sleep onset and that exogenous melatonin may be useful in treating insomnia.
We previously observed that low oral doses of melatonin given at noon increase blood melatonin co... more We previously observed that low oral doses of melatonin given at noon increase blood melatonin con- centrations to those normally occurring nocturnally and facilitate sleep onset, as assessed using an invol- untary muscle relaxation test. In this study we examined the induction of polysomnographically re- corded sleep by similar doses given later in the evening, dose to the times of
Regulatory toxicology and pharmacology : RTP, 2002
Over 20 years have elapsed since aspartame was approved by regulatory agencies as a sweetener and... more Over 20 years have elapsed since aspartame was approved by regulatory agencies as a sweetener and flavor enhancer. The safety of aspartame and its metabolic constituents was established through extensive toxicology studies in laboratory animals, using much greater doses than people could possibly consume. Its safety was further confirmed through studies in several human subpopulations, including healthy infants, children, adolescents, and adults; obese individuals; diabetics; lactating women; and individuals heterozygous (PKUH) for the genetic disease phenylketonuria (PKU) who have a decreased ability to metabolize the essential amino acid, phenylalanine. Several scientific issues continued to be raised after approval, largely as a concern for theoretical toxicity from its metabolic components--the amino acids, aspartate and phenylalanine, and methanol--even though dietary exposure to these components is much greater than from aspartame. Nonetheless, additional research, including e...
Ophthalmic Plastic and Reconstructive Surgery, 2014
To determine the viability of lacrimal sinus diversion by using a novel Sinopsys Surgical Lacrima... more To determine the viability of lacrimal sinus diversion by using a novel Sinopsys Surgical Lacrimal Stent. Two disarticulated cadaveric heads were used in the laboratory. First, bilateral conjunctivodacryocystorhinostomies (CDCR) were performed by using a traditional Pyrex Jones tube and the Sinopsys Surgical Lacrimal Stent. The fluiditics were then evaluated by using contrast agent and fluroscopy. Subsequently, conjunctivoethmoidectomies (CE) and conjunctivomaxillectomies (CM) were performed by using the Sinopsys Surgical Lacrimal Stent, of which the fluiditics were also studied. The conjunctivodacryocystorhinostomy (CDCR) placement experience of the Jones tube and the Sinopsys Surgical Lacrimal Stent were similar. The CDCR fluiditics as measured by using contrast agent and fluoroscopy were identical with each draining 0.5 mL over 5 to 10 seconds. Placement of the Sinopsys Surgical Lacrimal Stent in the 4 ethmoid (CE) and 4 maxillary (CM) sinuses was similar to the CDCR experience. Fluiditics of lacrimal sinus diversion were similar to CDCR with drainage of 0.5 mL over 5 seconds. The Sinopsys Surgical Lacrimal Stent has flow characteristics that are similar to a Pyrex Jones tube. Drainage in the nose via a CDCR procedure is similar to drainage in the ethmoid and maxillary sinuses via a CE and CM, respectively.
It is still generally believed that complex visual analysis is not carried out within the first 1... more It is still generally believed that complex visual analysis is not carried out within the first 100 ms. Here we show that intra- and extracranial visual evoked potentials (VEPs) differentiate previously seen faces from novel faces as early as 50 ms after stimulus onset. EEG was recorded from scalp electrodes in 12 male healthy volunteers (group I) and intracranially from implanted depth electrodes in the temporal and frontal cortex of seven epilepsy patients (group II). Both groups were engaged in a face recognition task. All subjects showed significant differential responses which occurred very early (50-90 ms) and later (190-600 ms). In group II, the early responses were recorded more frequently in the right hemisphere, whereas the late differential VEPs were found in both hemispheres. Both types of VEPs were more frequent in the temporal neocortex, underlining its role as a major contributor to these fast recognition processes.
Kainic acid-triggered seizures (KATS) induce Fos-like immunoreactivity (FLI) in limbic structures... more Kainic acid-triggered seizures (KATS) induce Fos-like immunoreactivity (FLI) in limbic structures, which send efferents to the locus coeruleus (LC). Following KATS, brain stem sections were stained for Fos immunocytochemistry and double immunostained for Fos and dopamine beta-hydroxylase (DBH). KA-treated animals showed significantly greater numbers of FLI neurons in the LC than control animals (p < 0.05). Co-localization of DBH/Fos was observed in 89.7% of the LC neurons in KA-treated animals and in 1.4% of LC neurons in control animals. Thus, KATS heavily induce Fos in DBH-containing neurons in the LC, which are known to project to the hippocampus. However, the role of activation of the LC noradrenergic neurons during KATS is not well understood at this present time.
We investigated whether: (1) EEG recordings could be successfully performed in an MRI imager, (2)... more We investigated whether: (1) EEG recordings could be successfully performed in an MRI imager, (2) subclinical epileptic discharges could be used to trigger ultrafast functional MRI images, (3) artifact-free functional MRI images could be obtained while the patient was having the EEG monitored, and (4) the functional MRI images so obtained would show focal signal increases in relation to epileptic discharges. We report our results in two patients who showed focally higher signal intensity, reflective of increased local blood flow, in ultrafast functional MRI timed to epileptic discharges recorded while the patients were in the imager and compared with images not associated with discharges. One patient showed a focal increase despite a clinical and EEG history of generalized discharges. This approach may have the potential to identify brain regions activated during brief focal epileptic discharges.
Medications are the most common treatment for epilepsy. Regimens vary from once per day dosing to... more Medications are the most common treatment for epilepsy. Regimens vary from once per day dosing to several pills several times per day. More complex regimens have been associated with lower adherence rates. To date, medication complexity has been measured by the number of pills and the number of times per day the pills are taken. However, complexity also includes special instructions (e.g., take at a separate time than other medications) and the specific administration actions (e.g., take 1/2 pill). This article describes the development of an instrument designed to measure the complexity associated with epilepsy treatment regimens. The medication complexity tool (MCI) was modified to create the Epilepsy Medication and Treatment Complexity Index (EMTCI). The EMTCI comprises four sections: (a) general medication information, (b) frequency of administration, (c) special instructions, and (d) administration actions. Points are given for dosing schedules, special instructions, and administration actions. A total complexity score is calculated by adding points for each section. One form is completed for each medication prescribed for each person. The initial development of the EMTCI included revising the MCI to make it applicable to epilepsy medication. Interrater and intrarater reliability assessments were conducted. The EMTCI was administered to adults with epilepsy as part of a larger study of self-management in people with epilepsy. Data from that study were used for further assessments of the EMTCI including test-retest reliability, criterion validity, and construct validity. The EMTCI shows evidence of both reliability and validity. Information from the tool can be used to describe the medication complexity of epilepsy medication regimens in much greater detail than has been done previously for this population. This information is useful in describing the treatment and adherence issues for persons with epilepsy.
The purpose of this study was to document seizure events associated with the use of a computer-ba... more The purpose of this study was to document seizure events associated with the use of a computer-based assessment and to describe the contextual factors surrounding these seizure episodes. Study participants were adults with epilepsy who were enrolled at research sites in Atlanta and Boston. Subjects were asked to complete a computer-based assessment at 3 time points. Fourteen seizure events were documented; they occurred during 1.6% of all completed assessments (896) and affected 4.4% of the participants (320). The mean age of participants who experienced seizure events was 41.4 years; about 70% were female, and 70% were white. A variety of possible precipitating factors for seizure events included hunger, fatigue, stress, and medication changes. Participants indicated computer use could have triggered their seizures in 2 instances. These findings suggest use of computer-based assessments may pose minimal risks for adults with epilepsy, particularly those without a history of photosensitivity epilepsy.
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Papers by Donald Schomer