and patients with BEB. Notably, glucose hypermetabolism in the thalamus also was found in drug he... more and patients with BEB. Notably, glucose hypermetabolism in the thalamus also was found in drug healthy subjects compared to healthy controls, although drug healthy individual had no symptoms of blepharospasm. In the 21 patients with drug-induced blepharospasm, eleven patients successfully lowered the dosage or completely discontinued using the medication, and blepharospasm improved in six of these patients. From these observations, we concluded that benzodiazepines are one of the environmental triggers leading to blepharospasm. We suspect that blepharospasm did not occur in drug healthy subjects because they were not genetically predisposed. Furthermore, we hypothesize that the symptoms of blepharospasm improved in patients with drug-related blepharospasm after benzodiazepines withdrawal because this medication was the environmental trigger. Based on our observations, the drug-induced alteration of the GABAergic inhibition system may be one of the major environmental trigger factors inducing blepharospasm. Currently, the injection of botulinum toxin A is the most effective treatment for blepharospasm. However, besides dry eyes, blepharitis, and medications, there may exist other environmental triggers, and simply removing of these triggers may be an effective treatment for blepharospasm. PET is a powerful and effective tool to understand blepharospasm pathophysiology; thus, we will continue using PET to research the causes of blepharospasm and identify possible treatment options.
Parkinson's disease (PD) patients and the 6-hydroxydopamine (6-OHDA) lesioned rat model share bli... more Parkinson's disease (PD) patients and the 6-hydroxydopamine (6-OHDA) lesioned rat model share blink abnormalities. In view of the evolutionarily conserved organization of blinking, characterization of blink reflex circuits in rodents may elucidate the neural mechanisms of PD reflex abnormalities. We examine the extent of this shared pattern of blink abnormalities by measuring blink reflex excitability, blink reflex plasticity, and spontaneous blinking in 6-OHDA lesioned rats. We also investigate whether 130-Hz subthalamic nucleus deep brain stimulation (STN DBS) affects blink abnormalities, as it does in PD patients. Like PD patients, 6-OHDA-lesioned rats exhibit reflex blink hyperexcitability, impaired blink plasticity, and a reduced spontaneous blink rate. At 130 Hz, but not 16 Hz, STN DBS eliminates reflex blink hyperexcitability and restores both short- and long-term blink plasticity. Replicating its lack of effect in PD patients, 130-Hz STN DBS does not reinstate a normal temporal pattern or rate to spontaneous blinking in 6-OHDA lesioned rats. These data show that the 6-OHDA lesioned rat is an ideal model system for investigating the neural bases of reflex abnormalities in PD and highlight the complexity of PD's effects on motor control, by showing that dopamine depletion does not affect all blink systems via the same neural mechanisms.
sensory-motor transformation in blink circuits following a subclinical basal ganglia dysfunction ... more sensory-motor transformation in blink circuits following a subclinical basal ganglia dysfunction produces blepharo-spasm that exhibits many of the characteristics of BEB.
The primary purpose of the eyelids is to ensure corneal integrity. An important component of this... more The primary purpose of the eyelids is to ensure corneal integrity. An important component of this protective function is maintaining the corneal tear film. Blink characteristics can determine tear film stability. Increasing blink amplitude thickens the lipid layer that overlies the aqueous layer of the tear film. This thickening reduces evaporation of the aqueous layer. Because each blink reforms the tear film, increasing blink frequency reduces tear film break-up. 1–4 Both innocuous stimuli such as air across the eyelashes, and noxious stimuli such as touching the cornea, elicit trigeminal reflex blinks. If abnormal corneal afferent activity caused by corneal irritation acts as an “error signal ” that adjusts the amplitude and frequency of reflex blinks evoked by both innocuous and corneal stimuli, then corneal irritation creates an adaptive
This study provides a comprehensive description of upper eyelid movement in normal human subjects... more This study provides a comprehensive description of upper eyelid movement in normal human subjects. Using the magnetic search coil technique to monitor lid position and modified skin electrodes to record orbicularis oculi electromyographic (EMG) activity, the authors found that the basic eyelid movements, blinks, and saccadic lid movements, can be uniquely and reliably characterized by their amplitude-maximum velocity relationships. The data show that similar increases in levator palpebrae activity produce the upward lid movements that accompany upward saccadic eye movements as well as the upward phase of a blink. The lid movements that accompany downward saccadic eye movements arise almost exclusively from the passive downward forces and relaxation of the levator palpebrae muscle. In contrast, active orbicularis oculi contraction and the passive downward forces act together to generate lid closure with a blink. These normative data and techniques provide the basis for the clinical a...
Spontaneous eye blink rate (SBR) has been associated with central dopamine (DA) levels, raising t... more Spontaneous eye blink rate (SBR) has been associated with central dopamine (DA) levels, raising the intriguing possibility that SBR is related to cognitive functions dependent on DA, such as spatial working memory (WM). We tested this hypothesis in two behavioral experiments, examining the relationship between SBR, WM load and individual differences in spatial WM performance in 126 young adults. In Experiment 1, we examined the temporal profile of SBR during a spatial delayed recognition task requiring maintenance of 1, 2, 4, 6 or 7 dot locations. We observed a suppression in SBR during dot- and recognition probe-presentation, and a significant increase in SBR afterwards. High performers showed significantly lower SBR than low performers during the first 500 ms of the delay period. In Experiment 2, we used a similar spatial WM task as Experiment 1 to test whether an instructed voluntary blink during the early delay would directly dampen WM performance. While the temporal dynamics of...
... Introduclion In mammals, b!inking oeeurs through the interaction of four forees aeling on the... more ... Introduclion In mammals, b!inking oeeurs through the interaction of four forees aeling on the upper eyelid. First ... fUDction. Morcover, the ehanges in lid kim:matics were similar 10 those oceur-ring in humans (Manning el al. 1990). ...
The paired-stimulus paradigm, presentation of a pair of identical reflex-eliciting stimuli to the... more The paired-stimulus paradigm, presentation of a pair of identical reflex-eliciting stimuli to the supraorbital nerve (SO) with an interstimulus interval of less than 2 s, evokes a response to the second, test, stimulus which is less than that elicited by the first, conditioning, stimulus. In this study, we investigated the site of this suppression and its pharmacology in the alert guinea pig. Both the early (R1) and the late (R2) component of the SO-evoked blink reflex exhibited suppression in the paired-stimulus paradigm. Initiation of suppression appeared to be specific to the afferent limb of the reflex rather than the result of motor activity generated by the conditioning stimulus. Neither acoustic conditioning stimuli nor air puffs that elicited blinks via another branch of the trigeminal nerve suppressed the test response. Extremely weak SO shocks, however, that did not directly elicit a reflex, caused suppression of the response to subsequent SO stimuli of normal intensity. Paired stimulus suppression of the R1 component appeared to involve activation of GABAB receptors within the spinal trigeminal nucleus. Both systemic injections and microinjections of baclofen into the spinal trigeminal nucleus enhanced R1 suppression, whereas identical injections of CGP35348, a GABAB antagonist, diminished R1 suppression. Furthermore, single-unit recordings in alert animals revealed that spinal trigeminal neurons exhibited suppression in the paired-stimulus paradigm that resembled that of the R1 component of the blink reflex. These findings showed that sensory gating underlies paired-stimulus suppression of the SO-evoked blink reflex and that activation of GABAB receptors plays an important role in this process.
This study provides a comprehensive description of upper eyelid movement in normal human subjects... more This study provides a comprehensive description of upper eyelid movement in normal human subjects. Using the magnetic search coil technique to monitor lid position and modified skin electrodes to record orbicularis oculi electromyographic (EMG) activity, the authors found that the basic eyelid move- ments, blinks, and saccadic lid movements, can be uniquely and reliably characterized by their ampli- tude-maximum velocity
This study provides a comprehensive description of upper eyelid movement in normal human subjects... more This study provides a comprehensive description of upper eyelid movement in normal human subjects. Using the magnetic search coil technique to monitor lid position and modified skin electrodes to record orbicularis oculi electromyographic (EMG) activity, the authors found that the basic eyelid move- ments, blinks, and saccadic lid movements, can be uniquely and reliably characterized by their ampli- tude-maximum velocity
and patients with BEB. Notably, glucose hypermetabolism in the thalamus also was found in drug he... more and patients with BEB. Notably, glucose hypermetabolism in the thalamus also was found in drug healthy subjects compared to healthy controls, although drug healthy individual had no symptoms of blepharospasm. In the 21 patients with drug-induced blepharospasm, eleven patients successfully lowered the dosage or completely discontinued using the medication, and blepharospasm improved in six of these patients. From these observations, we concluded that benzodiazepines are one of the environmental triggers leading to blepharospasm. We suspect that blepharospasm did not occur in drug healthy subjects because they were not genetically predisposed. Furthermore, we hypothesize that the symptoms of blepharospasm improved in patients with drug-related blepharospasm after benzodiazepines withdrawal because this medication was the environmental trigger. Based on our observations, the drug-induced alteration of the GABAergic inhibition system may be one of the major environmental trigger factors inducing blepharospasm. Currently, the injection of botulinum toxin A is the most effective treatment for blepharospasm. However, besides dry eyes, blepharitis, and medications, there may exist other environmental triggers, and simply removing of these triggers may be an effective treatment for blepharospasm. PET is a powerful and effective tool to understand blepharospasm pathophysiology; thus, we will continue using PET to research the causes of blepharospasm and identify possible treatment options.
Parkinson's disease (PD) patients and the 6-hydroxydopamine (6-OHDA) lesioned rat model share bli... more Parkinson's disease (PD) patients and the 6-hydroxydopamine (6-OHDA) lesioned rat model share blink abnormalities. In view of the evolutionarily conserved organization of blinking, characterization of blink reflex circuits in rodents may elucidate the neural mechanisms of PD reflex abnormalities. We examine the extent of this shared pattern of blink abnormalities by measuring blink reflex excitability, blink reflex plasticity, and spontaneous blinking in 6-OHDA lesioned rats. We also investigate whether 130-Hz subthalamic nucleus deep brain stimulation (STN DBS) affects blink abnormalities, as it does in PD patients. Like PD patients, 6-OHDA-lesioned rats exhibit reflex blink hyperexcitability, impaired blink plasticity, and a reduced spontaneous blink rate. At 130 Hz, but not 16 Hz, STN DBS eliminates reflex blink hyperexcitability and restores both short- and long-term blink plasticity. Replicating its lack of effect in PD patients, 130-Hz STN DBS does not reinstate a normal temporal pattern or rate to spontaneous blinking in 6-OHDA lesioned rats. These data show that the 6-OHDA lesioned rat is an ideal model system for investigating the neural bases of reflex abnormalities in PD and highlight the complexity of PD's effects on motor control, by showing that dopamine depletion does not affect all blink systems via the same neural mechanisms.
sensory-motor transformation in blink circuits following a subclinical basal ganglia dysfunction ... more sensory-motor transformation in blink circuits following a subclinical basal ganglia dysfunction produces blepharo-spasm that exhibits many of the characteristics of BEB.
The primary purpose of the eyelids is to ensure corneal integrity. An important component of this... more The primary purpose of the eyelids is to ensure corneal integrity. An important component of this protective function is maintaining the corneal tear film. Blink characteristics can determine tear film stability. Increasing blink amplitude thickens the lipid layer that overlies the aqueous layer of the tear film. This thickening reduces evaporation of the aqueous layer. Because each blink reforms the tear film, increasing blink frequency reduces tear film break-up. 1–4 Both innocuous stimuli such as air across the eyelashes, and noxious stimuli such as touching the cornea, elicit trigeminal reflex blinks. If abnormal corneal afferent activity caused by corneal irritation acts as an “error signal ” that adjusts the amplitude and frequency of reflex blinks evoked by both innocuous and corneal stimuli, then corneal irritation creates an adaptive
This study provides a comprehensive description of upper eyelid movement in normal human subjects... more This study provides a comprehensive description of upper eyelid movement in normal human subjects. Using the magnetic search coil technique to monitor lid position and modified skin electrodes to record orbicularis oculi electromyographic (EMG) activity, the authors found that the basic eyelid movements, blinks, and saccadic lid movements, can be uniquely and reliably characterized by their amplitude-maximum velocity relationships. The data show that similar increases in levator palpebrae activity produce the upward lid movements that accompany upward saccadic eye movements as well as the upward phase of a blink. The lid movements that accompany downward saccadic eye movements arise almost exclusively from the passive downward forces and relaxation of the levator palpebrae muscle. In contrast, active orbicularis oculi contraction and the passive downward forces act together to generate lid closure with a blink. These normative data and techniques provide the basis for the clinical a...
Spontaneous eye blink rate (SBR) has been associated with central dopamine (DA) levels, raising t... more Spontaneous eye blink rate (SBR) has been associated with central dopamine (DA) levels, raising the intriguing possibility that SBR is related to cognitive functions dependent on DA, such as spatial working memory (WM). We tested this hypothesis in two behavioral experiments, examining the relationship between SBR, WM load and individual differences in spatial WM performance in 126 young adults. In Experiment 1, we examined the temporal profile of SBR during a spatial delayed recognition task requiring maintenance of 1, 2, 4, 6 or 7 dot locations. We observed a suppression in SBR during dot- and recognition probe-presentation, and a significant increase in SBR afterwards. High performers showed significantly lower SBR than low performers during the first 500 ms of the delay period. In Experiment 2, we used a similar spatial WM task as Experiment 1 to test whether an instructed voluntary blink during the early delay would directly dampen WM performance. While the temporal dynamics of...
... Introduclion In mammals, b!inking oeeurs through the interaction of four forees aeling on the... more ... Introduclion In mammals, b!inking oeeurs through the interaction of four forees aeling on the upper eyelid. First ... fUDction. Morcover, the ehanges in lid kim:matics were similar 10 those oceur-ring in humans (Manning el al. 1990). ...
The paired-stimulus paradigm, presentation of a pair of identical reflex-eliciting stimuli to the... more The paired-stimulus paradigm, presentation of a pair of identical reflex-eliciting stimuli to the supraorbital nerve (SO) with an interstimulus interval of less than 2 s, evokes a response to the second, test, stimulus which is less than that elicited by the first, conditioning, stimulus. In this study, we investigated the site of this suppression and its pharmacology in the alert guinea pig. Both the early (R1) and the late (R2) component of the SO-evoked blink reflex exhibited suppression in the paired-stimulus paradigm. Initiation of suppression appeared to be specific to the afferent limb of the reflex rather than the result of motor activity generated by the conditioning stimulus. Neither acoustic conditioning stimuli nor air puffs that elicited blinks via another branch of the trigeminal nerve suppressed the test response. Extremely weak SO shocks, however, that did not directly elicit a reflex, caused suppression of the response to subsequent SO stimuli of normal intensity. Paired stimulus suppression of the R1 component appeared to involve activation of GABAB receptors within the spinal trigeminal nucleus. Both systemic injections and microinjections of baclofen into the spinal trigeminal nucleus enhanced R1 suppression, whereas identical injections of CGP35348, a GABAB antagonist, diminished R1 suppression. Furthermore, single-unit recordings in alert animals revealed that spinal trigeminal neurons exhibited suppression in the paired-stimulus paradigm that resembled that of the R1 component of the blink reflex. These findings showed that sensory gating underlies paired-stimulus suppression of the SO-evoked blink reflex and that activation of GABAB receptors plays an important role in this process.
This study provides a comprehensive description of upper eyelid movement in normal human subjects... more This study provides a comprehensive description of upper eyelid movement in normal human subjects. Using the magnetic search coil technique to monitor lid position and modified skin electrodes to record orbicularis oculi electromyographic (EMG) activity, the authors found that the basic eyelid move- ments, blinks, and saccadic lid movements, can be uniquely and reliably characterized by their ampli- tude-maximum velocity
This study provides a comprehensive description of upper eyelid movement in normal human subjects... more This study provides a comprehensive description of upper eyelid movement in normal human subjects. Using the magnetic search coil technique to monitor lid position and modified skin electrodes to record orbicularis oculi electromyographic (EMG) activity, the authors found that the basic eyelid move- ments, blinks, and saccadic lid movements, can be uniquely and reliably characterized by their ampli- tude-maximum velocity
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