Prolonged Cortical Silent Period Research Articles

Effects of Clozapine on Cortical Inhibition

Abstract Background Preclinical and clinical investigations have revealed deficits in cortical inhibition in individuals with schizophrenia. Transcranial magnetic stimulation, a commonly used noninvasive measurement technique, is used for assessing these deficits. Limited research has been conducted on the effects of antipsychotic medications on cortical inhibition. This study aimed to evaluate the effects of clozapine on cortical inhibition with transcranial magnetic stimulation longitudinally and compare it with unaffected controls. Methods Ten patients who started clozapine were assessed at baseline, with 8 reassessed after 4 months. Eight age- and sex-matched unaffected controls were included. Psychopathology, neurocognitive performance, formal thought disorder, and disability were assessed, and the cortical excitability parameters (resting motor threshold, cortical silent period, short-interval intracortical inhibition, intracortical facilitation, and short-latency afferent inhibition [SAI]) were measured at baseline and four months after clozapine treatment. Results Resting motor threshold, ICF, and SAI were significantly different between patients and controls at baseline, whereas resting motor threshold, SAI, and ICF became similar to controls after clozapine with only ICF having a trend for significance. Clozapine prolonged cortical silent period significantly in the patients. Conclusions This is the first study to investigate the effect of clozapine on SAI, a potential cholinergic biomarker, and the first follow-up study to investigate the relationship between the effects of clozapine on cortical inhibition and cognition. Clozapine seems to cause an increase in cortical inhibition through GABAergic and possibly cholinergic mechanisms. However, additional follow-up studies with larger sample sizes are required to reach more robust conclusions.

Intracortical and intercortical networks in patients after stroke: a concurrent TMS-EEG study

BackgroundConcurrent transcranial magnetic stimulation and electroencephalography (TMS-EEG) recording provides information on both intracortical reorganization and networking, and that information could yield new insights into post-stroke neuroplasticity. However, a comprehensive investigation using both concurrent TMS-EEG and motor-evoked potential-based outcomes has not been carried out in patients with chronic stroke. Therefore, this study sought to investigate the intracortical and network neurophysiological features of patients with chronic stroke, using concurrent TMS-EEG and motor-evoked potential-based outcomes.MethodsA battery of motor-evoked potential-based measures and concurrent TMS-EEG recording were performed in 23 patients with chronic stroke and 21 age-matched healthy controls.ResultsThe ipsilesional primary motor cortex (M1) of the patients with stroke showed significantly higher resting motor threshold (P = 0.002), reduced active motor-evoked potential amplitudes (P = 0.001) and a prolonged cortical silent period (P = 0.007), compared with their contralesional M1. The ipsilesional stimulation also produced a reduction in N100 amplitude of TMS-evoked potentials around the stimulated M1 (P = 0.007), which was significantly correlated with the ipsilesional resting motor threshold (P = 0.011) and motor-evoked potential amplitudes (P = 0.020). In addition, TMS-related oscillatory power was significantly reduced over the ipsilesional midline-prefrontal and parietal regions. Both intra/interhemispheric connectivity and network measures in the theta band were significantly reduced in the ipsilesional hemisphere compared with those in the contralesional hemisphere.ConclusionsThe ipsilesional M1 demonstrated impaired GABA-B receptor-mediated intracortical inhibition characterized by reduced duration, but reduced magnitude. The N100 of TMS-evoked potentials appears to be a useful biomarker of post-stroke recovery.

Repeated Sub-Concussive Impacts and the Negative Effects of Contact Sports on Cognition and Brain Integrity.

Sports are yielding a wealth of benefits for cardiovascular fitness, for psychological resilience, and for cognition. The amount of practice, and the type of practiced sports, are of importance to obtain these benefits and avoid any side effects. This is especially important in the context of contact sports. Contact sports are not only known to be a major source of injuries of the musculoskeletal apparatus, they are also significantly related to concussion and sub-concussion. Sub-concussive head impacts accumulate throughout the active sports career, and thus can cause measurable deficits and changes to brain health. Emerging research in the area of cumulative sub-concussions in contact sports has revealed several associated markers of brain injury. For example, recent studies discovered that repeated headers in soccer not only cause measurable signs of cognitive impairment but are also related to a prolonged cortical silent period in transcranial magnetic stimulation measurements. Other cognitive and neuroimaging biomarkers are also pointing to adverse effects of heading. A range of fluid biomarkers completes the picture of cumulating effects of sub-concussive impacts. Those accumulating effects can cause significant cognitive impairment later in life of active contact sportswomen and men. The aim of this review is to highlight the current scientific evidence on the effects of repeated sub-concussive head impacts on contact sports athletes’ brains, identify the areas in need of further investigation, highlight the potential of advanced neuroscientific methods, and comment on the steps governing bodies have made to address this issue. We conclude that there are indeed neural and biofluid markers that can help better understand the effects of repeated sub-concussive head impacts and that some aspects of contact sports should be redefined, especially in situations where sub-concussive impacts and concussions can be minimized.

Emotional detachment, gait ataxia, and cerebellar dysconnectivity associated with compound heterozygous mutations in the SPG7 gene

ABSTRACT We report a patient with autism-like deficits in emotional connectedness, executive dysfunction, and ataxia beginning at age 39. He had compound heterozygous variants in SPG7 (A510V and 1552+1 G>T substitutions), mutation of which is classically associated with spastic paraparesis. Diffusion MRI demonstrated abnormalities in the cerebellar outflow tracts. Transcranial magnetic stimulation showed a prolonged cortical silent period representing exaggerated cortical inhibition, as previously described with pure cerebellar degeneration. The acquired cerebellar cognitive affective syndrome in association with specific anatomic and neurophysiological abnormalities in the cerebellum expand the spectrum of SPG7-related neurodegeneration and support a role for cerebellar output in socio-emotional behavior.

Obstructive Sleep Apnea Syndrome: A Preliminary Navigated Transcranial Magnetic Stimulation Study.

PurposeAn increase in resting motor threshold (RMT), prolonged cortical silent period duration (CSP), and reduced short-latency afferent inhibition (SAI), confirmed with previous transcranial magnetic stimulation (TMS), suggest decreased cortical excitability in obstructive sleep apnea syndrome (OSAS). The present study included MRI of OSAS patients for navigated TMS assessment of the RMT, as an index of the threshold for corticospinal activation at rest, and SAI as an index of cholinergic neurotransmission. We hypothesize to confirm findings on SAI and RMT with adding precision in the targeting of motor cortex in OSAS.Subjects and MethodsAfter acquiring head MRIs for 17 severe right-handed OSAS and 12 healthy subjects, the motor cortex was mapped with nTMS to assess the RMT and SAI, with motor evoked potentials (MEPs) recorded from the abductor-pollicis brevis (APB) muscle. The 120%RMT intensity was used for the SAI by a paired-pulse paradigm in which the electrical stimulation to the median nerve is followed by magnetic stimulation of the motor cortex at inter-stimulus intervals (ISIs) of 18–28 ms (ISIs18-28). The SAI control condition included a recording of MEPs without peripheral stimulation. Latency and amplitude of MEP at RMT at 120%RMT for eleven different at ISIs18-28 were analyzed.ResultsThe study showed a significantly lower percentage deviation of MEP amplitude at ISIs(18-28ms) from the control condition between OSAS and healthy subjects (U=44.0, p=0.01). The intensity of stimulation at RMT was significantly higher in OSAS subjects (U=55.0, p=0.04*). Correlation analysis showed that BMI significantly negatively correlated (ρ=−0.47) with MEP amplitude percentage deviation in OSAS patients.ConclusionThe nTMS study results in increased RMT, and reduced cortical afferent inhibition in OSAS patients for SAI at ISIs18-28, confirming previous findings of impaired cortical afferent inhibition in OSAS. Future nTMS studies are desirable to elucidate the role of RMT and SAI in diagnostics and treatment of OSAS, and to elucidate the usefulness of nTMS in OSAS research.

Prolonged cortical silent period is related to poor fitness and fatigue, but not tumor necrosis factor, in Multiple Sclerosis

ObjectivePoor fitness among people with Multiple Sclerosis (MS) aggravates disease symptoms. Whether low fitness levels accompany brain functioning changes is unknown. MethodsMS patients (n = 82) completed a graded maximal exercise test, blood was drawn, and transcranial magnetic stimulation determined resting and active motor thresholds, motor evoked potential latency, and cortical silent period (CSP). ResultsSixty-two percent of participants had fitness levels ranked below 10th percentile. Fitness was not associated with disability measured using the Expanded Disability Status Scale (EDSS). Regression analyses revealed that, cardiorespiratory fitness, when controlling for disease demographics, contributed 23.7% (p < 0.001) to the model explaining variance in CSP. Regression analysis using cardiorespiratory fitness and CSP as predictors showed that CSP alone explained 19.9% of variance in subjective fatigue (p = 0.002). Tumor necrosis factor was not associated with any variable. ConclusionLow fitness was associated with longer CSP in MS. Longer CSP was, in turn, related to greater MS fatigue. SignificanceMS patients had extremely low levels of cardiorespiratory fitness. Poor fitness predicted longer CSP, a marker of greater intracortical inhibition, which was linked to MS fatigue. Future research should examine whether aerobic training could shorten CSP and potentially lessen inhibition of cortical networks.

Effect of repetitive transcranial magnetic stimulation on action myoclonus: A pilot study in patients with EPM1

ObjectiveThe objective of this study was to explore the short-term effects of repetitive transcranial magnetic stimulation (rTMS) on action myoclonus. MethodsNine patients with Unverricht–Lundborg (EPM1) progressive myoclonus epilepsy type underwent two series of 500 stimuli at 0.3Hz through round coil twice a day for five consecutive days. Clinical and neurophysiological examinations were performed two hours before starting the first rTMS session and two hours after the end of the last rTMS session. ResultsEight patients completed the protocol; one discontinued because of a transient increase in spontaneous jerks. The unified myoclonus rating scale indicated a 25% reduction in posttreatment myoclonus with action score associated with an increase in the cortical motor threshold and lengthening of the cortical silent period (CSP). The decrease in the myoclonus with action scores correlated with the prolongation of CSP. ConclusionsRepetitive transcranial magnetic stimulation can be safely used in patients with EPM1, improves action myoclonus, and partially restores deficient cortical inhibition.

Single and paired pulse transcranial magnetic stimulation in drug naïve epilepsy

Transcranial magnetic stimulation (TMS) measures cortical excitability and is therefore potentially suitable as an additional tool for epilepsy diagnostics and therapy evaluation. In this review we discuss the application of TMS in epilepsy research and systematically analyze single and paired pulse TMS outcomes from 31 drug naïve patient studies. Despite a large variety in used TMS protocols, there was no relation between specific protocol aspects and the occurrence of significant results. Protocols were often not in accordance with latest guidelines and recommendations. Cortical excitability, as measured by TMS, was increased in drug naïve epilepsy patients, being most prominent for generalized epilepsy. Single pulse TMS indicated a trend towards a lower resting motor threshold (rMT) and a prolonged cortical silent period (CSP) for generalized epilepsy, while inconclusive results were found for focal epilepsy. The paired pulse TMS outcomes, short intracortical inhibition (SICI) and long intracortical inhibition (LICI), showed the most consistent significant increase in cortical excitability in generalized and focal epilepsy patients. Future epilepsy research should especially focus on the interstimulus intervals 2 and 5ms for SICI, and 250 and 300ms for LICI. Furthermore, combining TMS with electroencephalography (EEG) may contribute to analysis on an individual patient level.

Intracortical inhibition abnormality during the remission phase of multiple sclerosis is related to upper limb dexterity and lesions

ObjectiveThe impact of inhibitory cortical activity on motor impairment of people with relapsing-remitting multiple sclerosis (RRMS) has not been fully elucidated despite its relevance to neurorehabilitation. The present study assessed the extent to which transcranial magnetic stimulation (TMS)-based metrics of intracortical inhibition are related to motor disability and brain damage. MethodsParticipants included forty-three persons with RRMS in the remitting phase and twenty-nine healthy controls. We stimulated the dominant hemisphere and recorded from the dominant hand to assess short-interval intracortical inhibition (SICI) and cortical silent period (CSP) duration. Disability was evaluated with the Multiple Sclerosis Functional Composite (MSFC). Regional cortical thickness and lesion volume were measured. ResultsRRMS participants with dominant upper limb dexterity impairments had prolonged CSP, but equivalent SICI, compared to participants with preserved function. CSP was not related to walking or cognitive performance. Higher normalized lesion volume correlated with longer CSP duration. When adjusting for normalized lesion volume, longer CSP significantly predicted worse dominant upper extremity impairment. ConclusionsHigh intracortical inhibition possibly contributes to (or prevents remission from) motor impairment. Lesions may be associated with intracortical inhibition shifts. SignificanceCSP duration and lesion burden should be considered when developing interventions aiming to mitigate motor impairment.

Prolonged cortical silent period among drug-naive subjects at ultra-high risk of psychosis

BackgroundDeficits in gamma-aminobutyric acid (GABA) inhibitory neurotransmission have been associated with pathophysiological mechanisms underlying schizophrenia. However, little is known about whether these deficits occur before or after the onset of psychosis. MethodWe recruited 16 drug-naive subjects at ultra-high risk of psychosis (UHR), 17 schizophrenia patients and 28 healthy controls. Cortical inhibition was determined using transcranial magnetic stimulation (TMS) over the left primary motor cortex. TMS markers such as short-interval cortical inhibition (SICI), cortical silent period (CSP) and intracortical facilitation (ICF) were obtained from each subject. While SICI can reflect GABA type A (GABAA) mediated inhibition, CSP is thought to indicate GABA type B (GABAB) mediated inhibitory circuits. ResultsAs compared with healthy controls, UHR subjects showed a prolonged CSP with no change in SICI, whereas schizophrenia patients demonstrated both a prolonged CSP and a reduced SICI. No group differences were found for ICF. CSP in schizophrenia patients also had a positive correlation with positive symptom score of the positive and negative symptom scale (PANSS). ConclusionsCortical inhibitory deficits among UHR subjects were relatively limited compared to those among schizophrenia patients. Alterations might occur in some subgroup of GABA-mediated neurotransmitter systems before the onset of psychosis, while alterations in both GABAA and GABAB networks might contribute to full-blown psychosis.

Impairments in motor-cortical inhibitory networks across recent-onset and chronic schizophrenia: A cross-sectional TMS Study

Transcranial magnetic stimulation is an established method to probe inhibitory and facilitatory networks within the human motor cortex. Reduced motor-cortical inhibition is a common finding in schizophrenia patients. Based on neuropathological findings, the reduced cortical inhibition in schizophrenia has been linked mainly to alterations in GABAergic neurotransmission. The aim of this study was to investigate the impact of disease state on intracortical inhibitory and facilitatory networks measured by TMS in schizophrenia. Cortical excitability was investigated in a pooled cross-sectional sample of recent-onset-schizophrenia (RO–SZ), chronically-ill schizophrenia patients (CH–SZ) and healthy controls (HC) using single- and paired-pulse TMS applied to the left primary motor cortex. The sample included 41 RO–SZ, 42 CH–SZ and 59 HC. Analyses were focused on resting motor threshold (RMT), short-interval intracortical inhibition (SICI), intracortical facilitation (ICF) and cortical silent period (CSP). There was a significant difference regarding the mean CSP durations across our three study groups (p=0.002). Subgroup comparisons revealed a shorter CSP in HC compared to RO–SZ (p<0.001). Three group comparisons of SICI (p=0.098) and RMT (p=0.075) showed differences at a trend-level. An overall comparison between HC and all patients showed a significantly reduced SICI (p=0.031) and prolonged CSP (p=0.003) in schizophrenia patients. This is the largest and first cross-sectional investigation of various excitability parameters in schizophrenia patients. These findings indicate general alterations of cortical inhibition, with differences between recent-onset and chronically-ill schizophrenia patients.

Neurophysiological assessment of fatigue in electrical injury patients

To investigate for the presence of central and peripheral physiological fatigue in electrical injury (EI) patients with experiential fatigue. Eight EI patients and eight age-matched healthy volunteers were recruited. Motor evoked potentials (MEP) following transcranial magnetic stimulation (TMS) and M-waves from ulnar nerve stimulation at the wrist were measured from the right abductor digiti minimi. Fatigue was induced by 2 min of maximal voluntary contraction, and subjects were followed for 15 min of recovery. The experiment was performed twice for each subject. In one of the two sessions (randomly assigned), a blood pressure (BP) cuff was inflated during the first 75 s of recovery period to prolong muscle ischemia. Baseline measures showed no difference in central and peripheral conduction times. Cortical silent period was prolonged in patients compared to controls with no differences in abduction force. Decrement of MEP amplitude with consecutive TMS pulses was observed in the post-recovery period only with EI patients who had prolonged muscle ischemia induced by the BP cuff. The post-exercise M-wave area during contraction was significantly higher for patients. Prolonged cortical silent period in EI patients suggests that they had increased GABAB receptor-mediated cortical inhibition. The ischemia-induced decrement in consecutive MEP amplitudes post-exercise demonstrates greater physiological fatigue in EI patients after exercise. The greater increase in M-wave area of EI patients post-exercise suggests larger decrease in conduction velocity of muscle action potentials with exercise. These findings provide preliminary physiological correlates for increased central and peripheral fatigue in EI patients with experiential fatigue.

Selective Effects of Baclofen on Use-Dependent Modulation of GABAB Inhibition after Tetraplegia

Baclofen is a GABAB receptor agonist commonly used to relief spasticity related to motor disorders. The effects of baclofen on voluntary motor output are limited and not yet understood. Using noninvasive transcranial magnetic and electrical stimulation techniques, we examined electrophysiological measures probably involving GABAB (long-interval intracortical inhibition and the cortical silent period) and GABAA (short-interval intracortical inhibition) receptors, which are inhibitory effects mediated by subcortical and cortical mechanisms. We demonstrate increased active long-interval intracortical inhibition and prolonged cortical silent period during voluntary activity of an intrinsic finger muscle in humans with chronic incomplete cervical spinal cord injury (SCI) compared with age-matched controls, whereas resting long-interval intracortical inhibition was unchanged. However, long-term (~6 years) use of baclofen decreased active long-interval intracortical inhibition to similar levels as controls but did not affect the duration of the cortical silent period. We found a correlation between signs of spasticity and long-interval intracortical inhibition in patients with SCI. Short-interval intracortical inhibition was decreased during voluntary contraction compared with rest but there was no effect of SCI or baclofen use. Together, these results demonstrate that baclofen selectively maintains use-dependent modulation of largely subcortical but not cortical GABAB neuronal pathways after human SCI. Thus, cortical GABA(B) circuits may be less sensitive to baclofen than spinal GABAB circuits. This may contribute to the limited effects of baclofen on voluntary motor output in subjects with motor disorders affected by spasticity.

Cortical excitability in drug naive juvenile myoclonic epilepsy

PurposeTo evaluate the effect of diurnal variability on cortical excitability using single pulse transcranial magnetic stimulation (TMS), in drug naive patients with juvenile myoclonic epilepsy (JME) and to look for any differences in cortical excitability between males and females. MethodsThirty drug-naive patients with JME and 10 healthy controls were studied. Resting motor threshold (RMT), motor evoked potential (MEP), the duration of central motor conduction time (CMCT) and cortical silent period (CSP) were measured, twice, first early in the morning and again in the afternoon of the same day. ResultsDiurnal variation with higher evening values of CMCT and CSP were observed in the control group. In the study group, diurnal variation in RMT, CMCT and CSP was found with higher values in the morning than in control group. However, only the raised values of CSP [mean, 110.7ms, morning and 96.44ms, evening] were of statistical significance [p=0.005, morning and 0.039, evening] as compared to controls. In the study group, males had higher values of RMT, CMCT and CSP than in females. However, the CMCT in males was lower in the evening study than in females. Further, RMT and morning CMCT was lower in females than in controls. In females, the morning CSP [mean, 100.91ms, morning versus 87.86ms, evening] was significantly prolonged [p=0.017, morning versus 0.221, evening] as compared to controls. ConclusionThe study is suggestive of the existence of impaired supraspinal/intracortical inhibitory circuits which may account for the hyperexcitability of the motor system being prominent in the morning among drug naïve patients with JME. In this study, increased activity of cortical inhibitory networks, as evidenced by prolonged cortical silent period existed among drug naïve JME patients, but was found to be significant only in female patients. This may explain the increased seizure susceptibility in this cohort, at this time of the day and an increased manifestation of JME in females.

Multiple sessions of low-frequency repetitive transcranial magnetic stimulation in focal hand dystonia: clinical and physiological effects

The ability of low-frequency repetitive transcranial magnetic stimulation (rTMS) to enhance intracortical inhibition has motivated its use as a potential therapeutic intervention in focal hand dystonia (FHD). In this preliminary investigation, we assessed the physiologic and behavioral effects of multiple sessions of rTMS in FHD. 12 patients with FHD underwent five daily-sessions of 1 Hz rTMS to contralateral dorsal premotor cortex (dPMC). Patients held a pencil and made movements that did not elicit dystonic symptoms during rTMS. We hypothesized that an active but non-dystonic motor state would increase beneficial effects of rTMS. Five additional patients received sham-rTMS protocol. The area under curve (AUC) of the motor evoked potentials and the cortical silent period (CSP) were measured to assess changes in corticospinal excitability and intracortical inhibition, respectively. Behavioral measures included pen force and velocity during handwriting and subjective report. Multiple-session rTMS strengthened intracortical inhibition causing a prolongation of CSP after 3 days of intervention and pen force was reduced at day 1 and 5, leaving other measures unchanged. 68% of patients self-reported as 'responders' at day 5, and 58% at follow-up. Age predicted responders. A strong therapeutic potential of this rTMS paradigm in FHD was not supported but findings warrant further investigation.

Can Cortical Silent Period and Motor Threshold Be Practical Parameters in the Comparison of Patients with Generalized Epilepsy and Patients with Psychogenic Non-Epileptic Seizures?

Background/Aim: This study aimed to compare the cortical excitability of patients with generalized tonic-clonic seizures (GTCSs) and that of patients with psychogenic non-epileptic seizures (PNESs). Methods: Patients were classified into groups according to their electroencephalogram (EEG) findings and seizure types: group 1 = GTCS with an abnormal EEG, group 2 = GTCS with a normal EEG and group 3 = PNES with a normal EEG. The control group included healthy volunteers with normal EEGs. Cortical silent period (CSP) and motor threshold (MT) were measured for all groups and the results were compared. Results: CSPs were significantly prolonged in groups 1 and 2 when compared with group 3 and the control group. No differences were found between the MT measurements of all groups. Conclusion: The prolongation of CSP may demonstrate the differences between the pathophysiological mechanisms of GTCS and those of PNES.

Electrophysiological Investigation of Fatigue in Electrical Injury Patients (P02.019)

Objective: To investigate central and peripheral fatigue in electrical injury (EI) patients. Background Although experiential fatigue is common with EI patients, little is known about the cause of this fatigue. Design/Methods: EI patients and age and sex-matched healthy volunteers completed fatigue severity scale questionnaire (FSSQ). The study is designed to measure central and peripheral fatigue. Motor evoked potentials (MEP) and M-waves were measured using surface electromyogram of right abductor digiti minimi (ADM) using transcranial magnetic stimulation (TMS) and ulnar nerve stimulation (UNS) at rest and during maximal voluntary contraction (MVC). Fatigue was induced using 2 minutes of MVC and subjects were followed for 15 minutes of recovery. The experiment was repeated with inflated blood-pressure (BP) cuff during the first 75 seconds of recovery to maintain muscle ischemia. Results: 8 EI patients and 8 volunteers were studied (all men, 46±7.8 years vs. 45.5±7.3 years). FSSQ confirmed greater experiential fatigue reported by EI patients compared to healthy volunteers (p=0.04). Cortical silent period was prolonged in patients compared to volunteers (177ms vs. 145ms, p=0.04). Drop in MEP amplitude with consecutive TMS at rest (5 pulses at 0.3Hz) was observed immediately after exercise but was present only for EI patients with BP cuff after 2 minutes of recovery (p Conclusions: Prolonged cortical silent period in EI patients suggests that GABA-B receptor-mediated cortical inhibition may be increased with EI. BP-induced delay in recovery from decrease in amplitude of consecutive MEP9s demonstrates greater peripheral fatigue in EI patients after exercise. Higher increase in M-wave area post-exercise suggests greater decrease in conduction velocity of muscle action potential with exercise in EI patients. In conclusion, experiential fatigue reported by EI patients is shown to have both central and peripheral components. Supported by: Catherine Manson Chair in Movement Disorder. Disclosure: Dr. Udupa has nothing to disclose. Dr. Kashigar has nothing to disclose. Dr. Fish has nothing to disclose. Dr. Chen has received personal compensation for activities with Allergan, Inc., Medtronic, Inc., Biovail, EMD Serono, Merz Pharma, the American Academy of Neurology, the Douglas Mental Health University Institute, Movement Disorders Society, the University of Pittsburg, Merz, CHIR, the Michael J. Fox Foundation for Parkinson9s Research, the Dystonia Medical Research Foundation, and has provided expert testimony and affidavit in welding related litigations. Dr. Chen has received research support from Medtronic, Inc.

Paradoxical Alteration in Cortical Excitability Following 10 Hz rTMS in Patients with Untreated Obstructive Sleep Apnea Syndrome (OSAS) (P05.007)

Objective: To investigate changes in cortical excitability in patients with obstructive sleep apnea syndrome (OSAS) undergoing 10Hz repetitive transcranial magnetic stimulation (rTMS) during wakefulness. Background OSAS is a syndrome characterized by repetitive upper airway collapse or narrowing during sleep with sequelae include adverse cardiovascular and metabolic outcomes, decline in quality of life, and neurocognitive impairment. Although altered cortical excitability in OSAS is well documented, the effect of rTMS on the excitability changes in OSAS patients has not previously been studied. This is important as rTMS can potentially be used as an adjunct therapy in OSAS. Design/Methods: We recruited 13 untreated severe OSAS (10 males, mean apnea-hypopnea index=54.6±13.01h) patients and 12 age-matched healthy volunteers. The TMS parameters measured were resting motor threshold (RMT), motor evoked potential (MEP) amplitude, central motor conduction time (CMCT), cortical silent period (CSP) and short-interval intracortical inhibition (SICI). These parameters were measured in the morning more than 2h after arising. After the baseline TMS studies, the patients and healthy volunteers were subjected to 10 Hz rTMS over left dorsolateral prefrontal cortex. The TMS parameters (RMT, MEP, CMCT, CSP and SICI) were repeated thereafter. Results: OSAS patients had a significantly higher RMT and a longer CSP duration (t-test, p 0.05). The rTMS showed an prolongation of CSP in OSAS subjects (ANOVA, p Conclusions: This TMS-based study suggests that untreated severe OSAS patients have imbalanced cortical excitabilities that enhanced inhibition or decreased brain excitability when awake during the day. The paradoxical response of rTMS in OSAS patients highlights the complex interplay of excitatory and inhibitory cortical circuits in OSAS. This intriguing result needs further replication. Disclosure: Dr. Das has nothing to disclose. Dr. Vijayakumari has nothing to disclose. Dr. Radhakrishnan has nothing to disclose.

Efficacy of pregabalin in a case of stiff-person syndrome: Clinical and neurophysiological evidence

Symptomatic treatment of stiff-person syndrome (SPS) might be challenging and a significant improvement of stiffness and rigidity is generally reached with high doses of benzodiazepines or baclofen causing side effects.A 71-year old woman diagnosed with SPS complained of marked stiffness of trunk and lower limb muscles with sudden painful spasms. She was unable to walk and she could not lean on her right leg. Cortical silent period (CSP) duration evaluated from right abductor pollicis brevis (APB) with transcranial magnetic stimulation was shortened. Polygraphic electromyographic (EMG) evaluation from paraspinal and leg muscles disclosed continuous motor unit activity at rest with interference muscular pattern. Symptomatic treatment with diazepam was withdrawn because of excessive sedation. In order to relieve the intense lumbar pain, she was prescribed pregabalin; since the day after, rigidity and painful spasms dramatically improved and she could walk without assistance. The clinical benefit persisted at 3months follow-up and was paralleled by almost complete disappearance of EMG activity at rest and prolongation of CSP. The clinical and electrophysiological data in this SPS patient suggest the possible efficacy of pregabalin as symptomatic treatment without any significant side effects, which needs to be replicated in larger case series.

Motor Circuit Abnormalities in First-episode Schizophrenia Assessed with Transcranial Magnetic Stimulation

Abnormalities in corticosubcortical circuits in schizophrenia have been described by previous neuroimaging and electrophysiological studies. Previous studies assessing excitability of the motoneural system by measuring cortical silent period (CSP), short interval intracortical inhibition (SICI) and intracortical facilitation (ICF) with transcranial magnetic stimulation (TMS) revealed conflicting results. We assessed resting motor threshold (RMT), SICI (interstimulus interval 3 milliseconds), ICF (interstimulus interval 7 milliseconds) and the duration of the contralateral CSP in the left and right first dorsal interosseus muscles (FDI) in 29 first-episode schizophrenia patients (FE-SZ) with limited exposure to antipsychotic treatment compared to 44 healthy control subjects (HC). CSP was measured during isometric contraction using stimulation intensities of 120, 140, 160 and 180% of RMT. Patients with FE-SZ demonstrated significant prolongation of CSP using stimulation intensities of 120% RMT (p=0.027), 140% RMT (p=0.015) and 160% RMT (p =0.010) of left motor cortex (right FDI) compared to HC. In addition, reduced SICI after stimulation of the right motor cortex was observed in FE-SZ (58.9% in FE-SZ vs. 31.4% in HC; p=0.050). RMT was similar in patients and controls. The reduced SICI in first-episode patients points towards a GABA(A)ergic deficit in schizophrenia. The prolonged CSP may reflect compensatory increased GABA(B)ergic transmission induced by hyperactivity of the dopaminergic system, although effects of antipsychotic medication could not be excluded.