Enhanced intracortical inhibition in cerebellar patients

OBJECTIVE: The aim of the study was to examine intracortical excitability in cerebellar patients. METHODS: Short-latency intracortical inhibition (SICI), long-latency intracortical inhibition (LICI) and intracortical facilitation (ICF) to paired transcranial magnetic stimulation (TMS) were investigated in 8 patients with 'pure' cerebellar syndromes and in 14 age-matched normal controls. The conditioning stimulus for short-latency intracortical inhibition and intracortical facilitation was set at 70% of the resting motor threshold (RMT) and preceded the test stimulus (110-120% of the resting motor threshold) by interstimulus intervals (ISIs) of 1-30 ms. For the long-latency intracortical inhibition determinations, the conditioning stimulus was set at 120% of the resting motor threshold and preceded the test stimulus (also 120% of the resting motor threshold) by interstimulus intervals of 30-500 ms. RESULTS: No statistically significant differences were found between patients and controls as regards either short-latency intracortical inhibition or intracortical facilitation. A significant prevalence of long-latency intracortical inhibition was present in cerebellar patients at interstimulus intervals of 200-500 ms (conditioned MEP amplitude=29-41% of test MEP) as compared to controls (71-96% of test MEP). The amplitude of conditioned MEPs was persistently less than 45% of the test MEP in six patients, who were studied at interstimulus intervals up to 1000 ms. CONCLUSIONS: Long-latency intracortical inhibition was prevalent and abnormally longer-lasting in patients. Tonic hyperactivation of a subpopulation of GABAergic interneurons in the motor cortex of patients may be the mechanism responsible for this abnormality. Our findings seem to be specific to cerebellar diseases and are the opposite of those found in movement disorders such as dystonia and Parkinson's disease. These data suggest that the cerebellum and the basal ganglia may have opposite influences in tuning the excitability of the motor cortex.     

Decreased short-interval intracortical inhibition correlates with better pinch strength in patients with stroke and good motor recovery

Background

Deeper short-interval intracortical inhibition (SICI), a marker of GABA_A activity, correlates with better motor performance in patients with moderate to severe hand impairments in the chronic phase after stroke.

Modulation of intracortical inhibition in response to acute psychosocial stress is impaired among individuals with chronic neck pain

Objective

Psychosocial stress has been associated with a variety of chronic pain disorders although the mechanisms responsible for this relationship are unknown. The purpose of this study was to compare the excitability of intracortical and corticospinal pathways to the trapezius muscle in individuals with and without chronic neck pain during exposure to low and high levels of psychosocial stress.

Methods

Single and paired-pulse transcranial magnetic stimulation was used to assess motor evoked potentials (MEPs) and short-interval intracortical inhibition (SICI) during mental math performed in the presence and absence of social evaluative threat.

Results

All participants demonstrated higher amplitude MEPs in the high stress compared to the low stress condition (p < 0.01). Participants with chronic neck pain had significantly greater SICI than healthy participants in the low stress condition (p = 0.03). During exposure to the stressor, healthy participants showed an increase in SICI, whereas participants with neck pain showed no change (group difference for change in SICI, p < 0.01).

Conclusions

These findings suggest that individuals with chronic neck pain inhibit motor output to the trapezius in the presence of minor stressors, and are unable to compensate for additional stress-evoked increases in corticospinal excitability through further modulation of SICI. This observation has potential implications for the management of patients who have difficulty relaxing painful muscles during times of stress.     

Longitudinal changes of motor cortical excitability and transcallosal inhibition after subcortical stroke

Objective

A general lack of longitudinal studies on interhemispheric interactions following stroke led us to use transcranial magnetic stimulation (TMS) to examine changes in corticospinal/intracortical excitability and transcallosal inhibition over a 1-year period following subcortical stroke.

Methods

We measured TMS parameters such as motor threshold (MT), short-interval intracortical inhibition (SICI), and ipsilateral silent period (iSP) and evaluated clinical scores at three time-points (T1, T2, and T3) in 24 patients and 25 age-matched healthy subjects.

Results

At T1, we observed reduced MTs and SICIs with prolonged iSPs in the unaffected hemisphere (UH). In contrast, increased MTs and reduced SICIs were observed in the affected hemisphere (AH). These abnormalities gradually reduced and no MEP response to TMS at T1 predicted a worse prognosis. The prolonged iSP at T1 was associated with more severe impairments, but it did not necessarily predict a worse prognosis after 1 year.

Conclusions

UH excitability was increased at the post-acute time-period, which may have resulted in enhanced transcallosal inhibition to the AH. However, it is unclear whether there was a causal relationship between the enhanced transcallosal inhibition and the extent of clinical recovery.

Significance

This is the first study to demonstrate changes in transcallosal inhibition over a longitudinal period following stroke.     

Supplementary motor area plays a causal role in automatic inhibition of motor responses

BackgroundThe masked-priming paradigm is used to test unconscious inhibitory processes of the brain. A tendency towards responses that are incompatible with the prime, designated as negative compatibility effect (NCE), emerges when the perception of a priming visual stimulus is “masked” afterwards. This effect presumably stems from a subliminal inhibitory process against the masked-prime. Prior lesions as well as activation studies suggest a key role of SMA in this effect.ObjectiveThis study was conducted to elucidate a causal role of SMA in the subliminal response inhibition represented by the NCE.MethodsUsing a repeated-measures pre–post design with a group of healthy people, physiological measures (resting and active motor thresholds and motor evoked potential (MEP) amplitude) and behavioral ones (choice reaction time (CRT), positive compatibility effect (PCE) and NCE) were obtained before and after three quadripulse stimulation (QPS), namely sham, M1-QPS, and SMA-QPS, on different days. CRT and PCE served as indices for different aspects of motor execution.ResultsMotor thresholds were not altered after any QPS, although the M1-QPS increased MEP amplitude. Neither CRT nor PCE was altered significantly after QPS protocols. NCE was abolished after the SMA-QPS.ConclusionsAbolished NCE after the SMA-QPS in the absence of MEP changes suggests that (1) SMA plays a cardinal role in the NCE, and (2) the network involved in NCE is different from that of MEP generation.     

Combined endogenous and exogenous disinhibition of intracortical circuits augments plasticity induction in the human motor cortex

BackgroundMotor imagery (MI) engages cortical areas in the human brain similar to motor practice. Corticospinal excitability (CSE) is facilitated during but not after MI practice. We hypothesized that lasting CSE changes could be achieved by associatively pairing this endogenous modulation with exogenous stimulation of the same intracortical circuits.MethodsWe combined MI with a disinhibition protocol (DIS) targeting intracortical circuits by paired-pulse repetitive transcranial magnetic stimulation in one main and three subsequent experiments. The follow-up experiments were applied to increase effects, e.g., by individualizing inter-stimulus intervals, adding neuromuscular stimulation and expanding the intervention period. CSE was captured during (online) and after (offline) the interventions via input-output changes and cortical maps of motor evoked potentials. A total of 35 healthy subjects (mean age 26.1 ± 2.6 years, 20 females) participated in this study.ResultsA short intervention (48 stimuli within ∼90s) increased CSE. This plasticity developed rapidly, was associative (with MI_on, but not MI_off or REST) and persisted beyond the intervention period. Follow-up experiments revealed the relevance of individualizing inter-stimulus intervals and of consistent inter-burst periods for online and offline effects, respectively. Expanding this combined MI/DIS intervention to 480 stimuli amplified the sustainability of CSE changes. When concurrent neuromuscular electrical stimulation was applied, the plasticity induction was cancelled.ConclusionsThis novel associative stimulation protocol augmented plasticity induction in the human motor cortex within a remarkably short period of time and in the absence of active movements. The combination of endogenous and exogenous disinhibition of intracortical circuits may provide a therapeutic backdoor when active movements are no longer possible, e.g., for hand paralysis after stroke.     

脑血管病患者经颅磁刺激运动诱发电位的研究

采用经颅磁刺激运动诱发电位（ＭＥＰ）对７２例脑血管病（ＣＶＤ）患者和５０例正常人进行检测。结果：ＣＶＤ患者瘫痪侧上肢磁刺激无反应或皮层潜伏期和中枢传导时间（ＣＭＣＴ）较正常对照组和健侧显著延长（Ｐ＜０．００１）；瘫痪侧下肢磁刺激无反应或ＣＭＣＴ较正常对照组和健侧显著延长（Ｐ＜０．０５）。脑出血与脑梗塞患者ＭＥＰ异常率无显著差异（Ｐ＞０．０５），而与临床病情轻重和病变部位密切相关。提示ＭＥＰ能客观反映ＣＶＤ患者中枢运动传导通路功能受损的情况。     

Depressed intracortical inhibition after long trains of subthreshold repetitive magnetic stimuli at low frequency

OBJECTIVE: Repetitive transcranial magnetic stimulation (rTMS) modulates cortical excitability. These effects outlast the rTMS train, and range from inhibition to facilitation according to the variables used for rTMS. Several studies have demonstrated short and long-term effects on motor evoked potential (MEP) size, whereas the effects on intracortical inhibition (ICI) and facilitation (ICF) are still unclear. We investigated short- (1-15 min), intermediate- (16-30 min), and long-term (6 h) effects on intracortical excitability. METHODS: Fourteen healthy subjects were stimulated with rTMS trains of 900 pulses (1 Hz, 90% resting motor threshold (rMTh)), delivered over the primary motor cortex and the occipital area. MTh, MEP size, silent period, intracortical inhibition at short (ICI) and long inter-stimulus intervals, and ICF were tested before and after rTMS. RESULTS: ICI was reduced 16-30 min after 1 Hz rTMS trains over the primary motor area, whereas the other response variables remained unchanged. The ICI reduction at 16-30 min was reproducible on different days in the same subjects; it was absent at 6 h and after stimulation of the occipital area. CONCLUSIONS: Subthreshold 1 Hz rTMS decreases ICI by reducing the excitability of intracortical inhibitory interneurones or by altering the electrical properties of the facilitatory chain of neurons responsible for the I waves.     

Observation-execution matching and action inhibition in human primary motor cortex during viewing of speech-related lip movements or listening to speech

One influential theory posits that language has evolved from gestural communication through observation-execution matching processes in the mirror neuron system (MNS). This theory predicts that observation of speech-related lip movements or even listening to speech would result in effector and task specific increase of the excitability of the corresponding motor representations in the primary motor cortex (M1), since actual movement execution is known be effector and task specific. In addition, effector and task specific inhibitory control mechanisms should be important to prevent overt motor activation during observation of speech-related lip movements or listening to speech. We tested these predictions by applying focal transcranial magnetic stimulation to the left M1 of 12 healthy right-handed volunteers and measuring motor evoked potentials (MEPs) and short-interval intracortical inhibition (SICI) in a lip muscle, the right orbicularis oris (OO), vs. a hand muscle, the right first dorsal interosseus (FDI). We found that MEP and SICI increased only in the OO but not in the FDI during viewing of speech-related lip movements or listening to speech. These changes were highly task specific because they were absent when lip movements non-related to speech were viewed. Finally, the increase in MEP amplitude in the OO correlated inversely with accuracy of speech perception, i.e. the MEP increase was directly related to task difficulty. The MEP findings support the notion that observation-execution matching is an operating process in the putative human MNS that might have been fundamental for evolution of language. Furthermore, the SICI findings provide evidence that inhibitory mechanisms are recruited to prevent unwanted overt motor activation during action observation.     

Topiramate selectively decreases intracortical excitability in human motor cortex

PURPOSE: Topiramate (TPM) is a novel drug with broad antiepileptic effect in children and adults. In vitro studies suggest activity as sodium-channel blocker, as gamma-aminobutyric acid type A (GABAA)-receptor agonist and as non-N-methyl-D-aspartate (NMDA)-glutamate receptor antagonist. METHODS: With transcranial magnetic stimulation (TMS), we evaluated which of the mechanisms of action of TPM detected in vitro are relevant for the modulation of human motor cortex excitability. In a double-blind, placebo-controlled, crossover study design, we investigated the effect of single oral doses of 50 mg and 200 mg TPM on motor thresholds, cortical silent period (CSP), and on intracortical inhibition (ICI) and intracortical facilitation (ICF) in 20 healthy subjects. RESULTS: A significant dose-dependent increase of ICI was noticed after 200 mg TPM as compared with placebo at short interstimulus intervals of 2 to 4 ms. TPM had no effect on motor thresholds or the CSP. CONCLUSIONS: We conclude that a single dose of TPM selectively increases ICI by GABAAergic and/or glutamatergic mechanisms without a relevant influence on measures, depending on ion-channel blockade or GABAB-receptor activity. The decrease of intracortical excitability (as measured by ICI and ICF) caused by TPM may correlate with its lack of proconvulsive potential in idiopathic generalized epilepsy, because drugs without this action or with less pronounced action may exacerbate seizures in this condition.     

Short-interval and long-interval intracortical inhibition of TMS-evoked EEG potentials

Background

Inhibition in the human motor cortex can be probed by means of paired-pulse transcranial magnetic stimulation (ppTMS) at interstimulus intervals of 2–3 ms (short-interval intracortical inhibition, SICI) or ～100?ms (long-interval intracortical inhibition, LICI). Conventionally, SICI and LICI are recorded as motor evoked potential (MEP) inhibition in the hand muscle. Pharmacological experiments indicate that they are mediated by GABAA and GABAB receptors, respectively.Objective/Hypothesis: SICI and LICI of TMS-evoked EEG potentials (TEPs) and their pharmacological properties have not been systematically studied. Here, we sought to examine SICI by ppTMS-evoked compared to single-pulse TMS-evoked TEPs, to investigate its pharmacological manipulation and to compare SICI with our previous results on LICI.

Automated-parameterization of the motor evoked potential and cortical silent period induced by transcranial magnetic stimulation

ObjectiveTo standardize the characterization of motor evoked potential (MEP) and cortical silent period (CSP) recordings elicited with transcranial magnetic stimulation (TMS).MethodsA computer-based, automated-parameterization program (APP) was developed and tested which provides a comprehensive set of electromyography (EMG) magnitude and temporal measures. The APP was tested using MEP, CSP, and isolated CSP (iCSP) TMS stimulus–response data from a healthy adult population (N = 13).ResultsThe APP had the highest internal reliability (Cronbach’s alpha = .98) for CSP offset time compared with two prominent automated methods. The immediate post-CSP EMG recovery level was 49% higher than the pre-TMS EMG level. MEP size (peak amplitude, mean amplitude, peak-to-peak amplitude, and area) correlated higher with effective E-field (E_eff) than other intensity measures (r ≈ 0.5 vs. r ≈ 0.3) suggesting that E_eff is better suited for standardizing MEP stimulus–response relationships.ConclusionsThe APP successfully characterized individual and mean epochs containing MEP, CSP, and iCSP responses. The APP provided common signal and temporal measures consistent with previous studies and novel additional parameters.SignificanceWith the use of the APP modeling method and the E_eff, a standard approach for the analysis and reporting of MEP–CSP complex and iCSP measurements is achievable.     

Transcranial magnetic and electrical stimulation compared: Does TES activate intracortical neuronal circuits?

OBJECTIVE: To determine whether, and under which conditions, transcranial electrical stimulation (TES) and transcranial magnetic stimulation (TMS) can activate similar neuronal structures of the human motor cortex, as indicated by electromyographic recordings. METHODS: Focal TMS was performed on three subjects inducing a postero-anterior directed current (p-a), TES with postero-anteriorly (p-a) and latero-medially (l-m) oriented electrodes. We analyzed the onset latencies and amplitudes (single-pulse) and intracortical inhibition and excitation (paired-pulse). RESULTS: TMS p-a and TES p-a produced muscle responses with the same onset latency, while TES l-m led to 1.4-1.9 ms shorter latencies. Paired-pulse TMS p-a and TES p-a induced inhibition at short inter-stimulus intervals (ISI) (maximum: 2-3 ms) and facilitation at longer ISIs (maximum: 10 ms). No inhibition but a strong facilitation was obtained from paired-pulse TES l-m (ISIs 1-5 ms). CONCLUSIONS: Our findings support the hypothesis, that current direction is the most relevant factor in determining the mode of activation for both TMS and TES: TMS p-a and TES p-a are likely to activate the corticospinal neurons indirectly. In contrast, TES l-m may preferentially activate the corticospinal fibres directly, distant of the neuronal body. SIGNIFICANCE: TES is a suitable tool to induce intracortical inhibition and excitation.     

Age-related Differences in Short- and Long-interval Intracortical Inhibition in a Human Hand Muscle

BackgroundEffects of age on the assessment of intracortical inhibition with paired-pulse transcranial magnetic stimulation (TMS) have been variable, which may be due to between-study differences in test TMS intensity and test motor evoked potential (MEP) amplitude.ObjectiveTo investigate age-related differences in short- (SICI) and long-interval intracortical inhibition (LICI) across a range of test TMS intensities and test MEP amplitudes.MethodsIn 22 young and 18 older subjects, SICI and LICI were recorded at a range of test TMS intensities (110%–150% of motor threshold) while the first dorsal interosseous (FDI) muscle was at rest, or producing a precision grip of the index finger and thumb. Data were subsequently compared according to the amplitude of the MEP produced by the test alone TMS.ResultsWhen pooled across all test TMS intensities, SICI in resting muscle and LICI in active muscle were similar in young and older adults, whereas SICI in active muscle and LICI in resting muscle were reduced in older adults. Regrouping data based on test MEP amplitude demonstrated similar effects of age for SICI and LICI in resting muscle, whereas more subtle differences between age groups were revealed for SICI and LICI in active muscle.ConclusionsAdvancing age influences GABA-mediated intracortical inhibition, but the outcome is dependent on the experimental conditions. Age-related differences in SICI and LICI were influenced by test TMS intensity and test MEP amplitude, suggesting that these are important considerations when assessing intracortical inhibition in older adults, particularly in an active muscle.     

Transcranial magnetic stimulation: specific and non-specific facilitation of magnetic motor evoked potentials

Summary Different physiological mechanisms of facilitation of latencies and amplitudes of magnetic motor evoked potentials (MEPs) were evaluated in a cohort of 140 healthy volunteers. The potentials were induced at the vertex and recorded at the abductor pollicis brevis. The aim of the present investigation was to compare physiological mechanisms which presumably facilitate motor pathways at the cortical level with those known to occur during contraction of small hand muscles. When compared with MEPs at rest, the maximum average decrease of latencies (1.5, SD 1.1 ms) as well as the highest increase of peak to peak amplitudes (2.6, SD 2.1 mV) was observed during exertion of a voluntary background force, at the muscle recorded from. Pre-innervation of a neighbouring muscle (abductor digiti minimi) led to a lesser average decrease of latencies by 1.0, SD 1.1 ms and an average increase of amplitudes by only 0.5, SD 1.5 mV. Non-specific manoeuvres, like sticking out the tongue or counting aloud, reduced mean latencies slightly by 0.4 ms, SD 0.8 ms and 0.3 SD 0.85 ms respectively, but increased amplitudes markedly by an average of 1.0, SD 1.6 mV and 0.8, SD 1.4mV respectively. It is concluded that facilitation of MEPs by non-specific manoeuvres occurs and must be taken into account when evaluating MEPs.     

Size variance of motor evoked potential at initiation of voluntary contraction in palsy of conversion disorder

Aim:  To investigate the efficacy of transcranial magnetic stimulation (TMS) with a cue signal for the objective diagnosis of palsy of conversion disorder (CD).
Methods:  Ten patients with palsy of CD, nine with amyotrophic lateral sclerosis (ALS), and eight control subjects were examined. Motor evoked potential (MEP) was recorded from the abductor digiti minimi muscle under three conditions: at rest, during tonic contraction, and with an audio cue signal. In the cue signal paradigm, subjects were asked to perform ramp-and-hold contraction in response to a cue signal.
Results:  MEP size increased in the cue signal paradigm in both controls and patients with ALS, but was not obvious in some CD patients. This was likely due to variance among trials in the cue signal paradigm in each CD patient. The coefficients of variance (CV) among trials in the cue signal paradigm were 15 ± 4.3 in controls, 25 ± 11 in ALS, and 70 ± 40 in CD.
Conclusions:  CV of MEP size with cue signal was larger in CD than in controls ( P  < 0.005) and in ALS patients ( P  < 0.01). The size variance among MEP trials with the cue signal is a supportive parameter for the diagnosis of CD.     

Evidence for normal intracortical inhibitory recruitment properties in cervical dystonia

ObjectiveDystonia is associated with reduced intracortical inhibition as measured by the cortical silent period (cSP); however, this may be due to abnormal cSP threshold or input-output properties. This study evaluated cSP recruitment properties in people with cervical dystonia (CD).MethodsBilateral electromyographic recordings were collected in the upper trapezius muscle in response to transcranial magnetic stimulation of the left and right primary motor cortex in a group with CD (n = 19) and controls (n = 21). cSP threshold, cSP input-output properties at stimulation intensities from 1 to 1.4x the cSP threshold, ipsilateral silent period duration (iSP) and timing and magnitude of the contralateral and ipsilateral motor evoked potential (MEP) were assessed.ResultsThe cSP threshold, input-output properties, and contralateral MEP magnitude were not significantly different between groups (all p > 0.07). Hemispheric symmetry was present in the control group while the CD group had reduced iSP (p < 0.01) and a trend for reduced ipsilateral MEP response (p = 0.053) in the left hemisphere.ConclusionsRecruitment properties of intracortical inhibition are similar between control and CD groups. Transcallosal inhibition is asymmetric between hemispheres in people with CD.SignificanceEvidence of normal intracortical inhibition recruitment properties challenge the commonly held view that cortical inhibition is reduced in dystonia.     

经颅电刺激咀嚼肌诱发电位的检测方法与正常值

目的　对健康个体进行经颅电刺激咀嚼肌运动诱发电位的研究 ,建立评估皮质脑干束的检查方法。方法　对 5 6名健康志愿者进行经颅电刺激 ,在双侧咀嚼肌同时接受 ,分别记录同侧的根运动诱发电位 ( R- MEP)和对侧的皮层运动诱发电位 ( C- MEP)的潜伏期、波幅。结果　在同侧记录的是兴奋同侧的三叉神经根所产生的动作电位 ,因此称为“root”MEP( R- MEP) ;在对侧轻收缩状态下记录的是兴奋对侧的皮质延髓束所产生的动作电位 ,因此称为“cortical”MEP( C- MEP)。 R- MEP的潜期为 3.5 5± 0 .44 ms,波幅为 3.49± 2 .73m V;C- MEP的潜期为5 .83± 1.40 ms,波幅为 5 6 3.84± 5 2 5 .0 7μV。C- MEP的潜期与年龄无明显相关性 ( P>0 .1)。结论　 C- MEP是一种非创伤性评估皮质脑干束的检测方法。     

Motor cortical excitability and plasticity in patients with neurofibromatosis type 1

ObjectiveNeurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder that is associated with cognitive disabilities. Based on studies involving animals, the hypothesized cause of these disabilities results from increased activity of inhibitory interneurons that decreases synaptic plasticity. We obtained transcranial magnetic stimulation (TMS)-based measures of cortical inhibition, excitability and plasticity in individuals with NF1.MethodsWe included 32 NF1 adults and 32 neurotypical controls. Cortical inhibition was measured with short-interval intracortical inhibition (SICI) and cortical silent period (CSP). Excitability and plasticity were studied with intermittent theta burst stimulation (iTBS).ResultsThe SICI and CSP response did not differ between NF1 adults and controls. The response upon iTBS induction was significantly increased in controls (70%) and in NF1 adults (83%). This potentiation lasted longer in controls than in individuals with NF1. Overall, the TMS response was significantly lower in NF1 patients (F(1, 41) = 7.552, p = 0.009).ConclusionsIndividuals with NF1 may have reduced excitability and plasticity, as indicated by their lower TMS response and attenuation of the initial potentiated response upon iTBS induction. However, our findings did not provide evidence for increased inhibition in NF1 patients.SignificanceThese findings have potential utility as neurophysiological outcome measures for intervention studies to treat cognitive deficits associated with NF1.     

Abnormal postexcitatory and interhemispheric motor cortex inhibition in writer's cramp

Focal transcranial magnetic stimulation (TMS) of the motor cortex was used to study excitatory and inhibitory stimulation effects in 25 patients with writer's cramp and 25 healthy volunteers. We investigated excitatory and inhibitory corticospinally mediated motor effects in muscles contralateral to the stimulation side as well as interhemispheric inhibition of tonic motor activity in muscles ipsilateral to stimulation. Motor evoked potentials (MEPs) were recorded from both first dorsal interosseus muscles. Motor thresholds at rest and amplitudes and latencies of MEPs obtained during maximal contraction were always bilaterally normal. The duration of postexcitatory inhibition was significantly shortened (168±55 vs. 198±39 ms in normal subjects, P=0.001) and the duration of interhemispheric inhibition prolonged (30.3±6.6 vs. 26±3.9 ms in normal subjects, P < 0.001). Both observations would be compatible with a decreased inhibition of corticospinal and transcallosal outputs of the motor cortex. The results were not influenced by fatigue effects. Abnormal motor cortex inhibition seems to be a generalized phenomenon in writer's cramp since it was detected in both hemispheres and during a simple isometric motor task which did not evoke dystonic symptoms. Received: 28 February 2000 / Received in revised form: 29 June 2000 / Accepted: 1 August 2000