Cerebellar Modulation of Sensorimotor Associative Plasticity Is Impaired in Cervical Dystonia

Background

In recent years, cervical dystonia (CD) has been recognized as a network disorder that involves not only the basal ganglia but other brain regions, such as the primary motor and somatosensory cortex, brainstem, and cerebellum. So far, the role of the cerebellum in the pathophysiology of dystonia is only poorly understood.

Objective

The objective of this study was to investigate the role of the cerebellum on sensorimotor associative plasticity in patients with CD.

Methods

Sixteen patients with CD and 13 healthy subjects received cerebellar transcranial direct current stimulation (ctDCS) followed by a paired associative stimulation (PAS) protocol based on transcranial magnetic stimulation that induces sensorimotor associative plasticity. Across three sessions the participants received excitatory anodal, inhibitory cathodal, and sham ctDCS in a double-blind crossover design. Before and after the intervention, motor cortical excitability and motor symptom severity were assessed.

Results

PAS induced an increase in motor cortical excitability in both healthy control subjects and patients with CD. In healthy subjects this effect was attenuated by both anodal and cathodal ctDCS with a stronger effect of cathodal stimulation. In patients with CD, anodal stimulation suppressed the PAS effect, whereas cathodal stimulation had no influence on PAS. Motor symptom severity was unchanged after the intervention.

Conclusions

Cerebellar modulation with cathodal ctDCS had no effect on sensorimotor associative plasticity in patients with CD, in contrast with the net inhibitory effect in healthy subjects. This is further evidence that the cerebello-thalamo-cortical network plays a role in the pathophysiology of dystonia. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.     

Botulinum toxin injections reduce associative plasticity in patients with primary dystonia

Botulinum toxin injections ameliorate dystonic symptoms by blocking the neuromuscular junction and weakening dystonic contractions. We asked if botulinum toxin injections in dystonia patients might also affect the integrity of sensorimotor cortical plasticity, one of the key pathophysiological features of dystonia. We applied a paired associative stimulation protocol, known to induce long‐term potentiation–like changes in the primary motor cortex hand area to 12 patients with cervical dystonia before and 1 and 3 months after botulinum toxin injections to the neck muscles. Primary motor cortex excitability was probed by measuring transcranial magnetic stimulation‐evoked motor evoked potentials before and after paired associative stimulation. We also measured the input–output curve, short‐interval intracortical inhibition, intracortical facilitation, short afferent inhibition, and long afferent inhibition in hand muscles and the clinical severity of dystonia. Before botulinum toxin injections, paired associative stimulation significantly facilitated motor evoked potentials in hand muscles. One month after injections, this effect was abolished, with partial recovery after 3 months. There were significant positive correlations between the facilitation produced by paired associative stimulation and (1) the time elapsed since botulinum toxin injections and (2) the clinical dystonia score. One effect of botulinum toxin injection treatment is to modulate afferent input from the neck. We propose that subsequent reorganization of the motor cortex representation of hand muscles may explain the effect of botulinum toxin on motor cortical plasticity. © The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.     

Cerebellar transcranial direct current stimulation modulates the fMRI signal in the cerebellar nuclei in a simple motor task

BackgroundIn a seminal paper, Galea et al. (Modulation of cerebellar excitability by polarity-specific noninvasive direct current stimulation. 2009. J Neurosci 29, 9115–9122) showed that cerebellar transcranial direct current stimulation (ctDCS) alters cerebellar-M1 connectivity. This effect has been explained by ctDCS-related changes of excitability of the cerebellar cortex with consecutive modulation of its main output, the dentate-thalamo-cortical pathway.ObjectivesThe aim of this functional magnetic resonance imaging (fMRI) study was to provide evidence that cathodal ctDCS decreases the activity of the cerebellar cortex, resulting in increased activity of the cerebellar nuclei, whereas anodal ctDCS has the opposite effect.MethodsA total of 48 participants (female/male: 23/25, age: 23.8 ± 4.1yrs., mean ± standard deviation) performed a finger tapping task with the right hand in a 3T MRI scanner. Functional MR images were acquired prior, during and after tDCS of the right cerebellum. Participants were assigned randomly to anodal, cathodal or sham ctDCS.ResultsNo significant difference of cerebellar cortical activation was found after comparing the three modes of stimulation. On the level of the dentate nuclei, however, a significant increase of activation was detected during and after cathodal stimulation. Furthermore, dentate nuclei activation was suppressed on a trend level following anodal stimulation.ConclusionsThe present findings support the hypothesis that cathodal ctDCS leads to a disinhibition of the dentate nucleus, whereas anodal ctDCS may have the opposite effect.     

Changes in the balance between motor cortical excitation and inhibition in focal, task specific dystonia.

Transcranial magnetic stimulation has been used in a double pulse paradigm to investigate the excitability of intrinsic motor cortical circuits in 15 patients with focal task specific dystonia of the right hand and a group of eight age matched controls. The left hemisphere was examined in five patients; in the remainder, both hemispheres were tested. There was no significant difference in stimulation threshold between patients and controls nor between the left and right hemispheres in the patients. There was a significant decrease in early corticocortical suppression when comparing stimulation of the left hemisphere in the patients and controls at interstimulus intervals of 1-15 ms (P < 0.01). There was no difference in the amount of suppression in the right and left hemispheres of the patients. It is concluded that in focal task specific dystonia there is shift in the balance between excitation and inhibition in local circuits of the motor cortex which leads to a net decrease in the amount of short latency suppression. These changes reflect disturbed basal ganglia input to the motor cortex. Reduced excitability of cortical inhibitory circuits may be one factor which contributes to the excessive and inappropriate muscle contraction which occurs during fine motor tasks in patients with focal dystonia.     

Early‐life‐stress affects the homeostasis of glutamatergic synapses

Early‐life stress induces several neuropsychological disorders in adulthood, including depression. Such disorders may be induced by functional alteration of the glutamatergic system. However, their underlying mechanisms have not yet been fully clarified. Furthermore, the involvement of glucocorticoids, which are representative stress hormones, has not yet been fully clarified. In this study, we used maternal deprivation (MD) mice as an early‐life‐stress model, and studied the changes in the glutamatergic system in adulthood. The glutamate concentration and neuronal activity in the somatosensory cortex (SSC) increased under basal conditions in MD mice. Stressful physical stimulation (SPS) increased the concentration of corticosterone, but not of glutamate, in the control mouse SSC. On the other hand, in the MD mice, although the basal concentration of corticosterone in the SSC increased, no SPS‐induced increase was observed. In contrast, the concentration of glutamate increased greatly during SPS. It was significantly high for 30 min after stimulation. The expression level of α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionic acid/N‐methyl‐d ‐aspartate receptors in the MD mice was also changed compared with that in the control mice after stimulation. These findings indicate that early‐life stress disrupts the homeostasis of glutamatergic synapses.     

Restoration of motor inhibition through an abnormal premotor‐motor connection in dystonia

To clarify the rationale for using rTMS of dorsal premotor cortex (PMd) to treat dystonia, we examined how the motor system reacts to an inhibitory form of rTMS applied to the PMd in healthy subjects and in a group of patients with focal hand dystonia and DYT1 gene carriers. Continuous theta burst transcranial magnetic stimulation (cTBS) with 300 and 600 pulses (cTBS300 and cTBS600) was applied to PMd, and its after‐effects were quantified by measuring the amplitude of MEPs evoked by single pulse transcranial magnetic stimulation (TMS) over the primary motor cortex (M1), short interval intracortical inhibition/facilitation (SICI/ICF) within M1, the third phase of spinal reciprocal inhibition (RI), and writing tests. In addition, in DYT1 gene carriers, the effects of cTBS300 over M1 and PMd on MEPs were studied in separate experiments. In healthy subjects, cTBS300 and cTBS600 over PMd suppressed MEPs for 30 min or more and cTBS600 decreased SICI and RI. In contrast, neither form of cTBS over PMd had any significant effect on MEPs, while cTBS600 increased effectiveness of SICI and RI and improved writing in patients with writer's cramp. NMDYT1 had a normal response to cTBS300 over left PMd. We suggest that the reduced PMd to M1 interaction in dystonic patients is likely to be due to reduced excitability of PMd‐M1 connections. The possible therapeutic effects of premotor rTMS may therefore involve indirect effects of PMd on SICI and RI, which this study has shown can be normalised by cTBS. © 2010 Movement Disorder Society     

Motor training as treatment in focal hand dystonia.

Focal hand dystonia may arise as a result of aberrant plasticity from excessive repetitive use. Improvement might be possible with appropriate motor training. Focusing on trying to decrease abnormal overflow of movement to fingers not involved in a task, we developed a motor training program for individualized finger movements. Ten patients with writer's cramp participated in the motor training program. Evaluation was done with the Fahn dystonia scale, kinematic analysis of handwriting, transcranial magnetic stimulation (TMS), and electroencephalography (EEG). Clinical improvement of dystonia was significant using the Fahn dystonia scale, and 6 patients reported an improvement in writing. The handwriting analysis showed a trend for improvement after training in simple exercises. There were no changes in cortical excitability measured by TMS and EEG. Whereas this method of motor training for 4 weeks led to mild subjective improvement and some improvement in handwriting, it is not sufficient to reverse motor cortex abnormalities measured by TMS and EEG.     

Pallidal and thalamic deep brain stimulation in myoclonus‐dystonia

Deep brain stimulation (DBS) of the internal globus pallidus (GPi) and ventral intermediate thalamic nucleus (VIM) are established treatment options in primary dystonia and tremor syndromes and have been reported anecdotally to be efficacious in myoclonus‐dystonia (MD). We investigated short‐ and long‐term effects on motor function, cognition, affective state, and quality of life (QoL) of GPi‐ and VIM‐DBS in MD. Ten MD‐patients (nine ε‐sarcoglycan‐mutation‐positive) were evaluated pre‐ and post‐surgically following continuous bilateral GPi‐ and VIM‐DBS at four time points: presurgical, 6, 12, and as a last follow‐up at a mean of 62.3 months postsurgically, and in OFF‐, GPi‐, VIM‐, and GPi‐VIM‐DBS conditions by validated motor [unified myoclonus rating scale (UMRS), TSUI Score, Burke‐Fahn‐Marsden dystonia rating scale (BFMDRS)], cognitive, affective, and QoL‐scores. MD‐symptoms significantly improved at 6 months post‐surgery (UMRS: 61.5%, TSUI Score: 36.5%, BFMDRS: 47.3%). Beneficial effects were sustained at long‐term evaluation post‐surgery (UMRS: 65.5%, TSUI Score: 35.1%, BFMDRS: 48.2%). QoL was significantly ameliorated; affective status and cognition remained unchanged postsurgically irrespective of the stimulation conditions. No serious long‐lasting stimulation‐related adverse events (AEs) were observed. Both GPi‐ and VIM‐DBS offer equally effective and safe treatment options for MD. With respect to fewer adverse, stimulation‐induced events of GPi‐DBS in comparison with VIM‐DBS, GPi‐DBS seems to be preferable. Combined GPi‐VIM‐DBS can be useful in cases of incapaciting myoclonus, refractory to GPi‐DBS alone. © 2010 Movement Disorder Society     

Defective inhibition and inter‐regional phase synchronization in pianists with musician's dystonia: An EEG study

Recent neurophysiological studies have associated focal‐task specific dystonia (FTSD) with impaired inhibitory function. However, it remains unknown whether FTSD also affects the inhibition (INH) of long‐term overlearned motor programs. Consequently, we investigated in a Go/NoGo paradigm the neural correlates associated with the activation (ACT) and inhibition of long‐term overlearned motor memory traces in pianists with musician's dystonia (MD), a form of FTSD, during a relevant motor task under constraint timing conditions with multichannel EEG. In NoGo trials, the movement related cortical potentials showed a positive shift after the NoGo signal related to inhibition and was significantly smaller over sensorimotor areas in musicians with MD. Further, we observed an increase at 850–900 ms in the power of beta oscillations which was significantly weaker for the patient group. The role of the inter‐electrode phase coupling in the sensorimotor integration of inhibitory processes turned out to be the most relevant physiological marker: the global phase synchronization during INH exhibited an increase between 230 and 330 ms and 7–8 Hz, increase which was significantly smaller for pianists with MD. This effect was due to a weaker phase synchronization between the supplementary motor cortex and left premotor and sensorimotor electrodes in patients. Thus, our findings support the hypothesis of a deficient phase coupling between the neuronal assemblies required to inhibit motor memory traces in patients with MD. EMG recorded from the right flexor pollicis longus muscle confirmed that patients with MD had a disrupted INH in NoGo trials. Hum Brain Mapp 2009. © 2008 Wiley‐Liss, Inc.     

Effects of cerebellar transcranial direct current stimulation on cerebellar-brain inhibition in humans: A systematic evaluation

BackgroundCerebellar transcranial direct current stimulation (ctDCS) is increasingly used to modulate cerebellar excitability and plasticity in healthy subjects and various patient populations. ctDCS parameters are poorly standardized, and its physiology remains little understood. Our aim was to compare the physiological effects of three different non-target electrode positions (buccinator muscle, supraorbital region, deltoid muscle).MethodsIn the first experiment, physiological after-effects of ctDCS were compared based on cerebellar-brain inhibition (CBI) in a group of 15 healthy right-handed participants. In the second experiment, CBI after-effects of ctDCS were assessed using different transcranial magnetic stimulation (TMS) intensities in 14 participants (CBI recruitment curve). The electric field distribution was calculated for each of the electrode montages based on a single anatomically accurate head model.ResultsAnodal and cathodal ctDCS polarities significantly decreased cerebellar-brain inhibition (CBI) with no substantial differences between the montages. Lower cerebellar TMS intensities resulted in decreased CBI following cathodal and increased CBI after anodal ctDCS. Computational modeling revealed minor differences in the electric field distribution between non-target electrode positions based on the effect size.ConclusionOur results show that the non-target electrode position has no significant impact on modeling results and physiological ctDCS after-effects. The recruitment of the cerebellar-M1 connection, however, varied depending on ctDCS polarity and cerebellar transcranial magnetic stimulation intensity, possibly due to diverse effects on different cell populations in the cerebellar cortex. This may be one of the reasons why ctDCS effects on functional measures are difficult to predict.     

Pallidal stimulation modifies after-effects of paired associative stimulation on motor cortex excitability in primary generalised dystonia

OBJECTIVE: To determine the effect of globus pallidus internus (GPi) deep brain stimulation (DBS) on motor cortex plasticity in patients with primary generalised dystonia. METHODS: We studied 10 patients with primary generalised dystonia (5 DYT1+, 5 idiopathic, 5 female, mean age 42) following GPi DBS and 10 healthy subjects. Motor cortex plasticity was assessed using transcranial magnetic stimulation (TMS) paired associative stimulation (PAS) of motor cortex and median nerve, a method which has been shown in healthy subjects to produce LTP-like effects. Thresholds and TMS intensity to produce a resting motor evoked potential (MEP) of 1 mV were determined. Resting MEP amplitude and stimulus response curves were recorded before and after PAS. Patients were recorded ON and OFF DBS in separate sessions. RESULTS: The mean TMS intensity to produce a resting MEP of 1 mV was 54% of maximum stimulator output when OFF and 52% ON DBS. Fifteen minutes after PAS the resting MEP amplitude increased in patients OFF DBS and in control subjects whereas it decreased in patients ON DBS. Similarly, after PAS, the mean amplitude of the stimulus response curve increased OFF DBS, but this effect was abolished with DBS ON. Furthermore, patients who had the largest clinical response to chronic DBS also had the largest difference in the effect of PAS with DBS ON vs. OFF. CONCLUSIONS: After PAS, patients with primary generalised dystonia showed a similar pattern of increased motor cortex excitability as healthy subjects when GPi DBS was OFF but not with GPi DBS ON. These results suggest that GPi DBS may reduce LTP-like motor cortex plasticity, which could contribute to its mechanism of action in dystonia.     

Loss of topographic specificity of LTD-like plasticity is a trait marker in focal dystonia

In focal hand dystonia, long-term potentiation (LTP) and depression (LTD)-like neuronal plasticity, as assessed by paired associative stimulation (PAS) targeting the hand-associated motor cortex, is enhanced and the topographic organization of plasticity is lost. However, if any of these abnormalities alone is sufficient to cause focal dystonia (FD) remains unknown. Ten patients with cervical dystonia (CD), 9 with blepharospasm (BS) and 16 age- and sex-matched controls were examined. PAS was performed by combining repetitively electric stimulation of the median nerve with subsequent transcranial magnetic stimulation of the contralateral motor cortex at 21.5ms (PAS21.5) and 10ms (PAS10). Corticospinal excitability was indexed by the magnitude of motor evoked potentials (MEPs) recorded from abductor pollicis brevis (APB) and abductor digiti minimi (ADM) muscles. In controls, MEP size of the homotopically conditioned APB increased after PAS21.5 whereas the MEP size of the heterotopically conditioned ADM remained stable. PAS10 led to a decrease of MEP size of the APB and to an increase of the heterotopic ADM. In contrast, after PAS21.5 and PAS10 in CD and BS MEP size increased and decreased, respectively, in both muscles. The magnitude of excitability changes, however, did not differ between dystonic patients and healthy controls. In FD the topographic organization of PAS21.5 and PAS10-induced plasticity is deranged in cortical areas not involved in the control of the dystonic body part. Somatotopical disorganization of plasticity may represent an endophenotypic trait in FD but may not be sufficient to generate a dystonic phenotype. Development of a dystonic phenotype may require that the gain of plasticity is additionally enhanced. This article is part of a Special Issue entitled "Advances in dystonia".     

1 Hz rTMS preconditioned by tDCS over the primary motor cortex in Parkinson’s disease: effects on bradykinesia of arm and hand

To investigate whether a period of 1 Hz repetitive transcranial magnetic stimulation (rTMS) over M1 preconditioned by tDCS improves bradykinesia of the upper limb in Parkinson’s disease (PD). Fifteen patients with PD performed index finger, hand tapping and horizontal pointing movements as well as reach-to-grasp movements with either hand before (baseline conditions) and after a period of 1 Hz rTMS preconditioned by (1) sham, (2) anodal or (3) cathodal tDCS over the primary motor cortex contralateral to the more affected body side. Movement kinematics was analysed using an ultrasound-based motion analyser at baseline, immediately after and 30 min after each stimulation session. Dopaminergic medication was continued. Compared to baseline, 1 Hz rTMS significantly increased the frequency of index finger and hand tapping as well as horizontal pointing movements performed with the contralateral hand. Movement frequency increased up to 40% over 30 min after cessation of the stimulation. Preconditioning with cathodal tDCS, but not with anodal tDCS, reduced the effectiveness of 1 Hz rTMS to improve tapping and pointing movements. There was no significant increase of movement frequencies of the ipsilateral hand induced by 1 Hz rTMS preconditioned by either tDCS session. Movement kinematics of reach-to-grasp movements were not significantly influenced by either stimulation session. In PD the beneficial effects of 1 Hz rTMS over the primary motor cortex on bradykinesia of simple finger, hand and pointing movements is reduced by preconditioning with cathodal tDCS, but not with anodal tDCS. Preconditioning with tDCS is a powerful tool to modulate the behavioural effect of 1 Hz rTMS over the primary motor cortex in PD.     

Transcranial direct current stimulation for the treatment of focal hand dystonia

The treatment of writer's cramp, a task‐specific focal hand dystonia, needs new approaches. A deficiency of inhibition in the motor cortex might cause writer's cramp. Transcranial direct current stimulation modulates cortical excitability and may provide a therapeutic alternative. In this randomized, double‐blind, sham‐controlled study, we investigated the efficacy of cathodal stimulation of the contralateral motor cortex in 3 sessions in 1 week. Assessment over a 2‐week period included clinical scales, subjective ratings, kinematic handwriting analysis, and neurophysiological evaluation. Twelve patients with unilateral dystonic writer's cramp were investigated; 6 received transcranial direct current and 6 sham stimulation. Cathodal transcranial direct current stimulation had no favorable effects on clinical scales and failed to restore normal handwriting kinematics and cortical inhibition. Subjective worsening remained unexplained, leading to premature study termination. Repeated sessions of cathodal transcranial direct current stimulation of the motor cortex yielded no favorable results supporting a therapeutic potential in writer's cramp. © 2011 Movement Disorder Society     

Augmenting mirror visual feedback‐induced performance improvements in older adults

Previous studies have indicated that age‐related behavioral alterations are not irreversible but are subject to amelioration through specific training interventions. Both training paradigms and non‐invasive brain stimulation (NIBS) can be used to modulate age‐related brain alterations and thereby influence behavior. It has been shown that mirror visual feedback (MVF) during motor skill training improves performance of the trained and untrained hands in young adults. The question remains of whether MVF also improves motor performance in older adults and how performance improvements can be optimised via NIBS. Here, we sought to determine whether anodal transcranial direct current stimulation (a‐tDCS) can be used to augment MVF‐induced performance improvements in manual dexterity. We found that older adults receiving a‐tDCS over the right primary motor cortex (M1) during MVF showed superior performance improvements of the (left) untrained hand relative to sham stimulation. An additional control experiment in participants receiving a‐tDCS over the right M1 only (without MVF/motor training of the right hand) revealed no significant behavioral gains in the left (untrained) hand. On the basis of these findings, we propose that combining a‐tDCS with MVF might be relevant for future clinical studies that aim to optimise the outcome of neurorehabilitation.     

Enhancement of precise hand movement by transcranial direct current stimulation

The effect of transcranial direct current stimulation (tDCS) on the precise nondominant hand movement was investigated by applying anodal stimulation over the right primary motor cortex. We recruited 14 healthy participants for this single-blind, sham-controlled crossover trial. A circle-drawing task was performed before, immediately after, and at 30 min after 20 min of 1 mA anodal or sham tDCS. Anodal tDCS, compared with sham stimulation, significantly improved the circle-drawing task compared with sham stimulation. The deviation area and path length of the task were significantly decreased after anodal tDCS application and were further enhanced at 30 min after stimulation. These results suggest that anodal tDCS over the primary motor cortex enhances the precise movement of the nondominant hand for 30 min in healthy participants.     

Altered dorsal premotor–motor interhemispheric pathway activity in focal arm dystonia

Given the possible role of dorsal premotor cortex (PMd) in the pathophysiology of dystonia, we used transcranial magnetic stimulation (TMS) methods to study PMd and PMd–primary motor cortex (M1) interactions in patients with focal arm dystonia. Here, we tested the connectivity between left PMd and right M1 as well as the intracortical excitability of PMd in 11 right‐handed patients with focal arm/hand dystonia and nine age‐matched healthy controls. The results showed that excitability of the inhibitory connection between PMd and M1 was reduced in patients, but there was no significant difference to healthy subjects in the excitability of the facilitatory connection. A triple stimulation technique in which pairs of TMS pulses are given over PMd and their interaction measured in terms of the effect on the baseline PMd‐M1 connection failed to reveal the usual pattern of interaction between the pairs of PMd stimuli. Indeed, the results in patients were similar to those seen in a group of young healthy subjects after the excitability of PMd had been changed by pretreatment with high‐frequency rTMS. We suggest that reduced transcallosal inhibition from the PMd may be involved in the altered pattern of abnormal muscle contractions of agonists and antagonists (overflow). © 2007 Movement Disorder Society     

Electrophysiological features of myoclonus‐dystonia

Inherited myoclonus‐dystonia (M‐D) is an autosomal dominant disorder characterized by myoclonus and dystonia that often improves with alcohol. To examine the electrophysiologic characteristics of M‐D, we studied 6 patients from 4 different families and 9 age‐matched healthy subjects. Neurophysiological studies performed include electromyography (EMG)‐electroencephalography (EEG) polygraphy, jerk‐locked back‐averaged EEG, somatosensory evoked potentials (SEP), long‐latency reflex (LLR) to median and digital nerve stimulation, and transcranial magnetic stimulation studies with short‐interval intracortical inhibition (SICI), intracortical facilitation (ICF), and long‐interval intracortical inhibition (LICI). All 6 patients showed myoclonus and dystonia on clinical examination and EMG testing. The EMG burst durations ranged from 30.4 to 750.6 milliseconds (mean, 101.5 milliseconds). Jerk‐locked back‐averaged EEG failed to reveal any preceding cortical correlates. Median nerve SEP revealed no giant potential. No patients had exaggerated LLR to median or digital nerve stimulation. There was no significant difference in SICI, ICF, and LICI between M‐D patients and normal subjects. Myoclonus in inherited M‐D is likely of subcortical origin. Normal intracortical inhibition and facilitation suggest that the GABAergic circuits in the motor cortex are largely intact and that the mechanisms of myoclonus and dystonia are different from those for cortical myoclonus and other dystonic disorders. © 2008 Movement Disorder Society     

Influence of area 5 on interhemispheric inhibition

Brodmann's area 5 is implicated in the sensorimotor control of hand movement in humans and nonhuman primates. However, little is known about the influence of area 5 on the neural circuitry within the primary motor cortex that underpins hand control. The present study investigated the neural circuitry of interhemispheric inhibition (IHI) that exists between homologous muscle representations in the motor cortex. Using paired-pulse transcranial magnetic stimulation, IHI was probed from the left-to-right hemisphere and vice versa for the first dorsal interosseous muscle of the hand at short (10 ms) and long (40 ms) latencies before and for up to 1 h after continuous θ-burst stimulation over left hemisphere area 5. The results indicate that continuous θ-burst over area 5 increases IHI at short latencies in the left hand (left-to-right inhibition) from 5-20 and 45-60 min after stimulation. Short latency inhibition in the right hand and bilateral long latency inhibition remain unaltered. The data indicate that area 5 influences the IHI that exists between the representations of the hand muscles. This effect occurs ipsilateral to the left area 5, suggesting that effects are mediated through changes in the excitability of transcallosal neurons originating in the left motor cortex.     

Isolated painless manual incoordination in 57 musicians.

Focal motor syndromes are reported in 57 instrumental musicians who presented with painless uncoordinated movement of the upper limbs. Three stereotyped afflictions were noted: flexion of the 4th and 5th fingers in pianists, flexion of the 3rd finger in guitarists, and extension of the 3rd finger in clarinetists. Our patients differed from those with generalised dystonia in that their disabilities were focal, activity-specific, and non-progressive. Because these disabilities represent entrained responses to peripheral stimuli, distinct from progressive dystonias, they may provide insights into control of fine limb movement and sensory triggers of abnormal movement.