Effects of botulinum toxin type A on intracortical inhibition in patients with dystonia

To find out whether botulinum toxin alters the excitability of cortical motor areas, we studied intracortical inhibition with transcranial magnetic stimulation in patients with upper limb dystonia before, 1 month after, and 3 months after the injection of botulinum toxin type A in the affected muscles. Eleven normal subjects and 12 patients with dystonia involving the upper limbs (7 with generalized dystonia, 2 with segmental dystonia, and 3 with focal dystonia) were studied. Patients were assessed clinically with the Dystonia Movement Scale. Paired magnetic stimuli were delivered by two Magstim 200 magnetic stimulators connected through a Bistim module to a figure-of-eight coil placed over the motor area of the forearm muscles. Paired stimulation was given at rest. A subthreshold (80% of motor threshold) conditioning stimulus was delivered 3 and 5 msec before the suprathreshold (120% of motor threshold) test stimulus. Electromyographic signals were recorded over the flexor or extensor muscles of the forearm on the affected side. We measured the amplitude of the test motor evoked potential (expressed as a percentage of the unconditioned motor evoked potential). All results were compared using ANOVA. In all patients, a botulinum toxin type A injection (50-100 mouse units) reduced dystonic movements in the arm. In normal subjects, electromyographic recordings showed significant inhibition of the test response. Before botulinum toxin injection, patients had less test response inhibition than normal subjects. One month after injection, patients had test response inhibition similar to that of normal subjects. At 3 months after injection, they again had less inhibition than normal subjects or patients at 1 month after injection. In conclusion, our data suggest that botulinum toxin can transiently alter the excitability of the cortical motor areas by reorganizing the inhibitory and excitatory intracortical circuits. The cortical changes probably originate through peripheral mechanisms.     

Effects of Two Weeks of Cerebellar Theta Burst Stimulation in Cervical Dystonia Patients

Dystonia is generally regarded as a disorder of the basal ganglia and their efferent connections to the thalamus and brainstem, but an important role of cerebellar-thalamo-cortical (CTC) circuits in the pathophysiology of dystonia has been invoked. Here in a sham controlled trial, we tested the effects of two-weeks of cerebellar continuous theta burst stimulation (cTBS) in a sample of cervical dystonia (CD) patients. Clinical evaluations were performed by administering the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) and the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). We used TMS to measure the inhibitory connectivity between the cerebellum and the contralateral motor cortex (cerebellar brain inhibition [CBI]), and the excitability of the contralateral primary motor cortex assessing intracortical inhibition (SICI), intracortical facilitation (ICF) and cortical silent period (CSP). Paired associative stimulation (PAS) was tested to evaluate the level and the topographical specificity of cortical plasticity, which is abnormally enhanced and non-focal in CD patients. Two weeks of cerebellar stimulation resulted in a small but significant clinical improvement as measured by the TWSTRS of approximately 15%. Cerebellar stimulation modified the CBI circuits and reduced the heterotopic PAS potentiation, leading to a normal pattern of topographic specific induced plasticity. These data provide novel evidence CTC circuits could be a potential target to partially control some dystonic symptoms in patients with cervical dystonia.     

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     

Impaired modulation of motor cortex excitability by homonymous and heteronymous muscle afferents in focal hand dystonia.

A decrease of heteronymous median nerve-evoked inhibition of corticospinal projections to forearm extensor muscles was reported in a group of 10 dystonic patients by Bertolasi and colleagues in 2003. Here we tested the excitability of corticomotoneuronal connections to both wrist extensor (ECR) and flexor (FCR) muscles after conditioning stimulation of median and also radial nerve at rest in a group of 25 patients with focal hand dystonia compared to 20 healthy subjects. We also investigated the effect of the wrist dystonic posture, either in flexion or in extension, on the afferent modulation of ECR and FCR motor evolved potentials (MEPs). The heteronymous (median-induced) but also homonymous (radial-induced) inhibitions (interstimuli intervals 13-21 ms) of ECR MEP size observed in healthy subjects were decreased in patients. In addition, homonymous (median-induced) facilitation of FCR MEP size was also decreased in patients while heteronymous inhibition (radial-induced) was not. Neither the involvement of the target muscle in the dystonic posture nor the origin of the afferent volley (from a dystonic muscle) influenced the degree of impairment of afferent modulation of the MEP. These findings support the view that a global abnormal somatosensory coupling in focal hand dystonia may contribute to an inadequate motor command to wrist muscles.     

Deep brain stimulation effects in dystonia: Time course of electrophysiological changes in early treatment

Deep brain stimulation to the internal globus pallidus is an effective treatment for primary dystonia. The optimal clinical effect often occurs only weeks to months after starting stimulation. To better understand the underlying electrophysiological changes in this period, we assessed longitudinally 2 pathophysiological markers of dystonia in patients prior to and in the early treatment period (1, 3, 6 months) after deep brain stimulation surgery. Transcranial magnetic stimulation was used to track changes in short‐latency intracortical inhibition, a measure of excitability of GABA_A‐ergic corticocortical connections and long‐term potentiation‐like synaptic plasticity (as a response to paired associative stimulation). Deep brain stimulation remained on for the duration of the study. Prior to surgery, inhibition was reduced and plasticity increased in patients compared with healthy controls. Following surgery and commencement of deep brain stimulation, short‐latency intracortical inhibition increased toward normal levels over the following months with the same monotonic time course as the patients' clinical benefit. In contrast, synaptic plasticity changed rapidly, following a nonmonotonic time course: it was absent early (1 month) after surgery, and then over the following months increased toward levels observed in healthy individuals. We postulate that before surgery preexisting high levels of plasticity form strong memories of dystonic movement patterns. When deep brain stimulation is turned on, it disrupts abnormal basal ganglia signals, resulting in the absent response to paired associative stimulation at 1 month. Clinical benefit is delayed because engrams of abnormal movement persist and take time to normalize. Our observations suggest that plasticity may be a driver of long‐term therapeutic effects of deep brain stimulation in dystonia. © 2011 Movement Disorder Society     

The effect of cutaneous input on intracortical inhibition in focal task‐specific dystonia

In normal subjects short interval intracortical inhibition (SICI) is topographically modulated by cutaneous input, which may be important for focusing muscle activation during tasks. In patients with writer's cramp, a task‐specific focal dystonia characterized by inappropriate and excessive muscle activation of the upper limb during certain motor tasks, intracortical inhibition is reduced at rest and lacks the normal topographically‐specific modulation during motor tasks. In the present study we investigated whether cutaneous input modulated SICI in a group of patients with writer's cramp and a control group of subjects. Electromyographic recordings were made from the right first dorsal interosseous (FDI), abductor pollicis brevis (APB), and abductor digiti minimi (ADM) muscles. Brief electrical stimuli were applied to either digit II or digit V with ring electrodes. SICI was investigated using a paired transcranial magnetic stimulation paradigm employing interstimulus intervals of 1–15 ms. Cutaneous input from both digit II and digit V modulated motor evoked potentials and SICI in a topographically‐specific manner in control subjects. In contrast, cutaneous input failed to modulate motor evoked potentials or SICI in the focal hand dystonia patients. These results provide further evidence of abnormal sensorimotor integration in focal hand dystonia. © 2007 Movement Disorder Society     

Lack of inhibitory interaction between somatosensory afferent inputs and intracortical inhibitory interneurons in focal hand dystonia.

We looked for an impaired interaction in the primary motor cortex between intracortical inhibitory circuits and circuits fed by somatosensory inputs in patients with writer's cramp. Short-interval intracortical inhibition (sICI) to wrist extensor carpi radialis muscle (ECR) was conditioned by stimulation of antagonist muscle afferents and sICI to first dorsal interosseus (FDI) muscle by homotopic cutaneous afferents stimulation. sICI was assessed at rest and during a tonic contraction of the target muscle. Eighteen patients with writer's cramp (10 having a wrist dystonic posture in flexion during writing and 8 in extension) were compared to 14 control subjects. Peripheral inputs decreased sICI in control subjects. This decrease was lost in patients in both FDI and ECR, regardless of the wrist dystonic posture. By contrast, contraction-induced depression of sICI appeared dependant on the dystonic status of the muscle: depression of sICI to ECR was abolished in patients with wrist dystonic posture in flexion, but not in patients with dystonic posture in extension, sICI even giving way to motor-evoked potential facilitation. Loss of interaction between interneurons mediating sICI and peripheral inputs probably belongs to the initial abnormalities underlying dystonia. Lack of peripherally induced sICI modulation may oppose wrist and/or hand muscles synergies.     

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     

Change in the pattern of cervical dystonia might be the cause of benefit loss during botulinum toxin treatment

The muscular patterns of cervical dystonia were identified by polymyographic recordings in 76 patients before botulinum toxin treatment. The leading muscles were considered to be those which started dystonic movement and which showed constant and maximal activity during all dystonic movements. The dystonic muscles were repeatedly treated by local Injections of botulinum toxin. Sixteen patients showed (after repeated injections) loss of the benefit of local applications of botulinum toxin after various periods of time. Repeated polymyographic recordings were performed in these patients during the loss of the benefit of injected botulinum toxin. In four patients repeated polymyographic recordings showed an Identical pattern of cervical dystonia, but the activity of previously injected muscles was apparently decreased. In 12 patients only minimum or no activity was recorded in muscles which had previously been treated with botulinum toxin, but the pattern of cervical dystonia was changed. Different patterns of cervical dystonia with different leading muscles, but with identical directions of head deviation, were observed in six patients. In another six patients, the head deviation direction was to the opposite side and was accompanied by a change of the leading muscle and a change of the muscular pattern of dystonia. These results suggest either that dystonic activity from the cerebral generator changes to new effectors during the peripheral blockade of primary dystonic muscles, or that a change of generators at different levels of the CNS occurs. It may be neccessary to carry out repeated polymyographic recordings throughout the period of loss of benefit of previously successful local botulinum toxin injections.     

Plasticity of cortical inhibition in dystonia is impaired after motor learning and paired-associative stimulation

Artificial induction of plasticity by paired associative stimulation (PAS) in healthy volunteers (HV) demonstrates Hebbian-like plasticity in selected inhibitory networks as well as excitatory networks. In a group of 17 patients with focal hand dystonia and a group of 19 HV, we evaluated how PAS and the learning of a simple motor task influence the circuits supporting long-interval intracortical inhibition (LICI, reflecting activity of GABA(B) interneurons) and long-latency afferent inhibition (LAI, reflecting activity of somatosensory inputs to the motor cortex). In HV, PAS and motor learning induced long-term potentiation (LTP)-like plasticity of excitatory networks and a lasting decrease of LAI and LICI in the motor representation of the targeted or trained muscle. The better the motor performance, the larger was the decrease of LAI. Although motor performance in the patient group was similar to that of the control group, LAI did not decrease during the motor learning as it did in the control group. In contrast, LICI was normally modulated. In patients the results after PAS did not match those obtained after motor learning: LAI was paradoxically increased and LICI did not exhibit any change. In the normal situation, decreased excitability in inhibitory circuits after induction of LTP-like plasticity may help to shape the cortical maps according to the new sensorimotor task. In patients, the abnormal or absent modulation of afferent and intracortical long-interval inhibition might indicate maladaptive plasticity that possibly contributes to the difficulty that they have to learn a new sensorimotor task.     

Impaired heteronymous somatosensory motor cortical inhibition in dystonia.

A typical pathophysiological abnormality in dystonia is cocontraction of antagonist muscles, with impaired reciprocal inhibitory mechanisms in the spinal cord. Recent experimental data have shown that inhibitory interactions between antagonist muscles have also a parallel control at the level of the sensorimotor cortex. The aim of this work was to study heteronymous effects of a median nerve stimulus on the corticospinal projections to forearm muscles in dystonia. We used the technique of antagonist cortical inhibition, which assesses the conditioning effect of median nerve afferent input on motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) in ipsilateral forearm extensor muscles at rest. Nine healthy subjects and 10 patients with torsion dystonia participated in the study. MEPs and somatosensory evoked potentials were normal in patients. In healthy subjects, median nerve stimulation at 15- to 18-msec intervals inhibited the test MEPs in forearm extensors. In dystonic patients, median nerve stimulation delivered at the same conditioning-test intervals elicited significantly less inhibition of the test MEP. On the whole, these data suggest an impaired sensory-motor integration in dystonia and, more specifically, the decreased antagonistic cortical inhibition could suggest that functional interactions between antagonist muscles are primarily impaired at the cortical level.     

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.     

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     

Afferent-induced facilitation of primary motor cortex excitability in the region controlling hand muscles in humans

Sensory inputs from cutaneous and limb receptors are known to influence motor cortex network excitability. Although most recent studies have focused on the inhibitory influences of afferent inputs on arm motor responses evoked by transcranial magnetic stimulation (TMS), facilitatory effects are rarely considered. In the present work, we sought to establish how proprioceptive sensory inputs modulate the excitability of the primary motor cortex region controlling certain hand and wrist muscles. Suprathreshold TMS pulses were preceded either by median nerve stimulation (MNS) or index finger stimulation with interstimulus intervals (ISIs) ranging from 20 to 200 ms (with particular focus on 40–80 ms). Motor-evoked potentials recorded in the abductor pollicis brevis (APB), first dorsalis interosseus and extensor carpi radialis muscles were strongly facilitated (by up to 150%) by MNS with ISIs of around 60 ms, whereas digit stimulation had only a weak effect. When MNS was delivered at the interval that evoked the optimal facilitatory effect, the H-reflex amplitude remained unchanged and APB motor responses evoked with transcranial electric stimulation were not increased as compared with TMS. Afferent-induced facilitation and short-latency intracortical inhibition (SICI) and intracortical facilitation (ICF) mechanisms are likely to interact in cortical circuits, as suggested by the strong facilitation observed when MNS was delivered concurrently with ICF and the reduction of SICI following MNS. We conclude that afferent-induced facilitation is a mechanism which probably involves muscle spindle afferents and should be considered when studying sensorimotor integration mechanisms in healthy and disease situations.     

Assessment of postexcitatory inhibition in patients with focal dystonia

The aim of our present study was to detect whether a generalized disturbance of intracortical inhibitory mechanisms as assessed by transcranial magnetic stimulation (TMS) can be observed in a movement disorder with localized clinical expression, that is, in focal cervical dystonia. We measured motor threshold intensity, central motor conduction time and the duration of postexcitatory inhibition evoked by single and paired stimuli TMS from a small hand muscle in 20 patients with idiopathic cervical dystonia, and 21 healthy volunteers. A significant difference could not be found in any of the neurophysiological parameters between patients and controls. These findings are unlike the observations made in Parkinson's disease and Huntington's disease, where significant changes of postexcitatory inhibition after TMS can be observed. This suggests a lack of widespread change in activity of underlying cortical inhibitory mechanisms, as seen in other diseases of the extrapyramidal system with more generalized clinical involvement.     

Treatment of cervical dystonia hand spasms and laryngeal dystonia with botulinum toxin

Summary One hundred and twenty-six patients with different forms of focal dystonia (89 with cervical dystonia, 12 with hand cramps and 25 with laryngeal dystonia) were treated with localised injections of botulinum toxin. Mean doses per muscle were 200 mouse units (m.u.) for treating cervical dystonia, 40–120 m.u. for forearm muscles in writers' cramp and 3.7 m. u. for the thyroarytenoid muscle in laryngeal dystonia. Responder rates have been above 80% in all patient groups and beneficial effects could be reproduced over follow-up periods of up to 4 years. The commonest side-effects were dysphagia after treatment of spasmodic torticollis, weakness of neighbouring muscles after injections for hand cramps and breathiness and hypophonia following laryngeal injections. All these were transient and generally well tolerated. It is concluded that botulinum toxin injections are a safe and effective treatment in all three types of focal dystonia.     

Failure of cathodal direct current stimulation to improve fine motor control in musician's dystonia

Musician's dystonia (MD) is a task‐specific movement disorder with a loss of voluntary motor control in highly trained movements. Defective inhibition on different levels of the central nervous system is involved in its pathophysiology. Cathodal transcranial direct current stimulation (ctDCS) diminishes excitability of the motor cortex and improves performance in overlearned tasks in healthy subjects. The aim of this study was to investigate whether ctDCS improves fine motor control in MD. Professional guitarists (n = 10) with MD played exercises before, directly after ctDCS, and 60 min after ctDCS. ctDCS (2 mA, 20 min) was applied on the primary motor cortex contralateral to the affected hand. Guitar exercises were video‐documented and symptoms were evaluated by three independent experts. No beneficial effect of ctDCS on fine motor control was found for the entire group. However, motor control of one guitarist improved after stimulation. This patient suffered from arm dystonia, whereas the other guitarists suffered from hand dystonia. © 2009 Movement Disorder Society     

Task-dependent intracortical inhibition is impaired in focal hand dystonia.

We tested whether task-dependent modulation of inhibition within the motor cortex is impaired in patients with dystonia. Paired-pulse transcranial magnetic stimulation (TMS) at an interstimulus interval of 2 msec was used to measure the effect of two different tasks on short ISI intracortical inhibition (SICI) in dystonic and normal subjects. In two experiments, SICI of the fourth dorsal interosseus (4DIO) and abductor pollicis brevis (APB) muscles were measured before and at the end of the training task. In the first experiment, subjects performed a nonselective task consisting of abducting the thumb, where the APB acted as agonist and the 4DIO as synergist. In the second experiment, the function of the 4DIO was changed as the subjects were asked to consciously inhibit this muscle while abducting the thumb (selective task). Therefore, while the APB was activated in both tasks, the 4DIO was activated in the nonselective task but was in the inhibitory surround in the selective task. We found that performance of the selective but not the nonselective task resulted in increased SICI in the 4DIO of normal but not in dystonic subjects. We conclude that task-dependent SICI is disturbed in patients with dystonia.     

Low-intensity repetitive paired associative stimulation targeting the motor hand area at theta frequency causes a lasting reduction in corticospinal excitability

ObjectiveSub-motor threshold 5 Hz repetitive paired associative stimulation (5 Hz-rPAS_25ms) produces a long-lasting increase in corticospinal excitability. Assuming a spike-timing dependent plasticity-like (STDP-like) mechanism, we hypothesized that 5 Hz-rPAS at a shorter inter-stimulus interval (ISI) of 15 ms (5 Hz-rPAS_15ms) would exert a lasting inhibitory effect on corticospinal excitability.Methods20 healthy volunteers received two minutes of 5 Hz-rPAS_15ms. Transcranial magnetic stimulation (TMS) was applied over the motor hotspot of the right abductor pollicis brevis muscle at 90% active motor threshold. Sub-motor threshold peripheral electrical stimulation was given to the left median nerve 15 ms before each TMS pulse. We assessed changes in mean amplitude of the unconditioned motor evoked potential (MEP), short-latency intracortical inhibition (SICI), intracortical facilitation (ICF), short-latency afferent inhibition (SAI), long-latency afferent inhibition (LAI), and cortical silent period (CSP) before and for 60 minutes after 5-Hz rPAS_15ms.ResultsSubthreshold 5-Hz rPAS_15ms produced a 20–40% decrease in mean MEP amplitude along with an attenuation in SAI, lasting at least 60 minutes. A follow-up experiment revealed that MEP facilitation was spatially restricted to the target muscle.ConclusionsSubthreshold 5-Hz rPAS_15ms effectively suppresses corticospinal excitability. Together with the facilitatory effects of subthreshold 5-Hz rPAS_25ms (Quartarone et al., J Physiol 2006;575:657–670), the results show that sub-motor threshold 5-Hz rPAS induces STDP-like bidirectional plasticity in the motor cortex.SignificanceThe results of the present study provide a new short-time paradigm of long term depression (LTD) induction in human sensory-motor cortex.     

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".