Reduced cerebral cortex inhibition in dystonia: Direct evidence in humans

ObjectiveA loss of inhibition in central motor circuits resulting in abnormal motor control is the hypothesised cause of dystonia. So far, changes in inhibitory function of cerebral cortex in dystonia, have been revealed only indirectly by recording muscle responses evoked by transcranial magnetic stimulation (TMS) of the brain. The aim of present study was to evaluate more directly cerebral cortex changes in dystonia. We had the almost unique opportunity to record directly motor cortex output after brain stimulation, in a dystonic patient who had epidural electrodes implanted in the upper cervical cord.MethodsWe evaluated descending activity evoked by single and paired pulse TMS together with the inhibitory effects produced by afferent stimuli on TMS evoked activity, and compared the results with those obtained in thirteen subjects with no central nervous system abnormality who also had cervical spinal electrodes.ResultsThe intrinsic inhibitory activity produced by paired TMS of the motor cortex, and the inhibitory effects produced by afferent inputs, were suppressed in the patient with dystonia.ConclusionsThese findings provide a direct evidence of the abnormality in motor cortex inhibitory systems in dystonia.SignificanceThe abnormality in cortical inhibitory system might have a role in the pathophysiology of dystonia.     

Transcranial magnetic stimulation (TMS) in movement disorders]

Transcranial magnetic stimulation (TMS) has been used to study several aspects of movement disorders: central motor conduction time (CMCT), electromyographic (EMG) silence evoked by TMS, reset of tremor rhythm by TMS, GABAergic inhibitory interneuronal function of the motor cortex studied with paired-pulse TMS. In this communication, We briefly summarize results of paired-pulse TMS in movement disorders. NORMAL SUBJECTS: A subthreshold conditioning stimulus over the motor cortex reduced the size of EMG responses to a succeeding suprathreshold test stimulus given to the same motor cortex. This inhibition is considered to be an inhibitory effect on the motor cortex because the same conditioning stimulus has no influence on H-reflexes or electrical cortical responses. Pharmacological effects on this inhibition suggested that it is mediated by GABAergic inhibitory systems in the motor cortex. PATIENTS: The cortical inhibition was reduced in cortical myoclonus, which is consistent with the notion that the studied effect is mediated by GABAergic systems. The inhibition was disturbed in focal dystonia, whereas normal inhibition was elicited in Segawa's disease. Reduced inhibition was seen in Parkinson's disease (PD), whereas normal inhibition in essential tremor. Normal inhibition was evoked in all patients with chorea. Abnormal inhibition in basal ganglia disorders must reflect damaged movement selection in the motor cortex secondary to the primary lesion in the basal ganglia. This abnormality occurs in some movement disorders and does not occur in the others, which indicates different pathomechanisms for involuntary movements. It is conspicuous that normal inhibition was evoked in Segawa's disease even though the patients had dystonia.     

Low-frequency repetitive transcranial magnetic stimulation of the motor cortex in writer's cramp

OBJECTIVE: To study the short-term effects of slow repetitive transcranial magnetic stimulation (rTMS) of the motor cortex on cortical excitability and handwriting in patients with writer's cramp. BACKGROUND: Cortical excitability of the primary motor cortex is abnormally enhanced in patients with writer's cramp. Therefore, reducing cortical excitability by low-frequency rTMS of the motor cortex might result in beneficial effects on handwriting in writer's cramp. DESIGN/METHODS: We studied the effects of subthreshold 1-Hz rTMS on motor threshold and cortico-cortical excitability using the paired-pulse technique in seven patients and seven controls. In another 16 patients and 11 age-matched controls we evaluated changes in cortical excitability by measuring the stimulus-response curve and the postexcitatory silent period before and after subthreshold 1-Hz rTMS. In addition, we analyzed the handwriting before and 20 minutes after 1-Hz rTMS. RESULTS: In the first experiment, low-frequency rTMS resulted in a normalization of the deficient cortico-cortical inhibition in the patients without affecting motor threshold. In the second experiment, 1-Hz rTMS resulted in a significant prolongation of the postexcitatory silent period without affecting the stimulus-response curve in the patient group. Moreover, the dystonic patients showed a significant reduction of mean writing pressure after subthreshold 1-Hz rTMS that was associated with clear but transient improvement in six patients. CONCLUSIONS: In some patients 1-Hz rTMS can reinforce deficient intracortical inhibition and may improve handwriting temporarily. Our data support the notion that reduced intracortical inhibition plays a part in the pathophysiology of focal dystonia.     

Abnormalities of inhibitory neuronal mechanisms in the motor cortex of patients with schizophrenia

BACKGROUND: Focal transcranial magnetic stimulation (TMS) of the motor cortex was used to study two cortically activated inhibitory neuronal mechanisms that suppress ongoing tonic voluntary electromyographic activity in contralateral (postexcitatory inhibition [PI]) and ipsilateral (transcallosal inhibition [TI]) hand muscles. The PI follows the corticospinally mediated excitatory motor response (MEP) and is influenced by dopaminergic neurotransmission. TI reflects transcallosally mediated inhibition of the contralateral motor cortex, leading to motor inhibition in muscles ipsilateral to stimulation. PI and TI were studied to explore whether dopaminergic neurotransmission or interhemispheric transfers are altered in schizophrenia. METHODS: TMS was performed in 16 patients with this disease and in 16 healthy control subjects. Surface electromyographic activity was recorded bilaterally from the first dorsal interosseous muscle during a sustained strong isometric contraction. RESULTS: When compared with the findings in healthy subjects, patients with schizophrenia had a significantly longer PI and TI. The changes of the PI support the notion of an overactivity of the central dopaminergic system in schizophrenia. CONCLUSION: The prolonged TI suggests an abnormal activation of interhemispheric connections between the motor cortices and may be related to previously reported pathology of the corpus callosum in schizophrenic patients.     

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.     

Altered cortical excitability in obsessive-compulsive disorder

OBJECTIVE: To assess cortical inhibitory and excitatory mechanisms in obsessive-compulsive disorder (OCD). BACKGROUND: Transcranial magnetic stimulation (TMS) studies have found decreased neuronal inhibition and a reduced cortical silent period in the primary motor area in Tourette's syndrome, focal dystonia, and other disorders believed to involve dysfunction of subcortical structures, including the basal ganglia. Dysfunction of the basal ganglia and linked regions also has been implicated in OCD, which has significant clinical and familial overlap with tic disorders. METHODS: We applied the TMS techniques previously used in Tourette's syndrome to a group of 16 OCD patients (seven unmedicated) and 11 age-matched healthy volunteers extensively screened for psychopathology. Measures of motor cortex excitability included resting and active motor threshold, cortical silent period duration, and intracortical inhibition and facilitation using a paired-pulse TMS technique with a subthreshold conditioning stimulus. RESULTS: Similar to recent findings in Tourette's syndrome and focal dystonia, this study reports significantly decreased intracortical inhibition (ICI) relative to the volunteers at interstimulus intervals from 2 to 5 msec. We also found decreased active and resting motor evoked potential threshold in the OCD patients, another indication of increased cortical excitability. Neither abnormality appeared medication related. The decreases in ICI and motor threshold were greatest in OCD patients with comorbid tics, but remained significant in patients without tics. CONCLUSIONS: The data suggest abnormal cortical excitability in obsessive-compulsive disorder. These findings are congruent with the hypothesis that Tourette's syndrome and obsessive-compulsive disorder (OCD) are analogous disorders with overlapping dysfunction in corticobasal circuits. Patients with tic-related OCD may have more abnormal motor cortex excitability than OCD patients without tics.     

Cervical dystonia: clinical and therapeutic features in 85 patients

We studied patients with cervical dystonia (CD) to determine clinical features and response to botulinum toxin A (BoNT/A). Patients were submitted to clinical, laboratory and neuroimaging evaluation. BoNT/A was injected locally in 81 patients using electromyographic guidance. Four patients who had had previous treatment were considered to be in remission. The average ages at onset of focal dystonia and segmental dystonia were greater than for generalized dystonia (p<0.0003). The severity of the abnormal head-neck movements were more severe among the patients with generalized dystonia (p<0.001). Pain in the cervical area was noted in 59 patients. It was not possible to determine the etiology of the disease in 62.3% of patients. Tardive dystonia was the most common secondary etiology. A major improvement in the motor symptoms of CD and pain was observed in patients following treatment with BoNT/A. The tardive dystonia subgroup did not respond to the treatment. Dysphagia was observed in 2.35% of the patients.     

Impaired sensorimotor integration in cervical dystonia: a study using transcranial magnetic stimulation and muscle vibration.

The authors studied the effects of sensorimotor integration (corticocortical inhibition and facilitation during muscle vibration [MV]) in dystonic patients. Eleven patients with cervical dystonia and 11 age-matched healthy control subjects were enrolled in the study. They were examined using transcranial magnetic stimulation (TMS) and tonic proprioceptive input (MV). Paired-pulse transcranial magnetic stimulation was done at interstimulus intervals of 3 msec (intracortical inhibition) and 13 msec, the intensity of the conditioning stimulus was 70% of the motor threshold, and the test stimulus was 120%. Motor evoked potentials were recorded from the vibrated extensor carpi radialis muscle and its antagonist, the flexor carpi radialis. Duration of MV trains (80 Hz; amplitude, 0.5 mm) was 4 seconds. The authors found differences between patients and healthy control subjects during MV only. Intracortical inhibition was pronounced significantly only in control subjects, whereas intracortical facilitation was significant in patients only (P < 0.05). Furthermore, the significant reduction of motor evoked potentials at 13-msec interstimulus intervals, which can be found in healthy subjects frequently, was observed in one dystonia patient only. The results of the current study suggest that sensorimotor integration is impaired in cervical dystonia, probably by an altered control of proprioceptive (vibratory) input.     

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.     

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     

Motor cortex stimulation for Parkinson's disease and dystonia: lessons from transcranial magnetic stimulation? A review of the literature

INTRODUCTION: Over the last few years, deep brain stimulation techniques, with targets such as the subthalamic nucleus or the pallidum, have bee found to be beneficial in the treatment of Parkinson's disease and dystonia. Conversely, therapeutic strategies of cortical stimulation have not yet been validated in these diseases, although they are known to be associated with various cortical dysfunctions. Transcranial magnetic stimulation (TMS) is a valuable tool for non-invasive study of the role played by the motor cortex in the pathophysiology of movement disorders, in particular by assessing various cortical excitability determinants using single or paired pulse paradigms. In addition, repetitive TMS (rTMS) trains can be used to study the effects of transient activity changes of a targeted cortical area. BACKGROUND: Studies with TMS revealed significant motor cortex excitability changes, particularly regarding intracortical inhibitory pathways, both in Parkinson's disease and in dystonia, and these changes can be distinguished owing to the resting state or to the phases of movement preparation or execution. However, more specific correlation between electrophysiological features and clinical symptoms remains to be established. In addition, the stimulation of various cortical targets by rTMS protocols applied at low or high frequencies have induced some clear clinical effects. PERSPECTIVES: The TMS effects are and will remain applied in movement disorders to better understand the role played by the motor cortex, to assess various types of treatment and appraise the therapeutic potential of cortical stimulation. CONCLUSION: TMS provides evidence for motor cortex dysfunction in Parkinson's disease or dystonia. Moreover, rTMS results have opened new perspectives for therapeutic strategies of implanted cortical stimulation. By these both aspects, TMS techniques show their usefulness in the assessment of movement disorders.     

Deep brain stimulation in dystonia

Renewed interest in stereotaxy for dystonia followed the introduction of deep brain stimulation (DBS) in Parkinson's disease and essential tremor in the 1990s. DBS evolved from ablative surgery, which was applied with varying results in the 1950s in patients with movement disorders such as Parkinson's disease, essential tremor and dystonia. The present review summarizes the current knowledge on clinical aspects of DBS in dystonia (Dec. 2002). Excellent results have been achieved in dystonic patients carrying a mutation in the DYT1 gene with improvements up to 90 %. Similar results may also be obtained in patients with idiopathic generalized dystonia, myoclonus-dystonia syndrome, and tardive dystonia. Substantial improvement has been observed in patients with focal dystonia (for instance cervical dystonia). Patients with secondary dystonia often display a lesser and more variable degree of improvement. Long-term studies are warranted to assess both motor and neuropsychological sequelae of DBS in dystonia. Furthermore, the optimal target for different dystonic disorders remains to be determined, although the globus pallidus internus has currently emerged as the most promising target for dystonia.     

Changes in short afferent inhibition during phasic movement in focal dystonia

Impaired surround inhibition could account for the abnormal motor control seen in patients with focal hand dystonia, but the neural mechanisms underlying surround inhibition in the motor system are not known. We sought to determine whether an abnormality of the influence of sensory input at short latency could contribute to the deficit of surround inhibition in patients with focal hand dystonia (FHD). To measure digital short afferent inhibition (dSAI), subjects received electrical stimulation at the digit followed after 23 ms by transcranial magnetic stimulation (TMS). Motor evoked potentials (MEPs) were recorded over abductor digiti minimi (ADM) during rest and during voluntary phasic flexion of the second digit. F-waves were also recorded. We studied 13 FHD patients and 17 healthy volunteers. FHD patients had increased homotopic dSAI in ADM during flexion of the second digit, suggesting that this process acts to diminish overflow during movement; this might be a compensatory mechanism. No group differences were observed in first dorsal interosseous. Further, no differences were seen in the F-waves between groups, suggesting that the changes in dSAI are mediated at the cortical level rather than at the spinal cord. Understanding the role of these inhibitory circuits in dystonia may lead to development of therapeutic agents aimed at restoring inhibition.     

Changes in motor cortex inhibition over time in patients with amyotrophic lateral sclerosis

Abnormal balance between intracortical inhibitory and excitatory mechanisms has been found to contribute to the genesis of motor cortex hyperexcitability in amyotrophic lateral sclerosis (ALS), but data are lacking on the role of these abnormalities in the pathophysiology of the disease. We evaluated the resting motor threshold (RMT), the cortical silent period (CSP) to single-pulse transcranial magnetic stimulation (TMS), early intracortical inhibition (ICI), early intracortical facilitation (ICF) and late ICI to paired-pulse TMS in 40 patients with ALS. These parameters were correlated with disease duration and clinical features. They were also monitored over time in selected patients.The main abnormal TMS findings were: (a). reduced or even absent early and late ICI; six out of 9 patients, with normal early ICI at the first recording, developed abnormal ICI after several months; (b). reduced cortical silent period duration with increasing TMS intensity. ICF and RMT were not affected. Impairment of early and late ICI correlated significantly with disease duration, the diagnostic categories and the clinical evidence of upper motor neuron involvement.The alteration of different cortical inhibitory functions seems to take place with disease progression, rather than being the primary event in the pathogenesis of ALS. The impaired inhibition is considered as being due to both depletion of specific subpopulations of intracortical GABAergic neurons and mechanisms involved in motor cortex reorganization following progressive neuronal loss. Clarification of the importance of these factors in the pathogenesis of the disease may have diagnostic and therapeutic implications.     

Cortical inhibitory function in cervical dystonia

Objective

To assess the specificity of cortical inhibitory deficits in cervical dystonia patients.

“Visual sensory trick” in patient with cervical dystonia

Sensory tricks are clinical maneuvers that may partially relieve dystonic contractions. Any clinical maneuver that modulates afferent sensory and efferent motor pathways could be used as a sensory trick in patients with cervical dystonia. Although various sensory tricks have been described to reduce cervical dystonia, little is known about the exact mechanisms by which they operate. We report a case of cervical dystonia that was alleviated through the use of a visual-sensory trick. Our findings suggest that visual stimulation might be an effective sensory trick in cervical dystonia by compensating for a defective sensory system, or because visual pathways might be also affected by sensory interactions in cervical dystonia.     

Intra- and inter-cortical motor excitability in Alzheimer’s disease

Transcranial magnetic stimulation (TMS) provides evidence for facilitatory and inhibitory motor dysfunctions in Alzheimer's disease (AD). The corpus callosum (CC) is affected in AD already at early stages consistent with the hypothesis that AD patients exhibit alterations in transcallosally mediated motor inhibition (ipsilateral silent period, iSP). Therefore, here we aimed at investigating the integrity not only of intra-, but also of inter-hemispheric mechanisms of cortical motor excitability in AD. We determined the iSP, the resting motor threshold (RMT), and the amplitude of motor evoked potentials (MEP) in 19 AD patients and 19 healthy controls using single-pulse TMS. Furthermore, we used paired-pulse TMS to study the intra-cortical inhibition (ICI) and intra-cortical facilitation (ICF). All subjects underwent comprehensive neuropsychologic, clinical, and laboratory testing, and neuroimaging to exclude significant co-morbidity. In AD patients, the RMT was significantly reduced (Oneway-ANOVA). An analysis of covariance (ANCOVA) revealed a strong group specific interaction of the inhibitory interstimulus intervals (p = 0.005) with a reduced ICI in AD. Furthermore, we found a significantly prolonged iSP-latency (p = 0.003) in AD compared to controls, whereas the iSP-duration was not different. The iSP-latency correlated significantly with the ICI (ANCOVA) (p = 0.02). The ICF did not differ significantly between groups. Our data suggest comprehensive but still subclinical dysfunctions of motor cortical inhibition in mild to moderate clinical stages of AD with strong interactions of intra- and inter-hemispheric inhibitory phenomena. Future studies are needed to show the potential prognostic relevance of these findings for the further course of the disease.     

Reduced intracortical facilitation in patients with cerebellar degeneration

Objectives - Transcranial magnetic stimulation (TMS) was used to study intracortical inhibitory and excitatory phenomena in patients with cerebellar ataxia. Methods - Motor evoked potentials (MEP) following single and paired TMS were recorded from the first dorsal interosseus muscle (FDI) in 15 patients with autosomal-dominant or idiopathic cerebellar ataxia and 15 age matched normal controls. Results- MEP amplitudes after paired TMS with short interstimulus intervals (1-4 ms) showing intracortical inhibition in the control group were not significantly different in the patient group. In contrast, with longer interstimulus intervals (8-20 ms) mean MEP amplitudes were significantly reduced in the patient group, indicating a decrease of intracortical facilitation. The mean postexcitatory inhibition after TMS was also significantly prolonged in the patient group. Conclusion -Our findings support the idea that the cerebellum physiologically exerts a facilitatory influence on the motor cortex which is decreased in patients with a cerebellar degeneration.     

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.     

Central motor conduction in cervical dystonia with cervical spondylotic myelopathy

OBJECTIVES: It has been known that cervical dystonia develops secondarily to spinal cord injuries as secondary dystonia. However, little is known about the pathophysiological mechanism. PATIENTS AND METHODS: We examined motor and sensory conduction in six patients with symptomatic cervical dystonia by transcranial magnetic stimulation (TMS). All of the patients exhibited unilateral head rotation. They had symptoms corresponding to cervical myelopathy and felt discomfort in the neck, shoulders or arms before involuntary movement occurred. RESULTS: Although the overall central motor conduction time (CMCT) was not different from that of normal controls, contralateral CMCT was significantly delayed compared to ipsilateral CMCT (p<0.05). The results of somatosensory evoked potential study demonstrated that contralateral central conduction time (CCT) was not significantly different from ipsilateral CCT. CONCLUSION: These findings indicate that there is a selective interference with the contralateral corticospinal tract in patients with symptomatic cervical dystonia.