Structural brain correlates of sensorimotor gating in antipsychotic-naive men with first-episode schizophrenia

Background: Prepulse inhibition (PPI) of the startle reflex is modulated by a complex neural network. Prepulse inhibition impairments are found at all stages of schizophrenia. Previous magnetic resonance imaging (MRI) studies suggest that brain correlates of PPI differ between patients with schizophrenia and healthy controls; however, these studies included only patients with chronic illness and medicated patients. Our aim was to examine the structural brain correlates of PPI in antipsychotic-naive patients with first-episode schizophrenia. Methods: We performed acoustic PPI assessment and structural MRI (1.5 and 3 T) in men with first-episode schizophrenia and age-matched controls. Voxel-based morphometry was used to investigate the association between PPI and grey matter volumes. Results: We included 27 patients and 38 controls in the study. Patients had lower PPI than controls. The brain areas in which PPI and grey matter volume correlated did not differ between the groups. Independent of group, PPI was significantly and positively associated with regional grey matter volume in the right superior parietal cortex. Prepulse inhibition and grey matter volume associations were also observed in the left rostral dorsal premotor cortex, the right presupplementary motor area and the anterior medial superior frontal gyrus bilaterally. Follow-up analyses suggested that the rostral dorsal premotor cortex and presupplementary motor area correlations were driven predominantly by the controls. Limitations: We used 2 different MRI scanners, which might have limited our ability to find subcortical associations since interscanner consistency is low for subcortical regions. Conclusion: The superior parietal cortex seems to be involved in the regulation of PPI in controls and antipsychotic-naive men with first-episode schizophrenia. Our observation that PPI deficits in schizophrenia may be related to the rostral dorsal premotor cortex and presupplementary motor area, brain areas involved in maintaining relevant sensory information and voluntary inhibition, warrants further study.     

Impaired mesial frontal and putamen activation in Parkinson's disease: a positron emission tomography study.

Selection of movement in normal subjects has been shown to involve the premotor, supplementary motor, anterior cingulate, posterior parietal, and dorsolateral prefrontal areas. In Parkinson's disease (PD), the primary pathological change is degeneration of the nigrostriatal dopaminergic projections, and this is associated with difficulty in initiating actions. We wished to investigate the effect of the nigral abnormality in PD on cortical activation during movement. Using C15O2 and positron emission tomography (PET), we studied regional cerebral blood flow in 6 patients with PD and 6 control subjects while they performed motor tasks. Subjects were scanned while at rest, while repeatedly moving a joystick forward, and while freely choosing which of four possible directions to move the joystick. Significant increases in regional cerebral blood flow were determined with covariance analysis. In normal subjects, compared to the rest condition, the free-choice task activated the left primary sensorimotor cortex, left premotor cortex, left putamen, right dorsolateral prefrontal cortex and supplementary motor area, anterior cingulate area, and parietal association areas bilaterally. In the patients with PD, for the free-choice task, compared with the rest condition, there was significant activation in the left sensorimotor and premotor cortices but there was impaired activation of the contralateral putamen, the anterior cingulate, supplementary motor area, and dorsolateral prefrontal cortex. Impaired activation of the medial frontal areas may account for the difficulties PD patients have in initiating movements.     

Cerebral compensation during motor imagery in Parkinson's disease

In neurodegenerative disorders, neural damage can trigger compensatory mechanisms that minimize behavioural impairments. Here, we aimed at characterizing cerebral compensation during motor imagery in Parkinson's disease (PD), while controlling for altered motor execution and sensory feedback. We used a within-patient design to compare the most and least affected hand in 19 right-handed PD patients with markedly right-lateralized symptoms. We used a motor imagery (MI) task in which the patients were required to judge the laterality of hand images, rotated either in a lateral or in a medial orientation with respect to the body sagittal plane. This design allowed us to compare cerebral activity (using fMRI) evoked by MI of each hand separately, while objectively monitoring task performance. Reaction times and parieto-premotor activity increased in a similar manner as a function of stimulus rotation during motor imagery of left and right hands. However, patients were markedly slower when judging images of the affected hand in lateral orientations, and there was a corresponding increase in activity in the right extrastriate body area (EBA) and occipito-parietal cortex during mental rotation of the affected hand. Furthermore, these regions increased their connectivity towards the left PMd for right (affected) hands in a lateral orientation. We infer that, in strongly lateralized PD patients, motor imagery of the most-affected hand exploits additional resources in extrastriate visual areas. These findings characterize the cerebral bases of the increased dependence on visual information processing during the generation of motor plans in PD, pointing to its compensatory role.     

Decreased corticospinal excitability after subthreshold 1 Hz rTMS over lateral premotor cortex

OBJECTIVE: To study whether trains of subthreshold 1 Hz repetitive transcranial magnetic stimulation (rTMS) over premotor, prefrontal, or parietal cortex can produce changes in excitability of motor cortex that outlast the application of the train. BACKGROUND: Prolonged 1 Hz rTMS over the motor cortex can suppress the amplitude of motor-evoked potentials (MEP) for several minutes after the end of the train. Because TMS can produce effects not only at the site of stimulation but also at distant sites to which it projects, the authors asked whether prolonged stimulation of sites distant but connected to motor cortex can also lead to lasting changes in MEP. METHODS: Eight subjects received 1500 magnetic stimuli given at 1 Hz over the left lateral frontal cortex, the left lateral premotor cortex, the hand area of the left motor cortex, and the left anterior parietal cortex on four separate days. Stimulus intensity was set at 90% active motor threshold. Corticospinal excitability was probed by measuring the amplitude of MEP evoked in the right first dorsal interosseous muscle by single suprathreshold stimuli over the left motor hand area before, during, and after the conditioning trains. RESULTS: rTMS over the left premotor cortex suppressed the amplitude of MEP in the right first dorsal interosseous muscle. The effect was maximized (approximately 50% suppression) after 900 pulses and outlasted the full train of 1500 stimuli for at least 15 minutes. Conditioning rTMS over the other sites did not modify the size of MEP. A control experiment showed that left premotor cortex conditioning had no effect on MEP evoked in the left first dorsal interosseous muscle. CONCLUSIONS: Subthreshold 1 Hz rTMS of the left premotor cortex induces a short-lasting inhibition of corticospinal excitability in the hand area of the ipsilateral motor cortex. This may provide a model for studying the functional interaction between premotor and motor cortex in healthy subjects and patients with movement disorders.     

Structural brain correlates of sensorimotor gating in antipsychotic-naive men with first-episode schizophrenia

Background

Prepulse inhibition (PPI) of the startle reflex is modulated by a complex neural network. Prepulse inhibition impairments are found at all stages of schizophrenia. Previous magnetic resonance imaging (MRI) studies suggest that brain correlates of PPI differ between patients with schizophrenia and healthy controls; however, these studies included only patients with chronic illness and medicated patients. Our aim was to examine the structural brain correlates of PPI in antipsychotic-naive patients with first-episode schizophrenia.

Methods

We performed acoustic PPI assessment and structural MRI (1.5 and 3 T) in men with first-episode schizophrenia and age-matched controls. Voxel-based morphometry was used to investigate the association between PPI and grey matter volumes.

Results

We included 27 patients and 38 controls in the study. Patients had lower PPI than controls. The brain areas in which PPI and grey matter volume correlated did not differ between the groups. Independent of group, PPI was significantly and positively associated with regional grey matter volume in the right superior parietal cortex. Prepulse inhibition and grey matter volume associations were also observed in the left rostral dorsal premotor cortex, the right presupplementary motor area and the anterior medial superior frontal gyrus bilaterally. Follow-up analyses suggested that the rostral dorsal premotor cortex and presupplementary motor area correlations were driven predominantly by the controls.

Limitations

We used 2 different MRI scanners, which might have limited our ability to find subcortical associations since interscanner consistency is low for subcortical regions.

Conclusion

The superior parietal cortex seems to be involved in the regulation of PPI in controls and antipsychotic-naive men with first-episode schizophrenia. Our observation that PPI deficits in schizophrenia may be related to the rostral dorsal premotor cortex and presupplementary motor area, brain areas involved in maintaining relevant sensory information and voluntary inhibition, warrants further study.     

Reduced cortical plasticity and GABAergic modulation in essential tremor

Essential tremor (ET) is the most common movement disorder among adults. Cerebellar dysfunction is thought to be involved in the pathogenesis of ET; however, imaging, electrophysiological studies, and clinical observations have suggested that the cerebral cortex also may participate. We sought to investigate the possible motor cortical contribution to ET by assessing response to continuous theta‐burst stimulation (cTBS), a recognized tool that can produce transient plastic changes, in the primary motor and premotor cortex of patients with ET. We compared parameters, including motor‐evoked potential amplitude, cortical silent period, and short‐interval intracortical inhibition, before and after applying cTBS in healthy controls and patients with ET. We found that, although cTBS applied to either the motor or premotor cortex was capable of producing a suppressive effect on motor cortical excitability in ET patients, the effects lasted for a significantly shorter time compared with the effect produced in healthy individuals. The change seen in measures of intracortical inhibition after motor cortical or premotor cTBS in healthy controls was reduced or absent in the ET patients. Tremor amplitude was decreased significantly after applying cTBS over either the motor or premotor cortex, but the tremor frequency remained unchanged. These findings suggest that inhibitory circuits within the motor cortex are aberrant and less modifiable in ET patients. The reduced plasticity in response to motor and premotor TBS supports the theory of abnormal gamma‐aminobutyric acid (GABA) modulation in ET. © 2014 International Parkinson and Movement Disorder Society     

The role of V5 (hMT+) in visually guided hand movements: an fMRI study

Electrophysiological studies in animals suggest that visuomotor control of forelimb and eye movements involves reciprocal connections between several areas (striate, extrastriate, parietal, motor and premotor) related to movement performance and visuospatial coding of movement direction. The extrastriate area MT [V5 (hMT+) in humans] located in the "dorsal pathway" of the primate brain is specialized in the processing of visual motion information. The aim of our study was to investigate the functional role of V5 (hMT+) in the control of visually guided hand movements and to identify the corresponding cortex activation implicated in the visuomotor tasks using functional magnetic resonance imaging. Eight human subjects performed visually guided hand movements, either continuously tracking a horizontally moving target or performing ballistic tracking movements of a cursor to an eccentric stationary target while fixating a central fixation cross. The tracking movements were back-projected onto the screen using a cursor which was moved by an MRI-compatible joystick. Both conditions activated area V5 (hMT+), right more than left, particularly during continuous tracking. In addition, a large-scale sensorimotor circuit which included sensorimotor cortex, premotor cortex, striatum, thalamus and cerebellum as well as a number of cortical areas along the intraparietal sulcus in both hemispheres were activated. Because activity was increased in V5 (hMT+) during continuous tracking but not during ballistic tracking as compared to motion perception, it has a pivotal role during the visual control of forelimb movements as well.     

Interconnections between the prefrontal cortex and the premotor areas in the frontal lobe

We examined interconnections between a portion of the prefrontal cortex and the premotor areas in the frontal lobe to provide insights into the routes by which the prefrontal cortex gains access to the primary motor cortex and the central control of movement. We placed multiple injections of one retrograde tracer in the arm area of the primary motor cortex to define the premotor areas in the frontal lobe. Then, in the same animal, we placed multiple injections of another retrograde tracer in and around the principal sulcus (Walker's area 46). This double labeling strategy enabled us to determine which premotor areas are interconnected with the prefrontal cortex. There are three major results of this study. First, we found that five of the six premotor areas in the frontal lobe are interconnected with the dorsolateral prefrontal cortex. Second, the major site for interactions between the prefrontal cortex and the premotor areas is the ventral premotor area. Third, the prefrontal cortex is interconnected with only a portion of the arm representation in three premotor areas (supplementary motor area, the caudal cingulate motor area on the ventral bank of the cingulate sulcus, and the dorsal premotor area), whereas it is interconnected with the entire arm representation in the ventral premotor area and the rostral cingulate motor area. These observations indicate that the output of the prefrontal cortex targets specific premotor areas and even subregions within individual premotor areas.     

Cortical involvement in a gait-related imagery task: comparison between Parkinson's disease and normal aging

PurposeWe employed imaginary tasks to investigate the neurophysiology of gait in patients with Parkinson’s disease (PD) using functional magnetic resonance imaging (fMRI).MethodsCortical activation of gait-related imagery was explored in 13 PD patients, 13 age-matched controls (Old), and 14 young volunteers (Young) using fMRI. The tasks included gait initiation, stepping over an obstacle and gait termination using an event-related design. Subjects watched a video clip showing an actor walking and imagined the walking process.ResultsAt gait initiation, no significant difference could be found between PD and the Old controls. Activation in the visual related areas in the Old subjects was increased compared to the Young subjects. While imagining stepping over obstacles, the right dorsal premotor area (PMd), precentral, right inferior parietal lobule, and bilateral precuneus were more activated in PD compared to the Old. An extensive network of bilateral SMA, PMd, posterior parietal lobe and visual association areas was activated in the Old versus the Young subjects. At gait termination, visual related areas were noted when PD was compared to the Old. In contrast, increased activation in bilateral pre-SMA, PMd, ventral premotor area, precentral, posterior parietal lobes and visual association areas were activated in the Old when compared to the Young.ConclusionsOur study provides image based evidence for gait disturbance in PD patients and during normal aging. The compensatory cortical mechanism in the findings could be a background resource for further therapeutic interventions.     

Motor imagery in Parkinson's disease: a PET study.

We used positron emission tomography (PET) with 15O-labelled water to record patterns of cerebral activation in six patients with Parkinson's disease (PD), studied when clinically "off" and after turning "on" as a result of dopaminergic stimulation. They were asked to imagine a finger opposition movement performed with their right hand, externally paced at a rate of 1 Hz. Trials alternating between motor imagery and rest were measured. A pilot study of three age-matched controls was also performed. We chose the task as a robust method of activating the supplementary motor area (SMA), defects of which have been reported in PD. The PD patients showed normal degrees of activation of the SMA (proper) when both "off" and "on." Significant activation with imagining movement also occurred in the ipsilateral inferior parietal cortex (both "off" and when "on") and ipsilateral premotor cortex (when "off" only). The patients showed significantly greater activation of the rostral anterior cingulate and significantly less activation of the left lingual gyrus and precuneus when performing the task "on" compared with their performance when "off." PD patients when imagining movement and "off" showed less activation of several sites including the right dorsolateral prefrontal cortex (DLPFC) when compared to the controls performing the same task. No significant differences from controls were present when the patients imagined when "on." Our results are consistent with other studies showing deficits of pre-SMA function in PD with preserved function of the SMA proper. In addition to the areas of reduced activation (anterior cingulate, DLPFC), there were also sites of activation (ipsilateral premotor and inferior parietal cortex) previously reported as locations of compensatory overactivity for PD patients performing similar tasks. Both failure of activation and compensatory changes are likely to contribute to the motor deficit in PD.     

Stuttered and fluent speech production: an ALE meta-analysis of functional neuroimaging studies

This study reports an activation likelihood estimation (ALE) meta-analysis of imaging studies of chronic developmental stuttering in adults. Two parallel meta-analyses were carried out: (1) stuttered production in the stutterers; (2) fluent production in the control subjects. The control subjects' data replicated previous analyses of single-word reading, identifying activation in primary motor cortex, premotor cortex, supplementary motor area, Rolandic operculum, lateral cerebellum, and auditory areas, among others. The stuttering subjects' analysis showed that similar brain areas are involved in stuttered speech as in fluent speech, but with some important differences. Motor areas were over-activated in stuttering, including primary motor cortex, supplementary motor area, cingulate motor area, and cerebellar vermis. Frontal operculum, Rolandic operculum, and anterior insula showed anomalous right-laterality in stutterers. Auditory activations, due to hearing one's own speech, were essentially undetectable in stutterers. The phenomenon of efference copy is proposed as a unifying account of the pattern activation revealed within this ALE meta-analysis. This provides the basis for a stuttering system model that is testable and should help to advance the understanding and treatment of this disorder.     

Parkinson's disease and healthy aging: Independent and interacting effects on action selection

Functional reorganization of the motor system occurs in response to both aging and Parkinson's disease (PD). Since PD typically develops in older adults, disease progression and the effects of treatment may interact with normal aging. Using event‐related functional magnetic resonance imaging, we studied patients “on” and “off” their normal dopaminergic medication, age‐matched controls and younger adults on tasks of action and action selection. For manual movements, aging increased activity in bilateral motor, premotor and cingulate cortex. Activation in the premotor regions of “on” patients was higher relative to age‐matched controls. However, in contrast to controls and “off” patients, the activations for patients when “on” decreased with age. Voluntary selection of actions was associated with activation in a bilateral network of fronto‐parietal cortex. Within this network, advancing severity of PD was associated with decreased activity particularly in premotor and ventrolateral prefrontal cortex. Together, these results reveal very different patterns of age‐related changes in health and PD. Younger patients are able to exert greater compensatory activity in premotor cortex than older patients, even after correction for disease severity. This effect is dopamine dependant, and may in part explain the clinical observation of reduced dopamine responsiveness in older patients with PD. Hum Brain Mapp, 2010. © 2010 Wiley‐Liss, Inc.     

Altered corticomotor representation in patients with Parkinson's disease.

In 6 patients with Parkinson's disease (PD) and 6 age-matched controls, transcranial magnetic stimulation was applied at 56 regions over the motor cortex and premotor cortex of each hemisphere, with the first dorsal interosseous (FDI) muscle of both hands activated at 15% maximum voluntary contraction during stimulation. For each site, motor evoked potential (MEP) landmarks were recovered, including MEP amplitude, MEP onset latency, and silent period duration. Scaled MEP amplitudes were used to construct individual cortical maps of the FDI muscles. The maps revealed an anterior displacement of the muscle representation in PD patients. This anterior shift over motor cortical areas may reflect increased contributions of corticocortical connections between motor cortex and premotor cortical areas, possibly enhanced by the visual feedback aspect of the task. These alterations may reflect adaptations to the impairments in striatocortical circuits in PD.     

Overactivation of primary motor cortex is asymmetrical in hemiparkinsonian patients

Regional cerebral blood flow (rCBF) was measured using PET and H2(15)O in Parkinson's disease (PD) patients with predominantly right-sided akinetic-rigid symptoms and in control subjects during the execution of an externally cued motor task either with the left or the right hand. During the execution of the task with the left, non-akinetic, hand, cerebral activation in PD patients appeared similar to that of controls. Activated areas were the primary motor cortex, premotor cortex, parietal cortex and cerebellum. When the task was executed with the right, akinetic, hand cerebral activation in PD patients differed from that of controls subjects. The most important change was a bilateral activation of the primary motor cortex. We conclude that overactivation of primary motor cortex is asymmetrical in hemiparkinsonian patients.     

Levodopa affects functional brain networks in parkinsonian resting tremor

Resting tremor in idiopathic Parkinson's disease (PD) is associated with an oscillatory network comprising cortical as well as subcortical brain areas. To shed light on the effect of levodopa on these network interactions, we investigated 10 patients with tremor‐dominant PD and reanalyzed data in 11 healthy volunteers mimicking PD resting tremor. To this end, we recorded surface electromyograms of forearm muscles and neuromagnetic activity using a 122‐channel whole‐head magnetometer (MEG). Measurements were performed after overnight withdrawal of levodopa (OFF) and 30 min after oral application of fast‐acting levodopa (ON). During OFF, patients showed the typical antagonistic resting tremor. Using the analysis tool Dynamic Imaging of Coherent Sources, we identified the oscillatory network associated with tremor comprising contralateral primary sensorimotor cortex (S1/M1), supplementary motor area (SMA), contralateral premotor cortex (PMC), thalamus, secondary somatosensory cortex (S2), posterior parietal cortex (PPC), and ipsilateral cerebellum oscillating at 8 to 10 Hz. After intake of levodopa, we found a significant decrease of cerebro‐cerebral coupling between thalamus and motor cortical areas. Similarly, in healthy controls mimicking resting tremor, we found a significant decrease of functional interaction within a thalamus–premotor–motor network during rest. However, in patients with PD, decrease of functional interaction between thalamus and PMC was significantly stronger when compared with healthy controls. These data support the hypothesis that (1) in patients with PD the basal ganglia and motor cortical structures become more closely entrained and (2) levodopa is associated with normalization of the functional interaction between thalamus and motor cortical areas. © 2008 Movement Disorder Society     

The relationship between brain activity and peak grip force is modulated by corticospinal system integrity after subcortical stroke

In healthy human subjects, the relative contribution of cortical regions to motor performance varies with the task parameters. Additionally, after stroke, recruitment of cortical areas during a simple motor task varies with corticospinal system integrity. We investigated whether the pattern of motor system recruitment in a task involving increasingly forceful hand grips is influenced by the degree of corticospinal system damage. Nine chronic subcortical stroke patients and nine age-matched controls underwent functional magnetic brain imaging whilst performing repetitive isometric hand grips. Target grip forces were varied between 15% and 45% of individual maximum grip force. Corticospinal system functional integrity was assessed with transcranial magnetic stimulation. Averaged across all forces, there was more task-related activation compared with rest in the secondary motor areas of patients with greater corticospinal system damage, confirming previous reports. However, here we were primarily interested in regional brain activation, which covaried with the amount of force generated, implying a prominent executive role in force production. We found that in control subjects and patients with lesser corticospinal system damage, signal change increased linearly with increasing force output in contralateral primary motor cortex, supplementary motor area and ipsilateral cerebellum. In contrast, in patients with greater corticospinal system damage, force-related signal changes were seen mainly in contralesional dorsolateral premotor cortex, bilateral ventrolateral premotor cortices and contralesional cerebellum, but not ipsilesional primary motor cortex. These findings suggest that the premotor cortices might play a new and functionally relevant role in controlling force production in patients with more severe corticospinal system disruption.     

Repetitive transcranial magnetic stimulation reveals abnormal plastic response to premotor cortex stimulation in schizophrenia.

BACKGROUND: Schizophrenia may be characterized by abnormal plastic modulation in cortical neuronal circuits. Activation of premotor cortex using repetitive transcranial magnetic stimulation (rTMS) produces suppression of cortical excitability in primary motor cortex. We hypothesized that premotor rTMS would cause less suppression of motor cortical excitability in patients with schizophrenia than in control subjects. METHODS: Twelve patients diagnosed with schizophrenia and twelve healthy control subjects underwent subthreshold rTMS to the premotor area in a 15-min conditioning train. Measurements of primary motor cortical excitability (motor evoked potential; MEP), the resting motor threshold (RMT), and cortical inhibition (CI) were taken before and after the rTMS. RESULTS: There was no difference in RMT between groups at baseline, although the patient group had less CI than the control group at baseline. Following rTMS, the change in both MEP size and RMT between groups was significant. After rTMS, MEP size was suppressed in the control group and increased in the patient group, whereas RMT increased in the normal control group and decreased in the patient group. CONCLUSIONS: Patients with schizophrenia demonstrate abnormal brain responses to rTMS applied to the premotor cortex that appear to relate to reduced motor cortical inhibition.     

Cerebral activation patterns in patients with writer's cramp: a functional magnetic resonance imaging study

Functional MRI (fMRI), visualizing changes in cerebral blood oxygenation, has to date not been performed either in patients with writer's cramp or in healthy subjects during writing. We compared the cerebral and cerebellar activation pattern of 12 patients with writer's cramp during writing with a group of 10 healthy subjects performing the same tasks over 30-s periods of rest or writing. Sixty echo planar imaging multi-slice datasets were analysed using SPM96 software. Data were analysed for each subject individually and groupwise for patients vs. controls. Healthy subjects showed a significant activation of the ipsilateral dentate nucleus, contralateral cerebellar hemisphere, contralateral primary sensorimotor cortex, and contralateral precentral gyrus during writing. Patients with writer's cramp showed significantly greater activation of the ipsilateral cerebellar hemisphere than controls. Also the activation in the primary sensorimotor cortex extended further caudally and anteriorly towards the premotor association area. Activation was observed in the thalamus during writing only among the patients. Our results indicate an increased basal ganglia output via the thalamus to the motor and premotor cortical areas in dystonia patients and support the notion of disinhibition of the motor cortex leading to coconcentrations and dystonic postures. Received: 10 November 1999 / Received in revised form: 4 April 2000 / Accepted: 26 April 2000     

Charting the excitability of premotor to motor connections while withholding or initiating a selected movement

In 19 healthy volunteers, we used transcranial magnetic stimulation (TMS) to probe the excitability in pathways linking the left dorsal premotor cortex and right primary motor cortex and those linking the left and right motor cortex during the response delay and the reaction time period while subjects performed a delayed response [symbol 1 (S1) - symbol 2 (S2)] Go-NoGo reaction time task with visual cues. Conditioning TMS pulses were applied to the left premotor or left motor cortex 8 ms before a test pulse was given to the right motor cortex at 300 or 1800 ms after S1 or 150 ms after S2. S1 coded for right-hand or left-hand movement, and S2 for release or stopping the prepared movement. Conditioning of the left premotor cortex led to interhemispheric inhibition at 300 ms post-S1, interhemispheric facilitation at 150 ms post-S2, and shorter reaction times in the move-left condition. Conditioning of the left motor cortex led to inhibition at 1800 ms post-S1 and 150 ms post-S2, and slower reaction times for move-right conditions, and inhibition at 300 and 1800 ms post-S1 for move-left conditions. Relative motor evoked potential amplitudes following premotor conditioning at 150 ms post-S2 were significantly smaller in 'NoGo' than in 'Go' trials for move-left instructions. We conclude that the excitability in left premotor/motor right motor pathways is context-dependent and affects motor behaviour. Thus, the left premotor cortex is engaged not only in action selection but also in withholding and releasing a preselected movement generated by the right motor cortex.     

Abnormal dorsal premotor–motor inhibition in writer's cramp

The authors hypothesized that a deficient premotor–motor inhibitory network contributes to the unwanted involuntary movements in dystonia. The authors studied nine controls and nine patients with writer's cramp (WC). Dorsal premotor–motor cortical inhibition (dPMI) was tested by applying conditioning transcranial magnetic stimulation (TMS) to the dorsal premotor cortex and then a test pulse to the ipsilateral motor cortex at an interval of 6 ms. The authors used an H‐reflex in flexor carpi radialis paired with TMS over the premotor cortex to assess for spinal cord excitability change. Finally, the authors interrupted a choice reaction time task with TMS over dorsal premotor cortex to assess performance in a nondystonic task. The results showed that WC patients exhibited dPMI at rest (88.5%, the ratio of conditioned to unconditioned test pulse), in contrast to controls, who did not show dPMI (109.6%) (P = 0.0198). This difference between patients and controls persisted during contraction (100% vs. 112%) and pen‐holding (95.6% vs. 111%). The H‐reflex in the arm was not modulated by the premotor cortex stimulation. The WC patients made more errors, and the error rate improved with TMS over the premotor cortex. These results suggest that abnormal premotor–motor interactions may play a role in the pathophysiology of focal dystonia. The dPMI was not modulated by task in either group, but was constantly greater in the patients. The significance of the increased inhibition is likely to be compensatory. It appears to be a robust finding and, in combination with other features, could be further explored as a biomarker. © 2014 International Parkinson and Movement Disorder Society