Altered modulation of intracortical excitability during movement preparation in Gilles de la Tourette syndrome

Gilles de la Tourette syndrome is a neuropsychiatric disorder in which cortical disinhibition has been proposed as a pathophysiological mechanism involved in the generation of tics. Tics are typically reduced during task performance and concentration. How this task-dependent reduction of motor symptoms is represented in the brain is not yet understood. The aim of the current research was to study motorcortical excitability at rest and during the preparation of a simple motor task. Transcranial magnetic stimulation was used to examine corticospinal excitability, short-interval intracortical inhibition and intracortical facilitation in a group of 11 patients with Gilles de la Tourette syndrome and age-matched healthy controls. Parameters of cortical excitability were evaluated at rest and at six points in time during the preparation of a simple finger movement. Patients with Gilles de la Tourette syndrome displayed significantly reduced short-interval intracortical inhibition at rest, while no differences were apparent for unconditioned motor evoked potential or intracortical facilitation. During the premovement phase, significant differences between groups were seen for single pulse motor evoked potential amplitudes and short-interval intracortical inhibition. Short-interval intracortical inhibition was reduced in the early phase of movement preparation (similar to rest) followed by a transition towards more inhibition. Subsequently modulation of short-interval intracortical inhibition was comparable to controls, while corticospinal recruitment was reduced in later phases of movement preparation. The present data support the hypothesis of motorcortical disinhibition in Gilles de la Tourette syndrome at rest. During performance of a motor task, patients start from an abnormally disinhibited level of short-interval intracortical inhibition early during movement preparation with subsequent modulation of inhibitory activity similar to healthy controls. We hypothesize that while at rest, abnormal subcortical inputs from aberrant striato-thalamic afferents target the motor cortex, during motor performance, motor cortical excitability most likely underlies top-down control from higher motor areas and prefrontal cortex, which override these abnormal subcortical inputs to guarantee adequate behavioural performance.

The role of the inferior parietal lobule in writer's cramp

Traian Popa

Humans have a distinguishing ability for fine motor control that is subserved by a highly evolved cortico-motor neuronal network. The acquisition of a particular motor skill involves a long series of practice movements, trial and error, adjustment and refinement. At the cortical level, this acquisition begins in the parieto-temporal sensory regions and is subsequently consolidated and stratified in the premotor-motor cortex. Task-specific dystonia can be viewed as a corruption or loss of motor control confined to a single motor skill. Using a multimodal experimental approach combining neuroimaging and non-invasive brain stimulation, we explored interactions between the principal nodes of the fine motor control network in patients with writer's cramp and healthy matched controls. Patients and healthy volunteers underwent clinical assessment, diffusion-weighted MRI for tractography, and functional MRI during a finger tapping task. Activation maps from the task-functional MRI scans were used for target selection and neuronavigation of the transcranial magnetic stimulation. Single- and double-pulse TMS evaluation included measurement of the input-output recruitment curve, cortical silent period, and amplitude of the motor evoked potentials conditioned by cortico-cortical interactions between premotor ventral (PMv)-motor cortex (M1), anterior inferior parietal lobule (aIPL)-M1, and dorsal inferior parietal lobule (dIPL)-M1 before and after inducing a long term depression-like plastic change to dIPL node with continuous thetaburst transcranial magnetic stimulation in a randomized, sham-controlled design. Baseline dIPL-M1 and aIPL-M1 cortico-cortical interactions were facilitatory and inhibitory, respectively, in healthy volunteers, whereas the interactions were converse and significantly different in writer's cramp. Baseline PMv-M1 interactions were inhibitory and similar between the groups. The dIPL-PMv resting state functional connectivity was increased in patients compared to controls, but no differences in structural connectivity between the nodes were observed. Cortical silent period was significantly prolonged in writer's cramp. Making a long term depression-like plastic change to dIPL node transformed the aIPL-M1 interaction to inhibitory (similar to healthy volunteers) and cancelled the PMv-M1 inhibition only in the writer's cramp group. These findings suggest that the parietal multimodal sensory association region could have an aberrant downstream influence on the fine motor control network in writer's cramp, which could be artificially restored to its normal function.

OXFORD UNIV PRESS2020

Inhibitory control of acquired motor programmes in the human brain

Friedhelm Christoph Hummel

An important basis of skilled human behaviour is the appropriate retrieval of acquired and memorized motor programmes ('motor memory traces'). Appropriate retrieval is warranted if motor programmes are only activated if necessary and are, probably more often, inhibited if required by the context of a given situation. It is unknown how this type of inhibition is accomplished in the brain. We studied context-dependent modulation of motor memory traces in 18 volunteers and six patients with focal dystonia. Cortical function was assessed with transcranial magnetic stimulation over the primary motor cortex (M1) and with task-related analysis of oscillatory EEG activity. An activation (ACT) and inhibition (INH) condition were compared. In both, visual cues were presented at 1/s. In ACT, subjects had to respond to these cues with individual finger movements as learned in a preceding training session. In INH, subjects had to observe the cues without retrieval of motor responses. During INH, inhibitory control of the motor memory trace was confirmed by significant amplitude reduction of motor evoked potentials (MEPs) compared with baseline. This was accompanied by a significant increase of 11-13 Hz oscillatory activity over the sensorimotor areas during INH. During active retrieval of the motor memory traces, the reverse was true (increased MEP amplitudes, decreased oscillatory 11-13 Hz activity). In a small sample of dystonic patients (n = 6), the increase of 11-13 Hz oscillatory activity during INH was consistently absent. The present data demonstrate for the first time cortical correlates of appropriate, context-dependent inhibition of motor memory traces. We propose that focal increases of oscillatory activity are instrumental for inhibitory control at the cortical level. This concept is supported by the preliminary observations in dystonic patients who are known to have deficits of inhibitory motor control and in whom these context-dependent focal increases of oscillatory activity were absent.

Oxford University Press2002

Disrupting the ipsilateral motor cortex interferes with training of a complex motor task in older adults

Friedhelm Christoph Hummel

Performance of unimanual movements is associated with bihemispheric activity in the motor cortex in old adults. However, the causal functional role of the ipsilateral MC (iMC) for motor control is still not completely known. Here, the behavioral consequences of interference of the iMC during training of a complex motor skill were tested. Healthy old (58-85 years) and young volunteers (22-35 years) were tested in a double-blind, cross-over, sham-controlled design. Participants attended 2 different study arms with either cathodal transcranial direct current stimulation (ctDCS) or sham concurrent with training. Motor performance was evaluated before, during, 90 min, and 24 h after training. During training, a reduced slope of performance with ctDCS relative to sham was observed in old compared with young (F = 5.8, P = 0.02), with a decrease of correctly rehearsed sequences, an effect that was evident even after 2 consecutive retraining periods without intervention. Furthermore, the older the subject, the more prominent was the disruptive effect of ctDCS (R(2) = 0.50, P = 0.01). These data provide direct evidence for a causal functional link between the iMC and motor skill acquisition in old subjects pointing toward the concept that the recruitment of iMC in old is an adaptive process in response to age-related declines in motor functions.

Oxford University Press2014

The role of the inferior parietal lobule in writer's cramp

Traian Popa

OXFORD UNIV PRESS2020

Inhibitory control of acquired motor programmes in the human brain

Friedhelm Christoph Hummel

Oxford University Press2002