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.

Functional meaning of oscillatory brain activity in various frequency bands in the human electroencephalogram (EEG) is increasingly researched. While most research focuses on event-related changes of brain activity in response to external events there is also increasing interest in internal brain states influencing information processing. Several studies suggest amplitude changes of EEG oscillatory activity selectively influencing cortical excitability, and more recently it was shown that phase of EEG activity (instantaneous phase) conveys additional meaning. Here we review this field with many conflicting findings and further investigate whether corticospinal excitability in the resting brain is dependent on a specific spontaneously occurring brain state reflected by amplitude and instantaneous phase of EEG oscillations. We applied single pulse transcranial magnetic stimulation (TMS) over the left sensorimotor cortex, while simultaneously recording ongoing oscillatory activity with EEG. Results indicate that brain oscillations reflect rapid, spontaneous fluctuations of cortical excitability. Instantaneous phase but not amplitude of oscillations at various frequency bands at stimulation site at the time of TMS-pulse is indicative for brain states associated with different levels of excitability (defined by size of the elicited motor evoked potential). These results are further evidence that ongoing brain oscillations directly influence neural excitability which puts further emphasis on their role in orchestrating neuronal firing in the brain.

Independent use of both hands is characteristic of human action in daily life. By nature, however, in-phase bimanual movements, for example clapping, are easier to accomplish than anti-phase movements, for example playing the piano. It is commonly agreed that interhemispheric interactions play a central role in the coordination of bimanual movements. However, the spatial, temporal, and physiological properties of the interhemispheric signals that coordinate different modes of bimanual movements are still not completely understood. More precisely, do individual interhemispheric connectivity parameters have behavioral relevance for bimanual rapid anti-phase coordination? To address this question, we measured movement-related interhemispheric interactions, i.e., inhibition and facilitation, and correlated them with the performance during bimanual coordination. We found that movement-related facilitation from right premotor to left primary motor cortex (rPMd-lM1) predicted performance in anti-phase bimanual movements. It is of note that only fast facilitation during the preparatory period of a movement was associated with success in anti-phase movements. Modulation of right to left primary motor interaction (rM1-lM1) was not related to anti-phase but predicted bimanual in-phase and unimanual behavior. These data suggest that strictly timed modulation of interhemispheric rPMd-lM1 connectivity is essential for independent highfrequency use of both hands. The rM1-lM1 results indicate that adjustment of connectivity between homologous M1 may be important for the regulation of homologous muscle synergies.

Current theoretical positions assume that action-related word meanings are established by functional connections between perisylvian language areas and the motor cortex (MC) according to Hebb's associative learning principle. To test this assumption, we probed the functional relevance of the left MC for learning of a novel action word vocabulary by disturbing neural plasticity in the MC with transcranial direct current stimulation (tDCS). In combination with tDCS, subjects learned a novel vocabulary of 76 concrete, body-related actions by means of an associative learning paradigm. Compared with a control condition with "sham" stimulation, cathodal tDCS reduced success rates in vocabulary acquisition, as shown by tests of novel action word translation into the native language. The analysis of learning behavior revealed a specific effect of cathodal tDCS on the ability to associatively couple actions with novel words. In contrast, we did not find these effects in control experiments, when tDCS was applied to the prefrontal cortex or when subjects learned object-related words. The present study lends direct evidence to the proposition that the left MC is causally involved in the acquisition of novel action-related words.

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The preparation of a voluntary unimanual action requires sequential processing in bihemispheric motor areas. In both animals and humans, activity in the dorsal premotor cortex (PMd) ipsilateral to the moving hand has been demonstrated to precede ipsilateral primary motor cortex (M1) activity. We investigated with double-pulse transcranial magnetic stimulation how right-hemispheric motor areas (rM1, rPMd) modulate left M1 (lM1) during the preparatory period of a finger movement with the dominant right hand. We tested the hypothesis that the influence of higher order motor areas such as rPMd on lM1 (rPMd-lM1) precedes interhemispheric interactions between homologue primary motor areas (rM1-lM1). rPMd-lM1 showed modulation in the early and late phase of movement preparation, whereas the intrinsic state of inhibition between rM1-lM1 was only modulated in the late phase. The present results complement existing hierarchical models of cortical movement control by demonstrating temporospatially distinct involvement of interhemispheric interactions from PMd and M1 during movement preparation.

Movement-related ICI one week after a subcortical stroke is associated with better outcome of hand motor function. Disinhibition in the ipsilesional primary motor cortex could be a mechanism of how the brain attempts to promote motor recovery after stroke.

Functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) are well-established tools for investigating the human motor system in-vivo. We here studied the relationship between movement-related fMRI signal changes in the primary motor cortex (M1) and electrophysiological properties of the hand motor area assessed with neuronavigated TMS in 17 healthy subjects. The voxel showing the highest task-related BOLD response in the left hand motor area during right hand movements was identified for each individual subject. This fMRI peak voxel in M1 served as spatial target for coil positioning during neuronavigated TMS. We performed correlation analyses between TMS parameters, BOLD signal estimates and effective connectivity parameters of M1 assessed with dynamic causal modeling (DCM). The results showed a negative correlation between the movement-related BOLD signal in left M1 and resting as well as active motor threshold (MT) obtained for left M1. The DCM analysis revealed that higher excitability of left M1 was associated with a stronger coupling between left supplementary motor area (SMA) and M1. Furthermore, BOLD activity in left M1 correlated with ipsilateral silent period (ISP), i.e. the stronger the task-related BOLD response in left M1, the higher interhemispheric inhibition effects targeting right M1. DCM analyses revealed a positive correlation between the coupling of left SMA with left M1 and the duration of ISP. The data show that TMS parameters assessed for the hand area of M1 do not only reflect the intrinsic properties at the stimulation site but also interactions with remote areas in the human motor system.