Multimodal investigation of neuronal circuits involved in execution and inhibition of self determined and externally guided movements in Tourette syndrome

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Gilles de la Tourette syndrome (GTS) is characterised by motor and phonic tics, i.e. sudden, repetitive, stereotyped movements or phonic productions preceded by an inner urge to move that can transiently be suppressed. An increased sensitivity to external stimuli triggering typical tics and mirror behaviour (echopraxia) are other salient feature of GTS. The presence of urges suggests that cortical areas engaged in decisions to move or not to move, predominantly frontomesial circuits including the supplementary motor area are involved in the generation of tics. Increased responsiveness to certain external stimuli might reflect abnormalities in dorsal premotor-motor circuits. Echopraxia points at dysfunctions in networks responsible for automatic imitative response tendencies, i.e. the human mirror neuron system including the ventral premotor cortex. In the intended projects we will therefore examine the functional neuroanatomy of frontomesial- and premotor-motor circuits in GTS using fMRI, DTI, MEG and TMS. In project 1, task related brain activity (fMRI and MEG), structural connectivity (DTI) and excitability (TMS) will be studied during execution and suppression of self-determined movements engaging frontomesial-motor circuits and responses determined by symbolic visual cues involving dorsal premotor-motor circuits, respectively. In project 2, echophenomena will be studied during observation and execution of simple finger movements and during observation of facial expressions and facial tics using the same methods. We hypothesise that in GTS i) activation in frontomesial networks will be increased, ii) physiological segregation of cortical 3 networks engaged in self generated and externally determined movements, respectively, will be reduced and iii) the human mirror system will be overactive.