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

抽动秽语综合征（GTS）的特征是运动和语音抽搐，即突然的、重复的、刻板的动作或语音产生，在此之前有一种可以暂时抑制的内在运动冲动。对外部刺激的敏感性增加，引发典型的抽搐和镜像行为（回声恐惧症）是GTS的另一个显著特征。冲动的存在表明，决定动或不动的皮质区域，主要是包括辅助运动区在内的额叶神经回路参与了抽搐的产生。对某些外部刺激的反应性增加可能反映了背侧运动前-运动回路的异常。回声恐惧症指出负责自动模仿反应倾向的网络功能障碍，即包括腹侧运动前皮层在内的人类镜像神经元系统。因此，在预定的项目中，我们将使用fMRI、DTI、MEG和TMS检查GTS的额叶和前运动-运动回路的功能神经解剖学。在项目1中，将分别研究与任务相关的大脑活动（fMRI和MEG）、结构连接（DTI）和兴奋性（TMS）在执行和抑制自我决定的运动（涉及额叶前运动回路）和由符号视觉线索决定的反应（涉及背叶前运动-运动回路）期间的情况。在project 2中，我们将使用相同的方法，在观察和执行简单的手指动作以及观察面部表情和面部抽搐时，研究回声现象。我们假设，在GTS中，i)额叶体网络的激活将增加，ii)分别参与自我产生和外部决定运动的皮层网络的生理隔离将减少，iii)人类镜像系统将过度活跃。

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.