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)的特征是运动和发音，即突然的、重复的、刻板印象的动作或发音，在此之前有一种内在的运动冲动，这种冲动可以暂时被抑制。GTS的另一个显著特征是对触发典型抽搐的外部刺激的敏感度增加和镜像行为(晕厥)。冲动的存在表明，参与决定移动或不移动的皮质区域，主要是包括辅助运动区在内的额内侧回路参与了抽搐的产生。对某些外部刺激的反应增强可能反映了背侧运动前-运动神经回路的异常。恐惧症指的是负责自动模仿反应倾向的网络中的功能障碍，即包括腹侧运动前皮质在内的人类镜像神经系统。因此，在计划的项目中，我们将使用fMRI、DTI、MEG和TMS检查GTS中额内侧和运动前运动神经回路的功能神经解剖学。在项目1中，任务相关的脑活动(fMRI和MEG)、结构连接性(DTI)和兴奋性(TMS)将分别在执行和抑制涉及额内侧运动回路的自主动作和涉及背侧运动前运动回路的象征性视觉线索确定的反应时被研究。在项目2中，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的过程中研究生态现象。我们假设，在GTS中，1)额内侧网络的激活将增加，2)分别参与自产生和外部决定运动的皮质3网络的生理分离将减少，3)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.