Multimodal investigation of cerebello-thalamo-cortical connectivity in cervical dystonia

肌张力障碍是一种运动障碍，其特征是肌肉持续或间歇性收缩，导致姿势或运动异常，或两者兼而有之。在德国，大约有160.000人患有肌张力障碍。根据临床分布可分为局灶性、节段性、多灶性、全身性肌张力障碍或偏侧肌张力障碍。颈部肌张力障碍(CD)是最常见的局灶性肌张力障碍，伴有头部和颈部的异常姿势和运动。CD经常与疼痛、抑郁、社会耻辱、继发性退行性疾病，特别是颈椎退行性疾病和生活质量受损有关。大量证据表明，基底神经节-丘脑皮质功能障碍在肌张力障碍的病理生理学中起着重要作用。然而，近年来，一些脑成像和神经生理学研究表明，小脑在该病的病理生理学中也有重要贡献。因此，有人提出肌张力障碍是一种累及基底节和小脑的网络障碍。在本研究中，我们旨在评估CD患者小脑-丘脑-皮质网络的兴奋性和连通性与运动症状严重程度的关系。我们假设，在CD患者中，小脑-丘脑-皮质束的结构连通性受损，初级运动皮质(M1)和小脑的兴奋性改变。一组CD患者将在一项多模式、多阶段的研究中接受检查。这项研究包括标准化的临床检查和基于视频的运动分析，经颅磁刺激(TMS)对感觉运动兴奋性的神经生理学检查，经颅直流电刺激(TDC)对小脑兴奋性的调节，以及磁共振成像(MRI)对结构上小脑-丘脑-皮质连接的研究。在每一次会议中，TMS将用于评估M1的感觉运动和皮质内兴奋性，并使用已知的反映肌张力障碍患者运动系统兴奋性增加的范例。为了调节小脑的兴奋性，促进性、抑制性或假的tdcs将在三个不同的日期以随机顺序应用。小脑tdcs对运动皮质兴奋性和运动症状严重程度的影响将被调查。扩散张量成像将用于研究小脑-丘脑-皮质网络的特性。将评估小脑-丘脑-皮质束的结构纤维连接，并研究其与个体对小脑tDCs反应的关系。

Dystonia is a movement disorders characterized by sustained or intermittent muscle contractions leading to abnormal postures or movements or both. In Germany about 160.000 people are affected by dystonia. According to the clinical distribution it may be classified into focal, segmental, multifocal, generalized dystonia or hemidystonia. Cervical dystonia (CD) with abnormal postures and movements of the head and neck is the most frequent form of focal dystonias. CD is frequently associated with pain, depression, social stigmatization, secondary degenerative disorders especially of the cervical spine and impaired quality of life. A large body of evidence points to a role of basalganglia-thalamo-cortical dysfunction in the pathophysiology of dystonia. In recent years though, several brain imaging as well as neurophysiological studies suggested that the cerebellum also has a substantial contribution to the pathophysiology of the disease. Consequently, it has been proposed that dystonia is a network disorder involving basal ganglia and cerebellum. In the present study, we aim to assess excitability and connectivity of the cerebello-thalamo-cortical network in relation to motor symptom severity in CD patients. We hypothesize that in CD patients, structural connectivity of the cerebello-thalamo-cortical tract is impaired and excitability of the primary motor cortex (M1) and cerebellum is altered.A group of CD patients will be examined in a multimodal, multi-session study. The study comprises a standardized clinical examination and video-based movement analyses, a neurophysiological examination of sensorimotor excitability with transcranial magnetic stimulation (TMS), modulation of cerebellar excitability with transcranial direct current stimulation (tDCS) and investigation of structural cerebello-thalamo-cortical connectivity with magnetic resonance imaging (MRI). In each session, TMS will be applied to assess sensorimotor and intracortical excitability of M1 with paradigms that are known to reflect increased excitability of the motor system in dystonia patients. To modulate cerebellar excitability either facilitatory, inhibitory or sham tDCS will be applied in a randomised order on three separate days. The impact of cerebellar tDCS on motor cortex excitability and on motor symptom severity will be investigated. Diffusion tensor imaging will be used to investigate properties of the cerebello-thalamo-cortical network. Structural fibre connectivity of the cerebello-thalamo-cortical tract will be assessed and the relation to individual responsiveness to cerebellar tDCS examined.