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

肌张力障碍是一种运动障碍，其特征是持续或间歇性肌肉收缩，导致异常姿势或运动或两者兼而有之。在德国，约有16万人患有肌张力障碍。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）与头部和颈部的异常姿势和运动是最常见的形式局灶性肌张力障碍。CD通常与疼痛、抑郁、社会污名化、继发性退行性疾病（尤其是颈椎）和生活质量受损相关。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发挥作用。然而，近年来，一些脑成像和神经生理学研究表明，小脑也对疾病的病理生理学有重大贡献。因此，有人提出肌张力障碍是一种涉及基底神经节和小脑的网络障碍。在本研究中，我们的目的是评估兴奋性和连通性的小脑-丘脑-皮质网络与CD患者的运动症状的严重程度。我们假设CD患者小脑-丘脑-皮质束的结构连接受损，初级运动皮层（M1）和小脑的兴奋性改变。该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）的感觉运动兴奋性的神经生理学检查，经颅直流电刺激（tDCS）的小脑兴奋性的调制和结构小脑-丘脑-皮质连接的磁共振成像（MRI）的调查。在每次治疗中，将应用TMS评估M1的感觉运动和皮质内兴奋性，其范例已知可反映肌张力障碍患者运动系统的兴奋性增加。为了调节小脑兴奋性，将在不同的三天以随机顺序应用易化、抑制或假tDCS。将研究小脑tDCS对运动皮层兴奋性和运动症状严重程度的影响。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，并检查与小脑tDCS个体反应性的关系。

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.