A Multimodal Assessment of Neurophysiology in Focal Dystonia

肌张力障碍是一组破坏性的神经运动障碍，其特征是不自主的肌肉收缩，可以影响身体的任何部位。目前还没有治愈或有效的治疗方法，因为这种疾病的病理生理机制在很大程度上仍不清楚。在局灶性肌张力障碍中，症状仅限于身体的一个特定部位。影响手部的肌张力障碍被称为局灶性手部肌张力障碍(FHD)，而当声带受到影响时，它被称为内收肌痉挛发音障碍(ADSD)。尽管临床表现不同(声音受损或手的使用)，但两者被认为具有共同的潜在机制。但是局灶性肌张力障碍在病理生理学上的共性还没有得到很好的研究。我们的中心假设是，局灶性肌张力障碍是一种大脑网络障碍，具有去同步连接(‘连接障碍’)，或在静息状态、活动状态或两者兼而有之的状态下，与肌张力障碍任务相关的网络内脑区之间的无效合作。这一假设可以用功能磁共振成像(FMRI)和经颅磁刺激(TMS)种子来验证，这两种种子代表了自愿运动网络中不同但相关的部分。因此，使用每个种子进行功能连通性(FC)评估可以更准确地阐明连接障碍的性质。我们将确定静息状态(静息状态FC)和活动状态(任务FC)时的Fc，它们之间以及整个大脑都是如此。目的1确定CTL和肌张力障碍患者发声和手部运动网络的fMRI和TMS基因座的个体Fc。子目标1.1将确定CTL和肌张力障碍之间的fMRI和TMS基因座之间的个体FC是否不同，以及这种差异是否依赖于状态，这意味着FC在静息(休息状态FC)和活动(任务FC)之间不同；子目标1.2将确定CTL和肌张力障碍之间的个体全脑FC图是否不同，这种差异是否与特定的基因座或状态有关；子目标1.3将确定在标准空间分析的FC是否揭示CTL和肌张力障碍之间的差异，以及这种差异是否依赖于状态。目标2将确定疾病严重程度与大脑行为表现之间的关系。相关性：局灶性肌张力障碍的病理生理学尚不清楚。该团队在神经成像和脑刺激方面取得的最新进展将使解剖和自愿脑网络的多模式评估成为可能，这将为FHD和ADSD的单独病理生理学提供一个新的窗口，并确定这两种疾病的统一特征。这些发现将使我们处于有利地位，根据特定的生理基础，开发所有局灶性肌张力障碍的通用治疗策略。此外，这种以大脑为基础的局灶性疾病的独特性质也意味着我们对一般大脑功能的理解。了解大脑网络是如何相互作用并形成错误联系的，可能会对许多其他疾病产生广泛的影响。

Dystonias are a group of devastating neurological movement disorders characterized by involuntary muscle contractions that can affect any body region. There is no cure or effective treatment as the pathophysiology of the disorder remains largely unknown. In focal dystonia, symptoms are restricted to one specific body part. Dystonia affecting the hand is called focal hand dystonia (FHD), whereas when the vocal chords are affected it is termed adductor spasmodic dysphonia (AdSD). Despite different clinical manifestations (impaired voice or use of hand), both are thought to share a common underlying mechanism. But commonalities in pathophysiology of focal dystonias have not been well explored. Our central hypothesis is that focal dystonia is a brain network disorder with desynchronized connectivity (‘dysconnectivity’), or ineffective collaboration between brain areas within the network associated with the dystonic task during either resting state, active state or both. This hypothesis can be tested with functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) seeds that represent different but related parts of the voluntary motor network. Therefore, using each seed for a functional connectivity (fc) assessment elucidates more precisely the nature of the dysconnectivity. We will determine the fc during resting state (resting state fc) and active state (task fc) between the loci and through the whole brain. Aim 1 will determine the individual fc of fMRI and TMS loci for the vocalization and hand motor networks in CTL and dystonia. Sub Aim 1.1 will determine if the individual fc between fMRI and TMS loci differs between CTL and dystonia and if this difference is state dependent, meaning the fc differs between resting (resting state fc) and active (task fc); Sub Aim 1.2 will determine if the individual whole brain fc map differs between CTL and dystonia and if this difference is related to a certain loci or state; Sub Aim 1.3 will determine if fc analyzed in standard space reveal differences between CTL and dystonia and if this difference is state dependent. Aim 2 will determine the relationship between disease severity and brain behavioral findings. Relevance: The pathophysiology of focal dystonia is unknown. Recent advances in neuroimaging and brain stimulation made by this team will allow multimodal assessments of anatomical and voluntary brain networks that will provide a novel window into the pathophysiology of both FHD and AdSD individually, as well as determine unifying features in both disorders. These findings will leave us well positioned to develop common treatment strategies in all focal dystonias based upon specific physiologic underpinnings. Further, the unique nature of this focal brain-based disease also has implications for our understanding of general brain function. Understanding how brain networks interact and form faulty associations could have wide reaching implications for many other disorders.