A Multimodal Assessment of Neurophysiology in Focal Dystonia

局灶性肌张力障碍神经生理学的多模式评估

• 批准号: 9239016
• 负责人: Teresa Jacobson Kimberley
• 金额: $ 7.99万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-01-01 至 2017-08-18
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9239016
• 关键词: Address; Adult; Affect; Anatomy; Area; Base of the Brain; Behavior; Behavioral; Body Regions; Body part; Brain; Brain Mapping; Characteristics; Chronic; Clinical; Collaborations; Data; Disease; Dystonia; Employee Strikes; Fingers; Focal Dystonias; Functional Magnetic Resonance Imaging; Functional disorder; Goals; Hand; Hand functions; Impairment; Individual; Larynx; Location; Maps; Measurement; Measures; Methods; Modeling; Motor; Motor Cortex; Movement; Movement Disorders; Muscle; Muscle Contraction; Nature; Neural Pathways; Neurologic; Participant; Patients; Physiological; Positioning Attribute; Pyramidal Tracts; Rest; Seeds; Severity of illness; Smooth Muscle; Source; Spastic Dysphonias; Symptoms; Task Performances; Techniques; Testing; Transcranial magnetic stimulation; Voice; Work; base; common treatment; effective intervention; effective therapy; indexing; interest; motor impairment; multimodality; neuroimaging; neurophysiology; novel; stem; therapy development; treatment strategy; vocal cord; vocalization

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.

肌张力障碍是一组破坏性的神经运动障碍，其特征是不随意肌肉收缩，可影响任何身体部位。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学仍然很大程度上是未知的。局灶性肌张力障碍的症状局限于一个特定的身体部位。影响手部的肌张力障碍称为局灶性手肌张力障碍（FHD），而影响声带的肌张力障碍称为内收肌痉挛性发声障碍（AdSD）。尽管临床表现不同（声音或手的使用受损），但两者被认为具有共同的潜在机制。但局灶性肌张力障碍的病理生理共性尚未得到很好的探讨。我们的中心假设是局灶性肌张力障碍是一种具有非同步连接（“连接障碍”）的大脑网络障碍，或者在静息状态、活动状态或两者兼而有之时，与肌张力障碍任务相关的大脑网络区域之间的无效协作。这一假设可以通过功能性磁共振成像（fMRI）和经颅磁刺激（TMS）来验证，它们代表了自主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接（fc）评估更准确地阐明了连接障碍的本质。我们将在这些位点和整个大脑之间确定静息状态（静息状态fc）和活动状态（任务fc）时的fc。目的1将确定CTL和肌张力障碍中发声和手部运动网络的fMRI和TMS位点的个体fc。子Aim 1.1将确定fMRI和TMS位点之间的个体fc在CTL和肌张力障碍之间是否存在差异，以及这种差异是否依赖于状态，这意味着fc在静息状态fc和活动（任务fc）之间存在差异；Sub Aim 1.2将确定CTL和肌张力障碍之间的个体全脑fc图谱是否不同，以及这种差异是否与某个位点或状态有关；Aim 1.3将确定在标准空间中分析的fc是否揭示了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。目的2将确定疾病严重程度与大脑行为发现之间的关系。相关性：局灶性肌张力障碍的病理生理机制尚不清楚。该团队在神经成像和脑刺激方面取得的最新进展将允许对解剖和自愿脑网络进行多模式评估，这将为FHD和AdSD的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。这些发现将使我们能够根据特定的生理基础，为所有局灶性肌张力障碍制定共同的治疗策略。此外，这种局灶性脑基疾病的独特性也影响了我们对一般脑功能的理解。了解大脑网络如何相互作用并形成错误的联系可能对许多其他疾病具有广泛的影响。