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

基本信息

批准号：
9564458
负责人：
Teresa Jacobson Kimberley
金额：
$ 24.64万
依托单位：
MGH INSTITUTE OF HEALTH PROFESSIONS
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-01-01 至 2021-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9564458
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

项目摘要

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神经区域，因为该疾病的病理生理学仍然很大程度上未知，在局灶性肌张力障碍中，症状仅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)，而影响声带时则称为内收肌痉挛性发声障碍 (AdSD)，尽管临床表现不同（声音受损或发声障碍）。但我们的中心假设是，局灶性肌张力障碍是一种具有不同步连接（“连接失调”）的大脑网络疾病。在静息状态、活动状态或两者期间，与肌张力障碍任务相关的网络内大脑区域之间的协作无效。可以通过功能磁共振成像（fMRI）和经颅磁刺激（TMS）来测试这一假设。因此，使用每个种子进行功能连接（fc）评估可以更准确地阐明静息状态（静息状态 fc）和活动状态下的 fc。基因座之间和整个大脑的状态（任务 fc）将确定 CTL 和肌张力障碍中发声和手部运动网络的功能磁共振成像和 TMS 基因座的个体 fc。 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不同，并且这种差异是否与状态相关，这意味着静息状态（静息状态 fc）和活动状态（任务 fc）之间的 fc 是否不同； CTL 和肌张力障碍之间的个体全脑 fc 图存在差异，并且这种差异是否与某个基因座或状态相关，子目标 1.3 将确定在标准空间中分析的 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行为，将决定疾病严重程度和大脑发现之间的关系。相关性：该团队在神经影像学和脑刺激方面的最新进展尚不清楚。对解剖学和自愿性大脑网络的多模式评估将为了解 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。这些发现将使我们处于有利的发展位置。基于特定生理基础的所有局灶性肌张力障碍的常见治疗策略此外，这种局灶性脑部疾病的独特性质也对我们了解大脑网络如何相互作用和形成错误关联具有广泛的影响。对于许多其他疾病。