FMRI Study of the Effects of DBS in Primary Generalized Dystonia (K23)

描述（由申请人提供）：该奖项将使候选人有必要的保护时间，专注于功能性MRI（fMRI）研究在原发性全身性肌张力障碍（PGD）的发展，并提供一个机会，成为精通与他的研究领域相关的新研究领域。在导师的指导下，候选人将在纵向临床研究和功能性磁共振技术方面发展独立的研究技能和能力。这种指导的培训经验将导致他在接下来的几年里成为一名独立的，以患者为导向的翻译研究者。本研究的总体目标是使用功能磁共振成像在休息和特定的感觉和运动任务的性能，旨在澄清原发性全身性肌张力障碍（PGD）的发展的病理生理学基础，并发生与PGD的症状改善作为一个结果，在苍白球（GPi）的内部部分的刺激的变化。PGD是一种始于儿童和年轻人的疾病，导致运动控制的逐渐丧失，同时保留智力功能。患者通常严重残疾，无法照顾自己，并且通常对药物治疗反应不佳。世界各地的一些中心，包括我们自己的中心，现在都在使用脑深部电刺激（DBS）来治疗肌张力障碍。虽然它已越来越多地被证明是一种有效的治疗方法，肌张力障碍运动减少> 50%，但PGD发展的病理生理学基础和DBS改善PGD的机制都不清楚。这些研究将提供深入了解肌张力障碍的病理生理学，以及脑深部电刺激产生其益处的机制。本研究的结果将提供一个更清楚的了解激活模式在皮质下和皮质结构的PGD相比，正常对照组，以及这些激活模式如何随着时间的推移在GPi DBS。激活模式的时间变化将与患者的症状相关联，以阐明它们与患者的神经病学的关系。这些数据不仅将推进肌张力障碍的治疗，而且还将提供有关DBS工作机制的重要新数据。这些信息可能对DBS目前正在探索的其他神经系统和精神疾病的治疗有用。

DESCRIPTION (provided by applicant): This Award will allow the candidate the protected time necessary to focus his efforts on the development of functional MRI (fMRI) research in Primary Generalized Dystonia (PGD) and provide an opportunity to become well-versed in new areas of study relevant to his research field. Under the guidance of his mentors, the candidate will develop independent research skills and abilities in longitudinal clinical investigations and functional magnetic resonance techniques. This mentored training experience will lead to his establishment as an independent, patient-oriented translational investigator in the following years. The overall goal of this study is to use fMRI both at rest and during the performance of specific sensory and motor tasks designed to clarify the pathophysiological basis underlying the development of primary generalized dystonia (PGD), and the changes that occur associated with the symptomatic improvement in PGD as a result of stimulation in the internal segment of the globus pallidus (GPi). PGD is a disorder that begins in children and young adults, and leads to progressive loss of motor control, while sparing intellectual function. The patients are often significantly disabled and unable to care for themselves and often do not respond well to medical therapy. Select centers around the world, including our own, are now using deep brain stimulation (DBS) to treat dystonia. Although it has increasingly been demonstrated as an effective therapy with > 50% reduction in dystonic movements, neither the pathophysiological basis underlying the development of PGD nor the mechanism underlying its improvement with DBS is known. These studies will provide insight into both the pathophysiology of dystonia, and the mechanism by which deep brain stimulation produces its benefit. The results of this study will provide a more clear understanding of the activation patterns in subcortical and cortical structures in PGD compared to normal controls and how these activation patterns are changed over time during GPi DBS. The temporal changes in activation patterns will be correlated with the patients' symptoms to clarify their relationship to the patients' symptomatology. These data will not only advance the treatment of dystonia but will also provide important new data regarding the mechanism by which DBS works. This information may be useful for the treatment of other neurologic and psychiatric disorders for which DBS is now being explored.