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

这一奖项将给予候选人必要的保护时间，以便集中精力开发 功能磁共振成像(FMRI)在原发性泛发性肌张力障碍(PGD)中的研究 精通与他的研究领域相关的新研究领域。在他的导师的指导下， 候选人将发展独立的研究技能和能力，在纵向临床调查和 功能性磁共振技术。这种有指导的培训经历将导致他的成立 在接下来的几年里，作为一名独立的、以患者为导向的翻译调查员。 这项研究的总体目标是在休息时和在特定感觉的执行过程中使用功能磁共振成像 和运动任务，旨在阐明小儿麻痹症发生的病理生理基础 全身性肌张力障碍(PGD)，以及与症状改善相关的变化 PGD是刺激苍白球内段(GPI)的结果。PGD是一种疾病， 开始于儿童和年轻人，并导致运动控制的进行性丧失，同时保留智力 功能。这些患者往往严重残疾，不能照顾自己，而且通常不会 对药物治疗反应良好。世界各地的精选中心，包括我们自己的中心，现在都在使用深度 脑刺激(DBS)治疗肌张力障碍。尽管它越来越多地被证明是一种有效的 肌张力障碍运动减少50%的治疗，既不是基础的病理生理学基础 PGD的发展及其与DBS改善的潜在机制尚不清楚。 这些研究将为肌张力障碍的病理生理学和机制提供洞察力。 深部脑刺激产生的益处。这项研究的结果将为我们提供更清晰的 与正常对照对PGD皮质下和皮质结构激活模式的认识 控件以及这些激活模式在GPI DBS期间随时间变化的方式。时间上的变化 激活模式将与患者的症状相关联，以澄清它们与患者的关系 症状学。这些数据不仅将促进肌张力障碍的治疗，而且还将为 关于星展银行运作机制的新数据。这一信息可能有助于治疗 星展银行目前正在探索的其他神经和精神障碍。

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 pathophysiojogicalbasis 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.