Elucidating the Temporality of Structural and Functional Connectivity Changes in Essential Tremor after successful Deep Brain Stimulation to the dentato-rubro-thalamic tract

项目摘要 原发性震颤(ET)是成人最常见的运动障碍，其症状严重。 致残，仅通过药物治疗只能略有改善。震颤控制有了很大的改善 深部脑刺激(DBS)对丘脑腹中间核(Vim)的应用 ET中从小脑齿状核到对侧红核的异常节律性输出回路 通过齿状-红斑-丘脑束(DRTt)的核和皮质。扩散成像的最新进展导致了 对纤维束成像技术的发展，其中纤维束的结构连接性 可以说明，然后，如我们所示，在星形细胞瘤手术中直接靶向，可获得良好的临床效果。 然而，尽管有如此新颖的靶向方法和初步的震颤改善，Side的发展 在多年的慢性刺激后，渐进性步态共济失调和疗效减弱等效果表明， 人们对特发性震颤的病理知之甚少。对网络的这种不完整的了解 慢性刺激对ET的影响是一个主要障碍，需要通过了解 随着时间的推移，小脑-丘脑-皮质(CTC)网络的功能障碍和连接的调节。 静息状态功能磁共振成像(RsfMRI)已成为探索脑功能连通性的有力工具 并改进了ET作为一种基于网络的疾病的想法，而不局限于 运动回路，包括顶叶视觉运动处理皮质；然而，比较DBS前后 都没有被执行过。正电子发射断层扫描(PET)的使用将共济失调副作用与 慢性DBS后的小脑代谢变化；然而，rsfMRI所见的相关变化尚不清楚。 我们的长期目标是了解随着时间的推移，对DRTT的刺激如何导致网络层面的影响。我们的 中心假设是DRTt的结构和功能连通性与临床相关 以随时间变化的方式回复DBS。为了追求这一假设，我们将招募新的ET患者 已经接受了DBS检查，另外还进行了成像分析，以阐明刺激的影响 并定义DRTT连通性。在目标1中，我们试图通过使用以下公式来定义DRTT的结构连接性 与临床反应和/或共济失调相关的纤维束成像方法和随时间的弥散系数变化的比较 副作用。在目标2中，我们试图通过使用连续获得的rsfMRI来检测由于DBS引起的功能网络变化 在开/关状态下，我们将跟踪更改后的连接随时间的变化情况。在《目标3》中，我们寻求 术中脑电地形图确认术中AIMS 1和2中确定的震颤的皮质介质 在DBS期间。这一创新的组合使用了一种新的目标定位技术和跨DBS的连续成像 各国将促进我们对星展银行更大网络响应的理解，这对于制定更多 对纤维进行特异性刺激，以改善ET的反应并避免副作用。

Project Summary The symptoms of Essential Tremor (ET), the most common movement disorder in adults, are seriously disabling and are only marginally improved by medication alone. Tremor control has improved greatly with the use of deep brain stimulation (DBS) to the ventrointermediate nucleus (Vim) of the thalamus, a node along a circuit of abnormal rhythmic output in ET that travels from the cerebellar dentate nucleus to the contralateral red nucleus and cortex via the dentato-rubro-thalamic tract (DRTt). Recent advances in diffusion imaging have led to the development of tractography techniques where the structural connectivity of fiber tracts such as the DRTt can be illustrated and then, as we have shown, directly targeted during DBS surgery for excellent clinical effect. Despite such novel targeting methodology and initial tremor improvement, however, the development of side effects such as progressive gait ataxia and waning efficacy after years of chronic stimulation points to the fact that the pathology of essential tremor is poorly understood. Such incomplete knowledge of the network effects of chronic stimulation in ET is a major barrier that needs to be overcome through understanding the dysfunction and modulation of the connectivity of the cerebellar-thalamic-cortical (CTC) network over time. Resting state functional MRI (rsfMRI) has emerged as a powerful tool to explore the functional connectivity between different brain regions and has improved the idea of ET as a network-based disease not confined to the motor circuit, including parietal visuomotor processing cortices; however, comparisons pre- and post- DBS have not been performed. The use of positron emission tomography (PET) has correlated ataxic side effect with cerebellar metabolic changes after chronic DBS; however, associated changes seen with rsfMRI are unknown. Our long-term goal is to understand how stimulation of the DRTt causes network-level effects over time. Our central hypothesis is that structural and functional connectivity of the DRTt correlates with clinical response to DBS in a time-dependent fashion. In pursuit of this hypothesis, we will recruit new ET patients already undergoing DBS and additionally perform imaging analysis to elucidate the effects of stimulation and define DRTt connectivity. In Aim 1, we seek to define the structural connectivity of the DRTt by using tractography methods and compare over time diffusivity changes correlated with clinical response and/or ataxic side effect. In Aim 2, we seek to detect functional network changes due to DBS by using rsfMRI obtained serially in ON/OFF states, where we will track the evolution of altered connectivity changes over time. In Aim 3, we seek to confirm the cortical mediators of tremor identified in Aims 1 and 2 by use of intraoperative electrocorticography during DBS. This innovative combination of using a novel targeting technique and serial imaging across DBS states will advance our understanding of the larger network response to DBS, which is essential to develop more specific stimulation of fibers to improve response and avoid side effects in ET.