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

阐明对齿状红丘脑束成功进行深部脑刺激后特发性震颤结构和功能连接变化的暂时性

• 批准号: 10252925
• 负责人: ALBERT J FENOY
• 金额: $ 45万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-15 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10252925
• 关键词: Acute; Adult; Ataxia; Atlases; Axon; Biological Markers; Blood flow; Brain; Brain region; Cell Nucleus; Cerebellum; Chronic; Clinical; Contralateral; Deep Brain Stimulation; Dentate nucleus; Development; Diffuse; Diffusion; Disease; Electrocorticogram; Electrophysiology (science); Essential Tremor; Evolution; Exhibits; Failure; Fiber; Functional Magnetic Resonance Imaging; Functional disorder; Future; Gait Ataxia; Goals; Image; Implant; Individual; Knowledge; Lesion; Limb Ataxia; Maps; Mediator of activation protein; Metabolic; Methodology; Methods; Modeling; Motor; Motor Cortex; Movement Disorders; Network-based; Operative Surgical Procedures; Output; Pacemakers; Paresthesia; Parietal; Parietal Lobe; Pathology; Pathway interactions; Patient Selection; Patients; Periodicity; Pharmaceutical Preparations; Positron-Emission Tomography; Red nucleus structure; Rest; Role; Structure; Symptoms; Techniques; Thalamic structure; Therapeutic; Therapeutic Intervention; Time; Travel; Tremor; Work; base; clinical effect; effective therapy; imaging modality; improved; innovation; insight; novel; prospective; recruit; response; serial imaging; side effect; theories; tool; tractography; treatment response; treatment strategy; visual motor

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.

项目摘要 基本震颤（ET）的症状是成人最常见的运动障碍，是认真的 禁用，仅通过药物略有改善。随着震颤的控制大大改善了 将深脑刺激（DBS）用于丘脑的腹膜核（VIM），沿A的节点 ET中异常节奏输出的电路，从小脑齿状核向对侧红色传播 细胞核和皮质通过dentato-rubro-丘脑道（DRTT）。扩散成像的最新进展已导致 拖拉技术的开发，其中纤维区的结构连通性（例如Drtt） 可以说明说明，然后如我们所示，在DBS手术期间直接靶向以获得出色的临床效果。 尽管这种新颖的靶向方法和初始震颤的改善，但侧面的发展 多年的慢性刺激后，诸如进行性步态共济失调和逐渐减弱的效果表明了这一事实 基本震颤的病理学知之甚少。网络的这种不完整的知识 慢性刺激在ET中的影响是一个主要障碍，需要通过理解 随着时间的推移，小脑 - 丘脑 - 皮层（CTC）网络的连通性的功能障碍和调制。 静止状态功能MRI（RSFMRI）已成为探索功能连接的强大工具 在不同的大脑区域之间，并改善了ET作为基于网络的疾病的观念 电机电路，包括顶侧敏机加工皮层；但是，比较前和DBS 尚未执行。正电子发射断层扫描（PET）的使用与共同副作用有关 慢性DBS后小脑代谢变化；但是，RSFMRI看到的相关更改尚不清楚。 我们的长期目标是了解DRTT的刺激如何随着时间的推移引起网络级别的影响。我们的 中心假设是DRTT的结构和功能连通性与临床相关 以时间依赖的方式对DBS的反应。为了追求这一假设，我们将招募新的ET患者 已经进行了DBS并执行成像分析以阐明刺激的影响 并定义DRTT连接。在AIM 1中，我们试图通过使用DRTT的结构连通性 拖拉方法和随着时间的扩散性变化与临床反应和/或共济 副作用。在AIM 2中，我们寻求通过使用串行获得的RSFMRI检测DBS引起的功能网络变化 在ON/OFF状态下，我们将跟踪随时间变化的连接变化的演变。在AIM 3中，我们寻求 为了确认AIM 1和2中鉴定的震颤的皮质介体，通过使用术中的皮质摄影 在DBS期间。使用新颖的靶向技术和跨DBS串行成像的创新组合 各国将促进我们对更大网络对DB的响应的理解，这对于开发更多的网络响应至关重要 特定刺激纤维以改善反应并避免ET中的副作用。