Cortical and basal ganglia local field potentials in human movement disorders

描述（由申请人提供）：本项目的目标是通过对人类基底神经节和皮质局部场电位（LFP）的研究，促进对运动障碍病理生理学的理解。LFP代表突触前末梢和突触后神经元中的同步阈下和阈上活动。最近对帕金森氏病（PD）丘脑底核（STN）LFP的研究提出了一个新的假设：帕金森氏症运动迟缓是由于过度的基底神经节同步振荡活动在β频率范围（13-30 Hz），β振荡的抑制是帕金森氏症脑深部电刺激（DBS）有效性的机制。 然而，这一框架留下了一些没有回答的问题。β振荡假说是否可以通过与没有运动障碍的受试者进行比较来证实？过度的β振荡是PD独有的，还是与基底神经节起源的其他运动障碍有关？运动皮层中是否也存在异常的β振荡，反映了基底节-丘脑皮层（BGTC）回路的网络特性？在这里，我们通过比较基底神经节疾病（PD和原发性肌张力障碍）患者的初级运动（M1）和初级感觉（S1）皮质LFP来解决这些问题，两个对照组没有基底神经节病变（特发性震颤（ET）和癫痫）。运动障碍患者进行研究，同时接受清醒的DBS电极放置。癫痫患者在接受住院视频监控时进行研究。我们假设PD和肌张力障碍的特征都是宽β带皮层活动，这将这些疾病与ET和无运动障碍的受试者区分开来。 我们的第二个主要目标是了解原发性肌张力障碍中的BGTC振荡，对它的研究比PD少。我们的方法是同时记录M1和S1的小脑和皮质LFP。我们假设：（1）肌张力障碍患者在自主运动期间在小脑中具有过量的高β（21-30）和低γ（30-55 Hz）振荡，而PD患者具有主要的低β（13- 20 Hz）活动，特别是在休息时。2.）在M1和S1以及STN-皮质相干性中观察到类似的模式。3.）第三章在感觉反馈被激活的条件下，将再现肌张力障碍中的运动相关异常。该建议的新功能是使用运动障碍的皮质电描记术，引入一个新的目标，肌张力障碍的研究，并通过同时LFP记录在这两个领域的皮质-基底神经节的相互作用的分析。拟议的工作应扩大PD的“振荡假说”的框架，包括其他主要的运动障碍，改善DBS的刺激频率的选择的理由，并可以为PD和肌张力障碍的皮质为基础的治疗提供依据。 公共卫生相关性：本研究的目的是提高对帕金森病和肌张力障碍等运动障碍患者异常脑电活动的理解。研究对象是通过植入脑刺激器接受常规神经外科治疗的患者。这项研究中获得的知识可能会导致比现在更简单的手术治疗，并可能帮助神经科医生通过了解如何更有效地编程植入式脑刺激器来改善现有的治疗方法。

DESCRIPTION (provided by applicant): The goal of this project is to advance the understanding of movement disorders pathophysiology through studies of basal ganglia and cortical local field potentials (LFPs) in humans. The LFP represents synchronized sub- and supra-threshold activity in presynaptic terminals and postsynaptic neurons. Recent studies of subthalamic nucleus (STN) LFPs in Parkinson's disease (PD) produced a novel hypothesis: that parkinsonian bradykinesia is due to excessive basal ganglia synchronized oscillatory activity in the beta frequency range (13-30 Hz), and that suppression of beta oscillations is the mechanism for the effectiveness of STN deep brain stimulation (DBS). However, this framework leaves unanswered questions. Can the beta oscillation hypothesis be confirmed by comparison to subjects without movement disorders? Are excessive beta oscillations unique to PD, or are they associated with other movement disorders of basal ganglia origin? Are abnormal beta oscillations present in motor cortex as well, reflecting a network property of the basal ganglia-thalamocortical (BGTC) circuit? Here, we address these questions by comparing primary motor (M1) and primary sensory (S1) cortex LFPs in patients with a basal ganglia disorder (PD and primary dystonia), with two comparison groups without basal ganglia pathology (essential tremor (ET) and epilepsy). Movement disorders patients are studied while undergoing awake placement of DBS electrodes. Epilepsy patients are studied while undergoing inpatient video monitoring. We hypothesize that PD and dystonia both are characterized by broad beta band cortical activity which distinguishes these disorders from ET and from subjects without movement disorders. Our second major goal is to understand BGTC oscillations in primary dystonia, which has been less studied than PD. Our approach is simultaneous recording of STN and cortical LFPs in M1 and S1. We hypothesize: (1) Dystonic patients have an excess of high beta (21-30) and low gamma (30-55 Hz) oscillations in the STN during voluntary movement, while PD patients have predominant low beta (13- 20 Hz) activity, particularly at rest. 2.) Similar patterns are seen in M1 and S1, and in STN-cortical coherence. 3.) Movement related abnormalities in dystonia will be reproduced under conditions in which sensory feedback is activated. The novel features of this proposal are the use of electrocorticography in movement disorders, the introduction of a new target, STN, into the study of dystonia, and the analysis of cortex-basal ganglia interactions through simultaneous LFP recording in both areas. The proposed work should expand the framework for the "oscillation hypothesis" of PD to include the other major movement disorders, improve the rationale for choice of stimulation frequencies in DBS and could provide a basis for cortically based therapies for PD and dystonia. PUBLIC HEALTH RELEVANCE: The goal of this study is to improve the understanding of abnormal brain electrical activity in persons with movement disorders such as Parkinson's disease and dystonia. Patients are studied while undergoing routine neurosurgical treatment of their disorder by implantation of brain stimulators. Knowledge gained in this study may lead to simpler surgical therapies than those now available, and may help neurologists improve existing treatments by understanding how to program implanted brain stimulators more effectively.