Cortical and basal ganglia local field potentials in human movement disorders

描述（由申请人提供）：本项目旨在通过研究人类基底神经节和皮质局部场电位（LFPs）来促进对运动障碍病理生理的理解。LFP代表突触前终末和突触后神经元同步的阈下和阈上活动。最近对帕金森病（PD）丘脑下核（STN） LFPs的研究提出了一个新的假设：帕金森运动迟缓是由于基底节区在β频率范围（13-30 Hz）过度的同步振荡活动，抑制β振荡是STN深部脑刺激（DBS）有效的机制。然而，这个框架留下了一些悬而未决的问题。通过与无运动障碍的受试者进行比较，β振荡假说能否得到证实？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？运动皮层是否也存在异常的β振荡，反映了基底神经节-丘脑皮质（BGTC）回路的网络特性？在这里，我们通过比较基底节节障碍（PD和原发性肌张力障碍）患者的初级运动（M1）和初级感觉（S1）皮层lfp，以及两个没有基底节节病理的对照组（特发性震颤（ET）和癫痫）来解决这些问题。运动障碍患者在接受DBS电极的清醒放置时进行研究。对癫痫患者进行住院视频监控的同时进行研究。我们假设PD和肌张力障碍都以宽β带皮层活动为特征，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的BGTC振荡，这方面的研究比PD少。我们的方法是同时记录M1和S1的STN和皮质lfp。我们假设：(1)肌张力障碍患者在自主运动期间，STN中有过量的高β(21-30)和低γ (30-55 Hz)振荡，而PD患者主要有低β (13- 20 Hz)活动，特别是在休息时。2)。类似的模式在M1和S1以及stn -皮质一致性中可见。3)。在感觉反馈被激活的情况下，肌张力障碍中与运动相关的异常将会重现。该建议的新颖之处在于在运动障碍中使用皮质电图，在肌张力障碍的研究中引入了一个新的靶点——STN，并通过同时记录两个区域的LFP来分析皮层-基底神经节的相互作用。本研究将扩展PD的“振荡假说”框架，将其他主要运动障碍纳入其中，完善DBS中刺激频率选择的理论基础，并为PD和肌张力障碍的皮质治疗提供基础。

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.