Cortical and basal ganglia local field potentials in human movement disorders

描述(申请人提供)：这个项目的目标是通过对人类基底节和皮质局部场电位(LFP)的研究来促进对运动障碍病理生理学的理解。LFP代表突触前终末和突触后神经元中同步的阈值下和阈值上的活动。最近对帕金森病(PD)丘脑底核(STN)LFP的研究提出了一个新的假说：帕金森病运动迟缓是由于在β频率范围(13-30赫兹)基底节同步振荡活动过度所致，抑制β振荡是STN脑深部刺激(DBS)有效的机制。然而，这个框架留下了一些悬而未决的问题。通过与没有运动障碍的受试者进行比较，可以证实β振荡假说吗？过度的β振荡是帕金森病独有的吗？还是与其他起源于基底节的运动障碍有关？运动皮质中是否也存在异常的β振荡，反映了基底节-丘脑皮质(BGTC)回路的网络特性？在这里，我们通过比较患有基底节疾病(PD和原发性肌张力障碍)的患者的初级运动(M1)和初级感觉(S1)皮质LFP与两个没有基底神经节病变(特发性震颤(ET)和癫痫)的对照组来解决这些问题。对运动障碍患者在清醒状态下放置DBS电极进行研究。癫痫患者在接受住院视频监护的同时进行研究。我们假设帕金森病和肌张力障碍都是以宽β带皮质活动为特征的，这将这些疾病与ET和非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，这方面的研究比帕金森病少。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时STN中高β(21-30)和低伽马(30-55赫兹)振荡过多，而帕金森病患者主要是低贝塔(13-20赫兹)活动，尤其是在静息状态。2.)在M1和S1以及STN-皮质连贯性中也可以看到类似的模式。3.)在感觉反馈被激活的情况下，肌张力障碍的运动相关异常将被重现。这一建议的新特点是在运动障碍中使用皮质脑电图术，在肌张力障碍的研究中引入新的靶点STN，并通过同时记录两个区域的LFP来分析皮质-基底节的相互作用。拟议的工作应扩大帕金森病“振荡假说”的框架，将其他主要运动障碍包括在内，改进DBS刺激频率选择的理论基础，并可为帕金森病和肌张力障碍的皮质疗法提供基础。 公共卫生相关性：这项研究的目标是提高对帕金森氏症和肌张力障碍等运动障碍患者异常脑电活动的理解。患者在接受通过植入脑刺激器进行常规神经外科治疗的同时进行研究。在这项研究中获得的知识可能会导致比目前可用的更简单的手术治疗，并可能帮助神经科医生通过了解如何更有效地对植入的脑刺激器进行编程来改进现有的治疗方法。

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.