Cortical and basal ganglia local field potentials in human movement disorders

人类运动障碍中的皮质和基底神经节局部场电位

• 批准号: 8038264
• 负责人: PHILIP Andrew STARR
• 金额: $ 33.12万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2013-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8038264
• 关键词: Abbreviations; Address; Affect; Analysis of Variance; Area; Basal Ganglia; Basal Ganglia Diseases; Behavioral; Bradykinesia; Brain; Cues; Deep Brain Stimulation; Disease; Dystonia; Effectiveness; Elbow; Electrocorticogram; Electrodes; Electromyography; Epilepsy; Essential Tremor; Frequencies; Functional disorder; Globus Pallidus; Goals; Hand; Human; Implant; Inpatients; Jaw; Joints; Knowledge; Lead; Location; Monitor; Motor; Motor Cortex; Movement; Movement Disorders; Neurologist; Neurons; Operative Surgical Procedures; Parkinson Disease; Parkinsonian Disorders; Pathology; Patients; Pattern; Persons; Presynaptic Terminals; Primary Dystonias; Property; Resolution; Rest; Scalp structure; Sensory; Shoulder; Somatosensory Evoked Potentials; Structure of subthalamic nucleus; Surface; Techniques; Thinking; Work; Wrist; arm; awake; base; brain electrical activity; comparison group; cranium; deep brain stimulator; density; foot; implantation; improved; novel; postsynaptic; programs; public health relevance; sensory cortex; sensory feedback; sensory system; theories; vibration

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.

描述（由申请人提供）：该项目的目的是通过研究人类的基底神经节和皮质局部田间电位（LFP）来提高对运动障碍的理解。 LFP代表突触前末端和突触后神经元中的同步亚阈值和上阈值活性。 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). 但是，该框架留下了未解决的问题。可以通过与没有运动障碍的受试者进行比较来确认β振荡假设吗？ PD的过多β振荡是否与基底神经节的其他运动障碍有关？运动皮层中也存在异常的β振荡，反映了基底神经节 - 丘脑皮质（BGTC）电路的网络特性吗？在这里，我们通过比较基础神经节障碍（PD和原发性肌张力障碍）患者的原发运动（M1）和原发性感觉（S1）皮质LFP，以及两个没有基础神经节病理学的比较组（Essentar Tremor（ET）和癫痫病）。运动障碍患者在经历DBS电极的清醒位置时进行了研究。在进行住院视频监测时，研究了癫痫患者。我们假设PD和Dystonia均具有广泛的β带皮质活性的特征，将这些疾病与ET和没有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，该肌张力障碍的研究次数少于PD。我们的方法是在M1和S1中同时记录STN和皮质LFP。我们假设：（1）肌张力障碍患者在自愿运动期间的STN中的β高（21-30）和低γ（30-55 Hz）振荡，而PD患者则主要具有低β（13-20 Hz）活性，尤其是在休息时。 2.）在M1和S1以及STN皮层相干性中也可以看到类似的模式。 3.）在激活感觉反馈的条件下，将复制肌张力障碍的运动异常。该提案的新特征是在运动障碍中使用电皮质学，将新靶标的引入肌张力障碍研究以及通过这两个地区的同时LFP记录来分析皮质 - 巴萨神经节相互作用。拟议的工作应扩大PD的“振荡假设”的框架，以包括其他主要运动障碍，改善DBS中选择刺激频率的基本原理，并可以为PD和Dystonia的皮质疗法提供基础。 公共卫生相关性：这项研究的目的是提高对帕金森氏病和肌张力障碍患者的脑电活动异常的理解。通过植入脑刺激剂对患者进行常规神经外科治疗，对患者进行常规神经外科治疗。在这项研究中获得的知识可能会导致比现在可用的知识更简单的手术疗法，并且可以通过了解如何更有效地对植入的大脑刺激剂进行编程，从而帮助神经病学家改善现有治疗方法。