Control of Repetitive Movement in Parkinson's Disease

描述（由申请人提供）：帕金森病（PD）影响美国超过一百万人。这些患者的自主运动的特征是缓慢和运动幅度降低（运动迟缓）和缺乏自发性自主运动（运动不能）。运动迟缓的严重程度随着疾病的进展而增加，并对生活质量产生重大影响。运动迟缓在快速重复运动的表现中最为明显，并且在外部线索被移除时恶化。本项目的目的是研究导致PD患者重复运动受损的机制，以及两种最成功的PD治疗方法左旋多巴和丘脑底核高频刺激（STN-DBS）对这些机制的影响。第一个具体目标将检查运动提示（外部与内部提示），频率（0.8 Hz与2 Hz）和左旋多巴对重复手指运动和使用脑电图（EEC）记录的运动相关皮层振荡的影响。第二个具体目标将检查相同因素（提示，运动频率和左旋多巴）对清醒PD患者基底神经节（一组脑深部结构）运动相关活动模式的影响。基底神经节活动将由植入PD患者丘脑底核（subthalamic nucleus，简称TH）的电极记录。第三个具体目标将比较左旋多巴与STN-DBS对运动相关皮层振荡的影响。运动皮层活动的高分辨率EEC记录将用于检查这些治疗如何影响重复运动。这些实验将是第一次检查的神经生理学基础的运动性能的恶化，在PD和皮质机制，左旋多巴和STN-DBS提高这些运动的性能的重复运动。该项目的长期目标有两个方面：开发改进的康复技术，利用促进运动表现的因素，并开发改进的脑深部电刺激方法。基底神经节功能障碍与多种神经系统疾病（包括PD）有关，这些疾病影响了大部分美国人群。该项目与公共卫生有关，因为这些发现将更好地了解人类基底神经节及其在运动障碍产生中的作用，并有助于开发更好的治疗方法。

DESCRIPTION (provided by applicant): Parkinson's disease (PD) affects more than a million people in the United States. Voluntary movement in these patients is characterized by slowness and reduced movement amplitude (bradykinesia) and a lack of spontaneous volitional movement (akinesia). The severity of bradykinesia increases with disease progression and has a significant impact on quality of life. Bradykinesia is most evident during the performance of fast repetitive movements and worsened when external cues are removed. The purpose of this project is to examine the mechanisms contributing to impaired repetitive movement in patients with PD and the effects of the two most successful treatments for PD, levodopa and high frequency stimulation of the subthalamic nucleus (STN-DBS), on these mechanisms. The first specific aim will examine the effects of movement cueing (external vs. internal cues), frequency (0.8 Hz vs. 2 Hz) and levodopa on repetitive finger movement and movement-related cortical oscillations recorded using electroencephalography (EEC). The second specific aim will examine the effects of the same factors (cueing, movement frequency and levodopa) on the patterns of movement-related activity in the basal ganglia (a group of deep brain structures) of awake patients with PD. Basal ganglia activity will be recorded from electrodes implanted in the subthalamic nucleus (STN) of patients with PD. The third specific aim will compare the effects of levodopa versus STN-DBS on movement-related cortical oscillations. High-resolution EEC recordings of motor cortical activity will be used to examine how these treatments affect repetitive movement. These experiments will be the first to examine the neurophysiological basis for the deterioration of motor performance during repetitive movements in PD and the cortical mechanisms by which levodopa and STN-DBS improve the performance of these movements. The long-term goals of this project are twofold: to develop improved rehabilitation techniques that take advantage of factors that facilitate movement performance and to develop improved methods for the delivery of deep brain stimulation. Dysfunction of the basal ganglia is implicated in a variety of neurological disorders, including PD, that affect a large segment of the US population. This project is relevant to public health because the findings will provide a better understanding of the human basal ganglia and its role in the production of disordered movement and help to develop improved treatments.