Control of Repetitive Movement in Parkinson's Disease

描述（由申请人提供）：帕金森病（PD）在美国影响超过100万人。这些患者的自主运动以缓慢和运动幅度减小（运动迟缓）和缺乏自发的意志运动（运动迟缓）为特征。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中表现得最为明显，当外界提示被移除时，情况会恶化。本项目的目的是研究PD患者重复性运动受损的机制，以及两种最成功的PD治疗方法左旋多巴和丘脑下核高频刺激（STN-DBS）对这些机制的影响。第一个具体目标是研究运动线索（外部和内部线索）、频率（0.8 Hz和2 Hz）和左旋多巴对重复手指运动和运动相关皮层振荡的影响，这些影响是用脑电图（EEC）记录的。第二个具体目标是检查相同因素（提示、运动频率和左旋多巴）对清醒PD患者基底神经节（一组深部脑结构）运动相关活动模式的影响。将通过植入PD患者丘脑下核（STN）的电极记录基底神经节的活动。第三个具体目标是比较左旋多巴和STN-DBS对运动相关皮层振荡的影响。运动皮质活动的高分辨率脑电图记录将用于检查这些治疗如何影响重复运动。这些实验将首次研究PD患者重复性运动中运动表现恶化的神经生理学基础，以及左旋多巴和STN-DBS改善这些运动表现的皮层机制。这个项目的长期目标有两个：开发改进的康复技术，利用促进运动表现的因素，开发改进的脑深部刺激方法。基底神经节功能障碍与包括PD在内的多种神经系统疾病有关，影响了很大一部分美国人口。这个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产生运动紊乱中的作用，并有助于开发改进的治疗方法。

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.