Control of Repetitive Movement in Parkinson's Disease

描述(由申请人提供)：帕金森氏症(PD)在美国有100多万人患病。这些患者的自主运动的特点是运动缓慢，运动幅度降低(运动迟缓)，缺乏自发的意志性运动(运动障碍)。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动作中最为明显，当外部线索被移除时，运动迟缓会恶化。本项目的目的是研究帕金森病患者重复运动障碍的机制，以及两种最成功的帕金森病治疗方法--左旋多巴和高频刺激丘脑底核(STN-DBS)对这些机制的影响。第一个具体目标将考察运动提示(外部和内部提示)、频率(0.8赫兹和2赫兹)和左旋多巴对使用脑电图仪记录的重复手指运动和与运动相关的皮质振荡的影响。第二个具体目标将考察相同因素(线索、运动频率和左旋多巴)对清醒帕金森病患者基底节(一组大脑深部结构)运动相关活动模式的影响。植入帕金森病患者丘脑底核(STN)的电极将记录下基底节的活动。第三个具体目标将比较左旋多巴和STN-DBS对运动相关皮质振荡的影响。运动皮质活动的高分辨率EEC记录将被用来检查这些治疗如何影响重复运动。这些实验将首次研究帕金森病患者重复运动中运动能力下降的神经生理学基础，以及左旋多巴和STN-DBS改善这些运动能力的皮质机制。该项目的长期目标有两个：开发改进的康复技术，利用促进运动能力的因素，以及开发改进的脑深部刺激方法。基底神经节功能障碍与包括帕金森病在内的各种神经疾病有关，这些疾病影响到美国人口的很大一部分。该项目与公共卫生有关，因为这些发现将提供对人类基底节及其在产生无序运动中的作用的更好了解，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.