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. ? ? ?
