Time Course of Subthalamic Deep Brain Stimulation

这是一份K-23以病人为导向的职业发展奖的申请表，名为《时代》 丘脑深部刺激的进程。“被提议的研究的主要目标是描绘 丘脑底核深部脑刺激治疗新机制。STN DBS 是一种高效、广泛使用的帕金森氏病(PD)治疗方法。STN DBS的疗效观察 在刺激停止后坚持一段时间。STN DBS的作用机制，特别是这种 “持久”的影响，还没有被很好地理解。 提出了实验，其中STN DBS对PD症状的影响随着时间的推移而被测量 在植入STN刺激器治疗PD的患者中打开和关闭DBS，以测试 认为持续效应的机制不同于“即时”效应的假说 刺激。实验与神经元生物物理学的计算机模拟相结合，以测试 假设DBS诱导的突触可塑性可以解释滞留效应。 应聘者在神经学/运动障碍方面接受过临床培训，包括帕金森氏症和星展银行，包括 STN DBS for PD。他在动物模型中接受过运动神经生理学方面的研究培训。的目标是 拟议的职业发展奖是使他能够将他的临床和研究培训结合在一起 以病人为中心的研究计划，重点是使用脑刺激来研究运动障碍 并改进治疗，使用计算机建模技术将细胞过程与临床联系起来 治疗效果明显。为此，应聘者寻求1)基底神经节生理学和 DBS的生物物理学；2)计算机建模技术；3)以病人为中心的研究。

This is an application for a K-23 Mentored Patient Oriented Career Development award entitled "Time Course of Subthalamic Deep Brain Stimulation." The primary goal of the proposed research is to delineate new therapeutic mechanisms of action of Subthalamic nucleus deep brain stimulation (STN DBS). STN DBS is a highly effective, widely used treatment for Parkinson's disease (PD). Therapeutic effects of STN DBS persist for some time after stimulation ceases. Mechanisms of action of STN DBS, particularly of such "persistent" effects, are not well understood. Experiments are proposed in which STN DBS effects on PD symptoms are measured over time when STN DBS is turned on and off in patients with STN stimulators implanted for treatment of PD, to test the hypothesis that the mechanism of lingering effects differs from that of "immediate" effects seen during stimulation. Experiments are integrated with a computer simulation of neuronal biophysics to test the hypothesis that DBS-induced synaptic plasticity accounts for lingering effects. The candidate has clinical training in neurology/movement disorders, including PD and in DBS, including STN DBS for PD. He has research training in motor neurophysiology, in animal models. The goal of the proposed Career Development Award is to enable him to merge his clinical and research training in a program of patient oriented research focusing on the use of brain stimulation to study movement disorders and improve their treatment, using computer modeling techniques to relate cellular processes to clinical observable therapeutic effects. To this end, the candidate seeks training in 1) basal ganglia physiology and biophysics of DBS, 2) computer modeling techniques 3) patient oriented research.