Time Course of Subthalamic Deep Brain Stimulation

这是申请 K-23 指导的以患者为导向的职业发展奖，题为“时间” 丘脑深部脑刺激过程。”拟议研究的主要目标是描绘 丘脑底核深部脑刺激（STN DBS）的新治疗作用机制。星展银行 是一种高效、广泛使用的帕金森病 (PD) 治疗方法。 STN DBS 的治疗效果 刺激停止后仍会持续一段时间。 STN DBS 的作用机制，特别是此类 “持久”效应尚未得到很好的理解。 提出了实验，其中当 STN 时，随着时间的推移测量 STN DBS 对 PD 症状的影响。 在植入 STN 刺激器治疗 PD 的患者中打开和关闭 DBS，以测试 假设挥之不去的影响机制与“直接”影响的机制不同 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 DBS 诱导的突触可塑性是造成挥之不去的影响的假设。 候选人接受过神经学/运动障碍方面的临床培训，包括 PD 和 DBS，包括 用于 PD 的 STN DBS。他接受过运动神经生理学和动物模型方面的研究培训。的目标 拟议的职业发展奖旨在使他能够将临床和研究培训结合起来 以患者为中心的研究计划，重点是利用大脑刺激来研究运动障碍 并改进他们的治疗，使用计算机建模技术将细胞过程与临床联系起来 可观察到的治疗效果。为此，候选人寻求以下方面的培训：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）以患者为导向的研究。

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.