Time Course of Subthalamic Deep Brain Stimulation

这是一份名为“时间”的K-23指导患者导向职业发展奖的申请书 丘脑底脑深部电刺激术（Subthalamic Deep Brain Stimulation）“拟议研究的主要目标是描绘 丘脑底核脑深部电刺激（Subthalamic nucleus deep brain stimulation，DBS）的新治疗机制。STN DBS 是一种高效、广泛使用的帕金森病（PD）治疗方法。DBS的治疗效果 刺激停止后持续一段时间。的作用机制，特别是这种 “持久性”的影响，没有得到很好的理解。 提出了实验，在实验中，随着时间的推移，测量PDDBS对PD症状的影响， 在植入了用于治疗PD的脑电刺激器的患者中打开和关闭DBS，以测试 这一假说认为，延迟效应的机制不同于“即时”效应， 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诱导的突触可塑性解释了延迟效应。 候选人接受过神经病学/运动障碍（包括PD）和DBS（包括）的临床培训 为PD植入DBS。他在运动神经生理学和动物模型方面接受过研究训练。的目标 拟议的职业发展奖是使他能够将他的临床和研究培训合并在一个 一个以病人为导向的研究项目，重点是使用脑刺激来研究运动障碍 并改善他们的治疗，使用计算机建模技术将细胞过程与临床 可观察到的治疗效果。为此，候选人寻求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.