Time Course of Subthalamic Deep Brain Stimulation

描述（由申请人提供）：这是一份申请K23指导患者导向职业发展奖的申请，题为“丘脑下深部脑刺激时间课程”。本研究的主要目的是描述丘脑下核深部脑刺激（STN DBS）新的治疗机制。STN DBS是一种高效且广泛应用于帕金森病（PD）的治疗方法。STN DBS的治疗效果在刺激停止后仍持续一段时间。STN - DBS的作用机制，特别是这种“持续”效应的机制，还没有得到很好的理解。我们提出了一些实验，在为治疗PD而植入STN刺激器的患者中，随着时间的推移，在STN DBS打开和关闭时，测量STN DBS对PD症状的影响，以检验挥之不去的效应机制不同于刺激期间看到的“即时”效应的假设。实验与神经元生物物理学的计算机模拟相结合，以验证dbs诱导的突触可塑性是挥之不去的影响的假设。候选人接受过神经病学/运动障碍（包括PD）和DBS（包括PD的STN DBS）方面的临床培训。他接受过运动神经生理学和动物模型方面的研究训练。拟议的职业发展奖的目标是使他能够将他的临床和研究培训合并到一个以患者为导向的研究项目中，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观察到的治疗效果联系起来。为此，候选人寻求1)基底神经节生理学和DBS生物物理学方面的培训，2)计算机建模技术，3)以患者为导向的研究。

DESCRIPTION (provided by applicant): This is an application for a K23 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.