Deep Brain Stimulation Using Microactuated Microprobes

描述（由申请人提供）：深部脑刺激（DBS）是FDA批准的治疗原发性震颤和帕金森病的治疗方法，可长期缓解症状。它也是治疗癫痫、运动障碍、强迫症和焦虑症的一种很有前景的疗法。然而，由于难以精确定位刺激微电极，DBS治疗的效果显著降低。此外，在麻醉下进行长时间的手术，包括电生理观察和放射学方法，通常需要确认微电极的位置。本项目的总体目标是开发一种微驱动微电极技术，该技术将使植入深部脑刺激后的行为动物的微电极精确定位和运动。该技术将提供前所未有的能力来监测单个神经元的电活动和行为相关的刺激，在未麻醉的动物，当刺激电极被移动到期望的目标结构。上述能力有望大大提高植入微电极DBS的精度、有效性和安全性。

DESCRIPTION (provided by applicant): Deep brain stimulation (DBS) is an FDA approved therapy for essential tremor and Parkinson's disease that provides symptomatic relief over long term. It is also a promising therapy for epilepsy, dyskinesias, obsessive-compulsive and anxiety disorder. However, the efficacy of the DBS therapy is significantly reduced due to difficulties in precisely localizing the stimulation microelectrodes. In addition, lengthy surgical sessions under anesthesia that include electrophysiological observations and radiological methods are often necessary to confirm the microelectrode location. The overall goal of this proposed project is to develop a microactuated microelectrode technology that will enable precise positioning and movement of microelectrodes in behaving animals after implantation for deep brain stimulation. The proposed technology will provide an unprecedented ability to monitor single neuronal electrical activity and behavioral correlates to stimulation in unanesthetized animals while the stimulation electrode is being moved towards the desired target structure. The above capability promises to greatly enhance the precision, efficacy and safety of DBS with implanted microelectrodes. Specifically, we propose to develop a thermal microactuator and associated microelectrode technology for precise positioning and optimal stimulation of the nigro-striatal bundle in behaving rat models of Parkinson's disease. The key technological barriers that must be overcome are (i). Developing microactuator technologies with enough translation capability to interrogate deep brain structures in rodents with sufficient precision in displacement (ii). Development and optimization of an integrated stimulation and recording capability in the nigro-striatal bundle using an array of microactuated microelectrodes. The proposed technology will be tested and validated in rodent models of Parkinson's disease. Successful development of this technology will make microelectrode implantation for deep brain stimulation precise leading to safe and an efficient therapy with shorter surgical times. Future developments of this technology could lead to an efficient delivery vehicle for drug or gene therapy.