Deep Brain Stimulation Using Microactuated Microprobes

描述（由申请人提供）：深部脑刺激 (DBS) 是 FDA 批准的一种治疗特发性震颤和帕金森病的疗法，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有前景的疗法。然而，由于难以精确定位刺激微电极，DBS 疗法的疗效显着降低。此外，通常需要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，以确认微电极的位置。该项目的总体目标是开发一种微驱动微电极技术，使微电极在植入深部脑刺激后能够在行为动物中精确定位和移动。所提出的技术将提供前所未有的能力，在刺激电极移向所需的目标结构时，监测与未麻醉动物的刺激相关的单个神经元电活动和行为。上述能力有望大大提高植入微电极的 DBS 的精度、有效性和安全性。 具体来说，我们建议开发一种热微致动器和相关的微电极技术，用于帕金森病大鼠模型中黑质纹状体束的精确定位和最佳刺激。必须克服的关键技术障碍是（i）。开发具有足够平移能力的微执行器技术，以足够的位移精度询问啮齿类动物的深层大脑结构 (ii)。使用微驱动微电极阵列开发和优化黑质纹状体束的集成刺激和记录能力。所提出的技术将在帕金森病的啮齿动物模型中进行测试和验证。 该技术的成功开发将使用于深部脑刺激的微电极植入变得精确，从而实现安全有效的治疗，并缩短手术时间。这项技术的未来发展可能会产生一种有效的药物或基因治疗输送工具。

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.