Deep Brain Stimulation Using Microactuated Microprobes

描述（由申请人提供）：脑深部电刺激（DBS）是FDA批准的治疗原发性震颤和帕金森病的疗法，可长期缓解症状。它也是一种很有前途的治疗癫痫，运动障碍，强迫症和焦虑症。然而，由于难以精确定位刺激微电极，DBS治疗的功效显著降低。此外，通常需要在麻醉下进行长时间手术，包括电生理观察和放射学方法，以确认微电极位置。该项目的总体目标是开发一种微驱动微电极技术，该技术将使微电极在植入深部脑刺激后在行为动物中精确定位和移动。所提出的技术将提供一种前所未有的能力，以监测单一神经元电活动和行为相关的刺激在未麻醉的动物，而刺激电极正朝着所需的目标结构。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，用于精确定位和最佳刺激的黑质纹状体束在帕金森病大鼠模型的行为。必须克服的主要技术障碍是（i）。开发具有足够翻译能力的微致动器技术，以足够的位移精度询问啮齿动物的深部脑结构（ii）。使用微驱动微电极阵列在黑质-纹状体束中开发和优化综合刺激和记录能力。这项技术将在帕金森病的啮齿动物模型中进行测试和验证。 这项技术的成功开发将使脑深部电刺激的微电极植入精确，从而在更短的手术时间内实现安全有效的治疗。这项技术的未来发展可能导致药物或基因治疗的有效载体。

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.