Deep Brain Stimulation Using Microactuated Microprobes

描述(申请人提供)：脑深部刺激(DBS)是FDA批准的一种治疗特发性震颤和帕金森氏症的方法，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有前途的疗法。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，通常是必要的，以确定微电极的位置。这一拟议项目的总体目标是开发一种微驱动微电极技术，该技术将使植入脑深部刺激后行为动物的微电极精确定位和移动。这项拟议的技术将提供前所未有的能力，在未麻醉的动物中监测单个神经元的电活动和与刺激相关的行为，同时刺激电极正朝着所需的目标结构移动。上述能力有望极大地提高植入微电极的DBS的精度、有效性和安全性。 具体地说，我们建议开发一种热微执行器和相关的微电极技术，用于精确定位和最佳刺激帕金森病大鼠模型的黑质-纹状体束。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致动器技术，以足够精确的位移来询问啮齿类动物的脑深部结构(Ii)。使用微驱动微电极阵列开发和优化黑质纹状体束的综合刺激和记录能力。建议的技术将在帕金森氏症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微电极植入脑深部刺激变得精确，从而以更短的手术时间实现安全有效的治疗。这项技术的未来发展可能会带来一种高效的药物或基因治疗载体。

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.