A New Device for Electrical & Chemical Modulation of Pathological Neural Activity

描述(申请人提供)：这项研究的目的是由麻省理工学院的化学工程师、材料工程师和神经学家组成的团队开发一种微型插管和脑深部电刺激相结合的设备，用于治疗焦虑和情绪障碍。焦虑和情绪障碍是困扰数百万美国人的常见和令人衰弱的疾病。新出现的想法是，这些障碍实际上根源于神经回路活动的中断，而不是任何一个区域的缺陷。目前的治疗方法包括口服和静脉注射。无论是在空间上还是在时间上，治疗药物的管理都太粗糙了，不能适当地减弱神经回路中的动态活动。我们的目标是开发一种植入式微导管装置，能够同时输注多种治疗药物，以及电刺激和实时化学传感。这种装置将以微创的方式进行制造，但耐用到足以扩展到非人类灵长类动物的用途。精确的解剖学定位和不同的刺激(电和化学)能力相结合，应该会提高我们通过适当的动力学调节特定神经回路活动的能力。这项提案和组建的研究团队结合了微制造、材料工程、化学、生物学和神经科学等不同领域。我们的具体目标概括如下：1)设计神经调节疗法的故障安全递送。这一目标将确保准确和可重复地提供所需剂量。2)评价通过金属沉积和化学功能化来提高器件结构完整性和生物相容性的方法。神经刺激电极已被证明在长时间植入后因胶质细胞增生症而丧失功能。我们建议的研究将开发一种通过延缓胶质细胞增生来延长设备功能的方法。3)将外围部件(储液器、泵和油管)细化为适合长期植入的独立部件。这将增加拟议设备的实用性，并代表着迈向临床应用的重要一步。4)在焦虑和情绪障碍的动物(非人类灵长类)模型中，通过所提出的装置提供刺激(电和化学)来演示行为变化。5)证明行为改变是由所提出的装置调节神经回路活动的结果。我们的目标是，在体内演示该设备的故障安全功能，并研究其通过精确的时空控制改善基于焦虑和情绪障碍的行为的能力。在最后一步，我们计划开发基于反馈的设备激活，通过实时检测病理活动。这是迈向临床应用的重要一步，在临床上，引起焦虑的刺激往往是未知和不可预测的。

DESCRIPTION (provided by applicant): The purpose of this study is for a team of chemical engineers, materials engineers and neuroscientists at MIT to develop a combined micro-cannula and deep brain electrical stimulation device for the treatment of anxiety and mood disorders. Anxiety and mood disorders are common and debilitating disorders that afflict millions of Americans. The emerging thought is that these disorders are actually rooted in disruptions in activity across neural circuits, as opposed to defects in any one region. Current treatments comprising oral and i.v. administration of therapeutics are too coarse, both spatially and temporally, to appropriately attenuate the dynamic activity across neural circuits. Our goal is to develop an implantable micro-cannula device that is capable of simultaneous infusion of multiple therapeutics, as well as electrical stimulation and real time chemical sensing. This device will be micro-fabricated in such a way as to be minimally invasive, yet durable enough to be scaled to non-human primate use. The combination of precise anatomical targeting and diverse stimulatory (electrical & chemical) capabilities should improve our ability to modulate activity across specific neural circuits with the appropriate kinetics. This proposal, and the assembled research team, combines the varied fields of micro-fabrication, materials engineering, chemistry, biology and neuroscience. Our specific goals are summarized as follows: 1) Design for failsafe delivery of neuro-modulatory therapeutics. This aim will ensure that the desired doses are delivered accurately and reproducibly. 2) Evaluate methods of improving the structural integrity and biocompatibility of the device via metal deposition and chemical functionalization. Neuro-stimulatory electrodes have been shown to lose function over prolonged periods of implantation due to gliosis. Our proposed studies will develop a method for prolonging device function by retarding gliosis. 3) Refine the peripheral components (reservoir, pump and tubing) to be a stand-alone unit suitable for chronic implantation. This will increase the utility of the proposed device, as well as represent an important step towards clinical usage. 4) Demonstrate behavior change in animal (non-human primate) models of anxiety and mood disorders by delivering stimulation (electrical & chemical) via the proposed device. 5) Demonstrate that the behavioral change is a result of modulating neural circuit activity by the proposed device. Our aim is to, demonstrate the failsafe function of the device in vivo and investigate its capability to ameliorate anxiety and mood disorder based behaviors via precise spatiotemporal control. In a final step we plan to develop feedback based activation of the device by real time sensing of pathological activity. This represents an important step towards clinical usage where anxiogenic stimuli are frequently unknown and un-predictable.