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

描述（由申请人提供）：本研究的目的是由麻省理工学院的化学工程师、材料工程师和神经科学家组成的团队开发一种联合微套管和深部脑电刺激装置，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使人衰弱的疾病。新出现的想法是，这些疾病实际上植根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治疗药物，在空间和时间上都过于粗糙，无法适当地减弱神经回路的动态活动。我们的目标是开发一种可植入的微型套管装置，能够同时输注多种治疗药物，以及电刺激和实时化学传感。这种装置将以一种微创的方式进行微型制造，但足够耐用，可以扩展到非人类灵长类动物的使用。精确的解剖定位和多种刺激（电和化学）能力的结合应该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。该方案和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各个领域。我们的具体目标总结如下：1)设计神经调节疗法的失效安全交付。这一目标将确保准确和可重复地提供所需剂量。2)评估通过金属沉积和化学功能化改善器件结构完整性和生物相容性的方法。神经刺激电极在长时间植入后由于神经胶质瘤而失去功能。我们提出的研究将开发一种通过延缓胶质瘤来延长装置功能的方法。3)将周边部件（储液器、泵和油管）完善为适合慢性植入的独立单元。这将增加所提出的设备的效用，并代表着临床使用的重要一步。4)通过提出的设备提供刺激（电和化学），证明动物（非人类灵长类动物）焦虑和情绪障碍模型的行为变化。5)证明行为改变是由所提出的设备调节神经回路活动的结果。我们的目标是在体内展示该设备的故障安全功能，并研究其通过精确的时空控制来改善焦虑和情绪障碍行为的能力。在最后一步，我们计划通过实时感知病理活动来开发基于反馈的设备激活。这是临床应用的重要一步，因为焦虑刺激通常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.