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

一种新的电气装置

• 批准号: 8502954
• 负责人: Michael J Cima
• 金额: $ 112.77万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-04-01 至 2018-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8502954
• 关键词: Address; Affect; American; Animal Model; Animals; Anxiety; Anxiety Disorders; Attenuated; Behavior; Behavioral; Biocompatible; Biocompatible Coated Materials; Biocompatible Materials; Biological Markers; Biology; Biomedical Engineering; Brain; Brain region; Caliber; Cannulas; Catheters; Chemical Engineering; Chemical Stimulation; Chemicals; Chemistry; Chronic; Clinical; Collaborations; Cues; Deep Brain Stimulation; Defect; Deposition; Detection; Development; Development Plans; Devices; Disease; Dose; Drug Delivery Systems; Electric Stimulation; Electrical Stimulation of the Brain; Electrodes; Electrophysiology (science); Engineering; Ensure; Feedback; Functional disorder; Glass; Gliosis; Goals; Hour; Implant; In Vitro; Infusion procedures; Injection of therapeutic agent; Kinetics; Laboratories; Mechanics; Mental disorders; Metals; Methods; Microfabrication; Modeling; Mood Disorders; Moods; Nature; Neuromodulator; Neuropharmacology; Neurosciences; Neurosciences Research; Oral; Performance; Peripheral; Pharmaceutical Preparations; Plant Roots; Property; Pump; Regimen; Research; Resolution; Science; Solutions; Stimulus; Surface; Technology; Testing; Therapeutic; Time; Tissues; Toxic effect; Treatment Efficacy; Work; awake; base; behavior change; biomaterial compatibility; design; implantable device; implantation; improved; in vivo; local drug delivery; minimally invasive; nanolitre; neural circuit; nonhuman primate; public health relevance; relating to nervous system; small molecule; spatiotemporal; tool; treatment strategy; vapor

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.

描述（由申请人提供）：本研究的目的是让麻省理工学院的化学工程师、材料工程师和神经科学家团队开发一种组合式微插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且令人衰弱的疾病。新兴的想法是，这些疾病实际上根源于神经回路活动的破坏，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。治疗的管理在空间和时间上都过于粗糙，无法适当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插管装置，能够同时输注多种治疗药物，以及电刺激和实时化学传感。该设备将以微创方式进行微制造，但又足够耐用，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样化的刺激（电和化学）能力的结合应该可以提高我们以适当的动力学调节特定神经回路活动的能力。该提案以及组建的研究团队结合了微制造、材料工程、化学、生物学和神经科学的不同领域。我们的具体目标总结如下：1）设计神经调节疗法的故障安全传递。这一目标将确保准确且可重复地输送所需剂量。 2) 评估通过金属沉积和化学功能化提高装置结构完整性和生物相容性的方法。神经刺激电极已被证明会因神经胶质增生而在长时间植入后丧失功能。我们提出的研究将开发一种通过延缓神经胶质增生来延长设备功能的方法。 3）将外围组件（储液器、泵和管道）细化为适合长期植入的独立单元。这将增加所提出设备的实用性，并代表向临床使用迈出的重要一步。 4）通过所提出的设备提供刺激（电和化学），展示焦虑和情绪障碍动物（非人类灵长类动物）模型的行为变化。 5) 证明行为改变是所提出的装置调节神经回路活动的结果。我们的目标是证明该设备在体内的故障保护功能，并研究其通过精确的时空控制改善焦虑和情绪障碍行为的能力。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。这代表了临床应用的重要一步，其中致焦虑刺激通常是未知且不可预测的。