Massively parallel microwire arrays for deep brain stimulation

用于深部脑刺激的大规模并行微线阵列

• 批准号: 9768582
• 负责人: Jun Ding
• 金额: $ 19.73万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2020-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9768582
• 关键词: Action Potentials; Acute; Address; Adverse effects; Anatomy; Area; Axon; Back; Basal Ganglia; Behavior; Brain; Calcium; Caliber; Cell Nucleus; Cell physiology; Cells; Clinical; Complex; Deep Brain Stimulation; Development; Devices; Disease; Dystonia; Electric Stimulation; Electrodes; Electrophysiology (science); Engineering; Epilepsy; Essential Tremor; FDA approved; Fiber; Freedom; Frequencies; Functional Imaging; Gilles de la Tourette syndrome; Glass; Image; Implant; Laser Scanning Microscopy; Major Depressive Disorder; Medical Device; Mental disorders; Metals; Methodology; Modernization; Movement Disorders; Nanotechnology; Neurologic; Neurons; Neurosciences; Obsessive-Compulsive Disorder; Parkinson Disease; Partner in relationship; Pathologic; Pattern; Performance; Physiologic pulse; Population; Protocols documentation; Role; Semiconductors; Site; Slice; Spatial Distribution; Specificity; Structure; System; Technology; Testing; Therapeutic; Therapeutic Effect; Tissues; Treatment Efficacy; base; deep brain stimulation array; density; design; experimental study; in vivo; innovation; insight; materials science; neural circuit; neural patterning; neuromechanism; neurophysiology; next generation; novel therapeutics; patch clamp; relating to nervous system; response; side effect; spatiotemporal; success; tool; two-photon

Project Summary: Deep brain stimulation (DBS) of basal ganglia is a well-established therapy for a variety of movement disorders, such as Parkinson's disease (PD) and essential tremor. In addition, it is also an emerging therapy for several psychiatric and neurological conditions, including epilepsy, major depression and obsessive- compulsive disorder (OCD). Despite its clinical success, there is a limited understanding of the neural mechanism behind DBS. Typical DBS system consists of a pulse generator, which deliveries the stimulation pulses via an implanted metal electrode. It is possible that DBS exerts is therapeutic effect through several different mechanisms including: (1) directly regulating neural firing at target nucleus; (2) activating nearby neuronal axons; (3) influencing passing long-range projection axons by activating antidromic and orthodromic action potentials. Because current DBS electrodes excite a large volume of neural tissue, it has been difficult to precisely determine which of these targets and mechanisms are responsible for the therapeutic effects of DBS. It is therefore critical to develop next generation DBS technology that enables selective targeting of different populations of neural structures, ideally with single neuron and single axon fiber precision. In addition, it would be beneficial to develop massively parallel DBS electrode arrays (10,000+ electrodes) to delivery different spatiotemporal patterns of activity that can be optimized for therapeutic efficacy. Recent methodological advances in material science and engineering now make such a device possible. This proposal describes a high-density, massively parallel single cell and single axon level stimulation device based on bundled microwires (BMWs): tens of thousands of metal-in-glass wires of less than 30 micrometers outer diameter. The approach will be revolutionary for neurophysiology, allowing break-through experiments both in movement disorders and fundamental understanding of neural circuit behavior. Here we propose: 1) To develop and characterize a BMW stimulation array and demonstrate its efficacy in acute brain slices and in vivo. 2) To couple the BMW array with modern semiconductor technology, demonstrating that driver circuit of a commercially available micro-display chip is capable of injecting patterned stimulation current through the BMW. We will validate the performance in brain slices and in vivo to test if different patterns of electrical stimulation reliably generate corresponding activity patterns in the brain slice and in vivo. Together, this proposal will bring neuroscience and engineering together to create the highest density electrophysiological stimulation interface ever made, and provide proof of principle demonstrations through the combined approaches of microwire stimulation, 2-photon functional imaging and classical electrophysiology. These microwire arrays would be a powerful tool, which would not only offer substantial clinical benefits for movement disorders, such as PD, but also provide mechanistic insights for DBS.   1

项目总结： 基底节深部脑刺激(DBS)是一种治疗各种运动的成熟疗法 疾病，如帕金森氏病(PD)和特发性震颤。此外，它也是一种新兴的疗法 几种精神和神经疾病，包括癫痫，严重抑郁症和强迫症- 强迫症(OCD)。尽管它在临床上取得了成功，但对神经的了解有限。 星展银行背后的机制。典型的DBS系统由一个脉冲发生器组成，该脉冲发生器提供刺激 通过植入的金属电极产生脉冲。DBS可能通过几种途径发挥其治疗作用。 不同的机制包括：(1)直接调节靶核的神经放电；(2)附近激活 神经元轴突；(3)激活逆行和顺行对传递长程投射轴突的影响 动作电位。由于目前的DBS电极会刺激大量的神经组织，因此很难 准确确定这些靶点和机制中的哪些对DBS的治疗效果负责。 因此，开发下一代DBS技术至关重要，该技术能够选择性地瞄准不同的 神经结构的群体，理想情况下具有单一神经元和单一轴突纤维的精度。此外，它还将 有利于开发大规模并行的DBS电极阵列(10,000多个电极)，以提供不同的 可针对治疗效果进行优化的活动时空模式。最新方法论 材料科学和工程学的进步现在使这种装置成为可能。本提案描述了一种 基于捆绑的高密度、大规模并行单细胞、单轴突水平刺激装置 微丝(BMW)：数以万计外径小于30微米的玻璃金属丝。这个 这种方法将是神经生理学的革命性方法，允许在运动中进行突破性实验 障碍和对神经回路行为的基本理解。在这里，我们建议：1)发展和发展 描述宝马刺激阵列的特征，并在急性脑片和活体中展示其有效性。2)至 将宝马阵列与现代半导体技术相结合，展示了一款 商用微显示芯片能够将图案化的刺激电流注入 宝马。我们将在脑片和活体中验证这一性能，以测试不同模式的电信号 刺激可以可靠地在脑片和活体内产生相应的活动模式。总而言之，这 该提案将神经科学和工程学结合在一起，创造出最高密度的电生理 制作了模拟界面，并通过组合提供了原理演示的证明 微丝刺激、双光子功能成像和经典电生理学的方法。这些 微丝阵列将是一个强大的工具，它不仅将为移动提供实质性的临床好处 障碍，如帕金森病，但也为星展银行提供了机械性的见解。 第1条