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

项目摘要： 基底神经节的深脑刺激（DB）是多种电影的完善疗法 疾病，例如帕金森氏病（PD）和本质震颤。 对于几种精神病和神经系统疾病，包括癫痫，重大疾病和强迫症 - 强迫性疾病（OCD）。 DBS背后的机制。 通过植入的金属电极脉冲。 不同的机制，包括：（1）直接调节在目标核上激活目标核的神经射击 神经元轴突（3）通过激活雄激素轴突传递长距离投影 动作电位。 精确确定哪种靶标和机制负责DBS的治疗作用。 开发下一代DBS技术是至关重要的，可以选择性定位不同 神经结构的种群，理想情况下具有单神经元和单轴突纤维精度。 有益于开发质量平行的DBS电极ARAY（10,000多电极）以交付不同 最近的方法。 材料科学和工程的进步现在是一种设备。 基于bundred 微管（BMW）：数以万计的金属玻璃电线少于30微米 神经生理学的方法将是革命性的，可以通过运动的经验进行分解 提出对神经电路行为的疾病和基本理解：1） 表征BMW刺激阵列，并在急性脑切片和体内表现出其功效 将宝马阵列与现代半导体技术相结合，证明了 市售的微型播放芯片能够通过您注入图案化的刺激急切 宝马。我们将验证脑部和体内的性能 刺激可靠地在大脑切片和体内产生相关活动模式 提案将使神经科学和工程融合在一起，以创建最高密度的电生理学 刺激界面曾经制作过，并通过合并的原理证明证明 微管刺激的方法，2-Photon功能成像和经典的电生理学。 Microwire Arrays WOOLD是一个强大的工具，它不仅会为运动提供可观的临床效益 疾病，例如PD，但也提供了DBS的机械见解。 1