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

基本信息

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
项目类别：
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

项目摘要

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

项目概要：基底神经节深部脑刺激 (DBS) 是一种针对多种运动的成熟疗法此外，它也是一种新兴疗法。用于治疗多种精神和神经系统疾病，包括癫痫、重度抑郁症和强迫症尽管强迫症（OCD）在临床上取得了成功，但人们对神经障碍的了解仍然有限。 DBS 背后的机制典型的 DBS 系统由一个提供刺激的脉冲发生器组成。 DBS 可能通过植入的金属电极产生脉冲，从而通过多种方式发挥治疗作用。不同的机制包括：（1）直接调节目标核的神经放电；（2）激活附近的神经元； (3)通过激活逆向和顺向影响传递的远程投射轴突由于当前的 DBS 电极可激发大量神经组织，因此很难实现动作电位。精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针对不同的目标神经结构群体，理想情况下具有单神经元和单轴突纤维精度。有利于开发大规模并行 DBS 电极阵列（10,000 多个电极）以提供不同的可以优化治疗效果的时空活动模式。现在材料科学和工程的进步使这种设备成为可能。基于捆绑的高密度、大规模并行单细胞和单轴突水平刺激装置微丝 (BMW)：数万根外径小于 30 微米的玻璃金属丝。该方法对于神经生理学来说将是革命性的，可以在运动方面进行突破性的实验在此我们建议： 1) 发展和理解神经回路行为。表征 BMW 刺激阵列并证明其在急性脑切片和体内的功效 2) To。将 BMW 阵列与现代半导体技术相结合，展示了商用微显示芯片能够通过注入图案化刺激电流宝马。我们将验证大脑切片和体内的性能，以测试不同的电模式是否有效。刺激可靠地在大脑切片和体内产生相应的活动模式。该提案将把神经科学和工程学结合起来，创造出最高密度的电生理学曾经制作过的刺激界面，并通过组合提供原理演示证明微线刺激、2 光子功能成像和经典电生理学方法。微丝阵列将是一个强大的工具，它不仅可以为运动提供实质性的临床益处疾病，如 PD，还为 DBS 提供机制见解。 1