Safe Direct Current for Neuroprosthetic Applications

用于神经修复应用的安全直流电

• 批准号: 9052334
• 负责人: Gene Yevgeny Fridman
• 金额: $ 33.98万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2020-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9052334
• 关键词: Action Potentials; Address; Advanced Development; Animal Experiments; Animal Model; Charge; Chinchilla (genus); Cochlear Implants; Consumption; Contralateral; Corrosion; Data; Development; Effectiveness; Electrodes; Engineering; Ensure; Equilibrium; Esthesia; Evaluation; Failure; Gel; Goals; Head; Head Movements; Histologic; Hydrolysis; Implant; Injection of therapeutic agent; Ipsilateral; Location; Longevity; Metals; Microfluidic Microchips; Microfluidics; Motion; Nerve; Nerve Block; Nervous system structure; Neurons; Operative Surgical Procedures; Pacemakers; Pain; Performance; Perilymph; Peripheral Nerves; Physiologic pulse; Physiological; Prostheses and Implants; Prosthesis; Proxy; Research; Rotation; Safety; Saline; Solutions; Specimen; Spinal Cord; Stimulus; System; Technology; Testing; Therapeutic; Tissues; Translations; Tube; Vestibular Labyrinth; Work; chronic pain; clinical application; deep brain stimulator; design; electric impedance; equilibration disorder; implantable device; improved; innovation; miniaturize; neural prosthesis; neuroprosthesis; neuroregulation; novel; prototype; public health relevance; relating to nervous system; research study; response; retina implantation; stem; vestibular prosthesis; vestibulo-ocular reflex; voltage

 DESCRIPTION (provided by applicant): The central goal of this project is to advance the therapeutic applications and the development of an exciting novel neuroprosthetic technology, Safe Direct Current Stimulation (SDCS). Direct current (DC) compared to biphasic charge balanced pulses normally used by neural prostheses to interface to the nervous system, can more naturally control neural activity. Unlike biphasic current pulses used to excite neurons, DC can excite, inhibit, and modulate sensitivity of neurons. However using DC for implantable prosthetic applications has not been possible due to the DC's inherent violation of the charge injection safety constraints at the metal electrode interfaces. Safe DC overcomes these constraints and opens a new avenue for research into exciting possibilities of using DC to interface to the nervous system. We will optimize the use of safe DC to improve the performance of a vestibular prosthesis for those suffering from balance disorders. Vestibular prostheses encounter difficulty encoding head motion away from the implanted vestibular labyrinth because encoding this motion requires inhibition of spontaneous activity of the nerve. We obtained preliminary data in a chinchilla animal model showing that modulating the amplitude and polarity of safe DC could encode both ipsilateral and contralateral head rotations. Here we propose to understand and overcome the hurdles that we encountered in our preliminary experiments stemming from the key safe DC stimulation challenge: the reversal of neural response as a function of increased safe DC intensity. That is, anodic (positive) stimulation causes inhibition at low DC intensities but excitation at higher intensities; and cathodic (negative) stimulation causes excitation at low DC intensities but inhibition as the amplitude increases. In the vestibular prosthetic stimulation this effect imposes a limit on the velocity of encoding head motion. We also propose to advance the SDCS technology by identifying and solving the key technical challenges with a miniaturized SDCS to improve longevity and power consumption. Aim 1) Improve the vestibular prosthetic encoding of head motion. We will investigate the origin of the response reversal and improve the head velocity encoding by eliminating or reducing the reversal with a bipolar stimulation paradigm. Aim 2) Examine the safety of SDCS. We will examine the physiological and histological limits of safe DC stimulation in chinchillas stimulated for 60 days. Aim 3) Address key technical challenges associated with longevity and low power consumption of the miniaturized SDCS.

 描述(由申请人提供)：该项目的中心目标是促进一种令人兴奋的新型神经假体技术--安全直流电刺激(SDCS)的治疗应用和开发。与神经假体通常用来连接神经系统的两相电荷平衡脉冲相比，直流电(DC)可以更自然地控制神经活动。与用于兴奋神经元的两相电流脉冲不同，DC可以兴奋、抑制和调节神经元的敏感性。然而，由于DC固有地违反了金属电极界面处的电荷注入安全限制，使用DC用于植入性假体应用是不可能的。安全DC克服了这些限制，为研究使用DC与神经系统接口的令人兴奋的可能性开辟了一条新的途径。我们将优化安全DC的使用，以提高前庭假体的性能，为那些患有平衡障碍的人服务。前庭假体很难编码头部离开植入的前庭迷路的运动，因为编码这种运动需要抑制神经的自发活动。我们在龙猫动物模型中获得的初步数据表明，调节安全DC的幅度和极性可以编码同侧和对侧头部旋转。在这里，我们建议了解并克服我们在初步实验中遇到的障碍，这些障碍源于关键的安全直流刺激挑战：作为安全直流强度增加的函数的神经反应的逆转。也就是说，阳极(正)刺激在低直流强度下引起抑制，但在较高强度下引起激发；阴极(负)刺激在低直流强度下引起激发，但随着幅度的增加而抑制。在前庭假体刺激中，这种效应对编码头运动的速度施加了限制。我们还建议通过使用小型化的SDCS来确定和解决关键的技术挑战，以提高寿命和功耗，从而推动SDCS技术的发展。目的1)改进前庭假体对头部运动的编码。我们将研究反应反转的起源，并通过双极刺激范式消除或减少反应反转来改善头部速度编码。目的2)检查SDC的安全性。我们将研究刺激60天的龙猫的安全DC刺激的生理和组织学极限。目的3)解决与小型化SDC的寿命和低功耗相关的关键技术挑战。