Optimization of Stimulus Protocols for a Vestibular Implant

前庭植入物刺激方案的优化

• 批准号: 10535429
• 负责人: Brian Morris
• 金额: $ 4.68万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10535429
• 关键词: 3-Dimensional; Adult; Afferent Neurons; Anatomy; Animals; Anodes; Anterior; Auditory Threshold; Bilateral; Biological Assay; Blurred vision; Cathodes; Charge; Chronic; Clinical; Clinical Trials; Cochlea; Cochlear Implants; Cochlear Nerve; Conscious; Data; Detection; Development; Devices; Disease; Dizziness; Electric Stimulation; Electrodes; Electrophysiology (science); Elements; End stage renal failure; Esthesia; Experimental Designs; Eye; Eye Movements; Facial Muscles; Facial nerve structure; Failure; Fatigue; Fellowship; Future; Goals; Gold; Head; Head Movements; Hearing Tests; Human; Implant; Individual; Injury; Interphase; Labyrinth; Macaca mulatta; Measurement; Measures; Methods; Modeling; Monkeys; Nerve; Neurons; Operating Rooms; Patients; Perception; Performance; Pharmaceutical Preparations; Phase; Physiologic pulse; Plant Roots; Prosthesis; Protocols documentation; Proxy; Publishing; Quality of life; Reflex action; Reflex eye movement; Rehabilitation therapy; Reporting; Research; Saccule and Utricle; Safety; Semicircular canal structure; Shapes; Stimulus; Symptoms; Techniques; Technology; Testing; Tissues; Vestibular Labyrinth; Vestibular Nerve; Vestibular loss; Vision; Walking; Work; base; design; evidence base; fall risk; first-in-human; gaze; implant design; implantation; improved; nonhuman primate; ototoxicity; relating to nervous system; response; theories; vestibulo-ocular reflex; visual image movement

Project Summary – Abstract Bilateral vestibular hypofunction (BVH) is a debilitating disorder caused by ototoxic drugs or other injuries to the inner ear that result in dizziness, imbalance, fatigue, difficulty stabilizing gaze, and decreased quality of life. It severely afflicts ~1.8M adults worldwide. Vestibular rehabilitation helps some individuals with BVH compensate for their symptoms but normal function is never restored and it is not effective for all patients. Electrical stimulation with a vestibular implant has shown promise as a viable treatment for these individuals with severe loss. Results from one study aiming to show efficacy and safety indicate that increasing stimulus current results in larger vestibulo-ocular reflex (VOR) responses and these eye movements are approximately aligned with the anatomical axis of the target canal. However, it is unclear why the reported VOR responses are modest in comparison to results from previous studies in animals, not all subjects have well aligned responses, and eye movements can be somewhat disconjugate. The present study aims to better understand the root of these discrepancies by investigating the effect of various stimulus paradigms on 3D VOR and vestibular afferents. Published studies investigating electrical stimulation via cochlear or vestibular implants have typically used symmetric pulse waveforms. However, some studies reported a significant improvement in human cochlear implant users’ auditory thresholds when using asymmetric pulses. It is hypothesized that a similar effect will occur in the context of vestibular implant stimulation. To quantify how VOR responses depend on stimulus waveform parameters in alert rhesus macaque monkeys, asymmetric vestibular implant parameters will be systematically varied while recording VOR responses. This will involve initially testing pulses with a constant cathodic first phase, then varying the cathodic first phase duration, and finally using an anodic first phase all while varying the interphase gap and second phase duration. Additionally, the field of clinical vestibular implantation assumes 3D VOR magnitude and axis reflect relative activity in each of the three semicircular canal nerve branches while ignoring the utricle and saccule. A study using finite element modeling has predicted that prosthetic currents meant to stimulate a semicircular canal usually also activate utricular and/or saccular neurons, and the authors speculate that such activity would elicit disconjugate VOR responses. To understand the correspondence between monkey vestibular afferent activity and 3-D VOR, this study also aims to record directly from individual afferents while electrically stimulating and compare the activity to VOR responses. We will use afferent recordings to quantify the spread of current, clarify utricle and saccule afferent activation, and understand afferent responses to asymmetric stimuli and their correlation to VOR. From this work, we can dictate changes to improve the implant design and identify evidence-based rules to guide the selection of stimulation parameters for use with vestibular implants in humans.

项目摘要-摘要 双侧前庭功能减退（BVH）是一种由耳毒性药物或其他损伤引起的衰弱性疾病， 内耳，导致头晕，不平衡，疲劳，稳定视线困难，生活质量下降。 它严重影响了全球约180万成年人。前庭康复有助于一些BVH患者 它可以补偿他们的症状，但正常功能永远不会恢复，并且不是对所有患者都有效。 电刺激与前庭植入物已显示出作为一个可行的治疗这些人的承诺 严重亏损。一项旨在显示有效性和安全性的研究结果表明，增加刺激 电流导致更大的前庭眼反射（VOR）反应，并且这些眼球运动大约是 与目标椎管的解剖轴对齐。然而，目前还不清楚为什么报告的VOR响应 与以前的动物研究结果相比，并不是所有的受试者都有很好的一致性。 反应和眼球运动可能有点不共轭。本研究旨在更好地了解 这些差异的根源，通过调查各种刺激范式对三维VOR的影响， 前庭传入神经研究通过耳蜗或前庭植入物进行电刺激的已发表研究 通常使用对称脉冲波形。然而，一些研究报告显示， 人工耳蜗使用者在使用非对称脉冲时的听觉阈值。据推测， 在前庭植入刺激的情况下也会发生类似的效果。为了量化VOR响应 依赖于刺激波形参数在警觉恒河猴，不对称前庭 当记录VOR响应时，将系统地改变注入参数。这将首先涉及 具有恒定阴极第一相位的测试脉冲，然后改变阴极第一相位持续时间，以及最后 使用阳极第一阶段，同时改变相间间隙和第二阶段持续时间。另夕h 临床前庭植入领域假设3D VOR幅度和轴反映了 半规管神经的三个分支，忽略椭圆囊和球囊。利用有限元的研究 模型预测，用于刺激半规管的假体电流通常也会激活 椭圆囊和/或囊状神经元，作者推测，这种活动将引起非共轭VOR 应答了解猴前庭传入活动与三维立体像之间的对应关系 VOR，这项研究的目的还在于记录直接从个人传入，而电刺激， 将活动与VOR响应进行比较。我们将使用传入记录来量化电流的传播， 阐明椭圆囊和球囊传入激活，并了解传入反应的不对称刺激， 与VOR的相关性。从这项工作中，我们可以决定改变，以改善种植体设计和识别 以证据为基础的规则，以指导前庭植入物使用的刺激参数的选择， 人类