Electrical Stimulation to Restore Three Dimensional Vestibular Sensation

电刺激恢复三维前庭感觉

• 批准号: 8789355
• 负责人: Charles C Della Santina
• 金额: $ 51.54万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8789355
• 关键词: 3-Dimensional; Acceleration; Acoustic Nerve; Action Potentials; Acute; Advanced Development; Affect; Animals; Automobile Driving; Bilateral; Biological Assay; Chinchilla (genus); Chronic; Clinical Treatment; Clinical Trials; Cochlear Implants; Computer Simulation; Computer-Aided Design; Data; Development; Devices; Disabled Persons; Dizziness; Ear; Electric Stimulation; Electrodes; Equilibrium; Esthesia; Exercise; Experimental Models; Face; Failure; Fiber; Foundations; Gait; Gentamicins; Goals; Head; Head Movements; Health; Hearing; Histology; Implant; Individual; Injury; Labyrinth; Macaca mulatta; Measurement; Measures; Medical; Methods; Modeling; Monkeys; Motion; Movement; Nerve; Nerve Fibers; Neuraxis; Neurons; Operative Surgical Procedures; Outcome; Patients; Pattern; Performance; Perilymph; Physiologic pulse; Pilot Projects; Primates; Prosthesis; Prosthesis Design; Protocols documentation; Pulse Rates; Quality of life; Recording of previous events; Reflex action; Regimen; Rehabilitation therapy; Relative (related person); Research; Residual state; Rodent; Rotation; Saccule and Utricle; Semicircular canal structure; Signal Transduction; Staging; Stimulus; Techniques; Technology; Testing; Tissues; Toxic effect; Translating; Translations; Vestibular Nerve; Vestibular loss; Vision; Walking; biophysical model; design; fall risk; falls; functional restoration; high risk; implantation; improved; in vivo; innovation; macula; novel; otoconia; rehabilitation paradigm; response; restoration; sensor; sound; tool; vector; vestibular prosthesis; vestibulo-ocular reflex; visual image movement

DESCRIPTION (provided by applicant): Bilateral loss of vestibular sensation due to ototoxic injury or other insults to both labyrinths is disabling. Affected individuals suffer chronic disequilibrium, increased risk of falls and unstable vision during head movements typical of common daily activities like walking and driving. Most individuals with mild or moderate loss eventually compensate through rehabilitative exercises that augment residual function, but those with profound loss who fail to compensate have no good treatment options. The vestibular nerves are intact in many such cases, so an implanted stimulator encoding signals from a head-mounted motion sensor can excite the vestibular nerve and - if it creates the right patterns of activity on the nerve's five branches - restore sensation of head movement (much as a cochlear implant restores sensation of sound). This proposal builds on substantial progress we have already made toward that goal, including: (1) characterization of the three dimensional vestibulo-ocular reflex (3D VOR), vestibular nerve activity, and inner ear histology in animals with ototoxic injury after gentamicin treatment; (2) development of a multi-channel vestibular prosthesis (MVP) that encodes head rotation via electrical stimulation of the three ampullary nerve branches innervating the semicircular canals (SCCs); (3) demonstration that the MVP can significantly restore the 3D VOR in rodents and rhesus monkeys with bilateral vestibular deficiency (BVD) while preserving hearing; (4) development of powerful computational strategies for minimizing the difference between MVP-evoked and ideal 3D VOR responses; and (5) confirmation that the central nervous system (CNS) rapidly adapts to correct much of the remaining error. While generating these promising results, we identified three major remaining challenges: (1) VOR misalignment (due to current spread activating nontarget nerve fibers outside the targeted branch of the vestibular nerve), (2) VOR asymmetry (due to the MVP's inability to suppress spontaneous neuronal activity when trying to encode inhibitory head movements) and (3) lack of utricle and saccule input (because we have focused effort on stimulating the ampullary nerves to restore SCC and angular VOR function and have not yet attempted prosthetic stimulation of the macular [utricular and saccular] nerves to restore tilt and translational VOR reflexes they normally drive). In this project, we will study ways to overcome these challenges using a unique combination of techniques including binocular 3D VOR measurements, single- unit recording in alert rodents and rhesus monkeys, a new MVP that encodes both rotational and translational movement, a powerful computational model of the implanted labyrinth, electrically-evoked compound action potentials (eCAPs), a novel rehabilitation paradigm, and a highly innovative method for controlling neuronal activity. These studies will yield new electrode designs, stimulus optimization protocols, computer-aided design tools, surgical techniques and rehab paradigms that set the stage for successful deployment of MVPs for clinical treatment of tens of thousands of individuals chronically disabled by loss of vestibular sensation.

描述（由申请人提供）：由于耳毒性损伤或对两个迷路的其他损伤而导致双侧前庭感觉丧失，从而致残。受影响的人会遭受慢性不平衡、跌倒风险增加以及在步行和驾驶等常见日常活动中典型的头部运动期间视力不稳定。大多数轻度或中度丧失的人最终可以通过增强残余功能的康复锻炼来补偿，但那些无法补偿的严重丧失的人没有好的治疗选择。在许多此类情况下，前庭神经是完整的，因此植入的刺激器对来自头戴式运动传感器的信号进行编码，可以刺激前庭神经 - 如果它在神经的五个分支上创建正确的活动模式 - 恢复头部运动的感觉。就像人工耳蜗恢复声音的感觉一样）。该提案建立在我们为实现这一目标已经取得的实质性进展的基础上，包括：（1）庆大霉素治疗后耳毒性损伤动物的三维前庭眼反射（3D VOR）、前庭神经活动和内耳组织学的表征； (2) 开发多通道前庭假体 (MVP)，通过电刺激支配半规管 (SCC) 的三个壶腹神经分支来编码头部旋转； (3) 证明 MVP 可以显着恢复患有双侧前庭缺陷 (BVD) 的啮齿动物和恒河猴的 3D VOR，同时保留听力； (4) 开发强大的计算策略，以最小化 MVP 诱发和理想 3D VOR 响应之间的差异； （5）确认中枢神经系统（CNS）能够快速适应以纠正大部分剩余的错误。在产生这些有希望的结果的同时，我们确定了三个主要的挑战：(1) VOR 错位（由于电流扩散激活前庭神经目标分支之外的非目标神经纤维），(2) VOR 不对称（由于 MVP 无法抑制尝试编码抑制性头部运动时的自发神经元活动）和（3）缺乏椭圆囊和球囊输入（因为我们集中精力刺激壶腹神经以恢复 SCC 和角 VOR 功能，并且尚未尝试对黄斑[椭圆囊和囊状]神经进行假体刺激以恢复倾斜和 它们通常驱动平移 VOR 反射）。在这个项目中，我们将研究如何使用独特的技术组合来克服这些挑战，包括双目 3D VOR 测量、警觉啮齿动物和恒河猴的单单元记录、编码旋转和平移运动的新 MVP、强大的计算模型植入迷路、电诱发复合动作电位（eCAP）、新颖的康复范例以及控制神经元活动的高度创新方法。这些研究将产生新的电极设计、刺激优化方案、计算机辅助设计工具、手术技术和康复范例，为成功部署 MVP 为数万名因前庭感觉丧失而长期致残的患者进行临床治疗奠定了基础。