Electrical Stimulation to Restore Three Dimensional Vestibular Sensation

电刺激恢复三维前庭感觉

• 批准号: 9198443
• 负责人: Charles C Della Santina
• 金额: $ 55.28万
• 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/9198443
• 关键词: 3-Dimensional; Acceleration; Acoustic Nerve; Action Potentials; Acute; Advanced Development; Affect; Anatomy; Animals; Automobile Driving; Bilateral; Biological Assay; Chinchilla (genus); Chronic; Clinical Treatment; Clinical Trials; Cochlear Implants; Computer Simulation; Computer-Aided Design; Data; Development; Devices; Dimensions; Disabled Persons; Dizziness; Ear; Electric Stimulation; Electrodes; Equilibrium; Esthesia; Experimental Models; Face; Failure; Fiber; Foundations; Gait; Gentamicins; Goals; Head; Head Movements; 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; Posture; Primates; Prosthesis; Prosthesis Design; Protocols documentation; Pulse Rates; Quality of life; Recording of previous events; Reflex action; Regimen; Research; Residual state; Rodent; Rotation; Saccule and Utricle; Semicircular canal structure; Signal Transduction; Solid; Stimulus; Techniques; Technology; Testing; Tissues; Toxic effect; Translating; Translations; Vestibular Nerve; Vestibular loss; Vision; Walking; biophysical model; design; exercise rehabilitation; fall risk; functional restoration; high risk; implantation; improved; in vivo; innovation; macula; novel; otoconia; ototoxicity; public health relevance; 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种迷宫的其他侮辱引起的前庭感觉的双侧丧失是残疾人的。受影响的个体遭受慢性不平衡，跌倒的风险增加以及在典型的日常活动（如步行和驾驶）的典型的头部移动期间。大多数患有轻度或中度损失的人最终通过康复的练习来补偿剩余功能，但是那些未能补偿的严重损失的人没有良好的治疗选择。在许多情况下，前庭神经完好无损，因此编码来自头部运动传感器的植入刺激器可以激发前庭神经，如果它在神经的五个分支上创建了正确的活动模式，则可以恢复头部运动的感觉（就像同志植入植入物还原声音一样）。这项提案以我们已经对该目标取得的重大进展为基础，包括：（1）表征三维前庭反射（3D VOR），前庭神经活动和内耳性组织学对庆大霉素治疗后的耳毒性损伤的内耳组织学； （2）开发多通道前庭假体（MVP），该假体（MVP）通过对三个隔离神经分支的电刺激来编码头部旋转，该分支支配了半圆形管（SCCS）； （3）证明MVP可以在保存听力的同时显着恢复具有双侧前庭缺乏症（BVD）的啮齿动物和恒河猴中的3D VOR； （4）制定强大的计算策略，以最大程度地减少MVP诱发与理想的3D VOR响应之间的差异； （5）确认中枢神经系统（CNS）迅速适应以纠正大部分剩余误差。在产生这些令人鼓舞的结果的同时，我们确定了三个主要的挑战：（1）for量不对（由于当前的差异而激活非目标神经纤维在前庭神经的靶向分支之外），（2）VOR不对称性（由于MVP无法抑制自发性的神经元活动，并且（由于intuped and intuper intuper and toction and toction and toction and toction）（3我们集中精力刺激隔膜神经来恢复SCC和角度的功能，并且尚未尝试对黄斑[uticular和saccular]神经的假肢刺激以恢复倾斜度 他们通常驾驶的翻译反射）。在这个项目中，我们将研究通过包括双目3D测量的独特组合来克服这些挑战的方法控制神经元活动的方法。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，手术技术和康复范式，这为成功部署MVP的临床治疗奠定了基础，以造成数以万计的成千上万个个体因前庭感觉而慢性残疾。