Electrical Stimulation to Restore Three Dimensional Vestibular Sensation

描述（由申请人提供）：双侧前庭感觉丧失是由于双侧迷路的耳毒性损伤或其他损伤造成的。受影响的人在步行和开车等常见日常活动中，头部运动时遭受慢性失衡，摔倒风险增加和视力不稳定。大多数轻度或中度丧失的个体最终通过增强残余功能的康复训练进行补偿，但那些不能补偿的严重丧失的个体没有好的治疗选择。在许多这样的情况下，前庭神经是完整的，所以植入的刺激器编码来自头戴式运动传感器的信号，可以刺激前庭神经，如果它在神经的五个分支上产生正确的活动模式，就可以恢复头部运动的感觉（就像人工耳蜗恢复声音感觉一样）。该建议建立在我们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特征；(2)开发一种多通道前庭假体（MVP），该假体通过电刺激支配半圆形管（SCCs）的三个壶腹神经分支来编码头部旋转；(3)研究结果表明，MVP能在保持听力的同时，显著恢复双侧前庭功能缺损（BVD）啮齿动物和恒河猴的3D VOR功能；(4)开发强大的计算策略，以最小化mvp诱发的与理想3D VOR响应之间的差异；(5)确认中枢神经系统（CNS）能迅速适应以纠正大部分剩余的错误。在取得这些有希望的成果的同时，我们确定了三个主要的挑战：(1) VOR错位（由于电流扩散激活了前庭神经目标分支外的非目标神经纤维）；(2) VOR不对称（由于MVP在试图编码抑制性头部运动时无法抑制自发的神经元活动）和(3)缺乏小囊和小囊输入(因为我们专注于刺激壶腹神经以恢复SCC和角状VOR功能，尚未尝试假体刺激黄斑[小囊和小囊]神经以恢复倾斜和

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.