Electrical Stimulation to Restore Three Dimensional Vestibular Sensation

摘要 耳毒性毛细胞损伤导致双侧前庭功能丧失(内耳平衡感觉) 致残，患者头部失去平衡，无法保持稳定的视力 日常生活中的典型动作。而大多数部分丧失的人通过康复来补偿 利用其他感官的策略，那些不能弥补深刻损失的策略是没有好处的 治疗选择。因为在许多这样的患者中，前庭神经应该是完整的，电信号 编码头部旋转的刺激应该能够驱动神经，恢复头部的感觉 运动，就像人工耳蜗一样，可以恢复听觉功能。这项拟议的研究是由 有两个广泛的目标。第一个是推动可植入神经电子假体的发展。 恢复因双侧前庭感觉丧失而致残的人的功能。第二个是开车 通过增加对前庭神经活动的了解，前庭神经生理学领域 对头部运动进行编码，并通过开发能够使用以前不可能的 实验范式。 这个项目建立在我们已经朝着这个目标取得重大进展的基础上，包括：(1) 一种可对三维头部进行编码的多通道头盔假体的研制 旋转作为对三个或更多前庭神经分支的电刺激；(2) 龙猫的三维角度前庭-眼反射、前庭神经活动和内脏组织学 经庆大霉素治疗的前庭耳毒性损伤后；(3)部分恢复前庭功能 假体刺激。这些研究发现，通道相互作用会导致眼球不对准和 头部旋转是恢复正常3D头像的关键挑战。我们假设错位 主要是由于旁观者前庭神经分支电刺激不充分所致 选择性电极。 在本项目中，我们将：(1)表征3D Avor眼球旋转对刺激的依赖性 参数；(2)确定对慢性假体输入的适应程度和时间进程；(3) 开发和验证植入迷宫中电流流动路径的精确模型；以及(4)扩展我们的 从龙猫到猕猴的研究，它们的内耳尺寸与人类相似。我们 假说植入的猕猴会比龙猫表现出更少的错位，而且 在龙猫身上开发的建模和设计技术可以准确地推广到灵长类。 通过外推电极设计、刺激优化方案、有限元模型和 从啮齿动物到非人类灵长类动物的外科技术，这个项目将为合理设计奠定基础 多通道前庭假体的初步临床研究，以帮助因丧失前庭功能而致残的人 前庭感觉。

Abstract Bilateral loss of vestibular function (inner ear balance sensation) due to ototoxic hair cell injury is disabling, with patients suffering disequilibrium and inability to maintain stable vision during head movements typical of daily life. While most individuals with partial loss compensate through rehabilitative strategies enlisting other senses, those who fail to compensate for profound loss have no good therapeutic options. Because the vestibular nerve should be intact in many of these patients, electrical stimuli encoding head rotation should be able to drive the nerve and restore sensation of head movement, much like a cochlear implant restores auditory function. The proposed research is guided by two broad goals. The first is to advance development toward an implantable neuroelectronic prosthesis that restores function to people disabled by bilateral loss of vestibular sensation. The second is to drive the field of vestibular neurophysiology though increased understanding of how vestibular nerve activity encodes head motion and through development of technologies that enable use of previously impossible experimental paradigms. This project builds upon significant progress we have already made toward this goal, including: (1) development of a multi-channel, head-mounted prosthesis able to encode three-dimensional (3D) head rotation as electrical stimulation of three or more vestibular nerve branches; (2) characterization of the 3D angular vestibulo-ocular reflex (AVOR), vestibular nerve activity and endorgan histology in chinchillas after vestibular ototoxic injury via gentamicin treatment; and (3) partial restoration of the AVOR via prosthetic stimulation. These studies have identified channel interaction causing misalignment of eye and head rotation as a key challenge to restoration of a normal 3D aVOR. We hypothesize that misalignment is mainly due to spurious electrical stimulation of bystander vestibular nerve branches by inadequately selective electrodes. In this project, we will: (1) characterize the dependence of 3D AVOR eye rotations on stimulus parameters; (2) determine the extent and time course of adaptation to chronic prosthetic input; (3) develop and validate a precise model of current flow paths in the implanted labyrinth; and (4) extend our studies from chinchillas to macaque monkeys, which have inner ear dimensions similar to humans. We hypothesize that implanted macaques will exhibit much less misalignment than do chinchillas, and that the modeling and design techniques developed in chinchillas can generalize accurately to primates. Through extrapolation of electrode designs, stimulus optimization protocols, finite element models and surgical techniques from rodents to nonhuman primates, this project will set the stage for rational design and initial clinical studies of a multichannel vestibular prosthesis to aid individuals disabled by loss of vestibular sensation.