Electrical Stimulation to Restore Three Dimensional Vestibular Sensation

描述（由申请人提供）：由于耳毒性毛细胞损伤导致的双侧前庭功能（内耳平衡感觉）丧失是致残的，患者在日常生活中典型的头部运动中遭受不平衡和无法保持稳定的视力。虽然大多数部分失忆的人通过其他感官的康复策略来补偿，但那些不能补偿严重失忆的人没有好的治疗选择。因为这些患者的前庭神经应该是完整的，编码头部旋转的电刺激应该能够驱动神经并恢复头部运动的感觉，就像人工耳蜗恢复听觉功能一样。拟议的研究以两个广泛目标为指导。第一个目标是推进植入式神经电子假体的发展，以恢复因双侧前庭感觉丧失而残疾的人的功能。第二是通过增加对前庭神经活动如何编码头部运动的理解以及通过开发能够使用以前不可能的实验范例的技术来推动前庭神经生理学领域。该项目建立在我们已经朝着这一目标取得的重大进展的基础上，包括：(1)开发一种多通道头戴式假体，能够通过电刺激三个或更多前庭神经分支来编码三维（3D）头部旋转；(2)庆大霉素所致前庭耳毒性损伤后龙猫前庭眼三维角反射（AVOR）、前庭神经活动及内器官组织学特征；(3)通过假体刺激部分修复3D AVOR。这些研究已经确定了通道相互作用导致眼睛和头部旋转错位，这是恢复正常3D aVOR的关键挑战。我们假设失调主要是由于不充分选择电极对旁观者前庭神经分支的虚假电刺激。在本项目中，我们将：(1)表征3D AVOR眼睛旋转对刺激参数的依赖性；(2)确定对慢性假体输入的适应程度和时间过程；(3)将我们的研究从龙猫扩展到猕猴，它们的内耳尺寸与人类相似。我们假设植入的猕猴会比龙猫表现出更少的错位，并且龙猫的建模和设计技术可以准确地推广到灵长类动物。通过从啮齿类动物到非人类灵长类动物的电极设计、刺激优化方案和手术技术的外推，该项目将为合理设计和初步临床研究多通道前庭假体奠定基础，以帮助因前庭感觉丧失而残疾的个体。

DESCRIPTION (provided by applicant): 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 via 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 due to gentamicin treatment; and (3) partial restoration of the 3D 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; and (3) 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, 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.