Electrical Stimulation to Restore Three Dimensional Vestibular Sensation

电刺激恢复三维前庭感觉

• 批准号: 7931012
• 负责人: Charles C Della Santina
• 金额: $ 27.91万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-24 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7931012
• 关键词: 3-Dimensional; Action Potentials; Advanced Development; Anatomy; Animals; Auditory; Bilateral; Chinchilla (genus); Chronic; Clinical; Clinical Research; Cochlear Implants; Cochlear Nerve; Coupling; Data; Dependence; Development; Dimensions; Disabled Persons; Distal; Dose; Electric Stimulation; Electrodes; Elements; Equilibrium; Esthesia; Exhibits; Eye; Eye Movements; Financial compensation; Generations; Gentamicins; Goals; Hair Cells; Head; Head Movements; Histology; Human; Image; Implant; Individual; Injury; Labyrinth; Life; Macaca; Magnetic Resonance Imaging; Measurement; Measures; Modeling; Monkeys; Motion; Nerve; Nervous system structure; Patients; Positioning Attribute; Primates; Procedures; Prosthesis; Prosthesis Design; Protocols documentation; Rehabilitation therapy; Relative (related person); Research; Resolution; Rodent; Rotation; Speech Intelligibility; Staging; Stimulus; Structure; Surgical Models; Techniques; Testing; Therapeutic; Time; Translations; Vestibular Nerve; Vestibular loss; Vision; abstracting; cell injury; design; functional restoration; implantation; improved; macula; model design; neurophysiology; nonhuman primate; response; restoration; scale up; technology development; vestibular prosthesis; vestibulo-ocular reflex

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.

摘要 由于耳毒性毛细胞损伤导致的双侧前庭功能（内耳平衡感）丧失， 致残，患者在头部活动期间视力不平衡，无法保持稳定视力 日常生活中典型的动作。虽然大多数部分损失的人通过康复来补偿， 战略招募其他感官，那些谁不能弥补深刻的损失没有好 治疗选择因为前庭神经应该是完整的，在许多这些患者，电 编码头部旋转的刺激应该能够驱动神经并恢复头部的感觉 运动，就像人工耳蜗恢复听觉功能一样。本研究的指导原则是： 两大目标。第一个是推进植入式神经电子假体的发展 它能帮助那些因双侧前庭感觉丧失而致残的人恢复功能。二是开车 前庭神经生理学领域虽然增加了对前庭神经活动如何 编码头部运动，并通过技术的发展，使以前不可能的使用 实验范例 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） 能够对三维（3D）头部进行编码的多通道头戴式假体的开发 旋转作为三个或更多前庭神经分支的电刺激;（2）表征 灰鼠的三维角前庭眼反射、前庭神经活动和内器官组织学 庆大霉素治疗前庭耳毒性损伤后;（3）AVOR部分恢复， 假体刺激这些研究已经确定了导致眼睛错位的通道相互作用， 头部旋转是恢复正常3D aVOR关键挑战。我们假设错位 主要是由于旁观者前庭神经分支的虚假电刺激， 选择性电极。 在本课题中，我们将：（1）表征三维AVOR眼旋转对刺激的依赖性 参数;（2）确定慢性假肢输入的适应程度和时间过程;（3） 开发并验证植入迷路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 假设被植入的猕猴会比龙猫表现出更少的错位， 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动物。 通过外推电极设计、刺激优化方案、有限元模型和 从啮齿类动物到非人类灵长类动物的外科技术，该项目将为合理设计奠定基础 和多通道前庭假体的初步临床研究，以帮助因丧失 前庭感觉