Electrical Stimulation to Restore Vestibular Function

描述(由申请人提供)：耳毒性毛细胞损伤导致的前庭功能障碍是导致严重残疾的常见原因，原因是头部运动时平衡不平衡和无法稳定凝视。虽然一些双侧前庭功能障碍患者能够通过身体康复和依赖其他感官进行补偿，但那些无法补偿的患者目前没有好的治疗选择。因为这些患者的前庭神经应该是完整的，所以选择性地施加电流应该能够驱动神经并引发能够稳定凝视的眼球运动。 该项目的中心目标是进一步开发一种植入式神经电子假体，能够恢复有症状的双侧前庭功能障碍的人的前庭功能。尽管前庭假体的发展落后于人工耳蜗的发展，但一个小组最近描述了第一个前庭假体原型。然而，在自然的头部运动中，它引起的眼球运动不足以稳定凝视，实验是在前庭功能正常的动物身上进行的。目前尚不清楚他们的结果是否适用于因耳毒性或梅尼埃病而受损的迷路。 拟议的项目将通过完善前庭耳毒性的哺乳动物模型和测试假体设计所依据的生物前提，为前庭假体的开发建立生理学和形态学基础。由于有活性的前庭神经传入必须存在才能刺激假体，我们将确定庆大霉素毒性对半规管嵴传入纤维的形态和生理的影响。我们将对双侧鼓室内注射庆大霉素耳毒性剂量治疗前后的前庭-眼反射进行分析。我们将描述双侧前庭缺陷动物在单通道和多通道模式电刺激半规管时的眼球运动特征。我们将测试在单个迷宫中刺激管道是否可以组合在一起来驱动覆盖正常生理范围的眼球运动。

DESCRIPTION (provided by applicant): Vestibular dysfunction due to ototoxic hair cell injury is a common cause of significant disability due to disequilibrium and inability to stabilize gaze during head movements. Although some patients with bilateral vestibular dysfunction are able to compensate through physical rehabilitation and reliance on other senses, those who fail to compensate currently have no good therapeutic options. Because the vestibular nerve should be intact in these patients, selectively applied electrical currents should be able to drive the nerve and elicit eye movements that can stabilize gaze. The central goal of this project is to further development toward an implantable neuroelectronic prosthesis capable of restoring vestibular function to people with symptomatic bilateral vestibular dysfunction. Although vestibular prosthesis development has lagged that of cochlear implants, one group has recently described a first prototype vestibular prosthesis. However, the eye movements it evoked were insufficient to stabilize gaze during natural head movements, and the experiments were performed on animals with normal vestibular function. It is unclear whether their results generalize to the case of a labyrinth damaged by ototoxicity or Meniere's disease. The proposed project will establish a physiologic and morphologic basis for vestibular prosthesis development, by refining a mammalian model of vestibular ototoxicity and by testing the biologic premises upon which prosthesis design is based. Because viable vestibular nerve afferents must exist for a prosthesis to stimulate, we will determine the effects of gentamicin toxicity on morphology and physiology of afferent fibers in semicircular canal crista. We will characterize the vestibulo-ocular reflex before and after bilateral treatment with ototoxic doses of intratympanic gentamicin. We will characterize the eye movements of bilaterally vestibular-deficient animals in response to single- and multi-canal patterned electrical stimulation of the semicircular canal cristae. We will test whether stimulation of canals in a single labyrinth can be combined to drive eye movements that cover the normal physiologic range.