Vestibular Prosthesis Tested in a Vestibulopathic Model

描述（由申请人提供）：本申请的长期目标是开发一种前庭假体，可用于减轻前庭疾病患者的不平衡、空间定向障碍和视力模糊等症状。具体目的是在非人类灵长类动物模型中测试一个前庭假体的原型，该原型使用支配半规管的神经的模式电刺激。我们打算确定由前庭功能永久性缺陷引起的慢性症状，如与耳毒素暴露相关的症状，是否可以通过长期使用假体装置得到改善。我们打算描述正常恒河猴的姿势控制、倾斜心理物理和前庭眼反射，然后使用鼓室内庆大霉素消融双耳前庭功能。然后，我们将重新检查动物的姿势、知觉和动眼力行为，以确定双侧前庭消融引起的缺陷。然后，猴子会习惯性地使用一个假肢，这个假肢可以感知头部在所有三个旋转轴上的角度运动，并向支配一只耳朵半规管的三个神经提供电刺激。刺激作为头部角速度的函数，以一种再现正常半规管传入活动的方式进行调节。我们预测，动物将逐渐学会使用假体提供的旋转信息来改善它们的姿势稳定性，根据重力估计头部方向，以及头部运动引起的眼动反应。接受慢性假体刺激的猴子将与接受鼓室内庆大霉素前庭消融的对照组动物进行比较，然后在没有假体刺激的情况下进行长期研究。这种比较将使我们能够区分假体的效果与由于中枢代偿或适应外周前庭缺陷而导致的姿势、知觉和眼球运动行为的自发改善。公共卫生相关性：涉及内耳平衡部分的疾病非常常见，使人衰弱，并且通常对现有的治疗模式无反应。基于这些原因，我们正在开发一种假体装置，作为治疗这些内耳疾病引起的不平衡、空间定向障碍和视觉障碍的新方法。成功完成这项任务将大大改善许多因内耳平衡部分失调而遭受衰弱症状的人的生活质量。

DESCRIPTION (provided by applicant): The long-term objectives of this application are to develop a vestibular prosthesis that can be used to reduce symptoms such as imbalance, spatial disorientation, and blurred vision in patients with vestibular disorders. The specific aims are to test a prototype vestibular prosthesis which uses patterned electrical stimulation of the nerves innervating the semicircular canals in a non-human primate model. We intend to determine if the chronic symptoms produced by a permanent deficit in vestibular function, such as those associated with ototoxin exposure, could be improved with long-term usage of a prosthetic device. We intend to characterize postural control, tilt psychophysics, and the vestibulo-ocular reflex in normal rhesus monkeys, and then to ablate vestibular function in both ears using intratympanic gentamicin. We will then re-examine the animals' postural, perceptual, and oculomotor behaviors to define the deficits caused by bilateral vestibular ablation. The monkeys will then habitually use a prosthesis which senses angular head motion about all three rotational axes, and provides electrical stimulation to the three nerves innervating the semicircular canals in one ear. The stimulation modulates as a function of head angular velocity in a manner that recapitulates afferent activity from the normal semicircular canals. We predict that the animals will gradually learn to use the rotational information provided by the prosthesis to improve their postural stability, estimates of head orientation with respect to gravity, and eye movement responses evoked by head motion. The monkeys that receive chronic prosthetic stimulation will be compared to a control group of animals who undergo vestibular ablation with intratympanic gentamicin, and are then studied chronically without prosthetic stimulation. This comparison will allow us to differentiate the effects of the prosthesis from any spontaneous improvement in postural, perceptual, and oculomotor behavior that results from central compensation or adaptation to the peripheral vestibular deficit. PUBLIC HEALTH RELEVANCE: Disorders involving the balance component of the inner ear are very common and debilitating, and often are unresponsive to the available modes of therapy. For these reasons, we are developing a prosthetic device as a new approach to treat the imbalance, spatial disorientation, and visual disturbances produced by these inner ear disorders. Successful completion of this task would significantly improve the quality of life for a large number of people who suffer from the debilitating symptoms produced by disorders of the balance portion of the inner ear.