Development of semicircular canal prostheses for studies of vestibular plasticity

描述（申请人提供）：超过9000万美国人（>40%）在他们的生活中的某个时候会因头晕或其他平衡障碍而寻求医疗照顾。美国国立卫生研究院的一个工作委员会报告说，至少有200万美国人因头晕或其他平衡障碍而遭受慢性损害，每年造成的医疗费用超过10亿美元。其中一些患者可以从前庭假体中受益，这类似于用于治疗深度感音神经性听力损失的人工耳蜗。我们的工作发展前庭假体是有限的，在我们的理解前庭可塑性的缺点，因为我们不能评估，如果我们的假体提供的慢性前庭刺激的反应是由设备的限制，或者如果实验观察到的塑料限制是基本的和生理的性质。我们对前庭可塑性的理解是有限的，因为传统的技术（例如，化学或外科前庭切除术、耳道堵塞）是不可控制和/或可逆的。为了解决这些临床和科学的局限性，我们建议开发一种新的假体装置，可以长期使用，以刺激半规管。我们的建议书是针对项目公告PA-04-006（“神经技术研究开发和增强”）而写的。我们建议开发的新设备将使科学研究成为可能，而使用现有技术是不可能的，同时也从根本上推进前庭假体。具体来说，我们建议设计，开发和测试一种新的动态，慢性，可控，流体动力，运河刺激器。该设备结合了微控制器电路，就像为我们的前庭假体开发的那样，具有慢性机械致动器，该致动器在单个半规管中推动内淋巴，从而使吸盘偏转。该装置将为单个管道提供内淋巴运动的慢性动态控制，这是正常旋转转导的重要部分，使得植入管道的增益、动力学和/或表观解剖平面可以在非人灵长类动物中可控地改变。该装置甚至能够在没有旋转的情况下提供耳道刺激。我们建议使用该器械进行4项假设驱动的科学研究。具体而言，我们建议：1）测量高频（>50 Hz）VOR响应，2）测量由前庭信号变化诱发的VOR适应，这与提供指导VOR运动学习的视觉反馈变化的标准方法相反，3）测量诱发电位以评估所提供的外周前庭刺激的功效和稳定性，（4）探讨神经管刺激对倾斜觉的影响，直接验证神经管信号影响倾斜觉的假设。

DESCRIPTION (provided by applicant): Over 90 million Americans (>40%) will seek medical attention for dizziness or some other balance disorder sometime in their life. An NIH working committee has reported that at least 2 million Americans experience chronic impairment due to dizziness or other balance disorders, causing medical expenses in excess of $1 billion per year. Some of these patients could benefit from a vestibular prosthesis that would be similar to the cochlear implant used to treat profound sensorineural hearing loss. Our work developing vestibular prosthetics is limited by shortcomings in our understanding of vestibular plasticity, since we cannot assess if responses to chronic vestibular stimulation provided by our prosthesis are restricted by device limitations or if the plastic limitations observed experimentally are fundamental and physiologic in nature. Our understanding of vestibular plasticity is limited because the traditional techniques (e.g., chemical or surgical labyrinthectomy, canal plugging) that are available to chronically manipulate the vestibular signals are not controllable and/or reversible. To address these clinical and scientific limitations, we propose to develop a new prosthetic device that can be used chronically to stimulate a semicircular canal. Our proposal is written in direct response to program announcement PA-04-006 ("Neurotechnology Research Development & Enhancement"). The new device that we propose to develop will enable scientific investigations that are not possible using existing techniques while also fundamentally advancing vestibular prostheses. Specifically, we propose to design, develop, and test a new dynamic, chronic, controllable, fluid-dynamic, canal stimulator. This device combines microcontroller circuitry, like that developed for our vestibular prosthesis, with a chronic mechanical actuator that pushes endolymph in an individual semicircular canal, which, in turn, deflects the cupula. This device will provide chronic dynamic control of endolymph movement, which is an essential part of normal rotation transduction, to an individual canal such that the gain, dynamics, and/or the apparent anatomic plane of the implanted canal can be controllably altered in non-human primates. The device will even be capable of providing canal stimulation in the absence of rotation. We propose to use this device to perform 4 hypothesis-driven scientific investigations. Specifically, we propose: 1) to measure high-frequency (>50 Hz) VOR responses, 2) to measure VOR adaptation evoked by changes in the vestibular signals as opposed to the standard approach of providing changes in the visual feedback that guides VOR motor learning, 3) to measure evoked potentials to evaluate efficacy and stability of the peripheral vestibular stimulation being provided, 4) to investigate the influence of canal stimulation on tilt perception, directly testing the hypothesis that canal signals influence tilt perception.