Development of semicircular canal prostheses for studies of vestibular plasticity

描述（由申请人提供）：超过9000万美国人（bbbb40 %）在他们的生活中会因为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获益，这种假体类似于用于治疗重度感音神经性听力损失的人工耳蜗。由于我们对前庭可塑性的理解不足，我们开发前庭假肢的工作受到了限制，因为我们无法评估我们的假肢对慢性前庭刺激的反应是否受到设备限制，或者实验观察到的可塑性限制是否是基本的和生理的。我们对前庭可塑性的理解是有限的，因为传统的技术（例如，化学或手术迷路切除术，管道堵塞）可用于长期操纵前庭信号是不可控和/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，可以长期用于刺激半规管。我们的提案是对项目公告PA-04-006（“神经技术研究发展与增强”）的直接回应。我们提议开发的新设备将使现有技术无法实现的科学研究成为可能，同时也从根本上推动了前庭假体的发展。具体而言，我们建议设计，开发和测试一种新的动态，慢性，可控，流体动力学，管道刺激器。这个装置结合了微控制器电路，就像我们为前庭假体开发的那样，还有一个慢性机械驱动器，它推动单个半规管中的内淋巴，从而使丘体偏转。该装置将为单个椎管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组成部分，从而可以在非人类灵长类动物中控制植入椎管的增益、动力学和/或表观解剖平面。该装置甚至能够在不旋转的情况下提供椎管刺激。我们建议使用这个设备进行4个假设驱动的科学调查。具体而言，我们建议：1)测量高频（> - 50 Hz）的VOR反应，2)测量由前庭信号变化引起的VOR适应，而不是提供指导VOR运动学习的视觉反馈变化的标准方法，3)测量诱发电位以评估所提供的前庭周围刺激的有效性和稳定性，4)研究管刺激对倾斜感知的影响。直接验证椎管信号影响倾斜感知的假设。

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.