Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21205, USA.
J Assoc Res Otolaryngol. 2013 Apr;14(2):233-48. doi: 10.1007/s10162-013-0370-7. Epub 2013 Jan 26.
An implantable prosthesis that stimulates vestibular nerve branches to restore the sensation of head rotation and the three-dimensional (3D) vestibular ocular reflex (VOR) could benefit individuals disabled by bilateral loss of vestibular sensation. Our group has developed a vestibular prosthesis that partly restores normal function in animals by delivering biphasic current pulses via electrodes implanted in semicircular canals. Despite otherwise promising results, this approach has been limited by insufficient velocity of VOR response to head movements that should inhibit the implanted labyrinth and by misalignment between direction of head motion and prosthetically elicited VOR. We report that significantly larger VOR eye velocities in the inhibitory direction can be elicited by adapting a monkey to elevated baseline stimulation rate and current prior to stimulus modulation and then concurrently modulating ("co-modulating") both rate and current below baseline levels to encode inhibitory angular head velocity. Co-modulation of pulse rate and current amplitude above baseline can also elicit larger VOR eye responses in the excitatory direction than do either pulse rate modulation or current modulation alone. Combining these stimulation strategies with a precompensatory 3D coordinate transformation improves alignment and magnitude of evoked VOR eye responses. By demonstrating that a combination of co-modulation and precompensatory transformation strategies achieves a robust VOR response in all directions with significantly improved alignment in an animal model that closely resembles humans with vestibular loss, these findings provide a solid preclinical foundation for application of vestibular stimulation in humans.
一种可植入的假体,通过刺激前庭神经分支来恢复头部旋转的感觉和三维(3D)前庭眼反射(VOR),可以使双侧丧失前庭感觉的个体受益。我们的团队开发了一种前庭假体,通过在半规管中植入的电极传递双相电流脉冲,在动物身上部分恢复了正常功能。尽管结果很有前景,但这种方法受到了一些限制,包括 VOR 对头部运动的反应速度不足,应该抑制植入的迷路,以及头部运动方向和假体诱发的 VOR 之间的对准问题。我们报告说,通过使猴子适应在刺激调制之前提高基线刺激率和电流,然后同时将两者调制(“共调制”)低于基线水平以编码抑制性角头速度,可以诱发出更大的抑制性 VOR 眼速度。基线以上的脉冲率和电流幅度的共调制也可以比单独的脉冲率调制或电流调制诱发出更大的兴奋性 VOR 眼反应。将这些刺激策略与预补偿的 3D 坐标变换相结合,可以改善诱发 VOR 眼反应的对准和幅度。通过证明共调制和预补偿变换策略的组合在所有方向上都能产生强大的 VOR 反应,并且在与丧失前庭感觉的人类非常相似的动物模型中,对准和诱发 VOR 眼反应的幅度都有了显著改善,这些发现为前庭刺激在人类中的应用提供了坚实的临床前基础。