Phillips Christopher, Shepherd Sarah J, Nowack Amy, Nie Kaibao, Kaneko Chris R S, Rubinstein Jay T, Ling Leo, Phillips James O
Otolaryngology-Head and Neck Surgery, University of Washington, Box 357923, Seattle, WA, 98195, USA.
Vanderbilt University Medical Center, Nashville, TN, USA.
J Assoc Res Otolaryngol. 2016 Feb;17(1):19-35. doi: 10.1007/s10162-015-0544-6. Epub 2015 Oct 5.
Implanted vestibular neurostimulators are effective in driving slow phase eye movements in monkeys and humans. Furthermore, increases in slow phase velocity and electrically evoked compound action potential (vECAP) amplitudes occur with increasing current amplitude of electrical stimulation. In intact monkeys, protracted intermittent stimulation continues to produce robust behavioral responses and preserved vECAPs. In lesioned monkeys, shorter duration studies show preserved but with somewhat lower or higher velocity behavioral responses. It has been proposed that such changes are due to central adaptive changes in the electrically elicited vestibulo-ocular reflex (VOR). It is equally possible that these differences are due to changes in the vestibular periphery in response to activation of the vestibular efferent system. In order to investigate the site of adaptive change in response to electrical stimulation, we performed transtympanic gentamicin perfusions to induce rapid changes in vestibular input in monkeys with long-standing stably functioning vestibular neurostimulators, disambiguating the effects of implantation from the effects of ototoxic lesion. Gentamicin injection was effective in producing a large reduction in natural VOR only when it was performed in the non-implanted ear, suggesting that the implanted ear contributed little to the natural rotational response before injection. Injection of the implanted ear produced a reduction in the vECAP responses in that ear, suggesting that the intact hair cells in the non-functional ipsilateral ear were successfully lesioned by gentamicin, reducing the efficacy of stimulation in that ear. Despite this, injection of both ears produced central plastic changes that resulted in a dramatically increased slow phase velocity nystagmus elicited by electrical stimulation. These results suggest that loss of vestibular afferent activity, and a concurrent loss of electrically elicited vestibular input, produces an increase in the efficacy of a vestibular neurostimulator by eliciting centrally adapted behavioral responses without concurrent adaptive increase of galvanic afferent activation in the periphery.
植入式前庭神经刺激器在驱动猴子和人类的慢相眼动方面是有效的。此外，随着电刺激电流幅度的增加，慢相速度和电诱发复合动作电位（vECAP）幅度也会增加。在完整的猴子中，长时间的间歇性刺激继续产生强烈的行为反应并保留vECAP。在受损的猴子中，较短时间的研究表明行为反应得以保留，但速度有所降低或升高。有人提出，这种变化是由于电诱发前庭眼反射（VOR）的中枢适应性变化所致。同样有可能的是，这些差异是由于前庭传出系统激活后前庭外周的变化引起的。为了研究电刺激后适应性变化的部位，我们对长期稳定运行前庭神经刺激器的猴子进行了经鼓膜庆大霉素灌注，以快速改变前庭输入，从而区分植入的影响和耳毒性损伤的影响。仅在未植入电极的耳朵中进行庆大霉素注射时，才有效地大幅降低了自然VOR，这表明在注射前植入电极的耳朵对自然旋转反应的贡献很小。对植入电极的耳朵进行注射会使该耳朵的vECAP反应降低，这表明庆大霉素成功损伤了无功能的同侧耳朵中完整的毛细胞，降低了该耳朵的刺激效果。尽管如此，对双耳进行注射会产生中枢可塑性变化，导致电刺激诱发的慢相速度眼球震颤显著增加。这些结果表明，前庭传入活动的丧失以及电诱发前庭输入的同时丧失，通过引发中枢适应性行为反应而不会同时使外周电刺激传入激活适应性增加，从而提高了前庭神经刺激器的功效。
