title: Loss of Afferent Vestibular Input Produces Central Adaptation and Increased Gain of Vestibular Prosthetic Stimulation.
abstract: 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.
authors.affiliation: Otolaryngology-Head and Neck Surgery, University of Washington, Box 357923, Seattle, WA, 98195, USA. cmtp@uw.edu.
authors.forename: Christopher
authors.initials: C
authors.lastname: Phillips
authors.affiliation: Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Shepherd
authors.affiliation: Washington National Primate Research Center, University of Washington, Seattle, WA, 98195, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Nowack
authors.affiliation: Otolaryngology-Head and Neck Surgery, University of Washington, Box 357923, Seattle, WA, 98195, USA.
authors.forename: Kaibao
authors.initials: K
authors.lastname: Nie
authors.affiliation: Physiology and Biophysics, University of Washington, Seattle, WA, 98195, USA.|Washington National Primate Research Center, University of Washington, Seattle, WA, 98195, USA.
authors.forename: Chris R S
authors.initials: CR
authors.lastname: Kaneko
authors.affiliation: Otolaryngology-Head and Neck Surgery, University of Washington, Box 357923, Seattle, WA, 98195, USA.|Bioengineering, University of Washington, Seattle, WA, 98195, USA.
authors.forename: Jay T
authors.initials: JT
authors.lastname: Rubinstein
authors.affiliation: Otolaryngology-Head and Neck Surgery, University of Washington, Box 357923, Seattle, WA, 98195, USA.|Washington National Primate Research Center, University of Washington, Seattle, WA, 98195, USA.
authors.forename: Leo
authors.initials: L
authors.lastname: Ling
authors.affiliation: Otolaryngology-Head and Neck Surgery, University of Washington, Box 357923, Seattle, WA, 98195, USA.|Washington National Primate Research Center, University of Washington, Seattle, WA, 98195, USA.
authors.forename: James O
authors.initials: JO
authors.lastname: Phillips
mesh_terms: D000200:Action Potentials; D000222:Adaptation, Physiological; D000818:Animals; D004558:Electric Stimulation; D005133:Eye Movements / Q000502:physiology; D005839:Gentamicins / Q000633:toxicity; D008253:Macaca mulatta; D058117:Neural Prostheses; D019919:Prosthesis Implantation; D012027:Reflex, Vestibulo-Ocular; D014722:Vestibule, Labyrinth / Q000294:innervation* / Q000502:physiology
chemical_list: D005839:Gentamicins
keywords: gentamicin; labyrinthectomy; prosthesis; vestibular; vestibulo-ocular reflex