Restoration of 3D vestibular sensation in rhesus monkeys using a multichannel vestibular prosthesis

Abstract

Profound bilateral loss of vestibular hair cell function can cause chronically disabling loss of balance and inability to maintain stable vision during head and body movements. We have previously shown that chinchillas rendered bilaterally vestibular-deficient via intratympanic administration of the ototoxic antibiotic gentamicin regain a more nearly normal 3-dimensional vestibulo-ocular reflex (3D VOR) when head motion information sensed by a head-mounted multichannel vestibular prosthesis (MVP) is encoded via rate-modulated pulsatile stimulation of vestibular nerve branches. Despite significant improvement versus the unaided condition, animals still exhibited some 3D VOR misalignment (i.e., the 3D axis of eye movement responses did not precisely align with the axis of head rotation), presumably due to current spread between a given ampullary nerve’s stimulating electrode(s) and afferent fibers in nontargeted branches of the vestibular nerve. Assuming that effects of current spread depend on relative orientation and separation between nerve branches, anatomic differences between chinchilla and human labyrinths may limit the extent to which results in chinchillas accurately predict MVP performance in humans. In this report, we describe the MVP-evoked 3D VOR measured in alert rhesus monkeys, which have labyrinths that are larger than chinchillas and temporal bone anatomy more similar to humans. Electrodes were implanted in five monkeys treated with intratympanic gentamicin to bilaterally ablate vestibular hair cell mechanosensitivity. Eye movements mediated by the 3D VOR were recorded during passive sinusoidal (0.2–5 Hz, peak 50°/s) and acceleration-step (1000°/s2 to 150°/s) whole-body rotations in darkness about each semicircular canal axis. During constant 100 pulse/s stimulation (i.e., MVP powered ON but set to stimulate each ampullary nerve at a constant mean baseline rate not modulated by head motion), 3D VOR responses to head rotation exhibited profoundly low gain [(mean eye velocity amplitude)/(mean head velocity amplitude) < 0.1] and large misalignment between ideal and actual eye movements. In contrast, motion-modulated sinusoidal MVP stimuli elicited a 3D VOR with gain 0.4–0.7 and axis misalignment of 21–38°, and responses to high-acceleration transient head rotations exhibited gain and asymmetry closer to those of unilaterally gentamicin-treated animals (i.e., with one intact labyrinth) than to bilaterally gentamicin-treated animals without MVP stimulation. In comparison to responses observed under similar conditions in chinchillas, acute responses to MVP stimulation in rhesus macaque monkeys were slightly better aligned to the desired rotation axis. Responses during combined rotation and prosthetic stimulation were greater than when either stimulus was presented alone, suggesting that the central nervous system uses MVP input in the context of multisensory integration. Considering the similarity in temporal bone anatomy and VOR performance between rhesus monkeys and humans, these observations suggest ...

Directional Plasticity Rapidly Improves 3D Vestibulo-Ocular Reflex Alignment in Monkeys Using a Multichannel Vestibular Prosthesis

“…Details of surgical techniques have been described previously Dai et al 2011). Briefly, under general anesthesia (isoflurane, 3-5 %), a plastic cylinder-shaped chamber was positioned on the skull in the midline, perpendicular to the mean horizontal SCC plane, to restrain the animal during VOR testing.…”

“…When this reflex fails due to labyrinthine injuries that spare the vestibular nerve, a multichannel vestibular prosthesis (MVP) can help stabilize images on the retinae and normalize perception of head movement by measuring 3D head movement and encoding that movement via electrical stimuli delivered to the ampullary nerves. We previously developed and described such a device, demonstrating its ability to partially restore a normal 3D VOR (Della Santina et al 2005bFridman et al 2010;Davidovics et al 2011;Dai et al 2011).…”

“…Despite promising results using this approach, current spread or imprecise electrode placement can reduce MVP efficacy through spurious activation of nontarget axons, which manifests as misalignment between the actual and perceived axis of head motion (Della Santina et al 2007;Fridman et al 2010;Davidovics et al 2011;Dai et al 2011). Reducing this misalignment is a key goal of efforts to translate this technology to clinical application.…”

Histopathologic Changes of the Inner ear in Rhesus Monkeys After Intratympanic Gentamicin Injection and Vestibular Prosthesis Electrode Array Implantation

“…These included three normal/ untreated temporal bone specimens from three animals (control), two temporal bone specimens from two animals treated only with ITG (ITG-only), two temporal bone specimens from two animals treated with MVP electrode implantation without ITG (MVPonly), and four temporal bone specimens from three animals treated with both ITG and subsequent MVP electrode implantation (ITG + MVP). Each was harvested after euthanasia and transcardiac perfusion following completion of physiologic studies resulting in eVOR and hearing assessment data that have been published previously Dai et al 2013Dai et al , 2011aDai et al , 2011bChiang et al 2011;Mitchell et al 2013). Diversity of physiologic study goals led to variation in the treatments to which each temporal bone was subjected.…”

“…The multichannel vestibular prosthesis (MVP) developed in our laboratory encodes 3D head rotation and elicits VOR responses approximately aligned to ideal response directions when assayed using 3D oculographic techniques (Della Santina et al 2007a;Fridman et al 2010;Davidovics et al 2013;Dai et al 2013 Despite physiologic data (Rubinstein et al 2012;Fridman et al 2010;Davidovics et al 2013;Perez Fornos et al 2014;Stokroos et al 2014;Dai et al 2011a) demonstrating well-aligned electrically evoked vestibulo-ocular reflex (eVOR) responses, and intact hearing in rhesus monkeys treated with intratympanic gentamicin (ITG) to ablate the natural VOR and then implanted with MVP electrode arrays (Dai et al 2011b), uncertainty remains regarding the status of the neuroepithelium after ITG injection and the extent of trauma caused by MVP electrode implantation. In contrast to the large body of evidence (Nadol and Eddington 2006;Nadol et al 2008;O'Leary et al 2013;Shepherd et al 1984) on the biocompatibility and tolerability of cochlear implant electrodes and the incidence of unfavorable tissue responses to implantation trauma that could hinder implant performance, there is a paucity of published data on the occurrence and extent of adverse reactions to implantation of vestibular prosthesis electrodes.…”