Binocular 3-D otolith-ocular reflexes: responses of chinchillas to natural and prosthetic stimulation after ototoxic injury and vestibular implantation

Abstract

The otolith end organs inform the brain about gravitational and linear accelerations, driving the otolith-ocular reflex (OOR) to stabilize the eyes during translational motion (e.g., moving forward without rotating) and head tilt with respect to gravity. We previously characterized OOR responses of normal chinchillas to whole-body tilt and translation and to prosthetic electrical stimulation targeting the utricle and saccule via electrodes implanted in otherwise normal ears. Here we extend that work to examine OOR responses to tilt and translation stimuli after unilateral intratympanic gentamicin injection and to natural/mechanical and prosthetic/electrical stimulation delivered separately or in combination to animals with bilateral vestibular hypofunction after right ear intratympanic gentamicin injection followed by surgical disruption of the left labyrinth at the time of electrode implantation. Unilateral intratympanic gentamicin injection decreased natural OOR response magnitude to about half of normal, without markedly changing OOR response direction or symmetry. Subsequent surgical disruption of the contralateral labyrinth at the time of electrode implantation surgery further decreased OOR magnitude during natural stimulation, consistent with bimodal-bilateral otolith end organ hypofunction (ototoxic on the right ear, surgical on the left ear). Delivery of pulse-frequency- or pulse-amplitude-modulated prosthetic/electrical stimulation targeting the left utricle and saccule in phase with whole-body tilt and translation motion stimuli yielded responses closer to normal than the deficient OOR responses of those same animals in response to head tilt and translation alone.

A Virtual Inner Ear Model Selects Ramped Pulse Shapes for Vestibular Afferent Stimulation

“…The electric stimulation provided by a current vestibular prosthesis (VP) was not efficient in terms of VOR gain in clinical trials [11] in comparison with results from rhesus monkey experiments [5,6]. One underlying problem is the poor efficiency with which information from electric pulses is transformed into vestibular afferent responses.…”

“…In recent years, VPs have been developed [1][2][3][4] with the capability to detect threedimensional (3D) head rotation and restore a 3D vestibulo-ocular reflex (VOR) in animals affected by BVD caused by gentamicin ototoxicity. Encouraging results have been observed in chinchillas and rhesus monkeys [5][6][7], demonstrating the potential of VPs.…”

“…The model computed the predicted eye velocity axes resulting from the activation of each electrode pair by summing the semicircular canal axes, weighted with the relative magnitude of the axial current along the corresponding ampullary nerves. These predic-tions were directly compared with the observed eye velocity axes measured during the experiments conducted in previous studies [5,6]. The model underwent iterative refinement based on the level of disparity between the model predictions and the measurements.…”