Optimization of Stimulus Protocols for a Vestibular Implant

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Project Summary – Abstract Bilateral vestibular hypofunction (BVH) is a debilitating disorder caused by ototoxic drugs or other injuries to the inner ear that result in dizziness, imbalance, fatigue, difficulty stabilizing gaze, and decreased quality of life. It severely afflicts ~1.8M adults worldwide. Vestibular rehabilitation helps some individuals with BVH compensate for their symptoms but normal function is never restored and it is not effective for all patients. Electrical stimulation with a vestibular implant has shown promise as a viable treatment for these individuals with severe loss. Results from one study aiming to show efficacy and safety indicate that increasing stimulus current results in larger vestibulo-ocular reflex (VOR) responses and these eye movements are approximately aligned with the anatomical axis of the target canal. However, it is unclear why the reported VOR responses are modest in comparison to results from previous studies in animals, not all subjects have well aligned responses, and eye movements can be somewhat disconjugate. The present study aims to better understand the root of these discrepancies by investigating the effect of various stimulus paradigms on 3D VOR and vestibular afferents. Published studies investigating electrical stimulation via cochlear or vestibular implants have typically used symmetric pulse waveforms. However, some studies reported a significant improvement in human cochlear implant users’ auditory thresholds when using asymmetric pulses. It is hypothesized that a similar effect will occur in the context of vestibular implant stimulation. To quantify how VOR responses depend on stimulus waveform parameters in alert rhesus macaque monkeys, asymmetric vestibular implant parameters will be systematically varied while recording VOR responses. This will involve initially testing pulses with a constant cathodic first phase, then varying the cathodic first phase duration, and finally using an anodic first phase all while varying the interphase gap and second phase duration. Additionally, the field of clinical vestibular implantation assumes 3D VOR magnitude and axis reflect relative activity in each of the three semicircular canal nerve branches while ignoring the utricle and saccule. A study using finite element modeling has predicted that prosthetic currents meant to stimulate a semicircular canal usually also activate utricular and/or saccular neurons, and the authors speculate that such activity would elicit disconjugate VOR responses. To understand the correspondence between monkey vestibular afferent activity and 3-D VOR, this study also aims to record directly from individual afferents while electrically stimulating and compare the activity to VOR responses. We will use afferent recordings to quantify the spread of current, clarify utricle and saccule afferent activation, and understand afferent responses to asymmetric stimuli and their correlation to VOR. From this work, we can dictate changes to improve the implant design and identify evidence-based rules to guide the selection of stimulation parameters for use with vestibular implants in humans.