Posture, Gait, Quality of Life, and Hearing with a Vestibular Implant.

BACKGROUND: Bilateral vestibular hypofunction is associated with chronic disequilibrium, postural instability, and unsteady gait owing to failure of vestibular reflexes that stabilize the eyes, head, and body. A vestibular implant may be effective in alleviating symptoms. METHODS: Persons who had had ototoxic (7 participants) or idiopathic (1 participant) bilateral vestibular hypofunction for 2 to 23 years underwent unilateral implantation of a prosthesis that electrically stimulates the three semicircular canal branches of the vestibular nerve. Clinical outcomes included the score on the Bruininks-Oseretsky Test of Motor Proficiency balance subtest (range, 0 to 36, with higher scores indicating better balance), time to failure on the modified Romberg test (range, 0 to 30 seconds), score on the Dynamic Gait Index (range, 0 to 24, with higher scores indicating better gait performance), time needed to complete the Timed Up and Go test, gait speed, pure-tone auditory detection thresholds, speech discrimination scores, and quality of life. We compared participants' results at baseline (before implantation) with those at 6 months (8 participants) and at 1 year (6 participants) with the device set in its usual treatment mode (varying stimulus pulse rate and amplitude to represent rotational head motion) and in a placebo mode (holding pulse rate and amplitude constant). RESULTS: The median scores at baseline and at 6 months on the Bruininks-Oseretsky test were 17.5 and 21.0, respectively (median within-participant difference, 5.5 points; 95% confidence interval [CI], 0 to 10.0); the median times on the modified Romberg test were 3.6 seconds and 8.3 seconds (difference, 5.1; 95% CI, 1.5 to 27.6); the median scores on the Dynamic Gait Index were 12.5 and 22.5 (difference, 10.5 points; 95% CI, 1.5 to 12.0); the median times on the Timed Up and Go test were 11.0 seconds and 8.7 seconds (difference, 2.3; 95% CI, -1.7 to 5.0); and the median speeds on the gait-speed test were 1.03 m per second and 1.10 m per second (difference, 0.13; 95% CI, -0.25 to 0.30). Placebo-mode testing confirmed that improvements were due to treatment-mode stimulation. Among the 6 participants who were also assessed at 1 year, the median within-participant changes from baseline to 1 year were generally consistent with results at 6 months. Implantation caused ipsilateral hearing loss, with the air-conducted pure-tone average detection threshold at 6 months increasing by 3 to 16 dB in 5 participants and by 74 to 104 dB in 3 participants. Changes in participant-reported disability and quality of life paralleled changes in posture and gait. CONCLUSIONS: Six months and 1 year after unilateral implantation of a vestibular prosthesis for bilateral vestibular hypofunction, measures of posture, gait, and quality of life were generally in the direction of improvement from baseline, but hearing was reduced in the ear with the implant in all but 1 participant. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT02725463.).

Binocular 3D otolith-ocular reflexes: responses of chinchillas to prosthetic electrical stimulation targeting the utricle and saccule.

From animal experiments by Cohen and Suzuki et al. in the 1960s to the first-in-human clinical trials now in progress, prosthetic electrical stimulation targeting semicircular canal branches of the vestibular nerve has proven effective at driving directionally appropriate vestibulo-ocular reflex eye movements, postural responses, and perception. That work was considerably facilitated by the fact that all hair cells and primary afferent neurons in each canal have the same directional sensitivity to head rotation, the three canals' ampullary nerves are geometrically distinct from one another, and electrically evoked three-dimensional (3D) canal-ocular reflex responses approximate a simple vector sum of linearly independent components representing relative excitation of each of the three canals. In contrast, selective prosthetic stimulation of the utricle and saccule has been difficult to achieve, because hair cells and afferents with many different directional sensitivities are densely packed in those endorgans and the relationship between 3D otolith-ocular reflex responses and the natural and/or prosthetic stimuli that elicit them is more complex. As a result, controversy exists regarding whether selective, controllable stimulation of electrically evoked otolith-ocular reflexes (eeOOR) is possible. Using micromachined, planar arrays of electrodes implanted in the labyrinth, we quantified 3D, binocular eeOOR responses to prosthetic electrical stimulation targeting the utricle, saccule, and semicircular canals of alert chinchillas. Stimuli delivered via near-bipolar electrode pairs near the maculae elicited sustained ocular countertilt responses that grew reliably with pulse rate and pulse amplitude, varied in direction according to which stimulating electrode was employed, and exhibited temporal dynamics consistent with responses expected for isolated macular stimulation.NEW & NOTEWORTHY As the second in a pair of papers on Binocular 3D Otolith-Ocular Reflexes, this paper describes new planar electrode arrays and vestibular prosthesis architecture designed to target the three semicircular canals and the utricle and saccule. With this technological advancement, electrically evoked otolith-ocular reflexes due to stimulation via utricle- and saccule-targeted electrodes were recorded in chinchillas. Results demonstrate advances toward achieving selective stimulation of the utricle and saccule.

Continuous vestibular implant stimulation partially restores eye-stabilizing reflexes.

BACKGROUNDBilateral loss of vestibular (inner ear inertial) sensation causes chronically blurred vision during head movement, postural instability, and increased fall risk. Individuals who fail to compensate despite rehabilitation therapy have no adequate treatment options. Analogous to hearing restoration via cochlear implants, prosthetic electrical stimulation of vestibular nerve branches to encode head motion has garnered interest as a potential treatment, but prior studies in humans have not included continuous long-term stimulation or 3D binocular vestibulo-ocular reflex (VOR) oculography, without which one cannot determine whether an implant selectively stimulates the implanted ear's 3 semicircular canals.METHODSWe report binocular 3D VOR responses of 4 human subjects with ototoxic bilateral vestibular loss unilaterally implanted with a Labyrinth Devices Multichannel Vestibular Implant System vestibular implant, which provides continuous, long-term, motion-modulated prosthetic stimulation via electrodes in 3 semicircular canals.RESULTSInitiation of prosthetic stimulation evoked nystagmus that decayed within 30 minutes. Stimulation targeting 1 canal produced 3D VOR responses approximately aligned with that canal's anatomic axis. Targeting multiple canals yielded responses aligned with a vector sum of individual responses. Over 350-812 days of continuous 24 h/d use, modulated electrical stimulation produced stable VOR responses that grew with stimulus intensity and aligned approximately with any specified 3D head rotation axis.CONCLUSIONThese results demonstrate that a vestibular implant can selectively, continuously, and chronically provide artificial sensory input to all 3 implanted semicircular canals in individuals disabled by bilateral vestibular loss, driving reflexive VOR eye movements that approximately align in 3D with the head motion axis encoded by the implant.TRIAL REGISTRATIONClinicalTrials.gov: NCT02725463.FUNDINGNIH/National Institute on Deafness and Other Communication Disorders: R01DC013536 and 2T32DC000023; Labyrinth Devices, LLC; and Med-El GmbH.

Nonhuman primate vestibuloocular reflex responses to prosthetic vestibular stimulation are robust to pulse timing errors caused by temporal discretization.

Electrical stimulation of vestibular afferent neurons to partially restore semicircular canal sensation of head rotation and the stabilizing reflexes that sensation supports has potential to effectively treat individuals disabled by bilateral vestibular hypofunction. Ideally, a vestibular implant system using this approach would be integrated with a cochlear implant, which would provide clinicians with a means to simultaneously treat loss of both vestibular and auditory sensation. Despite obvious similarities, merging these technologies poses several challenges, including stimulus pulse timing errors that arise when a system must implement a pulse frequency modulation-encoding scheme (as is used in vestibular implants to mimic normal vestibular nerve encoding of head movement) within fixed-rate continuous interleaved sampling (CIS) strategies used in cochlear implants. Pulse timing errors caused by temporal discretization inherent to CIS create stair step discontinuities of the vestibular implant's smooth mapping of head velocity to stimulus pulse frequency. In this study, we assayed electrically evoked vestibuloocular reflex responses in two rhesus macaques using both a smooth pulse frequency modulation map and a discretized map corrupted by temporal errors typical of those arising in a combined cochlear-vestibular implant. Responses were measured using three-dimensional scleral coil oculography for prosthetic electrical stimuli representing sinusoidal head velocity waveforms that varied over 50-400°/s and 0.1-5 Hz. Pulse timing errors produced negligible effects on responses across all canals in both animals, indicating that temporal discretization inherent to implementing a pulse frequency modulation-coding scheme within a cochlear implant's CIS fixed pulse timing framework need not sacrifice performance of the combined system's vestibular implant portion. NEW & NOTEWORTHY Merging a vestibular implant system with existing cochlear implant technology can provide clinicians with a means to restore both vestibular and auditory sensation. Pulse timing errors inherent to integration of pulse frequency modulation vestibular stimulation with fixed-rate, continuous interleaved sampling cochlear implant stimulation would discretize the smooth head velocity encoding of a combined device. In this study, we show these pulse timing errors produce negligible effects on electrically evoked vestibulo-ocular reflex responses in two rhesus macaques.

Heat pulse excitability of vestibular hair cells and afferent neurons.

In the present study we combined electrophysiology with optical heat pulse stimuli to examine thermodynamics of membrane electrical excitability in mammalian vestibular hair cells and afferent neurons. We recorded whole cell currents in mammalian type II vestibular hair cells using an excised preparation (mouse) and action potentials (APs) in afferent neurons in vivo (chinchilla) in response to optical heat pulses applied to the crista (ΔT ≈ 0.25°C per pulse). Afferent spike trains evoked by heat pulse stimuli were diverse and included asynchronous inhibition, asynchronous excitation, and/or phase-locked APs synchronized to each infrared heat pulse. Thermal responses of membrane currents responsible for APs in ganglion neurons were strictly excitatory, with Q10 ≈ 2. In contrast, hair cells responded with a mix of excitatory and inhibitory currents. Excitatory hair cell membrane currents included a thermoelectric capacitive current proportional to the rate of temperature rise (dT/dt) and an inward conduction current driven by ΔT An iberiotoxin-sensitive inhibitory conduction current was also evoked by ΔT, rising in <3 ms and decaying with a time constant of ∼24 ms. The inhibitory component dominated whole cell currents in 50% of hair cells at -68 mV and in 67% of hair cells at -60 mV. Responses were quantified and described on the basis of first principles of thermodynamics. Results identify key molecular targets underlying heat pulse excitability in vestibular sensory organs and provide quantitative methods for rational application of optical heat pulses to examine protein biophysics and manipulate cellular excitability.