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.).

Automated head motion system improves reliability and lessens operator dependence for head impulse testing of vestibular reflexes.

Deficiency of the eye-stabilizing vestibulo-ocular reflex (VOR) is a defining feature in multiple diseases of the vestibular labyrinth, which comprises the inner ear's sensors of head rotation, translation and orientation. Diagnosis of these disorders is facilitated by observation and measurement of eye movements during and after head motion. The video head impulse test has recently garnered interest as a clinical diagnostic assessment of vestibular dysfunction. In typical practice, it involves use of video-oculography goggles to measure eye movements while a clinician examiner grasps the subject's head and manually rotates it left or right at sufficient acceleration to cover ~20 deg over ~150 mS, reaching a peak velocity of >120 deg/S midway through the movement. Manual delivery of head impulses incurs significant trial-by-trial, inter-session and inter-operator variability, which lessens the test's reliability, efficiency, safety and standardization across testing facilities. We describe application of a novel, compact and portable automated head impulse test (aHIT™) device that delivers highly repeatable head motion stimuli about axes parallel to those of the vestibular labyrinth's six semicircular canals, with programmable Gaussian and sinusoidal motion profiles at amplitudes, velocities and accelerations sufficient to test VOR function over the spectral range for which the VOR dominates other vision-stabilizing reflexes. We tested the aHIT™ on human subjects and demonstrated its high reproducibility compared to manually delivered head impulses. This device has the potential to be a valuable clinical and research tool for diagnostic evaluation and investigation of the vestibular system.

A CMOS Neural Interface for a Multichannel Vestibular Prosthesis.

We present a high-voltage CMOS neural-interface chip for a multichannel vestibular prosthesis (MVP) that measures head motion and modulates vestibular nerve activity to restore vision- and posture-stabilizing reflexes. This application specific integrated circuit neural interface (ASIC-NI) chip was designed to work with a commercially available microcontroller, which controls the ASIC-NI via a fast parallel interface to deliver biphasic stimulation pulses with 9-bit programmable current amplitude via 16 stimulation channels. The chip was fabricated in the ONSemi C5 0.5 micron, high-voltage CMOS process and can accommodate compliance voltages up to 12 V, stimulating vestibular nerve branches using biphasic current pulses up to 1.45±0.06 mA with durations as short as 10 µs/phase. The ASIC-NI includes a dedicated digital-to-analog converter for each channel, enabling it to perform complex multipolar stimulation. The ASIC-NI replaces discrete components that cover nearly half of the 2nd generation MVP (MVP2) printed circuit board, reducing the MVP system size by 48% and power consumption by 17%. Physiological tests of the ASIC-based MVP system (MVP2A) in a rhesus monkey produced reflexive eye movement responses to prosthetic stimulation similar to those observed when using the MVP2. Sinusoidal modulation of stimulus pulse rate from 68-130 pulses per second at frequencies from 0.1 to 5 Hz elicited appropriately-directed slow phase eye velocities ranging in amplitude from 1.9-16.7 °/s for the MVP2 and 2.0-14.2 °/s for the MVP2A. The eye velocities evoked by MVP2 and MVP2A showed no significant difference ( t-test, p=0.34), suggesting that the MVP2A achieves performance at least as good as the larger MVP2.

Multichannel vestibular prosthesis employing modulation of pulse rate and current with alignment precompensation elicits improved VOR performance in monkeys.

An implantable prosthesis that stimulates vestibular nerve branches to restore the sensation of head rotation and the three-dimensional (3D) vestibular ocular reflex (VOR) could benefit individuals disabled by bilateral loss of vestibular sensation. Our group has developed a vestibular prosthesis that partly restores normal function in animals by delivering biphasic current pulses via electrodes implanted in semicircular canals. Despite otherwise promising results, this approach has been limited by insufficient velocity of VOR response to head movements that should inhibit the implanted labyrinth and by misalignment between direction of head motion and prosthetically elicited VOR. We report that significantly larger VOR eye velocities in the inhibitory direction can be elicited by adapting a monkey to elevated baseline stimulation rate and current prior to stimulus modulation and then concurrently modulating ("co-modulating") both rate and current below baseline levels to encode inhibitory angular head velocity. Co-modulation of pulse rate and current amplitude above baseline can also elicit larger VOR eye responses in the excitatory direction than do either pulse rate modulation or current modulation alone. Combining these stimulation strategies with a precompensatory 3D coordinate transformation improves alignment and magnitude of evoked VOR eye responses. By demonstrating that a combination of co-modulation and precompensatory transformation strategies achieves a robust VOR response in all directions with significantly improved alignment in an animal model that closely resembles humans with vestibular loss, these findings provide a solid preclinical foundation for application of vestibular stimulation in humans.

Directional plasticity rapidly improves 3D vestibulo-ocular reflex alignment in monkeys using a multichannel vestibular prosthesis.

Bilateral loss of vestibular sensation can be disabling. We have shown that a multichannel vestibular prosthesis (MVP) can partly restore vestibular sensation as evidenced by improvements in the 3-dimensional angular vestibulo-ocular reflex (3D VOR). However, a key challenge is to minimize misalignment between the axes of eye and head rotation, which is apparently caused by current spread beyond each electrode's targeted nerve branch. We recently reported that rodents wearing a MVP markedly improve 3D VOR alignment during the first week after MVP activation, probably through the same central nervous system adaptive mechanisms that mediate cross-axis adaptation over time in normal individuals wearing prisms that cause visual scene movement about an axis different than the axis of head rotation. We hypothesized that rhesus monkeys would exhibit similar improvements with continuous prosthetic stimulation over time. We created bilateral vestibular deficiency in four rhesus monkeys via intratympanic injection of gentamicin. A MVP was mounted to the cranium, and eye movements in response to whole-body passive rotation in darkness were measured repeatedly over 1 week of continuous head motion-modulated prosthetic electrical stimulation. 3D VOR responses to whole-body rotations about each semicircular canal axis were measured on days 1, 3, and 7 of chronic stimulation. Horizontal VOR gain during 1 Hz, 50 °/s peak whole-body rotations before the prosthesis was turned on was <0.1, which is profoundly below normal (0.94 ± 0.12). On stimulation day 1, VOR gain was 0.4-0.8, but the axis of observed eye movements aligned poorly with head rotation (misalignment range ∼30-40 °). Substantial improvement of axis misalignment was observed after 7 days of continuous motion-modulated prosthetic stimulation under normal diurnal lighting. Similar improvements were noted for all animals, all three axes of rotation tested, for all sinusoidal frequencies tested (0.05-5 Hz), and for high-acceleration transient rotations. VOR asymmetry changes did not reach statistical significance, although they did trend toward slight improvement over time. Prior studies had already shown that directional plasticity reduces misalignment when a subject with normal labyrinths views abnormal visual scene movement. Our results show that the converse is also true: individuals receiving misoriented vestibular sensation under normal viewing conditions rapidly adapt to restore a well-aligned 3D VOR. Considering the similarity of VOR physiology across primate species, similar effects are likely to occur in humans using a MVP to treat bilateral vestibular deficiency.

Head movements evoked in alert rhesus monkey by vestibular prosthesis stimulation: implications for postural and gaze stabilization.

The vestibular system detects motion of the head in space and in turn generates reflexes that are vital for our daily activities. The eye movements produced by the vestibulo-ocular reflex (VOR) play an essential role in stabilizing the visual axis (gaze), while vestibulo-spinal reflexes ensure the maintenance of head and body posture. The neuronal pathways from the vestibular periphery to the cervical spinal cord potentially serve a dual role, since they function to stabilize the head relative to inertial space and could thus contribute to gaze (eye-in-head + head-in-space) and posture stabilization. To date, however, the functional significance of vestibular-neck pathways in alert primates remains a matter of debate. Here we used a vestibular prosthesis to 1) quantify vestibularly-driven head movements in primates, and 2) assess whether these evoked head movements make a significant contribution to gaze as well as postural stabilization. We stimulated electrodes implanted in the horizontal semicircular canal of alert rhesus monkeys, and measured the head and eye movements evoked during a 100 ms time period for which the contribution of longer latency voluntary inputs to the neck would be minimal. Our results show that prosthetic stimulation evoked significant head movements with latencies consistent with known vestibulo-spinal pathways. Furthermore, while the evoked head movements were substantially smaller than the coincidently evoked eye movements, they made a significant contribution to gaze stabilization, complementing the VOR to ensure that the appropriate gaze response is achieved. We speculate that analogous compensatory head movements will be evoked when implanted prosthetic devices are transitioned to human patients.

Design and performance of a multichannel vestibular prosthesis that restores semicircular canal sensation in rhesus monkey.

In normal individuals, the vestibular labyrinths sense head movement and mediate reflexes that maintain stable gaze and posture. Bilateral loss of vestibular sensation causes chronic disequilibrium, oscillopsia, and postural instability. We describe a new multichannel vestibular prosthesis (MVP) intended to restore modulation of vestibular nerve activity with head rotation. The device comprises motion sensors to measure rotation and gravitoinertial acceleration, a microcontroller to calculate pulse timing, and stimulator units that deliver constant-current pulses to microelectrodes implanted in the labyrinth. This new MVP incorporates many improvements over previous prototypes, including a 50% decrease in implant size, a 50% decrease in power consumption, a new microelectrode array design meant to simplify implantation and reliably achieve selective nerve-electrode coupling, multiple current sources conferring ability to simultaneously stimulate on multiple electrodes, and circuitry for in vivo measurement of electrode impedances. We demonstrate the performance of this device through in vitro bench-top characterization and in vivo physiological experiments with a rhesus macaque monkey.

Chronic stimulation of the semicircular canals using a multichannel vestibular prosthesis: effects on locomotion and angular vestibulo-ocular reflex in chinchillas.

Bilateral loss of vestibular sensation causes difficulty maintaining stable vision, posture and gait. An implantable prosthesis that partly restores vestibular sensation could significantly improve quality of life for individuals disabled by this disorder. We have developed a head-mounted multichannel vestibular prosthesis (MVP) that restores sufficient semicircular canal function to recreate a 3D angular vestibulo-ocular reflex (aVOR). In this study, we evaluated effects of chronic MVP stimulation on locomotion in chinchillas. Two of three animals examined exhibited significant improvements in both locomotion and aVOR.

Restoring the 3D vestibulo-ocular reflex via electrical stimulation: the Johns Hopkins multichannel vestibular prosthesis project.

Bilateral loss of vestibular sensation causes difficulty maintaining stable vision, posture and gait. An implantable prosthesis that partly restores normal activity on branches of the vestibular nerve should improve quality of life for individuals disabled by this disorder. We have developed a head-mounted multichannel vestibular prosthesis that restores sufficient semicircular canal function to partially recreate a normal 3-dimensional angular vestibulo-ocular reflex in animals. Here we describe several parallel lines of investigation directed toward refinement of this approach toward eventual clinical application.