Progress toward development of a multichannel vestibular prosthesis for treatment of bilateral vestibular deficiency

Abstract

This article reviews vestibular pathology and the requirements and progress made in the design and construction of a vestibular prosthesis. Bilateral loss of vestibular sensation is disabling. When vestibular hair cells are injured by ototoxic medications or other insults to the labyrinth, the resulting loss of sensory input disrupts vestibulo-ocular reflexes (VORs) and vestibulo-spinal reflexes that normally stabilize the eyes and body. Affected individuals suffer poor vision during head movement, postural instability, chronic disequilibrium, and cognitive distraction. Although most individuals with residual sensation compensate for their loss over time, others fail to do so and have no adequate treatment options. A vestibular prosthesis analogous to cochlear implants but designed to modulate vestibular nerve activity during head movement should improve quality of life for these chronically dizzy individuals. We describe the impact of bilateral loss of vestibular sensation, animal studies supporting feasibility of prosthetic vestibular stimulation, the current status of multichannel vestibular sensory replacement prosthesis development, and challenges to successfully realizing this approach in clinical practice. In bilaterally vestibular-deficient rodents and rhesus monkeys, the Johns Hopkins multichannel vestibular prosthesis (MVP) partially restores the three-dimensional (3D) VOR for head rotations about any axis. Attempts at prosthetic vestibular stimulation of humans have not yet included the 3D eye movement assays necessary to accurately evaluate VOR alignment, but these initial forays have revealed responses that are otherwise comparable to observations in animals. Current efforts now focus on refining electrode design and surgical technique to enhance stimulus selectivity and preserve cochlear function, optimizing stimulus protocols to improve dynamic range and reduce excitation-inhibition asymmetry, and adapting laboratory MVP prototypes into devices appropriate for use in clinical trials.

Copyright © 2012 Wiley Periodicals, Inc.

Figures

Fig. 1

Johns Hopkins MVP1 multichannel vestibular prosthesis. (A) MVP1 is designed for conducting acute and chronic vestibular stimulation animal experiments. A top view of the 31 × 31 × 11 mm3 device shows the three orthogonally oriented gyroscopes and the microcontroller. (B) Functions used by MVP1 to map head angular velocity to pulse rate delivered to the corresponding electrode channel. (C) Bench tests of the prosthesis show output of the device directed to three electrode channels as the prosthesis is rotated sinusoidally about each of the three gyroscope axes (Horizontal, LARP, and RALP). (D) Experimental results obtained from chinchillas implanted with intra-labyrinthine electrodes show partial restoration of 3D VOR eye responses to head rotations about Horizontal, LARP, and RALP axes. Reprinted with permission from Della Santina et al., IEEE Trans Biomed Eng, 2007, 54:1016–1030.

Fig. 1

Johns Hopkins MVP1 multichannel vestibular prosthesis. (A) MVP1 is designed for conducting acute and chronic vestibular stimulation animal experiments. A top view of the 31 × 31 × 11 mm3 device shows the three orthogonally oriented gyroscopes and the microcontroller. (B) Functions used by MVP1 to map head angular velocity to pulse rate delivered to the corresponding electrode channel. (C) Bench tests of the prosthesis show output of the device directed to three electrode channels as the prosthesis is rotated sinusoidally about each of the three gyroscope axes (Horizontal, LARP, and RALP). (D) Experimental results obtained from chinchillas implanted with intra-labyrinthine electrodes show partial restoration of 3D VOR eye responses to head rotations about Horizontal, LARP, and RALP axes. Reprinted with permission from Della Santina et al., IEEE Trans Biomed Eng, 2007, 54:1016–1030.

Fig. 2

Common signal processing elements used in vestibular prosthesis design. Gyroscopes sense head rotation about each axis corresponding to the SCC orientations. These angular velocity signals are filtered to more closely emulate the transfer function of the SCC hydrodynamics. Linear coordinate transformation uses matrix M to precorrect for misalignment between the axis and the velocity of the actual head rotation, and those of the head movement sensation evoked by electrode stimulation. The corrected velocity signals are then mapped to amplitude and pulse rate specifications for each electrode implanted in the LARP, RALP, and Horizontal SCCs. These pulse-rate and pulse-amplitude specifications are combined with constant stimulus parameters (stimulation and reference electrode selection and pulse-width of current pulses) by the pulse-generation algorithm and circuitry to deliver biphasic charge-balanced stimuli to the electrodes. The same algorithm schedules the delivery of each pulse and ensures that the pulses delivered to the different electrodes do not overlap in time.

Fig. 3

VOR responses during a 2 Hz, 50°/sec RALP head rotation encoded by prosthetic stimulation delivered by a monopolar electrode in the LP SCC ampulla with respect to a distant reference. For each panel, stimulus current is labeled; all other parameters were kept constant. In each, the ordinate axis and inverted head velocity trace have been scaled to enhance visibility all components of the response. Barely visible at 50 μA, the response at 100 μA includes conjugate RALP rotations similar to normal chinchilla responses, except for a horizontal component that could indicate spurious stimulation of the horizontal SCC ampullary nerve or the otolithic endorgans. At 250 μA, the LP response has grown to over 150°/sec peak velocity, but the spurious horizontal component nearly equals it. Reprinted with permission from Della Santina et al., IEEE Trans Biomed Eng, 2007, 54:1016–1030.

Fig. 4

(A) Precompensatory remapping improves both axis and amplitude of prosthesis-encoded head velocity percepts as measured by 3D VOR responses in chinchillas. Column 1: Mean head and eye velocity for a normal chinchilla during 50°/sec peak 2 Hz whole-body rotations in darkness about the axis of each coplanar pair of SCCs: Horizontal (top row), LARP (middle row), and RALP (bottom row). For clarity, only mean responses are shown; the standard deviation for each trace was <6°/sec. Eye traces are inverted to compare with head. Normal chinchillas exhibit good alignment with head rotation axis and symmetric gain (eye velocity/head velocity) of about 0.5. Dashed curves indicate mean responses for all animals studied. Column 2: VOR responses for chinchillas treated with intratympanic gentamicin (ITG) in one ear are attenuated during ipsilesional rotation. Column 3: Head rotation of a bilaterally vestibular-deficient animal after ITG and canal plugging elicits no response for any axis when prosthesis is off. Column 4: Responses for the same animal when pulse rates on individual electrodes implanted in the left labyrinth SCCs are modulated without precompensatory 3D remapping. Misalignment owing to current spread is evident for all three axes of rotation. Column 5: VOR responses of the same animal to stimuli with precompensatory 3D remapping are more like those of animals with a single working labyrinth (Column 2). (B) 3D VOR responses to prosthetic stimuli encoding head rotation about each of the three SCC axes without (B1) and with (B2) precompensatory 3D remapping, for each of four implanted chinchillas. Reprinted with permission from Fridman et al., J Assoc Res Otolaryngol, 2010, 11:367–381.

Fig. 5

Changes in axis of eye response for one chinchilla over 7 days of stimulation during continual MVP use. Each data vector shows the 3D axis and magnitude of VOR responses during whole-body 2 Hz, 50°/sec peak head rotations in darkness about the mean horizontal, LARP, and RALP SCC axes. Vector length indicates the peak response velocity; for comparison, thick axes depict inverse of 50°/sec peak head rotations about each canal axis. Progression over time toward the ideal response is apparent for each axis of head rotation, indicating that crossaxis adaptation corrects VOR misalignment over the first week of MVP use. Reprinted with permission from Dai et al., Exp Brain Res 2011, 210:595–606.

Fig. 6

Peak VOR eye velocity of a BVD chinchilla in response to steps in MVP pulse rate from baseline to maximum of 400 pulse/sec or minimum of 0 pulse/sec. Baseline stimulation pulse rate is indicated for each symbol. Responses become more symmetric as baseline rate is increased, but the increase in symmetry is owing more to loss of excitatory response than to the modest increases in inhibitory response. Reprinted with permission from Davidovics et al., ARO, 2009.

Fig. 7

Vestibulo-cerebellar circuits adapt to power cycling of the vestibular prosthesis delivering stimulation to a guinea pig horizontal branch of the vestibular nerve via implanted SCC electrode in 1-week-ON, 1-week-OFF experimental paradigm. When the prosthesis was first turned ON at the beginning of the first week (A, purple dots), the nystagmus lasted for ~1,000 min. When it was turned OFF at the beginning of the second week, nystagmus again lasted ~1,000 min (B, purple dots). Post-transition nystagmus duration decreased after each cycle. Nystagmus in response to turning the prosthesis ON at week 5 was ~10 min (blue dots), and nystagmus owing to turning the prosthesis OFF at week 6 lasted only ~20 sec (red dots). Reprinted with permission from Merfeld et al., IEEE Trans Biomed Eng, 2006, 53:2362–2372.

Fig. 8

MVP stimulation helps reduce abnormal circling ambulation behavior in BVD chinchillas. Unlike normal animals, chinchillas rendered BVD via bilateral intratympanic gentamicin injection tend to run in tight circles repeatedly when startled. After these BVD animals wear a head-mounted MVP for 10 days, the circling behavior diminishes significantly. (It apparently also remains greater than normal; however, that difference did not achieve statistical significance, possibly owing to the small sample size.) The circling behavior returns after MVP removal. Asterisks denote significance at P < 0.05. Reprinted with permission from Sun et al, Proceedings of the IEEE 33rd Annual EMBC Conference, 2011.

Fig. 9

A human subject implanted with a modified cochlear implant electrode in the vestibular labyrinth exhibited nystagmus lasting 27 min after initial device activation and ~3 min after initial deactivation. After several ON→OFF→ON cycles, devices reactivation elicited