Optimizing electrical stimulation in the multichannel vestibular prosthesis

There is no effective treatment available for individuals who, despite vestibular rehabilitation exercises, are unable to compensate for bilateral profound loss of vestibular sensation, which causes chronic disequilibrium (dizziness) and blurs vision by disrupting vestibulo-ocular reflexes (VOR) that normally stabilize the eyes during head movement. The Johns Hopkins Vestibular NeuroEngineering Laboratory (VNEL) developed a multichannel vestibular prosthesis that partly restores normal function in animals with vestibular loss by detecting head movements via 3 mutually orthogonal gyroscopes affixed to the skull and electrically stimulating vestibular nerve branches to mimic the normal labyrinth, which encodes head movement by increasing or decreasing firing rate of the vestibular afferents about a baseline firing rate approximately in proportion to head rotation velocity. This prosthesis emulates the normal encoding scheme by modulating stimulus pulse rate and/or current amplitude above and below a baseline stimulation rate (BSR) and a baseline stimulation current (BSC). This approach has been limited by stimulation current spread, which results in misalignment between the direction of head motion and prosthetically-elicited VOR, and insufficient velocity of VOR response to head movements in the inhibitory direction (away from the implant). To accurately encode head movements, it is important to determine the optimal values for stimulation pulse parameters such as pulse rate, amplitude, duration and interphase gap. This dissertation presents the results of a series of stimulus optimization studies I performed with colleagues in VNEL.;First, we report that the electrically evoked VOR in chinchillas exhibits vector superposition and linearity to a sufficient degree that a multichannel vestibular prosthesis incorporating a precompensatory 3D coordinate transformation can correct misalignment in any direction. Increasing pulse rate increased response amplitude while maintaining a relatively constant axis of rotation.;Next, we report that increasing pulse amplitude (range 0-325 IAA) also increased response amplitude but spuriously shifted eye movement axis, probably due to current spread beyond the target nerve. Shorter pulse durations (range 28-340 us) required less charge to elicit a given response amplitude and caused less axis shift than longer durations. Varying interphase gap (range 25-175 us) had no significant effect.;Next, we report that significantly larger VOR eye velocities in the inhibitory direction were elicited by adapting chinchillas to an elevated BSR and BSC 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 significantly larger VOR eye responses in the excitatory direction (head movement toward the implant) than either pulse rate or current modulation alone. Time constants associated with the recovery of VOR excitability following adaptation to elevated BSRs implicate synaptic vesicle depletion as a possible mechanism for the small range of excitatory eye velocity elicited by rate modulation alone.;Finally, we report that following experiments in chinchillas, we extended these stimulation experiments to rhesus monkeys, which are more similar to humans than chinchillas in vestibular anatomy and physiology. Combining successful stimulation strategies of precompensatory 3D coordinate transformation, optimal pulse parameter values, elevated baseline stimulation, and co-modulation achieved accurate and robust VOR responses to stimulation representing head movements throughout the 3D range normally transduced by a healthy labyrinth.;Taken together, these findings provide a solid preclinical foundation for application of vestibular stimulation in humans.