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

Abstract

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.

A prosthesis utilizing natural vestibular encoding strategies improves sensorimotor performance in monkeys

“…However, we also observed substantially lower gains in 1 monkey. Comparable variability in evoked VOR gains has likewise been reported across subjects in prior human [ 15 , 21 ] and monkey [ 16 , 34 ] studies. One factor that could contribute to such gain variability is differences in the precise placement of the electrodes targeting the ampullae [ 52 ].…”

“…Notably, mappings used currently in clinical trials directly map instantaneous angular head velocity to a specific pulse rate—equivalent to the static mapping in our present study (e.g., [ 15 , 20 , 21 ]). Likewise, static mappings have largely been used in prior studies in primate animal models [ 16 , 34 – 36 ]. As expected, our static mapping generated VOR responses consistent with the results of these prior studies, which were characterized by poor phase compensation.…”

“…In this prior study, the experimentally measured afferent stimulation efficacy was only approximately 27%, for monkey with comparable VOR eye movement gain as Monkey G (see Fig 3 of [ 18 ])—a value similar to that estimated here (28%). We thus speculate that the generally low prosthesis-evoked VOR gains reported in the literature (human participants [ 15 , 21 ]; monkeys [ 16 , 34 ]) are, at least in part, due to artificially limiting the dynamic range of stimulation relative to the firing rate of the afferents. We propose that the use of mappings, which actually account for the efficacy of afferent activation ( Fig 6D ), would lead to improved VOR gains, while maintaining the dynamic range required to represent the natural range of head movements experienced in everyday life [ 28 , 29 , 45 ].…”

Pulsatile electrical stimulation creates predictable, correctable disruptions in neural firing

“…Electrical stimulation has a long history as an essential tool in neuroscience research and served to advance our understanding of both the functional roles of localized neuronal populations as well as the connectivity of neural circuits. Invasive electrical stimulation is also now becoming an increasingly popular clinical intervention to treat a wide range of neurological disorders (1, 2), including neural prostheses to restore sensory function (3)(4)(5)(6) (7), neural prostheses to restore motor function (8), and even neural implants for psychiatric disorders (9). Importantly, a feature of neural microsimulation that is common to all of these applications is that the stimulation waveform is based on a series of biphasic, charge-balanced pulses, because such pulsatile stimulation prevents damage to the local populations of activated neurons (10).…”

“…pulse amplitude with sound loudness, in the case of a cochlear prostheses) or fixed-amplitude pulses are delivered and pulse rate is varied (i.e. pulse rate with head velocity, in the case of a vestibular prostheses) (3,5,(11)(12)(13). An assumption that is generally inherent to these mappings is a one-to-one mapping between each pulse in a given stimulation train and firing rate (11).…”