Combined ionic direct current and pulse frequency modulation improves the dynamic range of vestibular canal stimulation

Abstract

BACKGROUND: Vestibular prostheses emulate normal vestibular function by electrically stimulating the semicircular canals using pulse frequency modulation (PFM). Spontaneous activity at the vestibular nerve may limit the dynamic range elicited by PFM. One proposed solution is the co-application of ionic direct current (iDC) to inhibit this spontaneous activity. OBJECTIVE: We aimed to test the hypothesis that a tonic iDC baseline delivered in conjunction with PFM to the vestibular semicircular canals could improve the dynamic range of evoked eye responses. METHODS: Gentamicin-treated chinchillas were implanted with microcatheter electrodes in the vestibular semicircular canals through which pulsatile and iDC current was delivered. PFM was used to modulate vestibulo-ocular reflex (VOR) once it was adapted to a preset iDC and pulse-frequency baseline. Responses to stimulation were assessed by recording the evoked VOR eye direction and velocity. RESULTS: PFM produced VOR responses aligned to the stimulated canal. Introduction of an iDC baseline lead to a small but statistically significant increase in eye response velocity, without influencing the direction of eye rotation. CONCLUSIONS: Tonic iDC baselines increase the dynamic range of encoding head velocity evoked by pulsatile stimulation, potentially via the inhibition of spontaneous activity in the vestibular nerve.

Direct current effects on afferent and hair cell to elicit natural firing patterns

“…However, it still requires testing to determine whether the naturalistic rate and statistics of firing produced by GVS stimulation is correctly received by downstream targets of GVS stimulation. Past experiments in which hair cells were impaired on one side of the vestibular system and replaced with GVS stimulation produced VORs that more closely resembled natural eye movements than stimulation with pulses ( Aplin et al., 2019a , 2019b ). This appears to indicate that the GVS-evoked afferent firing patterns are well received by downstream targets and therefore useful in connecting damaged neuron in neural circuitry.…”

“…Recent innovations with DC stimulation technology have also led to the development of safe direct current stimulation (SDCS) ( Fridman and Della Santina, 2013 ; Cheng et al., 2017 ; Fridman, 2017 ; Ou and Fridman, 2017 ; Aplin and Fridman, 2019 ), which makes it possible to chronically deliver localized direct ionic current from an implantable device. Preliminary behavioral testing of the SDCS for vestibular balance disorders as well as for the treatment of pain suppression revealed that DC neuromodulation has multiple beneficial effects on targeted neural populations that cannot be produced with pulsatile stimulation, including inhibiting, exciting, and sensitizing neural targets in a natural, desynchronized manner ( Yang et al., 2018 ; Aplin and Fridman, 2019 ; Aplin et al., 2019a , 2019b ). Although these behavioral results are encouraging, the cellular mechanisms that respond to electric fields are not well understood.…”

Ionic direct current modulation evokes spike-rate adaptation in the vestibular periphery

“…In one afferent recording, the response could be inverted by moving the iDC stimulator from outside to inside the tissue during recording. All further experiments were performed with the iDC stimulator in the tissue (second configuration) as the relationship between current polarity and spike rate response matched previous behavioral experiments in chinchilla 9,10 .…”

“…Spike rate adaptation in response to constant stimulation currents has been commonly reported in the nervous system, including in the central vestibular system 23 . Existing literature on galvanic stimulation has identified a possible adaptation effect but did not attempt to quantify the afferent response to long-duration DC steps 3,10 . To investigate the potential for time-dependent changes in the afferent response to iDC stimulation, 1 min long iDC steps of ±10 µA were applied, and afferent response rates were monitored (Fig.…”

“…Based on vestibular-ocular reflex responses to iDC stimulation in the awake chinchilla in-vivo , it was recently shown that an iDC-based neuro-modulation approach is functionally feasible and may have benefits over a comparable pulsatile methodology 9,10 . However, these studies suggest that the relationship between iDC and vestibulo-ocular reflex (VOR) output is dependent on whether short (150 ms) current steps were delivered independently or after long (=>1 minute) “adaptation” steps 9 .…”