Closed-Loop Efficient Searching of Optimal Electrical Stimulation Parameters for Preferential Excitation of Retinal Ganglion Cells

Abstract

The ability for visual prostheses to preferentially activate functionally-distinct retinal ganglion cells (RGCs) is important for improving visual perception. This study investigates the use of high frequency stimulation (HFS) to elicit RGC activation, using a closed-loop algorithm to search for optimal stimulation parameters for preferential ON and OFF RGC activation, resembling natural physiological neural encoding in response to visual stimuli. We evaluated the performance of a wide range of electrical stimulation amplitudes and frequencies on RGC responses in vitro using murine retinal preparations. It was possible to preferentially excite either ON or OFF RGCs by adjusting amplitudes and frequencies in HFS. ON RGCs can be preferentially activated at relatively higher stimulation amplitudes (>150 μA) and frequencies (2–6.25 kHz) while OFF RGCs are activated by lower stimulation amplitudes (40–90 μA) across all tested frequencies (1–6.25 kHz). These stimuli also showed great promise in eliciting RGC responses that parallel natural RGC encoding: ON RGCs exhibited an increase in spiking activity during electrical stimulation while OFF RGCs exhibited decreased spiking activity, given the same stimulation amplitude. In conjunction with the in vitro studies, in silico simulations indicated that optimal HFS parameters could be rapidly identified in practice, whilst sampling spiking activity of relevant neuronal subtypes. This closed-loop approach represents a step forward in modulating stimulation parameters to achieve appropriate neural encoding in retinal prostheses, advancing control over RGC subtypes activated by electrical stimulation.

Spike-triggered average electrical stimuli as input filters for bionic vision—a perspective

“…They found that visual ON cells tended to respond during the anodal phase of a slow (5 Hz) sine wave while OFF cells responded during the cathodal phase. Other recent contributions to growing evidence of cell-type selective stimulation include (Twyford & Fried 2016;Guo et al 2014;Im & Fried 2016;Goetz et al 2015;Im et al 2018;Guo et al 2018;Qin et al 2017).…”

Stimulation Strategies for Improving the Resolution of Retinal Prostheses

“…Recent years have also revealed an interesting observation known as the upper threshold phenomenon ( Figure 4B) in RGC activation, i.e., a drop of response efficacy instead of saturation when stimulus strength exceeds a certain amount. The upper thresholds phenomenon was first observed by Boinagrov et al (2012), and then reported again in several other studies (Barriga-Rivera et al, 2017;Guo et al, 2018;Kotsakidis et al, 2018;Meng et al, 2018). Meng et al (2018) found that 20/21 cells exhibited the upper threshold phenomenon when sufficiently high charge was injected.…”

“…Although different receptive field polarities were also observed in the degenerated retina, it was not possible to identify the cell type. Comparing the waveforms between healthy and degenerated retinas, they found significant Guo et al (2018).…”

“…Twyford et al (2014) used 2 kHz stimulation with amplitude modulation using a slower envelope and successfully modulated the activities of ON and OFF cells in a differential manner. Guo et al (2018) then systematically studied ON and OFF responses to high frequency stimulation (>1 kHz) with constant amplitudes (Figures 7C,D). With synaptic blockers, ON cells were preferentially activated at relatively higher stimulation amplitudes (>150 µA) and frequencies (2-6.25 kHz), however, OFF RGCs were activated by lower stimulation amplitudes (40-90 µA) across all tested frequencies.…”

“…With synaptic blockers, ON cells were preferentially activated at relatively higher stimulation amplitudes (>150 µA) and frequencies (2-6.25 kHz), however, OFF RGCs were activated by lower stimulation amplitudes (40-90 µA) across all tested frequencies. The mechanisms underlying differential responses of ON and OFF cells have not been revealed experimentally but may be due to different ionic currents present in ON and OFF cells and different cell morphologies, as illustrated computationally (Guo et al, 2014(Guo et al, , 2018Kameneva et al, 2016).…”