High-amplitude electrical stimulation can reduce elicited neuronal activity in visual prosthesis

Abstract

Retinal electrostimulation is promising a successful therapy to restore functional vision. However, a narrow stimulating current range exists between retinal neuron excitation and inhibition which may lead to misperformance of visual prostheses. As the conveyance of representation of complex visual scenes may require neighbouring electrodes to be activated simultaneously, electric field summation may contribute to reach this inhibitory threshold. This study used three approaches to assess the implications of relatively high stimulating conditions in visual prostheses: (1) in vivo, using a suprachoroidal prosthesis implanted in a feline model, (2) in vitro through electrostimulation of murine retinal preparations, and (3) in silico by computing the response of a population of retinal ganglion cells. Inhibitory stimulating conditions led to diminished cortical activity in the cat. Stimulus-response relationships showed non-monotonic profiles to increasing stimulating current. This was observed in vitro and in silico as the combined response of groups of neurons (close to the stimulating electrode) being inhibited at certain stimulating amplitudes, whilst other groups (far from the stimulating electrode) being recruited. These findings may explain the halo-like phosphene shapes reported in clinical trials and suggest that simultaneous stimulation in retinal prostheses is limited by the inhibitory threshold of the retinal ganglion cells.

Long‐term anesthetic protocol in rats: feasibility in electrophysiology studies in visual prosthesis

“…. The overall resulting P 50 threshold was 5.24 ± 0.24 μC/cm 2 ( n = 5), which is lower ( P ‐value < 0.05) than those obtained from a feline model using a similar combination of intravenous and gaseous anesthesia …”

“…The rat has a sufficiently large eye to implant an electrode array in a model of the disease. Acute procedures are however long and require extended periods of surgical anesthesia to maintain the animal and to ensure its well‐being over several hours or days . In light of the 3‐Rs principle (replacement, reduction, and refinement), this approach helps reduce the number of animals required during the investigation of retinal stimulation paradigms: With extended anesthetic protocols, more scientific questions can be attempted during a single trial.…”

“…All electrophysiological data in this study were analyzed off‐line using custom scripts in Matlab R2016b (The MathWorks, Natick, MA, USA). All signals were then band‐pass filtered between 0.3 and 5 kHz using a fifth‐order zero‐phase Butterworth filter as in previous publications . Spikes were detected using a threshold of 3.8 times the root‐mean‐square value of the recordings calculated by joining the 100 ms prestimulus bins for each channel.…”

“…Acute electrophysiology experimentation is the approach of choice of many areas of research and is particularly common in those fields in which functional models are not available or easily accessible. In the case of visual prosthesis research, a feline model has been traditionally used as it has a highly developed visual system with sufficiently large eye to implant a retinal electrode array . Natural cases of retinal degeneration have been reported in cats, and other researchers have induced it by administering adenosine triphosphate in the vitreous .…”

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.…”