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.
Highlights
Neural cross-talk[14,15]
The interaction between adjacent electrodes can be used, for example, to reduce activation thresholds in the vicinity of an active electrode[15] or to evoke intermediate percepts[25], the beneficial effects of field overlapping can be achieved with sub-threshold stimulus levels
If a group of electrodes are activated simultaneously using supra-threshold current densities, deleterious effects can result such as a reduced visual acuity[16] or an undesired neural inhibition[26] as shown in this study
Summary
Neural cross-talk[14,15]. This can be explained in terms of a wide electric field spread from single electrodes, causing excessive stimulation levels by summation of overlapping electric fields[16]. It is known that electrical stimulation can produce both activation and inhibition of the RGCs. Boinagrov and co-workers explained the inhibitory effect as sodium current reversal under strong stimulation conditions and demonstrated the existence of a so-called upper threshold in vitro, beyond which no spike can be elicited[19]. Boinagrov and co-workers explained the inhibitory effect as sodium current reversal under strong stimulation conditions and demonstrated the existence of a so-called upper threshold in vitro, beyond which no spike can be elicited[19] This threshold appears below harmful stimulation levels and not too far above the activation threshold. Based on previous experimental studies on electrical interference in visual prostheses[15,25], the authors hypothesize that additive effects of overlapping electric fields can inhibit the ability to evoke action potentials (APs) in the RGC regions close to stimulating electrodes[26]. A population-based RGC computational model was developed to examine the response of a RGC layer and to explain the experimental outcomes
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