Increasing Electrical Stimulation Efficacy in Degenerated Retina: Stimulus Waveform Design in a Multiscale Computational Model

Abstract

A computational model of electrical stimulation of the retina is proposed for investigating current waveforms used in prosthetic devices for restoring partial vision lost to retinal degenerative diseases. The model framework combines a connectome-based neural network model characterized by accurate morphological and synaptic properties with an admittance method model of bulk tissue and prosthetic electronics. In this model, the retina was computationally "degenerated," considering cellular death and anatomical changes that occur early in disease, as well as altered neural behavior that develops throughout the neurodegeneration and is likely interfering with current attempts at restoring vision. A resulting analysis of stimulation range and threshold of ON ganglion cells within the retina that are either healthy or in beginning stages of degeneration is presented for currently used stimulation waveforms, and an asymmetric biphasic current stimulation for subduing spontaneous firing to allow increased control over ganglion cell firing patterns in degenerated retina is proposed. Results show that stimulation thresholds of retinal ganglion cells do not notably vary after beginning stages of retina degeneration. In addition, simulation of proposed asymmetric waveforms showed the ability to enhance the control of ganglion cell firing via electrical stimulation.

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“…The results showed that retinal ganglion cell stimulation thresholds do not vary much after the early stages of retinal degeneration. The simulation of the proposed asymmetric waveforms also showed the ability to improve the control of the ganglion cell firing via electrical stimulation [41].…”

“…To restore vision in patients with degenerative diseases, retinal prosthetic devices have been developed, which through electrical stimulation of the local regions of retinal tissue, bring together spatiotemporal patterns to represent the patient-facing image. These devices have proven to be effective, which has led to the design of various types of devices, many of which are in trials and some are already in the market [41]. For example, Argus II by Second Sight Medical Products Inc. (Sylmar, CA, USA) is already in clinical trials and has been shown to provide patients considerable visual perception to the extent that subjects can recognize objects and differentiate letters.…”

“…Loizos et al proposed a computer model of electrical retinal stimulation to investigate waveforms already used in prosthetic devices to restore partial vision lost by retinal degenerative diseases [41]. To understand the degenerate retinal response to electrical stimulation used and to develop new electrode geometries and stimulus waveforms, the authors provided a simulation framework for increasing the effectiveness of electrical stimulation.…”

“…Based on a connectivity dataset, a model of a ganglion cell network with a realistic cell morphology and synaptic type, distribution, and weight is built on NEURON [132]. In the study by Loizos et al [41], the biophysical data available in the literature were incorporated into each cell and a script was also written to apply the extracellular electric field from Admittance Method simulations to observe the resulting network and cellular behavior at a given input. The intrinsic properties of AII amacrine cells within this model were altered (following Choi et al) to produce an oscillatory membrane potential and induce spontaneous neural activity that mimics a degenerated retina [116].…”

“…The simulation of the proposed asymmetric waveforms also showed the ability to improve the 751 control of the ganglion cell firing via electrical stimulation [41].…”