Epiretinal stimulation with local returns enhances selectivity at cellular resolution

Abstract

Objective. Epiretinal prostheses are designed to restore vision in people blinded by photoreceptor degenerative diseases, by directly activating retinal ganglion cells (RGCs) using an electrode array implanted on the retina. In present-day clinical devices, current spread from the stimulating electrode to a distant return electrode often results in the activation of many cells, potentially limiting the quality of artificial vision. In the laboratory, epiretinal activation of RGCs with cellular resolution has been demonstrated with small electrodes, but distant returns may still cause undesirable current spread. Here, the ability of local return stimulation to improve the selective activation of RGCs at cellular resolution was evaluated. Approach. A custom multi-electrode array (512 electrodes, 10 μm diameter, 60 μm pitch) was used to simultaneously stimulate and record from RGCs in isolated primate retina. Stimulation near the RGC soma with a single electrode and a distant return was compared to stimulation in which the return was provided by six neighboring electrodes. Main results. Local return stimulation enhanced the capability to activate cells near the central electrode (<30 µm) while avoiding cells farther away (>30 µm). This resulted in an improved ability to selectively activate ON and OFF cells, including cells encoding immediately adjacent regions in the visual field. Significance. These results suggest that a device that restricts the electric field through local returns could optimize activation of neurons at cellular resolution, improving the quality of artificial vision. (EJC) and P30 EY019005 (EJC) and F32EY025120 (LG), Stanford Neurosciences Institute Novelty & Significance: The effectiveness of local return stimulation for enhancing the electrical activation of retinal neurons was tested using high-density multi-electrode recording and stimulation in isolated macaque retina. The results suggest that local returns may reduce unwanted evoked activity and thus optimize the selectivity of stimulation at cellular resolution. Similar patterns could be implemented in a future high-resolution prosthesis to permit a more faithful replication of normal retinal activity for the treatment of incurable blindness.

Automatic Identification of Axon Bundle Activation for Epiretinal Prosthesis

“…Electrophysiology data were collected from retinas of terminally anesthetized rhesus macaque monkeys (male and female, ages 11–20 years), which were euthanized in the course of experiments in other laboratories. 1 Segments of peripheral retina were isolated and mounted on an array of extracellular microelectrodes as described in previous studies [ 4 ]–[ 6 ], [ 37 ], [ 38 ]. A custom multi-electrode system was used for stimulation and recording spikes in RGCs [ 5 ], [ 13 ], [ 36 ].…”

Probing and predicting ganglion cell responses to smooth electrical stimulation in healthy and blind mouse retina

“…First, it could be used to directly activate individual RGCs in a spatially confined manner, avoiding axonal stimulation which causes the occurrence of elongated phosphenes experienced by patients wearing a retinal implant 57 . In this case, however, differential activation of retinal pathways could probably not be achieved by using selective stimulus waveforms, but would have to occur through targeted stimulation of identified RGCs 22,58,59 . Second, the short and precise latencies found here are a result of fast and precise RGC responses to electrical stimulation.…”

Optimization of Electrical Stimulation for a High-Fidelity Artificial Retina

“…The modular nature of the greedy algorithm may help with design decisions for a future advanced device. For example, the impact of different electrical stimulation patterns such as current steering [17], [19], [20] and local return [21], [22] can be directly compared by evaluating the quality of the final inferred visual image.…”