Spatially Patterned Bi-electrode Epiretinal Stimulation for Axon Avoidance at Cellular Resolution

Vilkhu, R. S.; Madugula, S. S.; Grosberg, L. E.; Gogliettino, A. R.; Hottowy, P.; Dabrowski, W.; Sher, A.; Litke, A. M.; Mitra, S.; Chichilnisky, E. J.

doi:10.1101/2021.08.17.454395

bioRxiv · 10.1101/2021.08.17.454395

Spatially Patterned Bi-electrode Epiretinal Stimulation for Axon Avoidance at Cellular Resolution

Vilkhu, R. S.·Madugula, S. S.·Grosberg, L. E.·Gogliettino, A. R.·Hottowy, P.·Dabrowski, W.·Sher, A.·Litke, A. M.·Mitra, S.·Chichilnisky, E. J.

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Abstract

ObjectiveEpiretinal prostheses are designed to restore vision to people blinded by photoreceptor degenerative diseases by stimulating surviving retinal ganglion cells (RGCs), which carry visual signals to the brain. However, inadvertent stimulation of RGCs at their axons can result in non-focal visual percepts, limiting the quality of artificial vision. Theoretical work has suggested that axon activation can be avoided with current stimulation designed to minimize the second spatial derivative of the induced extracellular voltage along the axon. However, this approach has not been verified experimentally at the resolution of single cells. Approach. In this work, a custom multi-electrode array (512 electrodes, 10 m diameter, 60 m pitch) was used to stimulate and record RGCs in macaque retina ex vivo at single-cell, single-spike resolution. RGC activation thresholds resulting from bi-electrode stimulation, which consisted of bipolar currents simultaneously delivered through two electrodes straddling an axon, were compared to activation thresholds from traditional single-electrode stimulation. ResultsOn average, across three retinal preparations, the bi-electrode stimulation strategy reduced somatic activation thresholds ([~]21%) while increasing axonal activation thresholds ([~]14%), thus favoring selective somatic activation. Furthermore, individual examples revealed rescued selective activation of somas that was not possible with any individual electrode. Significance. This work suggests that a bi-electrode epiretinal stimulation strategy can reduce inadvertent axonal activation at cellular resolution, for high-fidelity artificial vision. Novelty & SignificanceThe effectiveness of bi-electrode 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 spatially patterned bi-electrode stimuli reduce unwanted axon activation and thus improve 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, at the resolution of single-cells and single-spikes, for the treatment of incurable blindness.

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Vilkhu, R. S., Madugula, S. S., Grosberg, L. E., Gogliettino, A. R., Hottowy, P., Dabrowski, W., Sher, A., Litke, A. M., Mitra, S., Chichilnisky, E. J.. 2021-08-18. Spatially Patterned Bi-electrode Epiretinal Stimulation for Axon Avoidance at Cellular Resolution. https://doi.org/10.1101/2021.08.17.454395

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