Spatially patterned bi-electrode epiretinal stimulation for axon avoidance at cellular resolution

Abstract

Objective. Epiretinal 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 μm diameter, 60 μm 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. Main results. On 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.

High spatial resolution artificial vision inferred from the spiking output of retinal ganglion cells stimulated by optogenetic and electrical means

“…More interestingly, we did not detect spiking activity caused by the grating stimulus for one of the reversals. This is in contrast to the results obtained for short pulsatile waveforms (Lorach et al, 2015;Chenais et al, 2021) and may help to solve the open question of avoidance of axonal stimulation (Beyeler et al, 2019;Tandon et al, 2021;Vilkhu et al, 2021) in epiretinal configuration. The grating stimulus used here isolates the source of activation, i.e., helps separate between activation of the soma and distal axons.…”

Factors affecting two-point discrimination in Argus II patients

“…We did not model the effects of axonal stimulation on amplitude thresholds. However, axonal stimulation is unlikely to affect current amplitude thresholds significantly—under most stimulation protocols axonal thresholds are very similar to thresholds near the ganglion soma ( Jensen et al, 2005 ; Vilkhu et al, 2021 ).…”

High-fidelity reproduction of visual signals by electrical stimulation in the central primate retina

“…Thus, stimulation with these electrodes must be avoided: activation of axon bundles is likely to produce widespread, poorly controlled spiking in neurons located off the electrode array, with the potential for large, irregular phosphenes, as has been observed with much coarser stimulation approaches used in present-day epiretinal implants (Nanduri, 2011). Recent work, however, suggests an active axon avoidance strategy: in the peripheral retina, a bipolar, bi-electrode electrical stimulus often preserved somatic activation thresholds, while increasing axonal activation thresholds (Vilkhu et al, 2021), as predicted from biophysical models of cellular activation (Rattay, 1986(Rattay, , 1999Rattay and Resatz, 2004). Such a stimulus could potentially be applied in a future device to minimize the activation of axon bundles without reducing the number of RGCs that can be targeted for stimulation.…”

“…Multi-electrode stimulation strategies (Townshend and White, 1987;Sweeney et al, 1990;Bonham and Litvak, 2008;Martens et al, 2011) can be used to augment single-electrode stimulation, which may potentially enhance reconstruction performance. These methods have been applied previously in the peripheral retina for minimizing inadvertent neighboring RGC activation (Jepson et al, 2014a;Fan et al, 2019) as well as distant RGC activation (Nanduri, 2011) by the active avoidance of axonal stimulation (Vilkhu et al, 2021), using biophysical models of cellular activation as a theoretical basis (Rattay, 1986(Rattay, , 1999Rattay and Resatz, 2004).…”