Activation of ganglion cells and axon bundles using epiretinal electrical stimulation

Abstract

Epiretinal prostheses for treating blindness activate axon bundles, causing large, arc-shaped visual percepts that limit the quality of artificial vision. Improving the function of epiretinal prostheses therefore requires understanding and avoiding axon bundle activation. This study introduces a method to detect axon bundle activation on the basis of its electrical signature and uses the method to test whether epiretinal stimulation can directly elicit spikes in individual retinal ganglion cells without activating nearby axon bundles. Combined electrical stimulation and recording from isolated primate retina were performed using a custom multielectrode system (512 electrodes, 10-μm diameter, 60-μm pitch). Axon bundle signals were identified by their bidirectional propagation, speed, and increasing amplitude as a function of stimulation current. The threshold for bundle activation varied across electrodes and retinas, and was in the same range as the threshold for activating retinal ganglion cells near their somas. In the peripheral retina, 45% of electrodes that activated individual ganglion cells (17% of all electrodes) did so without activating bundles. This permitted selective activation of 21% of recorded ganglion cells (7% of expected ganglion cells) over the array. In one recording in the central retina, 75% of electrodes that activated individual ganglion cells (16% of all electrodes) did so without activating bundles. The ability to selectively activate a subset of retinal ganglion cells without axon bundles suggests a possible novel architecture for future epiretinal prostheses. Large-scale multielectrode recording and stimulation were used to test how selectively retinal ganglion cells can be electrically activated without activating axon bundles. A novel method was developed to identify axon activation on the basis of its unique electrical signature and was used to find that a subset of ganglion cells can be activated at single-cell, single-spike resolution without producing bundle activity in peripheral and central retina. These findings have implications for the development of advanced retinal prostheses.

A model of ganglion axon pathways accounts for percepts elicited by retinal implants

“…Model fits to behavioral data suggest that sensitivity to electrical stimulation is not confined to the axon initial segment (38), but can be modeled as falling off with different decay constants along the axon (with ranging from 500-1,420 μm) and orthogonally from the axon (with ranging from 86-437 μm), resulting in visual percepts ranging from 'blobs' to 'streaks' and 'wedges' depending on both the relative values of and , and the retinal location of the stimulating electrode. These results are in agreement with theoretical work suggesting an anisotropic spread of current in the retinal tissue (29) as well as previous animal literature demonstrating that epiretinal stimulation leads to activation of passing axon fibers (18,38,39,41), which can severely distort the quality of the generated visual experience (16,18,40,42,43). Our findings suggest that the spatial distortions reported by patients are not arbitrary, but rather depend on the topographic organization of optic nerve fiber bundles in each subject's retina, which can be captured by a computational model.…”

Electrical Stimulus Artifact Cancellation and Neural Spike Detection on Large Multi-Electrode Arrays

“…the number of ways in which ways neurons can be stimulated) if the available stimulus space resulting from singleelectrode stimulation does not lead to a complete selective activation of neurons (in the retina, this will often be the case [44]). There is a caveat, though: allowing for arbitrary stimulation patterns is not possible without further assumptions, since the number of possible amplitude series, i.e., sequences of multi-dimensional stimuli with increasing amplitude, increases exponentially with the number of stimulating electrodes.…”

Stimulation Strategies for Improving the Resolution of Retinal Prostheses

“…As mentioned above, the epi-retinal stimulation using electrodes as small as 10 µm can also lead to a large spread of RGC activation due to axon bundle stimulation (Behrend et al, 2011). In another study, Grosberg et al (2017) found that only 45% of electrodes, also 10 µm in diameter, can stimulate individual RGCs using current amplitudes below threshold for axon bundle activation. Therefore, the activation of axon bundles has been identified as one the main sources of the spread of retinal cell activation.…”