Minimizing activation of overlying axons with epiretinal stimulation: The role of fiber orientation and electrode configuration

Abstract

Currently, a challenge in electrical stimulation of the retina with a visual prosthesis (bionic eye) is to excite only the cells lying directly under the electrode in the ganglion cell layer, while avoiding excitation of axon bundles that pass over the surface of the retina in the nerve fiber layer. Stimulation of overlying axons results in irregular visual percepts, limiting perceptual efficacy. This research explores how differences in fiber orientation between the nerve fiber layer and ganglion cell layer leads to differences in the electrical activation of the axon initial segment and axons of passage. Approach. Axons of passage of retinal ganglion cells in the nerve fiber layer are characterized by a narrow distribution of fiber orientations, causing highly anisotropic spread of applied current. In contrast, proximal axons in the ganglion cell layer have a wider distribution of orientations. A four-layer computational model of epiretinal extracellular stimulation that captures the effect of neurite orientation in anisotropic tissue has been developed using a volume conductor model known as the cellular composite model. Simulations are conducted to investigate the interaction of neural tissue orientation, stimulating electrode configuration, and stimulation pulse duration and amplitude. Main results. Our model shows that simultaneous stimulation with multiple electrodes aligned with the nerve fiber layer can be used to achieve selective activation of axon initial segments rather than passing fibers. This result can be achieved while reducing required stimulus charge density and with only modest increases in the spread of activation in the ganglion cell layer, and is shown to extend to the general case of arbitrary electrode array positioning and arbitrary target volume. Significance. These results elucidate a strategy for more targeted stimulation of retinal ganglion cells with experimentally-relevant multi-electrode geometries and achievable stimulation requirements.

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.…”

“…Despite the variability in phosphene shape, all subjects reported seeing elongated phosphenes on at least a subset of electrodes (Figure 3C). Although the electric field generated by a disk electrode is radially symmetric, the neural tissue induces anisotropies in the electric field, and stimulation of axon fibers produces even more striking anisotropies in patterns of neural activation within the retina (29). It has long been known that external stimulation of an axon induces an action potential that travels both backward to the cell body and forward to the synaptic terminals (63,64).…”

“…Both computational (29,30) and in vitro electrophysiological studies (Fried et al, 2009;Rizzo et al, 2003;Weitz et al, 2015) suggest that electrode configurations similar to those implanted in patients do not achieve focal activation, but rather produce significant activation of passing axon fibers, which may result in perceptual distortions in patients. Here, we are the first to directly examine whether axonal stimulation contributes to the rich repertoire of phosphene shapes reported by patients.…”

Stimulation Strategies for Improving the Resolution of Retinal Prostheses

“…For both epi-retinal and sub-retinal stimulation, ultrashort pulses (shorter than 0.15 ms in Chang et al, 2019, and shorter than 0.1 ms in Tong et al, 2019a) were demonstrated to be effective at avoiding axon bundle stimulation. Esler et al (2018a) proposed to simultaneously stimulate multiple electrodes aligned with the axon bundles to minimize the bundle activation. The proposal was based on the fact that the excitable parts of RGC are the AIS.…”

Biophysical model of axonal stimulation in epiretinal visual prostheses

“…However, a major challenge with current retinal prostheses is the inability to achieve focal tissue activation. Because epiretinal prostheses sit on top of the optic fiber layer, these devices may accidentally stimulate passing axon fibers, which could antidromically activate cell bodies located peripheral to the point of stimulation [3]- [5]. This can cause nontrivial perceptual distortions [6]- [8] that may severely limit the quality of the generated visual experience [9], [10].…”