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.
Highlights
There has been significant progress over the past decade in the development of retinal prostheses for those with retinal pathologies such as Retinitis Pigmentosa
To compare the activation of axons of passage (AOPs) in the nerve fiber layer (NFL) and axon initial segment (AIS) in the ganglion cell layer (GCL), we considered characteristic axons located just (z = 10 μm) below the surface of their respective retinal layer, as structures at these locations are most sensitive to epiretinal stimulation
The activation due to orientation is influenced via differences in the second spatial derivative of the extracellular potential, which manifests in the frequency domain in Eq (5a) as À k2y0^a
Summary
Recipients of epiretinal implants commonly describe irregular visual percept shapes due to stimulation of axons of passage [13, 15, 20, 21]. This effect has been confirmed experimentally and in simulations, and results in a reduction in the spatial selectivity of epiretinal stimulation [10, 11, 15,16,17, 20,21,22]. Recent experimental findings by Grosberg et al [10] have both reaffirmed the existence of this problem while suggesting that it may be overcome using electrode stimulus amplitudes carefully tuned via detection of RGC activation in response to stimulation
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