Color and cellular selectivity of retinal ganglion cell subtypes through frequency modulation of electrical stimulation

Abstract

Epiretinal prostheses aim at electrically stimulating the inner most surviving retinal cells—retinal ganglion cells (RGCs)—to restore partial sight to the blind. Recent tests in patients with epiretinal implants have revealed that electrical stimulation of the retina results in the percept of color of the elicited phosphenes, which depends on the frequency of stimulation. This paper presents computational results that are predictive of this finding and further support our understanding of the mechanisms of color encoding in electrical stimulation of retina, which could prove pivotal for the design of advanced retinal prosthetics that elicit both percept and color. This provides, for the first time, a directly applicable “amplitude-frequency” stimulation strategy to “encode color” in future retinal prosthetics through a predictive computational tool to selectively target small bistratified cells, which have been shown to contribute to “blue-yellow” color opponency in the retinal circuitry. The presented results are validated with experimental data reported in the literature and correlated with findings in blind patients with a retinal prosthetic implant collected by our group.

Selective Activation of Retinal Ganglion Cell Subtypes Through Targeted Electrical Stimulation Parameters

“…Using our combined AM-NEURON multi-scale computational platform [39]- [47], we developed morphologically and biophysically realistic models of two classified RGCs, A2-monostratified and D1-bistratified [32]. This modeling framework has enabled us to have a more precise prediction of retinal neuron activities due to electrical stimulation [34], and particularly in this work the response of RGCs to epiretinal electrical stimulation of various stimulation parameters. We assessed the impact of pulse duration and interphase gap in a symmetric cathodic-first biphasic waveform on the frequency response of RGCs, and their responsiveness to high stimulus frequency.…”

“…The ionic channel conductance values of both A2 and D1 cells for the soma, dendrites, and axon are listed in Tables I and II. More details on the NEURON modeling of these RGCs and AM simulations are discussed in [17], [32], [34]. The impacts of morphological variations including the sodium channel band (SOCB) length, soma diameter, and axon diameter as well as the position of the electrode with respect to cells and along the axon on the differential response of the two subtypes of RGCs have been comprehensively discussed in our previous works [17], [34].…”

“…For instance, small bistratified RGCs have been shown to contribute to blue/yellow color vision [ 29 ]–[ 31 ]. Also, clinical studies of subjects with epiretinal implants have demonstrated that blue color is perceived at high stimulus frequency [ 34 ]–[ 37 ]. The ability to characterize the response of RGCs to electrical stimulation and selectively target cells based on their morphological and physiological properties would represent a significant impact on the performance of current retinal prosthetic systems.…”

“…This differential response of RGCs offers potential for select activation of individual cells at high frequency (200 Hz). Our previous computational findings indicated that, with a careful selection of current amplitude, D1 small bistratified cells can be selectively targeted at high frequency with implications for encoding colors in future retinal prosthetic systems [ 34 ]. These results were verified with experimental data from the literature and correlated with the clinical data from the Argus II subjects [ 34 ]–[ 38 ].…”

“…In this work, using our combined Admittance method (AM)/NEURON multiscale computational platform [ 17 ], [ 34 ], [ 39 ]–[ 47 ], we further characterized the impacts of pulse duration and interphase gap on the differential response of RGCs at 200 Hz. To better understand the sensitivity of RGCs to different stimulus parameters, we analyzed the firing rates of cells as a function of modulations in current amplitude.…”