Inference of Electrical Stimulation Sensitivity from Recorded Activity of Primate Retinal Ganglion Cells

Madugula, Sasidhar; Grosberg, Lauren E.; Shah, Nishal P.; Kling, Alexandra; Gogliettino, Alex R.; Hottowy, Paweł; Sher, Alexander; Litke, A. M.; Chichilnisky, E. J.

doi:10.1101/2021.10.22.465478

Cited by 3 publications

(5 citation statements)

References 60 publications

(118 reference statements)

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“…For both human and macaque retina, spiking response probabilities had a sigmoidal relationship to stimulating current amplitude, with similar thresholds for axon and soma (figures 2(A) and (B), bottom). In general, electrodes near the dendrites did not evoke spikes in the current range tested (Madugula et al 2021). To compare electrical response characteristics across many cells of different cell types, 1807 activation thresholds resulting from somatic and axonal stimulation in the four major human RGC types were examined over five retinal preparations.…”

Section: Electrical Activation Characteristics Of Humanmentioning

confidence: 99%

“…Specifically the mean ± standard deviation across recordings of the median threshold of each recording for OFFmidget, ON-midget, OFF-parasol, and ON-parasol cells was, respectively, 1.9 ± 0.34 µA, 2.1 ± 0.38 µA, 2.3 ± 0.43 µA, and 2.2 ± 0.44 µA across 18 macaque preparations, and 2.3 ± 0.35 µA, 2.5 ± 0.38 µA, 2.6 ± 0.49 µA, and 2.4 ± 0.35 µA across 5 human preparations. The variation in activation thresholds likely arises from variation in the distance between the electrode and the site of spike initiation on the cell (Sekirnjak et al 2008a, Guo et al 2019, Madugula et al 2021.…”

Section: Electrical Activation Characteristics Of Humanmentioning

confidence: 99%

“…However, in many cases spike sorting was complicated by-sorting was often difficult or impossible in the context of simultaneous axon bundle activity and electrical artifact. The completeness of spike sorting is explored in more detail in (Madugula et al 2021) For each analyzed cell, spike probabilities were computed over the 25 repeats of each stimulus, and were modeled as a function of current amplitude by a sigmoidal relationship:…”

Section: Electrical Stimulation and Spike Sortingmentioning

confidence: 99%

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Focal electrical stimulation of human retinal ganglion cells for vision restoration

Madugula¹,

Gogliettino²,

Zaidi³

et al. 2022

J. Neural Eng.

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Vision restoration with retinal implants is limited by indiscriminate simultaneous activation of many cells and cell types, which is incompatible with reproducing the neural code of the retina. Recent work has shown that macaque retinal ganglion cells (RGCs), which transmit visual information to the brain, can be directly electrically activated with single-cell, single-spike, cell-type precision – however, this possibility has never been tested in the human retina. Here, the electrical activation properties of identified RGC types in the human retina were examined using large-scale, multi-electrode recording and stimulation ex vivo and were compared directly to results from macaque. Precise activation was often possible without activating overlying axon bundles, at low stimulation current levels similar to those observed in macaque. The major RGC types could be identified and targeted based on their distinctive electrical signatures. The measured electrical activation properties of RGCs, combined with a dynamic stimulation algorithm, was sufficient to produce a nearly optimal evoked visual signal. These results reveal the possibility of high-fidelity vision restoration using bi-directional retinal implants.

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Section: Electrical Activation Characteristics Of Humanmentioning

confidence: 99%

Section: Electrical Activation Characteristics Of Humanmentioning

confidence: 99%

Section: Electrical Stimulation and Spike Sortingmentioning

confidence: 99%

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Focal electrical stimulation of human retinal ganglion cells for vision restoration

Madugula¹,

Gogliettino²,

Zaidi³

et al. 2022

J. Neural Eng.

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“…In general, somatic and dendritic waveforms exhibit biphasic structure, whereas axonal waveforms exhibit triphasic structure, reflecting biophysical differences between compartments. Based on these known differences, a heuristic-based automated method (Madugula et al, 2022b) was applied to label each electrode as either “dendritic”, “somatic”, “axonal”, or “mixed” (either a superposition of somatic and dendritic or somatic and axonal waveforms, (Madugula et al, 2022b)). First, waveforms with a larger positive than negative phase were labeled as “dendritic”.…”

Section: Methodsmentioning

confidence: 99%

“…Reproduction of the neural code with electrical stimulation requires identifying cell types in the absence of light responses (which are degraded or absent during degeneration) as well as measuring the sensitivity of each cell to electrical stimulation (Li et al, 2015;Richard et al, 2016;Shah et al, 2019a;Madugula et al, 2022aMadugula et al, , 2022bZaidi et al, 2022). To probe these properties, electrical images, or the average spatiotemporal electrical footprint of a cell's spike (Litke et al, 2004;Petrusca et al, 2007), were examined for the recorded RGCs.…”

Section: Distinguishing Major Rgc Types Using Intrinsic Electrical Fe...mentioning

confidence: 99%

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

Gogliettino

Madugula

Grosberg

et al. 2022

Preprint

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Electrical stimulation of retinal ganglion cells (RGCs) with electronic implants provides rudimentary artificial vision to people blinded by retinal degeneration, but cannot reproduce the neural code of the retina. Recent work has demonstrated more precise activation of RGCs using focal electrical stimulation in the peripheral macaque retina, but high-resolution vision requires the central retina. This work probes the effectiveness of focal epiretinal stimulation in the central macaque retina, using large-scale recording and stimulation ex vivo. The functional organization of the major RGC types was similar between the peripheral and central retina, and these cell types could be distinguished by their electrical properties. Electrical stimulation revealed similar RGC activation thresholds and reduced axon bundle activation in the central retina, but diminished stimulation selectivity. However, a novel stimulation algorithm revealed higher expected acuity in the central retina. These results support the possibility of reproducing high-acuity vision in the central retina with an epiretinal implant.

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High-Fidelity Reproduction of Visual Signals by Electrical Stimulation in the Central Primate Retina

et al. 2023

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Electrical stimulation of retinal ganglion cells (RGCs) with electronic implants provides rudimentary artificial vision to people blinded by retinal degeneration. However, current devices stimulate indiscriminately and therefore cannot reproduce the intricate neural code of the retina. Recent work has demonstrated more precise activation of RGCs using focal electrical stimulation with multi-electrode arrays in the peripheral macaque retina, but it is unclear how effective this can be in the central retina, which is required for high-resolution vision. This work probes the neural code and effectiveness of focal epiretinal stimulation in the central macaque retina, using large-scale electrical recording and stimulationex vivo. The functional organization, light response properties, and electrical properties of the major RGC types in the central retina were mostly similar to the peripheral retina, with some notable differences in density, kinetics, linearity, spiking statistics and correlations. The major RGC types could be distinguished by their intrinsic electrical properties. Electrical stimulation targeting parasol cells revealed similar activation thresholds and reduced axon bundle activation in the central retina, but lower stimulation selectivity. Quantitative evaluation of the potential for image reconstruction from electrically-evoked parasol cell signals revealed higher overall expected image quality in the central retina. An exploration of inadvertent midget cell activation suggested that it could contribute high spatial frequency noise to the visual signal carried by parasol cells. These results support the possibility of reproducing high-acuity visual signals in the central retina with an epiretinal implant.SIGNIFICANCE STATEMENT:Artificial restoration of vision with retinal implants is a major treatment for blindness. However, present-day implants do not provide high-resolution visual perception, in part because they do not reproduce the natural neural code of the retina. Here we demonstrate the level of visual signal reproduction that is possible with a future implant by examining how accurately responses to electrical stimulation of parasol retinal ganglion cells (RGCs) can convey visual signals. Although the precision of electrical stimulation in the central retina was diminished relative to the peripheral retina, the quality of expected visual signal reconstruction in parasol cells was greater. These findings suggest that visual signals could be restored with high fidelity in the central retina using a future retinal implant.

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Inference of Electrical Stimulation Sensitivity from Recorded Activity of Primate Retinal Ganglion Cells

Cited by 3 publications

References 60 publications

Focal electrical stimulation of human retinal ganglion cells for vision restoration

Focal electrical stimulation of human retinal ganglion cells for vision restoration

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

High-Fidelity Reproduction of Visual Signals by Electrical Stimulation in the Central Primate Retina

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