Article
Identifying and probing the mechanism of nonlinear current summation during multi-electrode stimulation using a biophysical model
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Authors
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Ramandeep Vilkhu
- Stanford University
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P. Vasireddy
- Stanford University
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K. Kish
- University of Michigan
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A. Gogliettino
- Stanford University
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A. Lotlikar
- Stanford University
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P. Hottowy
- AGH University of Science and Technology, Krakow
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W. Dabrowski
- AGH University of Science and Technology, Krakow
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A. Sher
- University of California, Santa Cruz
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A. Litke
- University of California, Santa Cruz
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S. Mitra
- Stanford University
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E.J. Chichilnisky
- Stanford University
| Published: | May 9, 2025 |
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Outline
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Objective: The selectivity of stimulation using epiretinal implants may be improved using multi-electrode stimulation for current steering. However, currents passed simultaneously through many electrodes often combine nonlinearly to drive neural response. The nonlinear current summation has been hypothesized to be due to multi-site activation, however this is difficult to verify experimentally and exploit in practice.
Materials and Methods: We developed a biophysical model in NEURON to study retinal ganglion cell (RGC) responses to multi-electrode stimulation and validated it using data collected from ex-vivo preparations of the macaque retina using a microelectrode array (512 electrodes; 30μm pitch; 10 μm diameter).
Results: The model was used to probe the site of spike initiation in response to multi-electrode stimulation. Over a range of electrode placements, localized spike initiation sites were observed, and the number of these sites covaried with the degree of response nonlinearity. The degree of linearity could be predicted based on the placement of the stimulating electrodes relative to the soma, axon, and dendrites of the target cell. All of these trends were consistent with experimental observations.
Discussion: These findings support the multi-site activation hypothesis and provide a biophysical interpretation of previous experimental results, potentially enabling more efficient use of multi-electrode stimuli in future implants.
Acknowledgment: Supported by Stanford Bio-X and NIH NEI R01-EY021271.
