Morphological Factors that Underlie Neural Sensitivity to Stimulation in the Retina

Raghuram, Vineeth; Werginz, Paul; Fried, Shelley I.; Timko, Brian P.

doi:10.1002/anbr.202100069

Cited by 3 publications

(1 citation statement)

References 122 publications

(292 reference statements)

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“…Naturally, RGCs exhibit substantial variations in both somatodendritic and axonal morphometry [20]. To study the effects of cell morphometry modifications on model behavior, we conducted several sensitivity analyses.…”

Section: Cell Morphometrymentioning

confidence: 99%

Modeling extracellular stimulation of retinal ganglion cells: theoretical and practical aspects

Kish

Lempka²,

Weiland³

2023

J. Neural Eng.

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Objective. Retinal prostheses use electric current to activate inner retinal neurons, providing artificial vision for blind people. Epiretinal stimulation primarily targets retinal ganglion cells (RGCs), which can be modelled with cable equations. Computational models provide a tool to investigate the mechanisms of retinal activation, and improve stimulation paradigms. However, documentation of RGC model structure and parameters is limited, and model implementation can influence model predictions. Approach. We created a functional guide for building a mammalian RGC multi-compartment cable model and applying extracellular stimuli. Next, we investigated how the neuron’s three-dimensional shape will influence model predictions. Finally, we tested several strategies to maximize computational efficiency. Main Results. We conducted sensitivity analyses to examine how dendrite representation, axon trajectory, and axon diameter influence membrane dynamics and corresponding activation thresholds. We optimized the spatial and temporal discretization of our multi-compartment cable model. We also implemented several simplified threshold prediction theories based on activating function, but these did not match the prediction accuracy achieved by the cable equations. Significance. Through this work, we provide practical guidance for modelling the extracellular stimulation of RGCs to produce reliable and meaningful predictions. Robust computational models lay the groundwork for improving the performance of retinal prostheses.

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Section: Cell Morphometrymentioning

confidence: 99%

Modeling extracellular stimulation of retinal ganglion cells: theoretical and practical aspects

Kish

Lempka²,

Weiland³

2023

J. Neural Eng.

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Improving the spatial resolution of artificial vision using midget retinal ganglion cell populations modeled at the human fovea

Italiano¹,

Guo²,

Lovell³

et al. 2022

J. Neural Eng.

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Objective. Retinal prostheses seek to create artificial vision by stimulating surviving retinal neurons of patients with profound vision impairment. Notwithstanding tremendous research efforts, the performance of all implants tested to date has remained rudimentary, incapable of overcoming the threshold for legal blindness. To maximize the perceptual efficacy of retinal prostheses, a device must be capable of controlling retinal neurons with greater spatiotemporal precision. Most studies of retinal stimulation were derived from either non-primate species or the peripheral primate retina. We investigated if artificial stimulation could leverage the high spatial resolution afforded by the neural substrates at the primate fovea and surrounding regions to achieve improved percept qualities. Approach. We began by developing a new computational model capable of generating anatomically accurate retinal ganglion cell (RGC) populations within the human central retina. Next, multiple RGC populations across the central retina were stimulated in-silico to compare clinical and recently proposed neurostimulation configurations based on their ability to improve perceptual efficacy and reduce activation thresholds. Main results. Our model uniquely upholds eccentricity-dependent characteristics such as RGC density and dendritic field diameter, whilst incorporating anatomically accurate features such as axon projection and three-dimensional (3D) RGC layering, features often forgone in favor of reduced computational complexity. Following epiretinal stimulation, the RGCs in our model produced response patterns in shapes akin to the complex and non-trivial percepts reported in clinical trials. Our results also demonstrated that even within the neuron-dense central retina, epiretinal stimulation using a multi-return hexapolar electrode arrangement could reliably achieve spatially focused RGC activation and could achieve single-cell excitation in 56% of all tested locations. Significance. This study establishes an anatomically accurate 3D model of RGC populations within the human central retina and demonstrates the potential for an epiretinal hexapolar configuration to achieve consistent, spatially confined retinal responses, even within the unique and neuron-dense foveal region. Our results and model promote the prospect and optimization of higher spatial resolution in future epiretinal implants.

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Transparent and Conformal Microcoil Arrays for Spatially Selective Neuronal Activation

Raghuram

Datye

Fried

et al. 2021

Preprint

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Magnetic stimulation represents a compelling modality for achieving neuronal activation with high spatial resolution and low toxicity. Stimulation coils can be designed to achieve localized, spatially asymmetric fields that target neurons of a particular orientation. Furthermore, these devices may be encapsulated within biopolymers thereby avoiding direct metal/tissue interfaces that could induce chronic inflammation and glial scarring. Herein, we report a multiplexed microcoil array for localized activation of cortical neurons and retinal ganglion cells. We designed a computational model that related the activation function to the geometry and arrangement of coils, and selected a geometry with a region of activation <50 microns wide. We then fabricated SU8/Cu/SU8 tri-layer devices which were flexible, transparent and conformal and featured four individually-addressable microcoil stimulation elements. Interfaced with ex vivo cortex or retina slices from GCaMP6-transfected mice, we observed that individual neurons located within 40 microns of the element tip could be activated repeatedly and in a dose (power) dependent fashion. Taken together, these results highlight the potential of magnetic stimulation devices for brain-machine interfaces and could open new routes toward bioelectronic therapies including prosthetic vision devices.

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Morphological Factors that Underlie Neural Sensitivity to Stimulation in the Retina

Cited by 3 publications

References 122 publications

Modeling extracellular stimulation of retinal ganglion cells: theoretical and practical aspects

Modeling extracellular stimulation of retinal ganglion cells: theoretical and practical aspects

Improving the spatial resolution of artificial vision using midget retinal ganglion cell populations modeled at the human fovea

Transparent and Conformal Microcoil Arrays for Spatially Selective Neuronal Activation

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