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

Kish, Kathleen E.; Lempka, Scott F.; Weiland, James D.

doi:10.1088/1741-2552/acbf79

Cited by 5 publications

(4 citation statements)

References 54 publications

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“…We later found that ultrasound images, which we used to locate electrical ground, did not affect model predictions. Another improvement to our prior study was implementing a mammalian RGC model with dendrites that we optimized for run-time based on our sensitivity analysis, as opposed to a simpli ed, amphibian RGC model 29 Future work could apply this modelling framework to other retinal prostheses. In addition, we could apply optimization paradigms to these models to program patient-speci c stimulation settings.…”

Section: Discussionmentioning

confidence: 99%

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Patient-specific computational models of retinal prostheses

Kish

Yuan

Weiland

2023

Preprint

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Retinal prostheses stimulate inner retinal neurons to create visual perception for blind patients. Implanted arrays have many small electrodes, which act as pixels. Not all electrodes induce perception at the same stimulus amplitude, requiring clinicians to manually establish a visual perception threshold for each one. Phosphenes created by single-electrode stimuli can also vary in shape, size, and brightness. Computational models provide a tool to predict inter-electrode variability and automate device programming. In this study, we created statistical and patient-specific field-cable models to investigate inter-electrode variability across seven epiretinal prosthesis users. Our statistical analysis revealed that retinal thickness beneath the electrode correlated with perceptual threshold, with a significant fixed effect across participants. Electrode-retina distance and electrode impedance also correlated with perceptual threshold for some participants, but these effects varied by individual. We developed a novel method to construct patient-specific field-cable models from optical coherence tomography images. Predictions with these models significantly correlated with perceptual threshold for 80% of participants. Additionally, we demonstrated that patient-specific field-cable models could predict retinal activity and phosphene size. These computational models could be beneficial for determining optimal stimulation settings in silico, circumventing the trial-and-error testing of a large parameter space in clinic.

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Section: Discussionmentioning

confidence: 99%

“…The cable equations for RGC membrane dynamics are described in detail in our prior publication, and our biophysical model is open-source on GitHub 29 . Brie y, we determined the extracellular potential at the center of each neuron compartment from the FEM solution.…”

Section: Statistical Models For Perceptual Thresholdmentioning

confidence: 99%

Patient-specific computational models of retinal prostheses

Kish

Yuan

Weiland

2023

Preprint

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“…We therefore use the general term 'focal activation' in this work. The AIS represents the section of RGCs with the highest sodium channel density and therefore the lowest local stimulation threshold (Fried et al 2009, Werginz et al 2020, Kish et al 2023, Radivojevic et al 2016. Therefore, the most natural conclusion is that the focal activation reported here happens with the AIS in close proximity to the stimulation electrodes and the two different cellular compartments AIS and distal axon, have different strength-duration relationships.…”

Section: The Mechanism Underlying Focal Activation With Sinusoidal St...mentioning

confidence: 99%

Avoidance of axonal stimulation with sinusoidal epiretinal stimulation

Corna,

Cojocaru,

Bui

et al. 2024

J. Neural Eng.

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Objective. Neuromodulation, particularly electrical stimulation, necessitates high spatial resolution to achieve artificial vision with high acuity. In epiretinal implants, this is hindered by the undesired activation of distal axons. Here we investigate focal and axonal activation of Retinal Ganglion Cells (RGCs) for different sinusoidal stimulation frequencies. Our results can be exploited to define a selective stimulation strategy to avoid axonal activation in retina implants. Approach. RGC responses to epiretinal sinusoidal stimulation at frequencies between 40 and 100 Hz were tested in ex-vivo photoreceptor degenerated (rd10) retina explants. Experiments were conducted using a high-density CMOS-based Micro Electrode Array, which allows to locate RGC cell bodies and axons with high spatial resolution while performing simultaneous recording and stimulation. Main results. We report current and charge density threshold for focal and distal axon activation for sinusoidal stimulation at 40, 60, 80 and 100 Hz, in the order of 0.5 µA. We identify selective stimulation for 40 and 60 Hz up to 0.23 and 0.28 µA (173 and 148 nC/mm2), showing how the selective stimulation window increases when reducing the stimulation frequency. With the use of synaptic blockers, we demonstrate the underlying direct activation mechanism of the ganglion cells. Finally, with the use of high resolution electrical imaging and axon tracking, we investigated the extent of the activation in axonal bundles. Significance. 40 and 60 Hz sinusoidal electrical stimulation can be applied to achieve focal activation of RGCs in epiretinal configuration. The presented results can be implemented as a stimulation strategy to avoid axonal stimulation solving one of the major limitations of artificial vision and retina implants. The results could be extended to other fields of neuroprosthetics to achieve selective focal electrical stimulation.

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“…Moreover, both classes (i.e., BC and RGC) of retinal neurons are known to have numerous subtypes [72,73]; their unique sensitivities and morphological differences should be considered in the numerical stimulations. Eventually, it would be imperative to test the penetrating electrode structures presented in our modeling study in ex-/invivo additional experiments and/or extra cellular-level simulations using NEURON [36,74]. This comprehensive approach will provide a more accurate representation of the neural responses to electrical stimulation in the retina.…”

Section: B Limitation Of Our Studymentioning

confidence: 99%

Effects on Retinal Stimulation of the Geometry and the Insertion Location of Penetrating Electrodes

Son,

Chen,

Roh

et al. 2023

IEEE Trans. Neural Syst. Rehabil. Eng.

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Retinal implants have been developed and implanted to restore vision from outer retinal degeneration, but their performance is still limited due to the poor spatial resolution. To improve the localization of stimulation, microelectrodes in various three-dimensional (3D) shapes have been investigated. In particular, computational simulation is crucial for optimizing the performance of a novel microelectrode design before actual fabrication. However, most previous studies have assumed a uniform conductivity for the entire retina without testing the effect of electrodes placement in different layers. In this study, we used the finite element method to simulate electric fields created by 3D microelectrodes of three different designs in a retina model with a stratified conductivity profile. The three electrode designs included two conventional shapes -a conical electrode (CE) and a pillar electrode (PE); we also proposed a novel structure of pillar electrode with an insulating wall (PEIW). A quantitative comparison of these designs shows the PEIW generates a stronger and more confined electric field with the same current injection, which is preferred for highresolution retinal prostheses. Moreover, our results demonstrate both the magnitude and the shape of potential distribution generated by a penetrating electrode depend not only on the geometry, but also substantially on the insertion depth of the electrode. Although epiretinal insertions are mainly discussed, we also compared results for subretinal insertions. The results provide valuable insights for improving the spatial resolution of retinal implants using 3D penetrating microelectrodes and highlight the importance of considering the heterogeneity of conductivities in the retina.

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

Cited by 5 publications

References 54 publications

Patient-specific computational models of retinal prostheses

Patient-specific computational models of retinal prostheses

Avoidance of axonal stimulation with sinusoidal epiretinal stimulation

Effects on Retinal Stimulation of the Geometry and the Insertion Location of Penetrating Electrodes

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