Spike history neural response model.

There is a potential for improved efficacy of neural stimulation if stimulation levels can be modified dynamically based on the responses of neural tissue in real time. A neural model is developed that describes the response of neurons to electrical stimulation and that is suitable for feedback control neuroprosthetic stimulation. Experimental data from NZ white rabbit retinae is used with a data-driven technique to model neural dynamics. The linear-nonlinear approach is adapted to incorporate spike history and to predict the neural response of ganglion cells to electrical stimulation. To validate the fitness of the model, the penalty term is calculated based on the time difference between each simulated spike and the closest spike in time in the experimentally recorded train. The proposed model is able to robustly predict experimentally observed spike trains.

Activation and inhibition of retinal ganglion cells in response to epiretinal electrical stimulation: a computational modelling study.

OBJECTIVE: Retinal prosthetic devices aim to restore sight in visually impaired people by means of electrical stimulation of surviving retinal ganglion cells (RGCs). This modelling study aims to demonstrate that RGC inhibition caused by high-intensity cathodic pulses greatly influences their responses to epiretinal electrical stimulation and to investigate the impact of this inhibition on spatial activation profiles as well as their implications for retinal prosthetic device design. Another aim is to take advantage of this inhibition to reduce axonal activation in the nerve fibre layer. APPROACH: A three-dimensional finite-element model of epiretinal electrical stimulation was utilized to obtain RGC activation and inhibition threshold profiles for a range of parameters. MAIN RESULTS: RGC activation and inhibition thresholds were highly dependent on cell and stimulus parameters. Activation thresholds were 1.5, 3.4 and 11.3 µA for monopolar electrodes with 5, 20 and 50 µm radii, respectively. Inhibition to activation threshold ratios were mostly within the range 2-10. Inhibition significantly altered spatial patterns of RGC activation. With concentric electrodes and appropriately high levels of stimulus amplitudes, activation of passing axons was greatly reduced. SIGNIFICANCE: RGC inhibition significantly impacts their spatial activation profiles, and therefore it most likely influences patterns of perceived phosphenes induced by retinal prosthetic devices. Thus this inhibition should be taken into account in future studies concerning retinal prosthesis development. It might be possible to utilize this inhibitory effect to bypass activation of passing axons and selectively stimulate RGCs near their somas and dendrites to achieve more localized phosphenes.

Quasi-monopolar electrical stimulation of the retina: a computational modelling study.

OBJECTIVE: In this study we investigated the feasibility of quasi-monopolar (QMP) electrical stimulation for retinal implant devices, using a computational model of the retinal ganglion cell layer. APPROACH: When used with hexagonally arrayed multiple electrodes, QMP stimulation is a hybrid of hexapolar and conventional monopolar stimulus modes. In hexapolar mode, each active electrode is surrounded by six guards which collectively return the stimulus current, whereas in monopolar mode the injected stimulus current is returned through a distant return electrode. The QMP paradigm, on the other hand, distributes the return current between the guard electrodes as well as the distant return. The electrodes tested were 25, 50 and 100 µm in diameter, with hexagonally arranged centre-to-centre spacing of either double or quadruple this diameter. MAIN RESULTS: Simulation results indicated that electrode size had minimal effects on subretinal threshold currents, whilst electrode configuration and centre-to-centre spacing played major roles in determining thresholds and spatial activation patterns. Threshold charge densities for 50 and 100 µm electrodes were generally within the safe limit. SIGNIFICANCE: We found that QMP stimulation offers greater advantages compared to monopolar and hexapolar stimulation, in that it combines the low thresholds of monopolar stimulation with the localized spatial activation achieved with hexapolar electrodes during parallel stimulation.

Computational model of electrical stimulation of a retinal ganglion cell with hexagonally arranged electrodes.

In retinal prosthetic devices an electrode array is used for electrical stimulation of retinal neurons to induce phosphene perception. The shape and size of the evoked phosphenes are in part dependent on the spatial patterns of retinal activation. In this study, a computational model of a cat beta retinal ganglion cell (RGC) excitation following simulated electrical stimulation was investigated. Seven epiretinal disk electrodes with hexagonal configuration (Hex electrodes) were used. 100 µs/phase anodic-first biphasic pulses were injected at the center electrode and one sixth of the total current was returned at each surround electrode. The aim was to obtain a spatial threshold map of the RGC excitation. We found that the spatial threshold pattern was highly dominated by axonal excitation. With 50 µm Hex electrodes, relative thresholds for activation of the distal axon was almost the same as that for excitation of the axonal trigger segment (high sodium channel density region), causing an elongated activation pattern. The model presented in this study can be used to investigate the extent to which spatial RGC activation patterns are influenced by cell and stimulus parameters.

A continuum model of retinal electrical stimulation.

A continuum mathematical model of retinal electrical stimulation is described. The model is represented by a passive vitreous domain, a thin layer of active retinal ganglion cell (RGC) tissue adjacent to deeper passive neural layers of the retina, the retinal pigmented epithelium (RPE) and choroid thus ending at the sclera. To validate the model, in vitro epiretinal responses to stimuli from 50 µm disk electrodes, arranged in a hexagonal mosaic, were recorded from rabbit retinas. 100 µs/phase anodic-first biphasic current pulses were delivered to the retinal surface in both the mathematical model and experiments. RGC responses were simulated and recorded using extracellular microelectrodes. The model's epiretinal thresholds compared favorably with the in vitro data. In addition, simulations showed that single-return bipolar electrodes recruited a larger area of the retina than twin-return or six-return electrodes arranged in a hexagonal layout in which a central stimulating electrode is surrounded by six, eqi-spaced returns. Simulations were also undertaken to investigate the patterns of RGC activation in an anatomically-accurate model of the retina, as well as RGC activation patterns for subretinal and suprachoroidal bipolar stimulation.

Activation of retinal ganglion cells following epiretinal electrical stimulation with hexagonally arranged bipolar electrodes.

We investigated retinal ganglion cell (RGC) responses to epiretinal electrical stimulation delivered by hexagonally arranged bipolar (Hex) electrodes, in order to assess the feasibility of this electrode arrangement for future retinal implant devices. In vitro experiments were performed using rabbit retinal preparations, with results compared to a computational model of axonal stimulation. Single-unit RGC responses to electrical stimulation were recorded with extracellular microelectrodes. With 100 µs/phase biphasic pulses, the threshold charge densities were 24.0 ± 11.2 and 7.7 ± 3.2 µC cm(-2) for 50 and 125 µm diameter Hex electrodes, respectively. Threshold profiles and response characteristics strongly suggested that RGC axons were the neural activation site. Both the model and in vitro data indicated that localized tissue stimulation is achieved with Hex electrodes.

Activation of ganglion cell axons following epiretinal electrical stimulation with hexagonal electrodes.

A hexagonal electrode configuration has been proposed as an advantageous alternative to conventional electrode arrangements used in retinal prosthesis design. In the present study, the aim was to characterize retinal ganglion cell axonal responses to epiretinal electrical stimulation. 50 and 125 microm disk electrodes, arranged in a hexagonal configuration, were tested using in vitro rabbit retinal preparations. 100 micros/phase anodic-first biphasic current pulses were applied to the inner retinal surface, and ganglion cell responses were recorded differentially with extracellular microelectrodes. Axonal activation thresholds were 4.7 ± 2.5 microA for 50 microm, and 9.3 ± 4.0 microA for 125 microm electrodes. With anodic monophasic pulses there was a 3.3 ± 0.8 times increase in threshold, compared to anodic-first biphasic stimulation. Thresholds increased up to 20 times when stimulating electrodes were lifted 100 microm above the retinal surface. Overall, axonal activation thresholds were within the safe charge injection limits for platinum electrodes, given that these electrodes were positioned in close proximity to the retinal surface.