Improving Spatial Resolution and Selectivity of Transcorneal Electrical Stimulation by Temporal Interference Technology.

Transcorneal electrical stimulation (TES) used in a therapeutic device has been demonstrated significant neuroprotective effect for rescuing retinal function. However, the diffuse electric field induced by conventional TES devices reduced their spatial resolution and selectivity, limiting their capability of actively stimulating a severely diseased retina. A cutting-edge neuromodulation approach named temporal interference stimulation (TIS) was reported to induce electric fields focalizing on local neuronal targets. Despite the competent feasibility of application in retinal TIS, the interpretation of characteristics of spatial resolution and selectivity under TIS remains rudimentary. In this study, we conduct in silico investigations to understand the characteristics of spatial selectivity and resolution using a finite element model of a multi-layered eyeball and multiple electrode configuration. By simulating different metrics of electric potentials envelope modulated by TIS, our model supports the possibility of achieving mini-invasive and spatially selective electrical stimulation using retinal TIS. These simulations provide theoretical evidence on the basis of which sophisticated devices for improved spatial selectivity can be designed.Clinical Relevance- This study provides a theoretical basis for understanding how the design of electrode configuration impacts transcorneal TIS performance. This model can guide future development of transcorneal TIS configurations and stimulation strategies that may benefit patients with inherited retinal diseases.

Anin-silicoanalysis of electrically evoked responses of midget and parasol retinal ganglion cells in different retinal regions.

Objective. Visual outcomes provided by present retinal prostheses that primarily target retinal ganglion cells (RGCs) through epiretinal stimulation remain rudimentary, partly due to the limited knowledge of retinal responses under electrical stimulation. Better understanding of how different retinal regions can be quantitatively controlled with high spatial accuracy, will be beneficial to the design of micro-electrode arrays and stimulation strategies for next-generation wide-view, high-resolution epiretinal implants.Approach. A computational model was developed to assess neural activity at different eccentricities (2 mm and 5 mm) within the human retina. This model included midget and parasol RGCs with anatomically accurate cell distribution and cell-specific morphological information. We then performedin silicoinvestigations of region-specific RGC responses to epiretinal electrical stimulation using varied electrode sizes (5-210µm diameter), emulating both commercialized retinal implants and recently developed prototype devices.Main results. Our model of epiretinal stimulation predicted RGC population excitation analogous to the complex percepts reported in human subjects. Following this, our simulations suggest that midget and parasol RGCs have characteristic regional differences in excitation under preferred electrode sizes. Relatively central (2 mm) regions demonstrated higher number of excited RGCs but lower overall activated receptive field (RF) areas under the same stimulus amplitudes (two-way analysis of variance (ANOVA),p< 0.05). Furthermore, the activated RGC numbers per unit active RF area (number-RF ratio) were significantly higher in central than in peripheral regions, and higher in the midget than in the parasol population under all tested electrode sizes (two-way ANOVA,p< 0.05). Our simulations also suggested that smaller electrodes exhibit a higher range of controllable stimulation parameters to achieve pre-defined performance of RGC excitation. An empirical model:I=a· exp (b·D) +cof the stimulus amplitude (I)-electrode diameter (D) relationship was constructed to achieve the pre-defined objective function values in different retinal regions, indicating the ability of controlling retinal outputs by fine-tuning the stimulation amplitude with different electrode sizes. Finally, our multielectrode simulations predicted differential neural crosstalk between adjacent electrodes in central temporal and peripheral temporal regions, providing insights towards establishing a non-uniformly distributed multielectrode array geometry for wide-view retinal implants.Significance.Stimulus-response properties in central and peripheral retina can provide useful information to estimate electrode parameters for region-specific activation by retinal stimulation. Our findings support the possibility of improving the performance of epiretinal prostheses by exploring the influence of electrode array geometry on activation of different retinal regions.