Spatially Selective Retinal Ganglion Cell Activation Using Low Invasive Extraocular Temporal Interference Stimulation.

Conventional retinal implants involve complex surgical procedures and require invasive implantation. Temporal Interference Stimulation (TIS) has achieved noninvasive and focused stimulation of deep brain regions by delivering high-frequency currents with small frequency differences on multiple electrodes. In this study, we conducted in silico investigations to evaluate extraocular TIS's potential as a novel visual restoration approach. Different from the previously published retinal TIS model, the new model of extraocular TIS incorporated a biophysically detailed retinal ganglion cell (RGC) population, enabling a more accurate simulation of retinal outputs under electrical stimulation. Using this improved model, we made the following major discoveries: (1) the maximum value of TIS envelope electric potential ([Formula: see text] showed a strong correlation with TIS-induced RGC activation; (2) the preferred stimulating/return electrode (SE/RE) locations to achieve focalized TIS were predicted; (3) the performance of extraocular TIS was better than same-frequency sinusoidal stimulation (SSS) in terms of lower RGC threshold and more focused RGC activation; (4) the optimal stimulation parameters to achieve lower threshold and focused activation were identified; and (5) spatial selectivity of TIS could be improved by integrating current steering strategy and reducing electrode size. This study provides insights into the feasibility and effectiveness of a low-invasive stimulation approach in enhancing vision restoration.