A Modeling Study Of Retinal Spatially Selective Stimulation Based On Temporally Interfering Electric Fields

Vision is one of the most important ways for humans to perceive the outside world.The structural and functional damages to the visual system may cause visual impairment,or even blindness.Electrical stimulation of the retina plays an important role in the rehabilitation of visual system diseases,assessment of visual pathway and restoration of visual functions.For some patients with early and middle stage retinal degenerative diseases and optic nerve diseases,noninvasive transcorneal electrical stimulation(TES)can improve the survival of retinal cells and facilitate the visual restoration due to neuroprotective effects.For patients with advanced retinal degenerative diseases,invasive retinal prostheses can directly stimulate the surviving retinal neurons through implantable electrode array to restore partial visual function.However,there are challenges for both noninvasive and invasive methods of retinal electrical stimulation.TES using a single electrode preferentially activates peripheral visual field or directly activates the entire retina,while lacking the ability to spatially selectively regulate retinas.Retinal prosthesis results in a large trauma to the eye and small field of vision.Regarding the issue above,we innovatively proposed a retinal selective stimulation method based on temporally interfering(TI)electric fields.We used modeling method to simulate the convergent and movable interferential electric fields on the retina induced by multiple extraocular electrodes outflow the sinusoidal current with different frequencies and amplitudes.The results could be instructive for the study of retinal locoregional electrotherapy as well as precise functional evaluation,and further benefit for the innovative design of less invasive retinal prostheses.In this study,we first established an electrical conductivity model of eyeball and extraocular multiple electrodes.Then we calculated the TI electric fields with different electrode parameters(electrode positions,sizes and numbers)and stimulating parameters(current ratios).By evaluation of the theoretical convergence,mobility and safety,we analyzed the application feasibility of the retinal spatially selective stimulation based on TI electric fields.According to the modeling results,it can be concluded that the interferential stimulation with appropriate electrode configurations could target a specific area of retinal neurons.Additionally,the focal targeted region can be steerable.We found that the position of return electrodes and the electrode numbers would strongly affect the distribution of interferential electric fields.When the return electrodes were located at the retinal side of the eye,a focal region with high intensity of electric fields would be formed on the retina,and the range of this region would decrease and its amplitudes increased when the return electrodes got close and the number of electrodes increased.Moreover,the electric fields on the retina were anisotropic,in which the best resolution appeared at the direction of the electrode distribution.In addition,adjusting the current ratios could result in the convergent electric field region moving within a certain range on the retina and the steerable range was limited by the return electrode position.However,the shift of interferential electric fields compromised the stimulating spatial resolutions.In addition,as the number of electrodes increased and the return electrodes became closer to the retinal side of the eyeball,the range of focal region reduced and the amplitudes of interferential electric fields on the retina increased,which was at the expense of increasing invasiveness to the eye structure.Therefore,a variety of factors need to be considered when conducting a safety assessment.This study will provide a new idea for the spatially selective regulation of retinal neurons,and the simulation results also benefit the subsequent electrode fabrication,design of phantom and animal experiments.