Modelng-based Stimulation Analysis On Spatiotemporal Characteristics Of Retinal Ganglion Cells Responsing To Electrical Stimulation

Visual prostheses are proposed for the treatment of retinal degenerative diseases including aged-related macular degeneration and retinitis pigmentosa.For people who suffering from the above-mentioned retinal diseases,neurons in the inner retina,such as ganglion cells,have a relatively high survival rate,so that it is possible for them to repair partial visual function through direct electrical stimulation with epiretinal prosthesis and optic nerve Prosthesis.While great progress has been made in retinal prostheses,some challenges,such as poor visual restoration and insufficient visual resolution,face all research groups involved.There is still room for further improvement in the time-based regulation strategy,which is proposed by fried et al.to improve the temporal resolution of visual prostheses with a certain electrical stimulation paradigm.Nerve electrical stimulation is mainly divided into two ways: synchronous stimulation and asynchronous stimulation.Synchronous stimulus easily causes crosstalk between channels,but it is widely used to improve spatial resolution of electrical stimulation combined with current steering strategy,namely virtual channel stimulation strategy.Asynchronous stimulus can reduce cross-talk between channels,and it has demonstrated the ability to implement virtual channels to some extent in the field of cochlear implants.In addition,it has the technical advantage of enabling multiple electrodes to share the same driving source,which could reduce the requirements on hardware.However,limited data have been reported about whether virtual channels can be implemented in the visual prosthesis through asynchronous stimulus.Our laboratory animal experiments showed that the response threshold of visual cortex evoked potential could be decreased by changing the pulse waveform during the stimulation of optic nerve with penetrating electrode,but its direct influence on optic nerve fibers was not known.In view of the above problems,The following work was carried out in this study based on the computational model and simulation technology:The stimulation strategy proposed by fried et al.is improved according to the changes of excitability of neurons in an action potential cycle.We propose a stimulus method based on amplitude modulation,and combining the two is possible to improve the effectiveness of stimulation.In terms of virtual channel technology to improve spatial resolution,we focused on the temporal and spatial response of ganglion cells to electrical stimulation.We found the similarities and differences of virtual channels formed by synchronous and asynchronous stimulus.The results show that compared with asynchronous stimulus,synchronous mode combined with current steering technology is more conducive to the formation of a better focal virtual channel which also effected by electrodes parameter configuration,while asynchronous stimulus is not good but still capable of forming virtual channel to some extent.Consistent with relevant physiological studies,ganglion cells have a precise temporal properties when activated directly.The spatial characteristics of neuron population response under synchronous and asynchronous stimulation are the result of co-regulation of current ratio α and stimulus strength.The average latency of ganglion cells under synchronous stimulation is also affected by the influence of current steering and stimulus strength.At the same time,in asynchronous stimulation mode,the response of ganglion cells is also regulated by the time interval between stimulation pulses for what a variety of spikes patterns can be generated and visual perception of patients would be diversified in theory.The response of optic nerve fibers under different stimulation conditions is affected by the stimulation waveform and parameters.The ability for exciting nerve fibers of six kinds of commonly used biphasic square pulses rank from weak to strong: APS-A<PPS-C<BP-A<BP-C<PPS-A<APS-C.This study will provide a theoretical basis for improving the spatiotemporal resolution and design of stimulus strategy with visual prostheses in the future.