TY - JOUR T1 - Epiretinal stimulation with local returns enhances selectivity at cellular resolution JF - bioRxiv DO - 10.1101/275958 SP - 275958 AU - Victoria H. Fan AU - Lauren E. Grosberg AU - Sasidhar S. Madugula AU - Pawel Hottowy AU - Wladyslaw Dabrowski AU - Alexander Sher AU - Alan M. Litke AU - E.J. Chichilnisky Y1 - 2018/01/01 UR - http://biorxiv.org/content/early/2018/08/11/275958.abstract N2 - Epiretinal prostheses are designed to restore vision in people blinded by photoreceptor degenerative diseases, by directly activating retinal ganglion cells (RGCs) using an electrode array implanted on the retina. In present-day clinical devices, current spread from the stimulating electrode to a distant return electrode often results in the activation of many cells, potentially limiting the quality of artificial vision. In the laboratory, epiretinal activation of RGCs with cellular resolution has been demonstrated with small electrodes, but distant returns may still cause undesirable current spread. Here, the ability of local return stimulation to improve the selective activation of RGCs at cellular resolution was evaluated. A custom multi-electrode array (512 electrodes, 10 μm diameter, 60 μm pitch) was used to simultaneously stimulate and record from RGCs in isolated primate retina. Stimulation near the RGC soma with a single electrode and a distant return was compared to stimulation in which the return was provided by six neighboring electrodes. Local return stimulation enhanced the capability to activate cells near the central electrode (<30 µm) while avoiding cells farther away (>30 µm). This resulted in an improved ability to selectively activate ON and OFF cells, including cells encoding immediately adjacent regions in the visual field. These results suggest that a device that restricts the electric field through local returns could optimize activation of neurons at cellular resolution, improving the quality of artificial vision.Novelty & Significance The effectiveness of local return stimulation for enhancing the electrical activation of retinal neurons was tested using high-density multi-electrode recording and stimulation in isolated macaque retina. The results suggest that local returns may reduce unwanted evoked activity and thus optimize the selectivity of stimulation at cellular resolution. Similar patterns could be implemented in a future high-resolution prosthesis to permit a more faithful replication of normal retinal activity for the treatment of incurable blindness.This work was supported by National Eye Institute grants EY021271 (EJC) and P30 EY019005 (EJC) and F32EY025120 (LG), Stanford Neurosciences Institute (EJC), Stanford UAR Major Grant (VF), Stanford Bio-X USRP Fellowship (VF), Polish National Science Centre Grant DEC-2013/10/M/NZ4/00268 (PH). AGH UST, task No. 11.11.220.01/4 within subsidy of the Ministry of Science and Higher Education (WD), Pew Charitable Trusts Scholarship in the Biomedical Sciences (AS). We thank Bill Newsome, Tirin Moore, Adrienne Mueller, Jose Carmena, and Christie Ferrecchia for access to primate retinas, and Daniel Palanker for useful discussions. ER -