A mesoscale optogenetics system for precise and robust stimulation of the primate cortex

An ideal cortical stimulation technique should allow precise and robust stimulation of arbitrarily chosen sites on the cortex. However, current methods in primates fall short of this ideal, allowing stimulation only at fixed sites spaced apart at the millimeter scale. Capitalizing on recent advancements in microLED devices and opsins, we introduce a mesoscale optogenetics system that enables flexible million-pixel stimulation over a centimeter-sized area of the primate cortex. Stimulation from single pixels elicited distinct responses centered at the corresponding sites, allowing for cortical stimulation with arbitrary patterns at high resolution. We constructed a head-mounted system targeted at the monkey's primary visual cortex and showed that phosphenes could be accurately and robustly evoked over more than a year. Thus, the mesoscale optogenetics approach offers exceptional flexibility and robustness in cortical stimulation and could be particularly relevant to brain areas with prominent mesoscale columnar organization, such as the primate visual cortex.