PROJECT SUMMARY All animals that can form images in their retinas, from flies to humans, need ON and OFF brain pathways to process light and dark features in visual scenes. The traditional textbook view is that these ON and OFF pathways fully converge in visual cortex to make neurons selective to stimulus orientation but invariant to stimulus polarity and spatial phase. Against this traditional view, our recent work demonstrates that ON and OFF pathways segregate in visual cortex, specialize in different spatiotemporal functions, and process images relatively independently from each other. In addition, our preliminary results indicate that ON and OFF cortical pathways respond very differently to changes in luminance range, which varies continuously in our visual environment from sunrise to sunset. Based on our results, we hypothesize that luminance perception originates from the interaction between two separate and relatively independent ON and OFF pathways that are exquisitely matched to the statistics of light and dark features in natural scenes. This new understanding of ON and OFF cortical processing has important implications for human luminance perception, image brain processing analysis and could help improve the diagnostic tools available to manage treatment in human visual disease. In this proposal, we will investigate how ON and OFF cortical pathways interact to generate luminance perception, and how these interactions vary with background luminance, luminance range and the rod/cone retinal ratio available to sample the images. We will then use all these measurements to develop models that replicate human luminance perception more accurately than in the past and new diagnostic tools that measure human ON and OFF visual function in diseases that affect the retina (e.g. glaucoma) and visual cortex (e.g. amblyopia).