Three neural pathways carry information from the retina to cortex: the parvocellular (PC) and magnocellular (MC) pathways, driven by the dense arrays of long (L-) and medium (M-) wave-sensitive cone cells, and the koniocellular (KC) pathway, driven by differences between the L- and M- cone signals and signals from the sparser array of short-wave- sensitive (S) cones. Relatively little is known about the KC pathway but it appears to be an independent, rapid and developmentally-robust input to visual cortex. We will ask three questions about this pathway: (1) When and where do KC pathway signals reach cortex? (2) How do KC signals interact with luminance and chromatic signals from the other pathways? (3) Does the KC pathway play a privileged role in the feedback from visual cortex to the thalamus? We will use a tightly-integrated combination of fMRI, high-density EEG and psychophysics to address these questions in humans. We will use fMRI to map visual areas in each subject. We will then use high-density EEG and distributed source imaging to study KC signals in those visual areas with high temporal resolution. We will also use fMRI to measure KC signals in the lateral geniculate nucleus (LGN). Finally, we will use psychophysics to measure the perceptual correlates of these signals. Answers to these questions will elucidate the normal function of the early visual system. They will also shed light on the visual deficits caused by retinal diseases that cause early degeneration of S-cones. These include glaucoma, retinitis pigmentosa, diabetes, and HIV-related vision loss. Finally, because of its unusual properties (rapid input to lateral cortex, lack of plasticity during long-term visual deprivation), the KC pathway may represent an important alternative target for vision restoration therapies including stem cell therapy and visual prostheses. Understanding the type of information that can be transmitted to cortex through this pathway is therefore of considerable interest. ? ? ?