Neuronal plasticity is an important mechanism for memory and cognition, and also fundamental to fine-tune perception to the environment. It has long been thought that sensory neural systems are plastic only in very young animals, during the so-called “critical period”. However, recent evidence – including work from our laboratory – suggests that the adult brain may retain far more capacity for plastic change than previously assumed, even for basic visual properties like ocular dominance. This project probes the underlying neural mechanisms of adult human plasticity, and investigates its functional role in important processes such as response optimization, auto-calibration and recovery of function. We propose a range of experiments employing many experimental techniques, organized within four principle research lines. The first (and major) research line studies the effects of brief periods of monocular deprivation on functional cortical reorganization of adults, measured by psychophysics (binocular rivalry), ERP, functional imaging and MR spectroscopy. We will also investigate the clinical implications of monocular patching of children with amblyopia. Another research line looks at the effects of longer-term deprivation, such as those induced by hereditary cone dystrophy. Another examines the interplay between plasticity and visual adaptation in early visual cortex, with techniques aimed to modulate retinotopic organization of primary visual cortex. Finally we will use fMRI to study development and plasticity in newborns, providing benchmark data to assess residual plasticity of older humans. Pilot studies have been conducted on most of the proposed lines of research (including fMRI recording from alert newborns), attesting to their feasibility and the likelihood of them being completed within the timeframe of this grant. The PI has considerable experience in all these research areas.