PROJECT SUMMARY Amblyopia is a disorder of spatial vision despite good retinal image quality and eye health. It affects 2-3% of the population and almost always develops with early misalignment (strabismus) or unequal refractive power (anisometropia), or form deprivation (cataract). Most studies on human amblyopia concentrate on thresholds for contrast, size or offset, but striking perceptual distortions have been documented by asking amblyopes to describe or draw clearly visible high-contrast letters, rings, and sinusoidal gratings. Form distortions are likely to be at least as big a problem as loss of visual resolution for daily life. Forms are defined by local orientations, and almost all neurons in primary visual cortex (V1) are tuned for orientation, highlighting its importance in parsing visual images. The replicable systematic perceptual distortions of gratings drawn by amblyopes are unexplainable with a neural scrambling model or a systematic shift in the neural map, but are compatible with errors in the neural encoding of orientation in V1, while also involving decoding mechanisms in later cortical areas. Our team of researchers and clinicians proposes to examine the neural development and functional implications of the grating distortions by using our recent psychophysics, electrophysiology and modeling results in the domains of ON/OFF system imbalance in amblyopia, cortical map formation, orientation processing across V1, and the processing of parallel orientation signals for perceptions of 3-D shape, object pose and mirror symmetry. We aim to model the neural development of errors in orientation encoding as a consequence of ON-OFF imbalance caused by anisometropia and strabismus, which limits the orientation tuning and spatial resolution of V1 neurons and shrinks the ocular dominance columns for the amblyopic eye. We will also examine if orientation processing errors in the amblyopic eye make it difficult to do higher level tasks that rely on orientation cues, or if there is some compensatory mechanism, and if the fellow eye performs normally, overcompensates, or is handicapped because the lack of stereo makes it difficult to calibrate monocular cues during development. Psychophysical and electrophysiological data suggest that amblyopia also involves abnormalities in cortical areas after V1, suggesting that physiological changes may be propagated and amplified in higher cortical areas that may have prolonged windows of plasticity. In addition, regions of V1 that are unresponsive during passive viewing of visual stimuli in macular degeneration, can be activated by engaging the subjects in a stimulus-related task, suggesting a role for top-down influences on plasticity. The stimuli we use to identify deficits in functionally important visual tasks could be used to trigger top-down signals from higher brain areas as part of the design of future treatments for recovery of perceptual performance in adulthood, which would supplement treatme...