Mechanisms of multisensory rehabilitation in a primate model of hemianopia

Project Summary Damage to visual cortex by stroke or trauma often results in contralateral blindness, or hemianopia, a condition that markedly compromises quality of life. The goal of this project is to develop a primate model of multisensory rehabilitation from hemianopia. Although several therapeutic strategies have been tried over the years, they have met with limited success, mostly restricted to the recovery of visuomotor orienting without visual awareness. Recently, a novel, simple, noninvasive sensory training paradigm has been developed that produces far more promising and rapid results. This paradigm involves repeatedly presenting spatiotemporally congruent visual and auditory cues to the blinded hemifield, which engages plasticity within circuits that process both visual and auditory signals. Results from hemianopic cats have shown that, after several weeks of such multisensory exposure, animals recover the ability to detect and localize visual stimuli and perform rudimentary visual pattern discrimination in the contralesional field. Similar findings were recently obtained in two human patients, who were given a very similar multisensory rehabilitation paradigm, and were able to verbally report on their awareness of visual stimuli in the previously blind hemifield. However, the extent of visual capabilities that can be recovered is unknown. To overcome the limitations of using the cat model to explore these limits and its neurobiological bases, we propose to establish a primate model of multisensory rehabilitation with which we can detail the effectiveness, operation, and neural correlates of the paradigm. Our immediate objective is to examine the most pressing questions relating to the psychophysical and neurophysiological outcomes of the multisensory rehabilitation of hemianopia, including the quantification of visual stimulus detection and visual feature discrimination capacities. To do so we will assess the behavioral and perceptual capabilities of trained hemianopic monkeys on a battery of visual psychophysical tasks before and after multisensory rehabilitation and assess changes in the neurophysiological properties of subcortical and cortical areas (superior colliculus and area LIP) believed to underlie this recovery. These results will provide a foundation for understanding the mechanisms underlying this novel rehabilitative approach so that optimal translational strategies can be developed to ameliorate this condition in human patients.