Visual Cortical Plasticity and the Implications for Sight Restoration Technologies

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Project Summary While only limited treatment options for diseases such as age related macular degeneration, glaucoma and retinitis pigmentosa currently exist, there are variety of technologies being developed that attempt to restore some visual functioning, including electronic prostheses (either cortical or retinal), optogenetics, and gene therapy. These technologies are not likely to recreate normal vision, but rather provide essential visual input that can improve everyday functioning in patients. In the current state of sight restoration technology, electronic and optogenetic sight recovery technologies cause early on- and off-center retinal cells to fire simultaneously, rather than in a biologically complementary fashion (i.e. when on- cells fire, off-cells representing the same location are suppressed). This creates deeply unnatural population responses that propagate from the retina to cortex. The central question of this proposal is whether patients have the potential to access cortical plasticity in adulthood that improves their ability to decode the unnatural cell population responses in early visual processing elicited by electronic prosthesis or optogenetic technologies. Here, we propose a unique way to understand the role of cortical plasticity in adulthood by examining whether normally sighted individuals can learn to decode visually distorted images by playing action video games. We will manipulate the spatial frequency, orientation and contrast information presented dichoptically to each eye in a way that provides a similar decoding challenge to that posed by electronic or optogenetic prostheses. This distorted information will be used in real time in a video game training paradigm, and we will then use an object discrimination task as a test of perceptual learning. We will examine transfer of learning (for example, using monocular stimuli, and switching filter eye of origin) to uncover specific mechanisms of learning (Aim 1). Next, using functional magnetic resonance imaging, we will examine whether participants are learning to create novel neural representations of objects during perceptual learning or whether there is a convergence with previous existing object representations in object- selective brain areas (Aim 2). Finally, we will test whether perceptual learning is enhanced by short periods of binocular deprivation (Specific Aim 3). This work, examining the mechanisms underlying improvements in the ability to decode these distorted stimuli, will provide developers of sight recovery technologies with empirical data about the potential of human participants to learn to decode unnatural neural population responses in adulthood.