Kristina M. Visscher - US grants

? DESCRIPTION (provided by applicant): People who have macular degeneration often lose the ability to see in the part of vision normally used for daily tasks such as reading and recognizing faces. This often debilitating loss is expected to afflict 3 million US citizens by 202. An essential health-related goal is therefore to develop strategies that allow patients with macular degeneration to make better use of their spared peripheral vision. Despite loss of central vision, many patients learn to successfully navigate the world, becoming adept at using peripheral vision for tasks normally done with central vision. The mechanisms underlying this visual plasticity are not known, but are of great clinical interest, because better understanding can lead to improved treatment strategies following vision loss. Plasticity after macular degeneration is also of great basic science interest because it provides insight to nervous system plasticity in a human model, which is key for understanding and treating a host of neurological and psychiatric disorders. Most work examining plasticity after vision loss has studied bottom-up remapping of inputs, and this remapping appears to be minimal in adults. We propose to examine connections between the early visual cortex and frontal and parietal brain networks, which have the potential to be more plastic. We will make use of the Human Connectome Project dataset and protocols to identify how the structure and connections of early visual areas are altered following loss of central vision due to macular degeneration. The overall objective of this proposal is to identify the neuroplastic mechanisms that allow patients with MD to use peripheral vision for tasks, such as reading and recognizing faces, for which people with healthy vision use the macula. Our central hypothesis is that greater reliance on peripheral vision following MD leads visual cortical regions representing the periphery to become structurally and functionally more similar to those representing the macula, thus improving functional vision. The motivation for the proposed research is that better understanding of neural mechanisms that underlie enhanced peripheral vision in patients who suffer from macular degeneration is essential to developing the next generation of therapeutic interventions. We will test our central hypothesis by identifying how the following characteristics of early visual areas change after central vision loss: 1) functional connectivity to fronto-parietal control regions, (2 structural measures of white matter integrity, (3) cortical thickness. We will compare participants with age-related macular degeneration to matched controls using the Human Connectome Project protocols. These aims are expected to yield information about how top-down connections to early visual areas contribute to plasticity after vision loss. This contribution wil be significant because it will fundamentally alter our understanding of how the brain compensates after vision loss, and revise our understanding of neural plasticity in general. This knowledge wil guide the development of new strategies for training patients with vision loss to use their spared vision more effectively.

Project Summary Research on perceptual learning (PL) has been dominated by studies that seek to isolate and improve individual visual processes. However, an important translational outcome of PL research is to address the needs of patients with vision loss, who seek to improve performance on daily tasks such as reading, navigation, and face recognition. These more ecological cases of behavioral change and cortical plasticity, which are inherently complex and integrative, have revealed significant gaps in a more holistic understanding of how multiple visual processes and their associated brain systems jointly contribute to durable and generalizable PL. To address these gaps, here we study simulated and natural central vision loss. We focus on macular degeneration (MD), one of the most common causes of vision loss (projected to affect 248 million people worldwide by 2040), which results from damage to photoreceptors in the macula that disrupts central vision. Such central vision loss is a superb lens through which study to how ecologically relevant changes in the use of vision relate to changing brain activity and connectivity because it represents a massive alteration in visual experience requiring reliance on peripheral vision for daily tasks. With the use of eye-trackers and gaze-contingent displays that induce central scotomas, central vision loss can be simulated in normally seeing individuals, who then develop peripheral looking patterns that resemble compensatory vision strategies seen in MD patients. Ideal use of peripheral vision requires improvement in multiple vision domains, three of the most important being: early visual processing (e.g., visual sensitivity), mid-level visual processing (e.g., spatial integration), and attention and eye-movements. To date, no study has systematically investigated these three domains of PL and their neural underpinnings. The proposed research plan rests on rigorous prior work showing that PL influences multiple brain structures and functions related to these three domains. We propose a novel approach of systematically measuring how different training regimes related to the three domains influence a broad range of psychophysical and ecological behaviors (Aim 1), how these changes arise from plasticity in brain structure and function (Aim 2), and how PL after simulated central vision loss compares to PL in MD (Aim 3). This work is significant and innovative as it will be the first integrated study of PL characterizing multiple trainable factors and their impact on diverse behavioral outcomes and on cutting-edge assessments of neural representations and dynamics. It is also the first study to directly compare PL in MD patients with PL in a controlled model system of central visual field loss with simulated scotomas, which if validated will allow the use of this model system to interrogate MD in larger samples of healthy individuals. We will also share a unique dataset that will help the field to understand behavioral and neural plasticity after central vision loss and individual differences in responsiveness to training. Finally, this work will illuminate basic mechanisms of brain plasticity after sensory loss that may generalize to other forms of rehabilitation after peripheral or central damage.