Project Summary/Abstract Reading is vital to life in modern society. Loss of reading ability due to stroke, or alexia, affects approximately 1.3 million Americans and recovery is often incomplete. Reading relies on an area of the brain’s object recognition system that becomes specialized for word recognition as we learn to read, called the visual word for area (VWFA). Because reading is a learned skill, it relies on input from the VWFA into brain networks evolved for more general speech and language processing. There is some evidence that the VWFA also receives top- down information from language regions, but the importance of this feedback for reading is poorly understood. Most cases of alexia are caused by strokes to the language network, not the VWFA, raising the question of whether reading deficits in alexia relate to aberrant VWFA processing caused by disrupted feedback from the language network. Here, I propose to investigate the hypothesis that damage to the language network causes dysfunction and triggers plastic changes in visual word processing areas undamaged by the stroke, and that these changes correspond with reading deficits after stroke. Further, the brain basis of alexia recovery is poorly understood. Previous studies have shown that both spared left hemisphere (LH) language regions and their right hemisphere (RH) homotopes contribute to aphasia recovery, but the role of the RH homotope of the VWFA (rVWFA) in alexia recovery has only been tested in a few case studies, and only with direct damage to the LH VWFA. I hypothesize that the rVWFA is recruited in some cases of alexia caused by lesions to the language network, and that this recruitment contributes to reading performance after stroke, particularly for word comprehension. To test these hypotheses, this prospective study of 40 chronic left hemisphere stroke survivors and 40 demographically matched controls will identify post-stroke functional changes to the canonical left hemisphere VWFA (lVWFA) and the rVWFA (Aim 1), determine the relationship of VWFA activity to lesion locations and disconnections (Aim 2) and examine how this activity relates to reading deficits after stroke (Aim 3). Aim 1 will employ a novel fMRI VWFA localizer I designed to characterize activity in the lVWFA and rVWFA. Aim 2 will conduct voxelwise and structural connectome-based multivariate lesion-symptom mapping analyses to elucidate brain regions and disconnects related to atypical VWFA activity. Aim 3 will employ a hierarchical regression approach to determine the relationship of VWFA activity to deficits in oral word reading, silent word recognition, and silent word comprehension. The proposed research will advance our understanding of the interplay between language regions and visual word processing areas, and of the brain basis of alexia and alexia recovery. By completing this project and the associated training plan, I will learn to conduct fMRI and behavioral research in people with alexia an...