Characterizing the Organization of Networks with Neuromodulation to Enhance Communication Treatments in Aphasia (CONNECT Aphasia) - Although aphasia remains the most common focal cognitive deficit associated with stroke, affecting 1–2 million Americans, effective targeted treatments are still lacking. Transcranial magnetic stimulation (TMS) shows promise for aiding recovery by focally altering brain activity. However, the lack of a model that adequately explains how the brain’s language network reorganizes after stroke—and how TMS influences that reorganization—has hindered further optimization of this treatment approach. Current TMS strategies often focus on inhibiting the right pars triangularis (rPTr), based on the assumption that excessive right hemisphere activity impedes recovery. However, emerging evidence suggests a more nuanced role for the right hemisphere in aphasia recovery and highlights the complex ways in which TMS of the rPTr impacts language outcomes. This project aims to advance the understanding of post-stroke language reorganization by combining innovative computational and imaging techniques for structural network analysis with TMS to clarify the roles of the rPTr and other brain regions in recovery. Preliminary findings suggest that in individuals with left hemisphere strokes that result in aphasia, the rPTr undergoes changes in network controllability, a network property that facilitates guiding brain activity into specific states. We hypothesize that network controllability is a structural characteristic of brain regions involved in cognitive control of language, which is crucial for optimal language performance in many individuals with post-stroke aphasia. Thus, increased network controllability in the rPTr may reflect its capacity to support cognitive control of language in persons with aphasia. Conversely, when the rPTr exhibits inefficient network controllability, it may hinder recovery, which could explain why inhibiting its activity with TMS often improves language outcomes. This study will explore these concepts through three specific aims. First, we will simulate lesions in brain connectomes to predict how structural brain networks shift after stroke and how these changes correlate with language recovery in aphasia. Second, we will investigate the relationship between rPTr network controllability and response to TMS treatment in a cohort of individuals with aphasia who recently participated in a clinical trial involving TMS targeting the rPTr. Finally, we will conduct a prospective study to evaluate whether directing TMS to individually identified right hemisphere sites with high network controllability enhances language performance compared to rPTr stimulation. These findings aim to refine our understanding of how brain networks adapt after stroke and to develop personalized, network-guided approaches for optimizing TMS in aphasia therapy. Beyond aphasia, this work represents an innovative step toward leveraging individual brain connectivity to improve neuromodulation strategies across neurological conditions.
