PROJECT SUMMARY Approximately 43 million adults in the U.S. struggle to comprehend basic texts. This is a major public health crisis given the strong association between reading comprehension (RC) ability and broad health and economic outcomes, including more than 300 billion annual economic burden related to low literacy in the US. Despite the prevalence of low RC, meta-analyses of behavioral interventions and national statistics in the US reveal no significant RC gains over the past 30 years. This is due in part to limitations of behavioral approaches to characterize the complex processes involved in RC. Brain research has identified more granular mechanisms of RC/RC ability. This includes my own research that has identified brain pathways that promote behavioral resilience in RC disorders, i.e. brain pathways that mitigate severe symptoms in RC disorders. However, brain research has thus far been unable to apply brain network science for a direct, clinical benefit. The goal of the current proposal is to address the need for brain-based RC interventions by integrating recent breakthroughs in two separate fields: brain network science of RC resilience and non-invasive brain network stimulation. I have established a line of research that uses functional MRI and EEG to characterize brain signatures of RC ability and resilience. I have found that cross-network communication between the reading- language brain network (RLN) and a brain network responsible for goal-oriented thought (the cognitive control network; CCN) is more predictive of RC outcomes than within-network communication (e.g. RLN alone). These results mirror findings in a range of disorders that connect the CCN to resilience and provide a compelling target for brain intervention. In a separate field, brain stimulation has also seen a recent breakthrough: using EEG-guided, individually-tuned stimulation of full networks results in recovered memory capacity in older adults that outlasts stimulation, but this has not been applied to other domains. The proposed project will take advantage of recent advances in RC brain network science and non-invasive brain stimulation to develop a safe, brain-based RC intervention protocol. I hypothesize that promotion of cross-network connectivity will result in increased RC ability particularly in low RC groups. In this project, I will determine: the causal effects of cross- vs within-network stimulation on readers' RC ability and brain metrics (Aim 1); how stimulation outcomes interact with individual differences in baseline RC ability/brain metrics (Aim 2); and the efficacy of stimulation beyond behavioral training effects (Aim 3). N = 225 adults with good and poor RC ability will be tested across 3 visits: a pre-intervention visit for baseline behavior and fMRI/EEG metrics; a stimulation visits (randomized/subject for cross- vs. within-network targets) with behavior and fMRI/EEG metrics, and a post-intervention visit to measure prolonged behavior and fMRI/EEG effects. Before stimulation, subjects will receive a short RC intervention. This approach will allow us to establish the efficacy of cutting-edge stimulation approaches in adult literacy, with potential applications in a range of other disorders.

PROJECT NARRATIVE The goal of this project is to address the urgent need for effective, scalable adult literacy interventions by integrating breakthroughs in two separate fields: 1) the brain network science of resilience to reading disorders and 2) high-definition non-invasive brain network stimulation. This study will first establish the efficacy of a novel, non-invasive stimulation protocol on reading behavior and brain metrics; then will determine how stimulation-induced effects interact with baseline reading comprehension ability; and lastly, will identify whether stimulation-induced effects are more clinically-beneficial than canonical behavioral interventions. Results may foundationally change how we treat low adult literacy, and have the potential for wider reaching impacts on non-invasive stimulation protocols for other clinical disorders.