Prevention neuroscience investigates the brain basis of attitude and behavior change. Over the years, an increasingly structurally and functionally resolved “persuasion network” has emerged. However, current studies have only identified a small handful of neural structures that are commonly recruited during persuasive message processing, and the extent to which these (and other) structures are sensitive to numerous individual difference factors remains largely unknown. In this project we apply a multi-dimensional similarity-based individual differences analysis to explore which individual factors—including characteristics of (...) messages and target audiences—drive patterns of brain activity to be more or less similar across individuals encountering the same anti-drug public service announcements (PSAs). We demonstrate that several ensembles of brain regions show response patterns that are driven by a variety of unique factors. These results are discussed in terms of their implications for neural models of persuasion, prevention neuroscience and message tailoring, and methodological implications for future research. (shrink)