Individual Differences in Cognitive Performance Are Better Predicted by Global Rather Than Localized BOLD Activity Patterns Across the Cortex

Despite its central role in revealing the neurobiological mechanisms of behavior, neuroimaging research faces the challenge of producing reliable biomarkers for cognitive processes and clinical outcomes. Statistically significant brain regions, identified by mass univariate statistical models commonly used in neuroimaging studies, explain minimal phenotypic variation, limiting the translational utility of neuroimaging phenotypes. This is potentially due to the observation that behavioral traits are influenced by variations in neuroimaging phenotypes that are globally distributed across the cortex and are therefore not captured by thresholded, statistical parametric maps commonly reported in neuroimaging studies. Here, we developed a novel multivariate prediction method, the Bayesian polyvertex score, that turns a unthresholded statistical parametric map into a summary score that aggregates the many but small effects across the cortex for behavioral prediction. By explicitly assuming a globally distributed effect size pattern and operating on the mass univariate summary statistics, it was able to achieve higher out-of-sample variance explained than mass univariate and popular multivariate methods while still preserving the interpretability of a generative model. Our findings suggest that similar to the polygenicity observed in the field of genetics, the neural basis of complex behaviors may rest in the global patterning of effect size variation of neuroimaging phenotypes, rather than in localized, candidate brain regions and networks.