Reports of the death of brain-behavior associations have been greatly exaggerated.

Magnetic resonance imaging (MRI) has been a popular and useful non-invasive method to map patterns of brain structure and function to complex human traits. Recently published observations in multiple large-scale studies cast doubt upon these prospects, particularly for prediction of cognitive traits from structural and resting state functional MRI, which seems to account for little behavioral variability. We leverage baseline data from thousands of children in the Adolescent Brain Cognitive Development (ABCD) Study to inform the replication sample size required with both univariate and multivariate methods across different imaging modalities to detect reproducible brain-behavior associations. We demonstrate that by applying multivariate methods to high-dimensional brain imaging data, we can capture lower dimensional patterns of structural and functional brain architecture that correlate robustly with cognitive phenotypes and are reproducible with only 42 individuals in the replication sample for working memory-related functional MRI, and ∼100 subjects for structural MRI. Even with 50 subjects in the discovery sample, prediction can be adequately powered with 105 subjects in the replication sample for multivariate prediction of cognition with working memory task functional MRI. These results point to an important role for neuroimaging in translational neurodevelopmental research and showcase how findings in large samples can inform reproducible brain-behavior associations in small sample sizes that are at the heart of many investigators' research programs and grants.