How an individual's unique brain connectivity determines that individual's cognition, behavior, and risk for pathology is a fundamental question in basic and clinical neuroscience. In seeking answers, many have turned to machine learning, with some noting the particular promise of deep neural networks in modelling complex non-linear functions. However, it is not clear that complex functions actually exist between brain connectivity and behavior, and thus if deep neural networks necessarily outperform simpler linear models, or if their results would be interpretable. Here we show that, across 52 subject measures of cognition and behavior, deep neural networks fit to each brain region's connectivity outperform linear regression, particularly for the brain's connector hubs-regions with diverse brain connectivity-whereas the two approaches perform similarly when fit to brain systems. Critically, averaging deep neural network predictions across brain regions results in the most accurate predictions, demonstrating the ability of deep neural networks to easily model the various functions that exists between regional brain connectivity and behavior, carving the brain at its joints. Finally, we shine light into the black box of deep neural networks using multislice network models. We determined that the relationship between connector hubs and behavior is best captured by modular deep neural networks. Our results demonstrate that both simple and complex relationships exist between brain connectivity and behavior, and that deep neural networks can fit both. Moreover, deep neural networks are particularly powerful when they are first fit to the various functions of a system independently and then combined. Finally, deep neural networks are interpretable when their architectures are structurally characterized using multislice network models.
MainHuman cognitive neuroscience seeks to explain how the function of an individual's brain determines their behavior. The human brain's functional connectivity, as commonly measured by the pairwise Pearson's correlation coefficient between regional time series, has generated tremendous insight into the brain's network function [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] . A desire to leverage individual variability in these connections to predict cognition, behavior, and symptoms of mental illness has united neuroscientists, clinicians, and machine learning experts 20-32 . Yet, precisely which prediction algorithm will prove most efficacious is unknown. While deep neural networks display notable predictive power in other domains 33 , it is not clear whether their application to human brain connectivity is necessary or insightful 34 . Further, it is not known whether the mathematical functions that define the relationship between brain connectivity and a given outcome are sufficiently complex so as to require deep neural networks instead of simpler linear models 34,35 . Moreover, even should deep neural networks offer accurate predictions, their interpretability ha...