Sex differences in network controllability as a predictor of executive function in youth

Executive function is a quintessential human capacity that emerges late in development and displays different developmental trends in males and females. Sex differences in executive function in youth have been linked to vulnerability to psychopathology as well as to behaviors that impinge on health, wellbeing, and longevity. Yet, the neurobiological basis of these differences is not well understood, in part due to the spatiotemporal complexity inherent in patterns of brain network maturation supporting executive function. Here we test the hypothesis that sex differences in executive function in youth stem from sex differences in the controllability of structural brain networks as they rewire over development. Combining methods from network neuroscience and network control theory, we characterize the network control properties of structural brain networks estimated from diffusion imaging data acquired in males and females in a sample of 882 youth aged 8-22 years. We summarize the control properties of these networks by estimating average and modal controllability, two statistics that probe the ease with which brain areas can drive the network towards easyversus difficult-to-reach states. We find that females have higher modal controllability in frontal, parietal, and subcortical regions while males have higher average controllability in frontal and subcortical regions. Furthermore, average controllability values in the medial frontal cortex and subcortex, both higher in males, are negatively related to executive function. Finally, we find that average controllability predicts sex-dependent individual differences in activation during an n-back working memory task. Taken together, our findings support the notion that sex differences in the controllability of structural brain networks can partially explain sex differences in executive function. Controllability of structural brain networks also predicts features of task-relevant activation, suggesting the potential for controllability to represent context-specific constraints on network state more generally.