Ruben C. Gur

Eli J. Cornblath, Evelyn Tang, Graham L. Baum et al.

Executive function 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. Yet, the neurobiological basis of these differences is not well understood. 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 easy- versus 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.

Vishnu M. Bashyam, Jimit Doshi, Guray Erus et al.

Conventional and deep learning-based methods have shown great potential in the medical imaging domain, as means for deriving diagnostic, prognostic, and predictive biomarkers, and by contributing to precision medicine. However, these methods have yet to see widespread clinical adoption, in part due to limited generalization performance across various imaging devices, acquisition protocols, and patient populations. In this work, we propose a new paradigm in which data from a diverse range of acquisition conditions are "harmonized" to a common reference domain, where accurate model learning and prediction can take place. By learning an unsupervised image to image canonical mapping from diverse datasets to a reference domain using generative deep learning models, we aim to reduce confounding data variation while preserving semantic information, thereby rendering the learning task easier in the reference domain. We test this approach on two example problems, namely MRI-based brain age prediction and classification of schizophrenia, leveraging pooled cohorts of neuroimaging MRI data spanning 9 sites and 9701 subjects. Our results indicate a substantial improvement in these tasks in out-of-sample data, even when training is restricted to a single site.