Sex differences in the functional topography of association networks in youth

Prior work has shown that there is substantial interindividual variation in the spatial distribution of functional networks across the cerebral cortex, or functional topography. However, it remains unknown whether there are sex differences in the topography of individualized networks in youth. Here, we leveraged an advanced machine learning method (sparsity-regularized non-negative matrix factorization) to define individualized functional networks in 693 youth (ages 8 to 23 y) who underwent functional MRI as part of the Philadelphia Neurodevelopmental Cohort. Multivariate pattern analysis using support vector machines classified participant sex based on functional topography with 82.9% accuracy (P < 0.0001). Brain regions most effective in classifying participant sex belonged to association networks, including the ventral attention, default mode, and frontoparietal networks. Mass univariate analyses using generalized additive models with penalized splines provided convergent results. Furthermore, transcriptomic data from the Allen Human Brain Atlas revealed that sex differences in multivariate patterns of functional topography were spatially correlated with the expression of genes on the X chromosome. These results highlight the role of sex as a biological variable in shaping functional topography.

Automated summary

Prior work has shown substantial interindividual variation in the spatial distribution of functional networks across the cerebral cortex, but it remains unknown whether there are sex differences in the topography of individualized networks in youth. In this study, researchers leveraged advanced machine learning to define individualized functional networks in youth and found that there are sex-related spatial patterns in functional topography. These patterns showed high accuracy in classifying participant sex based on functional topography. Additionally, the study revealed that the sex differences in functional topography were correlated with gene expression on the X chromosome.