Combination of structural and functional connectivity explains unique variation in specific domains of cognitive function

The relationship between structural and functional brain networks has been characterised as complex: the two networks mirror each other and show mutual influence but they also diverge in their organisation. This work ex-plored whether a combination of structural and functional connectivity can improve the fit of regression models of cognitive performance. Principal Component Analysis (PCA) was first applied to cognitive data from the Hu-man Connectome Project to identify latent cognitive components: Executive Function, Self-regulation, Language, Encoding and Sequence Processing. A Principal Component Regression approach with embedded Step-Wise Re-gression (SWR-PCR) was then used to fit regression models of each cognitive domain based on structural (SC), functional (FC) or combined structural-functional (CC) connectivity. Executive Function was best explained by the CC model. Self-regulation was equally well explained by SC and FC. Language was equally well explained by CC and FC models. Encoding and Sequence Processing were best explained by SC. Evaluation of out-of-sample models' skill via cross-validation showed that SC, FC and CC produced generalisable models of Language perfor-mance. SC models performed most effectively at predicting Language performance in unseen sample. Executive Function was most effectively predicted by SC models, followed only by CC models. Self-regulation was only effectively predicted by CC models and Sequence Processing was only effectively predicted by FC models. The present study demonstrates that integrating structural and functional connectivity can help explaining cognitive performance, but that the added explanatory value (in-sample) may be domain-specific and can come at the expense of reduced generalisation performance (out-of-sample).