Shared and sex-differentiated brain-behavior associations at rest: A canonical correlation analysis of fMRI and...

Although resting-state thought content and brain activity have been extensively studied, large-scale covariation between these domains remains poorly understood. In this study, we applied fully data-driven canonical correlation analysis (CCA) to resting-state fMRI and Amsterdam Resting-State Questionnaire (ARSQ) data from 1616 healthy adults to investigate shared and sex-differentiated brain-behavior associations. For males, the first canonical correlation was 0.358 (p = 0.003, FDR-corrected p = 0.030), and for females, it was 0.331 (p < 0.001, FDR-corrected p < 0.001), with the first canonical variate explaining the largest proportion of covariance between ARSQ dimensions and network connectivity. Structure correlations revealed that "Sleepiness" was most strongly associated with Default Mode Network (DMN) connectivity in both sexes (male r = 0.764, p < 0.001; female r = 0.899, p < 0.001). Sex-differentiated patterns were observed in higher-order networks, including fronto-parietal, cingulo-opercular, and cerebellar networks. These results indicate a shared DMN-sleepiness coupling across sexes, alongside sex-specific associations in other large-scale networks. Our findings provide quantitative evidence for the neural embodiment of resting-state cognition and highlight the importance of considering both shared and sex-differentiated network in functional connectivity research.