Sex Differences in Dynamic and Static Measures of Brain Integration Derived from Resting-state Functional Magnetic Resonance Imaging

Background : Understanding the impact of biological sex on the functional organization and dynamics of the brain is crucial for elucidating sex-specific differences in cognitive functions and neuropsychiatric disorders. Systems neuroscience often models the brain as a network of interconnected brain regions with functional connectivity (FC), the correlation between signal time courses, as a measure of connection strength. FC matrices, here derived from resting-state functional magnetic resonance imaging (rs-fMRI), define a network graph that can be characterized by its segregation or, inversely, level of module integration. Such parameters can be generated for the full length of the acquired data (static) or for short periods implying dynamically changing brain states. We recently made the interesting observation in a separate study (N = 63) that measures of brain integration and segregation based on dynamic functional connectivity (dFC) data differed between sexes, while graph-based measures based on static FC (sFC) did not, which we investigated in more detail in this study. Methods: We preregistered to repeat our analysis from the small sample in N = 501 subjects of the Human Connectome Project dataset. We did cross-sectional comparisons between sexes of the static rs-fMRI graph parameters modularity and global efficiency, as well asthe dFC parameters state prevalence, mean dwell time, mean inter-state transition time ( ITI ), and variability derived from a two-state model. Additionally, we explore whether sex differences in 66 cognitive and behavioral parameters are mediated by the FC integration measure with the strongest sex effect. Results : All static and dynamic measures of integration/segregation showed higher levels of functional integration in males with effect sizes up to 0.60 for the dFC parameter prevalence. For 3 of the 66 explored cognitive and behavioral parameters, we observed that the prevalence of the integrated state mediated the sex difference: dexterity, agreeableness, and self-reported aggression. Conclusion: We found robust evidence in two data sets that rs-fMRI-based measures of brain integration are increased in males. An exploratory analysis, which needs replication, suggests that such differences mediate personality differences. This study highlights that biological sex differences in brain functional organization may explain sex-typical behaviors.