Abstract
BACKGROUND: Previous studies have identified sex differences in brain structure, function, and connectivity. However, the sex differences and age-related changes at the large-scale brain network level remain unclear. METHODS: Resting-state functional MRI data from 436 healthy adults were analyzed using independent component analysis to extract large-scale brain networks. Multivariate analysis of covariance was applied to investigate sex differences in inter-network connectivity between these networks, and further performed voxel-level analysis to examine intra-network connectivity differences. Additionally, Pearson correlation analysis was used to explore the relationship between inter-network and intra-network functional connectivity (FC) and age. RESULTS: Males exhibited stronger inter-network FC across multiple networks compared to females. In contrast, females demonstrated stronger intra-network FC in several networks, including the sensorimotor, salience, auditory, and executive control networks. Males showed stronger intra-network FC only in specific regions of the posterior default mode and left frontoparietal networks. Additionally, inter-network FC in females appeared more susceptible to age-related changes, whereas males demonstrated relatively stable inter-network connectivity across the lifespan. Intra-network FC generally decreases with age in both males and females, with the exception of the ventral attention network in females and the dorsal sensorimotor network in males. CONCLUSION: Males typically have stronger inter-network connectivity, while females show enhanced intra-network connectivity in key networks. Age-related inter-network connectivity declines are more pronounced in females, both sexes experience a reduction in most intra-network connectivity with age. The study offers valuable insights into how age and sex shape the large-scale brain networks.