Sex differences and age-related changes of large-scale brain networks

Shujun Zhang, Meiqin Li, Anqiang Chen, Liping Jiang, Hao Yu, Yueqin Chen

Abstract: 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. 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. 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. 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. The study explores how age and sex influence large-scale brain functional connectivity (FC). It finds that males typically exhibit stronger inter-network connectivity, which may suggest their brains are more engaged in cross-network communication, supporting global cognitive processing. This aligns with theories that males have a more global brain network structure, optimizing cognitive performance. In contrast, females show enhanced intra-network connectivity, reflecting specialized processing within certain networks for more efficient localized brain functions such as sensory processing and executive control. These differences imply that males may rely on broader coordination between networks, while females focus on more efficient, localized processing. As females age, their brains experience more pronounced changes in network interactions, possibly due to hormonal shifts or structural differences in the brain, making them more vulnerable to age-related alterations. Males, however, may show greater resilience in maintaining inter-network connectivity. Both sexes experience a decline in intra-network FC with age, suggesting reduced efficiency in communication within individual brain networks, potentially linked to neurodegeneration and other aging-related brain changes.