Sex and Age Effects of Functional Connectivity in Early Adulthood

Abstract

Functional connectivity (FC) in resting-state functional magnetic resonance imaging (rs-fMRI) is widely used to find coactivating regions in the human brain. Despite its widespread use, the effects of sex and age on resting FC are not well characterized, especially during early adulthood. Here we apply regression and graph theoretical analyses to explore the effects of sex and age on FC between the 116 AAL atlas parcellations (a total of 6670 FC measures). rs-fMRI data of 494 healthy subjects (203 males and 291 females; age range: 22–36 years) from the Human Connectome Project were analyzed. We report the following findings. (1) Males exhibited greater FC than females in 1352 FC measures (1025 survived Bonferroni correction; \documentclass{aastex}\usepackage{amsbsy}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{bm}\usepackage{mathrsfs}\usepackage{pifont}\usepackage{stmaryrd}\usepackage{textcomp}\usepackage{portland, xspace}\usepackage{amsmath, amsxtra}\pagestyle{empty}\DeclareMathSizes{10}{9}{7}{6}\begin{document}$$p < 7.49{ \rm{E}} - 6$$ \end{document} ). In 641 FC measures, females exhibited greater FC than males but none survived Bonferroni correction. Significant FC differences were mainly present in frontal, parietal, and temporal lobes. Although the average FC values for males and females were significantly different, FC values of males and females exhibited large overlap. (2) Age effects were present only in 29 FC measures and all significant age effects showed higher FC in younger subjects. Age and sex differences of FC remained significant after controlling for cognitive measures. (3) Although sex  \documentclass{aastex}\usepackage{amsbsy}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{bm}\usepackage{mathrsfs}\usepackage{pifont}\usepackage{stmaryrd}\usepackage{textcomp}\usepackage{portland, xspace}\usepackage{amsmath, amsxtra}\pagestyle{empty}\DeclareMathSizes{10}{9}{7}{6}\begin{document}$$\times$$ \end{document}  age interaction did not survive multiple comparison correction, FC in females exhibited a faster cross-sectional decline with age. (4) Male brains were more locally clustered in all lobes but the cerebellum; female brains had a higher clustering coefficient at the whole-brain level. Our results indicate that although both male and female brains show small-world network characteristics, male brains were more segregated and female brains were more integrated. Findings of this study further our understanding of FC in early adulthood and provide evidence to support that age and sex should be controlled for in FC studies of young adults.