Sex-by-age differences in the resting-state brain connectivity

TL;DR

This study introduces a novel method for analyzing brain connectivity, revealing age-dependent sex differences in resting-state networks and their potential links to mental health symptoms.

Contribution

The paper presents the PACE method for assessing hierarchical modularity in brain networks and applies it to uncover novel sex-by-age differences in resting-state connectivity.

Findings

Sex differences in brain connectivity become significant after age 25.

Key brain regions showing sex differences include prefrontal cortex, amygdala, and hippocampus.

Sex-specific connectivity patterns relate to differences in mental health symptoms.

Abstract

Recently we developed a novel method for assessing the hierarchical modularity of functional brain networks - the probability associated community estimation(PACE). The PACE algorithm is unique in that it permits a dual formulation, thus yielding equivalent connectome modular structure regardless of whether considering positive or negative edges. This method was rigorously validated using F1000 and HCP data. We detected novel sex differences in resting-state connectivity that were not previously reported. This current study more thoroughly examined sex differences as a function of age and their clinical correlates, with findings supporting a basal configuration framework. To this end, we found that men and women do not significantly differ in the 22-25 age range. However, these same non-significant differences attained statistical significance in the 26-30 age group, while becoming highly statistically significant in the 31-35 age group. At the most global level, areas of diverging sex difference include parts of the prefrontal cortex and the temporal lobe, amygdala, hippocampus, inferior parietal lobule, posterior cingulate, and precuneus. Further, we identified statistically different self-reported summary scores of inattention, hyperactivity, and anxiety problems between men and women. These self-reports additionally divergently interact with age and the basal configuration between sexes. In sum, our study supports a paradigm change in how we conceptualize the functional connectome, shifting away from simple concepts, and towards thinking globally and probabilistically how the brain exhibits dynamic sex-specific connectivity configuration as a function of age, and the role this sex-by-age configuration at rest might play in mental health frequency and presentation, including symptom patterns in depression.