Cross-state stability and maturational similarity of the social brain connectome in children and adolescents

Abstract

The intra-individual stability of functional connectivity (FC) across two or more scans and the inter-individual similarity of FC patterns relative to peers capture developmental variability in functional brain organization. Despite their different referents, these measures are strongly coupled at the whole brain level; however, it remains unclear whether this relationship emerges in development, whether it extends to the social brain, and whether it differs by sex. Based on the importance of social development in this age range, we hypothesized that known developmental relationships and sex-specific effects would be more pronounced in the social brain relative to the whole brain. Using a large psychiatrically enriched sample of 769 youth ages 6-21 (female N = 327, mean age = 12.27 years), we computed FC during rest and movie-watching scans and quantified stability across scans as well as similarity to mature subjects (n=36) within each condition. We then tested whether sex-dependent age relationships were captured by these measures or by the strength of their coupling. Our results showed that cross-state stability and maturational similarity are strongly coupled in development, and that this coupling is enhanced in the social brain relative to the whole brain. Furthermore, the strength of stability-similarity coupling increased as a function of age in females, while males showed the opposite effect. When assessing relationships between age and each FC measure independently, no individual effects were significant after FDR correction. However, our multivariate age-prediction models fared much better, demonstrating that edgewise stability and maturational similarity measures can capture spatially heterogeneous developmental effects that are lost when collapsing across edges. Together, these results support the emerging idea that the degree of FC stability across scans is related to how closely an individuals functional architecture aligns to a shared template. Here, we newly show that this stability-similarity coupling is stronger in the social brain and varies with age in sex-specific ways. Future longitudinal work is needed to establish whether these cross-sectional relationships also characterize within-person developmental change.