Characterizing the effects of age, puberty, and sex on variability in resting-state functional connectivity in late childhood and early adolescence

Neuroimage. 2025 Jun:313:121238. doi: 10.1016/j.neuroimage.2025.121238. Epub 2025 Apr 23.

Abstract

Understanding the relative influences of age, pubertal development, and sex assigned at birth on brain development is a key priority of developmental neuroscience given the complex interplay of these factors in the onset of psychopathology. Previous research has investigated how these factors relate to static (time-averaged) functional connectivity (FC), but little is known about their relationship with dynamic (time-varying) FC. The present study aimed to investigate the unique and overlapping roles of these factors on dynamic FC in children aged approximately 9 to 14 in the ABCD Study using a sample of 5122 low-motion resting-state scans (from 4136 unique participants). Time-varying correlations in the frontolimbic, default mode, and dorsal and ventral corticostriatal networks, estimated using the Dynamic Conditional Correlations (DCC) method, were used to calculate variability of within- and between-network connectivity and of graph theoretical measures of segregation and integration. We found decreased variability in global efficiency across the age range, and increased variability within the frontolimbic network driven primarily by those assigned female at birth (AFAB). AFAB youth specifically also showed increased variability in several other networks. Controlling for age, both advanced pubertal development and being AFAB were associated with decreased variability in all within- and between-network correlations and increased variability in measures of network segregation. These results potentially suggest advanced brain maturation in AFAB youth, particularly in key networks related to psychopathology, and lay the foundation for future investigations of dynamic FC.

Keywords: ABCD Study; Developmental neuroscience; Dynamic conditional correlations; Dynamic functional connectivity; Puberty; Sex differences.

MeSH terms

  • Adolescent
  • Age Factors
  • Brain* / diagnostic imaging
  • Brain* / growth & development
  • Brain* / physiology
  • Child
  • Connectome* / methods
  • Female
  • Humans
  • Magnetic Resonance Imaging / methods
  • Male
  • Nerve Net* / diagnostic imaging
  • Nerve Net* / growth & development
  • Nerve Net* / physiology
  • Neural Pathways / growth & development
  • Neural Pathways / physiology
  • Puberty* / physiology
  • Sex Characteristics*
  • Sex Factors