Pubertal timing predicts resting-state functional connectivity of cortical networks

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Background: Pubertal timing has profound implications for adolescent brain development and mental health outcomes; yet its influence on cortical resting-state functional connectivity (rs-FC) remains under explored. This study investigated whether individual differences in pubertal timing predict large-scale cortical rs-FC patterns during adolescence. Pubertal timing was quantified as puberty age gap (PAG); the difference between a model-predicted ‘puberty age’ and chronological age; where positive values reflect earlier timing and negative values indicate later timing. Methods: Leveraging data from the ABCD Study (N ≈ 3500), we examined the associations between PAG and resting-state functional connectivity across 12 large-scale brain networks defined by the Gordon parcellation. In addition to computing PAG using both physical and hormonal features, we also attempted to tease apart the contribution from adrenal and gonadal phases of maturation, and from physical (Pubertal Developmental Scale (PDS) items) vs hormonal features (testosterone, estradiaol, dehydroepiandrosterone (DHEA)). Cross-sectional associations between PAG and rs-FC, as well as prospective associations between PAG and change in rs-FC, were assessed separately in males and females. Results: Cross-sectionally, earlier pubertal timing (defined as a greater PAG) was associated with altered resting-state functional connectivity patterns within and between key large-scale cortical networks. Most associations showed similar directional patterns to normative age-related rs-FC development, while a subset of associations involving higher-order control and executive systems appeared to be specific to pubertal timing. The most implicated connections involved primary sensorimotor, attention/salience, and control/executive networks, with patterns evident in both sexes but more wide spread in males. The longitudinal analyses yielded weaker associations relative to the cross-sectional findings, with no effects surviving FDR correction. Conclusions: This study highlights the relevance of pubertal timing, beyond chronological age, in shaping cortical functional connectivity, particularly within sensorimotor, salience, and higher-order control networks. While many associations paralleled normative age-related rs-FC development, others appeared distinct from those observed for chronological age, suggesting that pubertal timing may explain additional variability in adolescent brain organization beyond age alone.

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