Divergence in neurodivergent brains: mapping the relationship between developmental trajectories in functional connectivity and clinical outcomes

Brain network development differs between neurodivergent (ND) and neurotypical (NT) youth, but its developmental trajectory, and relationship to clinical outcomes, remains unclear. We examined age-related changes in functional network connectivity and clinical symptoms in 861 participants (5-21 years) from the Healthy Brain Network, including NT youth and those with Neurodevelopmental Disorders (NDDs) and generalized anxiety disorder (GAD). Functional connectivity during movie-watching was modeled using generalized additive models across eight large-scale networks to characterize nonlinear developmental trajectories. Divergence in connectivity profiles between ND and NT groups first emerged during late childhood and were largest during adolescence. Importantly, divergence in connectivity patterns followed a similar trajectory path, but preceded, divergence in clinical outcomes. These findings identify adolescence as a sensitive period when differences in patterns of brain activity and clinical differences become increasingly pronounced, highlighting a potential window for targeted intervention.