Large-Scale Functional Brain Networks of Maladaptive Childhood Aggression Identified by Connectome-Based Predictive Modeling

Disruptions in frontoparietal networks supporting emotion regulation have been long implicated in maladaptive childhood aggression. However, the association of connectivity between large-scale functional networks with aggressive behavior has not been tested. The present study examined whether the functional organization of the connectome predicts severity of aggression in children. This cross-sectional study included a transdiagnostic sample of 100 children with aggressive behavior (27 females) and 29 healthy controls without aggression or psychiatric disorders (13 females). Severity of aggression was indexed by the total score on the parent-rated Reactive-Proactive Aggression Questionnaire. During fMRI, participants completed a face emotion perception task of fearful and calm faces. Connectome-based predictive modeling with internal cross-validation was conducted to identify brain networks that predicted aggression severity. The replication and generalizability of the aggression predictive model was then tested in an independent sample of children from the Adolescent Brain Cognitive Development (ABCD) study. Connectivity predictive of aggression was identified within and between networks implicated in cognitive control (medial frontal, frontoparietal), social functioning (default mode, salience), and emotion processing (subcortical, sensorimotor) (r=0.31, RMSE = 9.05, p=0.005). Out-of-sample replication (p<0.002) and generalization (p=0.007) of findings predicting aggression from the functional connectome was demonstrated in an independent sample of children from the ABCD study (n=1,791; n=1,701). Individual differences in large-scale functional networks contribute to variability in maladaptive aggression in children with psychiatric disorders. Linking these individual differences in the connectome to variation in behavioral phenotypes will advance identification of neural biomarkers of maladaptive childhood aggression to inform targeted treatments.