Abstract
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.
Highlights
Maladaptive aggression is among the most common reasons for referral to mental health services and spans across childhood psychiatric disorders, most notably disruptive behavior disorders, mood disorders, and autism spectrum disorder (ASD)[1]
The overall Connectome-Based Predictive Modeling (CPM) model revealed that patterns of brain-wide connectivity predicted severity of aggressive behavior (Fig. 1)
The CPM model remained significant after accounting for internalizing behaviors, social behavior impairments, and ADHD diagnosis (r>0.22 and p
Summary
Maladaptive aggression is among the most common reasons for referral to mental health services and spans across childhood psychiatric disorders, most notably disruptive behavior disorders, mood disorders, and autism spectrum disorder (ASD)[1]. The emotion dysregulation model of aggression implicates disruptions in frontoparietal circuitry involved in the cognitive control of emotion[5]. Consistent with this view, meta-analytic studies[3, 6] identified underactivity in the ventromedial and ventrolateral prefrontal cortices (vmPFC and vlPFC, respectively), dorsolateral prefrontal cortex (dlPFC), and temporal-parietal regions[7,8,9,10]. Altered connectivity between the amygdala and ventral prefrontal regions was reported during emotion perception tasks in children with aggressive behavior[7, 10, 11]. Recent functional MRI (fMRI) studies using emotional face perception tasks have reported associations of irritability, an elevated propensity for anger and aggression, with reduced amygdala-vmPFC connectivity[13] and reduced amygdala-dlPFC connectivity[14] in children with aggressive behavior
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