Cortical Thickness, Cortico-Amygdalar Networks, and Externalizing Behaviors in Healthy Children

Background: Fronto-amygdalar networks are implicated in childhood psychiatric disorders characterized by high rates of externalizing (aggressive, noncompliant, oppositional) behavior. Although externalizing behaviors are distributed continuously across clinical and nonclinical samples, little is known about how brain variations may confer risk for problematic behavior. Here, we studied cortical thickness, amygdala volume, and cortico-amygdalar network correlates of externalizing behavior in a large sample of healthy children. Methods: Two hundred ninety-seven healthy children (6-18 years; mean 12 +/- 3 years), with 517 magnetic resonance imaging scans, from the National Institutes of Health Magnetic Resonance Imaging Study of Normal Brain Development, were studied. Relationships between externalizing behaviors (measured with the Child Behavior Checklist) and cortical thickness, amygdala volume, and cortico-amygdalar structural networks were examined using first-order linear mixed-effects models, after controlling for age, sex, scanner, and total brain volume. Results significant at p <= .05, following multiple comparison correction, are reported. Results: Left orbitofrontal, right retrosplenial cingulate, and medial temporal cortex thickness were negatively correlated with externalizing behaviors. Although amygdala volume alone was not correlated with externalizing behaviors, an orbitofrontal cortex-amygdala network predicted rates of externalizing behavior. Children with lower levels of externalizing behaviors exhibited positive correlations between orbitofrontal cortex and amygdala structure, while these regions were not correlated in children with higher levels of externalizing behavior. Conclusions: Our findings identify key cortical nodes in frontal, cingulate, and temporal cortex associated with externalizing behaviors in children; and indicate that orbitofrontal-amygdala network properties may influence externalizing behaviors, along a continuum and across healthy and clinical samples.