Reduced Amygdala-Prefrontal Functional Connectivity in Children with Autism Spectrum Disorder and Co-Occurring Disruptive Behavior

Abstract Background Disruptive behaviors are prevalent in children with autism spectrum disorder (ASD) and cause substantial impairments. However, the underlying neural mechanisms of disruptive behaviors remain poorly understood in ASD. In children without ASD, disruptive behavior is associated with amygdala hyperactivity and reduced connectivity with the ventrolateral prefrontal cortex (vlPFC). The present study examined amygdala reactivity and connectivity in children with ASD with and without co-occurring disruptive behavior disorders. We also investigated differential contributions of externalizing behaviors and callous-unemotional (CU) traits to variance in amygdala connectivity and reactivity. Methods This cross-sectional study involved behavioral assessments and neuroimaging in three groups of children aged 8 to 16 years: 18 had ASD-plus-Disruptive-Behavior (ASD+DB), 20 had ASD without disruptive behavior (ASD), and 19 typically developing controls matched for age, gender, and IQ. During fMRI, participants completed an emotion perception task of fearful vs. calm faces. Task-specific changes in amygdala reactivity and connectivity were examined using whole-brain, psychophysiological interaction, and multiple-regression analyses. Results Children with ASD+DB showed reduced amygdala-vlPFC connectivity compared to the ASD group. Externalizing behaviors and CU traits were associated with amygdala reactivity to fearful faces in children with ASD after controlling for suppressor effects. Conclusions Reduced amygdala-vlPFC connectivity during fear processing may differentiate children with ASD+DB from children with ASD. The presence of CU traits may have implications for identifying differential patterns of amygdala activity associated with increased risk of aggression in ASD. These findings suggest a neural mechanism of emotion dysregulation associated with disruptive behavior in children with ASD.