Intrinsic affective network is impaired in children with attention-deficit/hyperactivity disorder

Abstract

Deficits in impulsivity and affect dysregulation are key features of attention-deficit/hyperactivity disorder (ADHD) besides impairing levels of hyperactivity and/or inattention. However, the neural substrates underlying these traits are relatively under-investigated. In this study, we use resting-state functional magnetic resonance imaging to test the hypothesis of diminished functional integration within the affective/limbic network (which includes the amygdala, hippocampus, subgenual cingulate cortex, orbitofrontal cortex and nucleus accumbens) of children with ADHD, which is associated with their behavioral measures of emotional control deficits. Resting state-fMRI data were obtained from 12 healthy control subjects and 15 children with ADHD, all who had a minimum onemonth washout period for medications and supplements. Children with ADHD demonstrated less integrated affective network, evidenced by increased bilateral amygdalar and decreased left orbitofrontal connectivity within the affective network compared to healthy controls. The hyper-connectivity at the left amygdalar within the affective network was associated with increased aggressiveness and conduct problems, as well as decline in functioning in children with ADHD. Similar findings in affective network dysconnectivity were replicated in a subset of children with ADHD three months later. Our findings of divergent changes in amygdala and orbitofrontal intrinsic connectivity support the hypothesis of an impaired functional integration within the affective network in childhood ADHD. Larger prospective studies of the intrinsic affective network in ADHD are required, which may provide further insight on the biological mechanisms of emotional control deficits observed in ADHD.