Characterizing the Neural Correlates of Response Inhibition and Error Processing in Children With Symptoms of Irritability and/or Attention-Deficit/Hyperactivity Disorder in the ABCD Study®

Attention-deficit/hyperactivity disorder (ADHD), characterized by symptoms of inattention and/or hyperactivity and impulsivity, is a neurodevelopmental disorder associated with executive dysfunctions, including response inhibition and error processing. Research has documented a common co-occurrence between ADHD and pediatric irritability. The latter is more characterized by affective symptoms, specifically frequent temper outbursts and low frustration tolerance relative to typically developing peers. Shared and non-shared neural correlates of youths with varied profiles of ADHD and irritability symptoms during childhood remain largely unknown. This study first classified a large sample of youths in the Adolescent Brain Cognitive Development (ABCD) study at baseline into distinct phenotypic groups based on ADHD and irritability symptoms (N = 11,748), and then examined shared and non-shared neural correlates of response inhibition and error processing during the Stop Signal Task in a subset of sample with quality neuroimaging data (N = 5,948). Latent class analysis (LCA) revealed four phenotypic groups, i.e., high ADHD with co-occurring irritability symptoms (n = 787, 6.7%), moderate ADHD with low irritability symptoms (n = 901, 7.7%), high irritability with no ADHD symptoms (n = 279, 2.4%), and typically developing peers with low ADHD and low irritability symptoms (n = 9,781, 83.3%). Latent variable modeling revealed group differences in the neural coactivation network supporting response inhibition in the fronto-parietal regions, but limited differences in error processing across frontal and posterior regions. These neural differences were marked by decreased coactivation in the irritability only group relative to youths with ADHD and co-occurring irritability symptoms and typically developing peers during response inhibition. Together, this study provided initial evidence for differential neural mechanisms of response inhibition associated with ADHD, irritability, and their co-occurrence. Precision medicine attending to individual differences in ADHD and irritability symptoms and the underlying mechanisms are warranted when treating affected children and families.