Mapping latent neuroanatomical substrates of behavioral and emotional dysregulation in ADHD

Abstract Background Children with attention-deficit/hyperactivity disorder (ADHD) frequently exhibit impairing emotional dysregulation along with inattention and hyperactivity. We aim to parse the heterogeneity of behavioral and emotional dysregulation in ADHD using latent brain factors based on cortical thickness (CT), and examine associated differences in intrinsic functional connectivity (iFC). Methods Data were collected from 123 children (39 ADHD, 47 ADHD with impairing emotional outbursts ADHD + IEO, 37 neurotypical controls NT, 5–9.9 years old). First, exploratory factor analysis revealed latent behavioral factors. Using Latent Dirichlet allocation, we decomposed heterogeneous CT patterns into parsimonious latent brain factors. We further investigated the functional relevance of brain regions showing structural differences in the ADHD + IEO group and examined associations between brain and behavioral latent factors. Results Among the four behavioral factors identified (Externalizing, Emotion Dysregulation, Internalizing, and Surgency/Impulsivity), the dominant factor – Externalizing behavior – significantly differentiated the ADHD + IEO from the ADHD and NT groups. A conjunction analysis of the three brain factors revealed significantly thicker CT in the dorsolateral prefrontal cortex for ADHD + IEO compared to NT. Using this region as a seed, we found reduced functional connectivity primarily in the default mode network, which differentiated ADHD + IEO and ADHD groups. Structural brain and iFC measures showed significant associations with the Externalizing behavior factor. Conclusions Parsing the neurobiology underlying the heterogeneous presentation of ADHD requires integrating multiple modalities and analytical methods. This study demonstrates that combining behavioral, structural, and functional data reveals unique neural features associated with behavioral and emotional dysregulation.