Working Memory-Related Neurofunctional Correlates Associated with the Frontal Lobe in Children with Familial vs. Non-Familial Attention Deficit/Hyperactivity Disorder

Attention deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder with high prevalence, heritability, and heterogeneity. Children with a positive family history of ADHD have a heightened risk of ADHD emergence, persistence, and executive function deficits, with the neural mechanisms having been under investigated. The objective of this study was to investigate working memory-related functional brain activation patterns in children with ADHD (with vs. without positive family histories (ADHD-F vs. ADHD-NF)) and matched typically developing children (TDC). Voxel-based and region of interest analyses were conducted on two-back task-based fMRI data of 362 subjects, including 186, 96, and 80 children in groups of TDC, ADHD-NF, and ADHD-F, respectively. Relative to TDC, both ADHD groups had significantly reduced activation in the left inferior frontal gyrus (IFG). And the ADHD-F group demonstrated a significant positive association of left IFG activation with task reaction time, a negative association of the right IFG with ADHD symptomatology, and a negative association of the IFG activation laterality index with the inattention symptom score. These results suggest that working memory-related functional alterations in bilateral IFGs may play distinct roles in ADHD-F, with the functional underdevelopment of the left IFG significantly informing the onset of ADHD symptoms. Our findings have the potential to assist in tailored diagnoses and targeted interventions in children with ADHD-F.