Atypical functional connectivity in adolescents and adults with persistent and remitted ADHD

Abstract

We previously provided initial evidence for cognitive and event-related potential markers of persistence/remission of attention-deficit/hyperactivity disorder (ADHD) from childhood to adolescence and adulthood. In this follow-up study, using a novel brain-network connectivity approach, we aimed to examine whether functional connectivity reflects a marker of ADHD remission, or an enduring deficit unrelated to ADHD outcome. High-density EEG was recorded in 110 adolescents and young adults with childhood ADHD (87 persisters, 23 remitters) and 169 typically-developing individuals during an arrow-flanker task, eliciting cognitive control. Functional connectivity was quantified with network-based graph-theory metrics before target onset (pre-stimulus), during target processing (post-stimulus) and in the degree of change between pre-stimulus/post-stimulus. ADHD outcome was examined with parent-reported symptoms and impairment using both a categorical (DSM-IV) and a dimensional approach. Graph-theory measures converged in indicating that, compared to controls, ADHD persisters showed increased connectivity in pre-stimulus theta, alpha and beta and in post-stimulus beta (all p<.01), and reduced pre-stimulus/post-stimulus change in theta connectivity (p<.01). In the majority of indices showing ADHD persister-control differences, ADHD remitters differed from controls (all p<.05), but not from persisters. Similarly, connectivity measures were not associated with continuous outcome measures of ADHD symptoms and impairment in participants with childhood ADHD. These findings indicate that adolescents and young adults with persistent and remitted ADHD share atypical over-connectivity profiles and reduced ability to modulate connectivity patterns with task demands, compared to controls. Brain connectivity impairments may represent enduring deficits in individuals with childhood ADHD irrespective of diagnostic status in adolescence/young adulthood.