Local functional connectivity suggests functional immaturity in children with attention‐deficit/hyperactivity disorder

Abstract

Previous studies have associated Attention-Deficit/Hyperactivity Disorder (ADHD) with a maturational lag of brain functional networks. Functional connectivity of the human brain changes from primarily local to more distant connectivity patterns during typical development. Under the maturational lag hypothesis, we expect children with ADHD to exhibit increased local connectivity and decreased distant connectivity compared with neurotypically developing (ND) children. We applied a graph-theory method to compute local and distant connectivity levels and cross-sectionally compared them in a sample of 120 children with ADHD and 120 age-matched ND children (age range = 7-17 years). In addition, we measured if potential group differences in local and distant connectivity were stable across the age range considered. Finally, we assessed the clinical relevance of observed group differences by correlating the connectivity levels and ADHD symptoms severity separately for each group. Children with ADHD exhibited more local connectivity than age-matched ND children in multiple brain regions, mainly overlapping with default mode, fronto-parietal and ventral attentional functional networks (p < .05- threshold free-cluster enhancement-family-wise error). We detected an atypical developmental pattern of local connectivity in somatomotor regions, that is, decreases with age in ND children, and increases with age in children with ADHD. Furthermore, local connectivity within somatomotor areas correlated positively with clinical severity of ADHD symptoms, both in ADHD and ND children. Results suggest an immature functional state of multiple brain networks in children with ADHD. Whereas the ADHD diagnosis is associated with the integrity of the system comprising the fronto-parietal, default mode and ventral attentional networks, the severity of clinical symptoms is related to atypical functional connectivity within somatomotor areas. Additionally, our findings are in line with the view of ADHD as a disorder of deviated maturational trajectories, mainly affecting somatomotor areas, rather than delays that normalize with age.

Disrupted brain functional networks in drug‐naïve children with attention deficit hyperactivity disorder assessed using graph theory analysis

“…In addition, we found different age‐related trends for path length and local efficiency between the ADHD and NC groups, suggesting that both segregation and integration of the brain functional network may decline or fail to develop appropriately in untreated ADHD patients during adolescence. These results are consistent with the view of ADHD as a disorder of abnormal brain maturational trajectory mainly affecting components of networks supporting cognitive control (Marcos‐Vidal et al, ; Shaw et al, ). While the mechanism of this effect is uncertain, decades of research have documented the involvement of neurotrophic polymorphisms in ADHD (Forero, Arboleda, Vasquez, & Arboleda, ), including monoamine polymorphisms that have been shown to be involved in ADHD and to play roles in modeling brain function connectivity during development (Ko et al, ; Nymberg et al, ).…”

Stepwise functional connectivity reveals altered sensory‐multimodal integration in medication‐naïve adults with attention deficit hyperactivity disorder

“…Our results indicate increased functional connectivity between primary sensory areas and the visual cortex in adults with ADHD We believe that increased connectivity at medium and long functional distances may reflect the general visual network hyperconnectivity frequently described in children with ADHD (Cao et al, 2006;Marcos-Vidal et al, 2018;Wang et al, 2009). Our results suggest that at least part of the sensory information in adults with ADHD keeps reverberating within the visual loops, decreasing the information flow between sensory regions and neural hubs supporting higher order cognitive functions.…”

“…increased local functional connectivity in the boundaries of the DMN (Marcos-Vidal et al, 2018). In adults with ADHD weaker segregation has been found between the DMN and cognitive control networks (Lin, Cocchi, et al, 2018).…”

“…Subplot We believe that increased connectivity at medium and long functional distances may reflect the general visual network hyperconnectivity frequently described in children with ADHD (Cao et al, 2006;Marcos-Vidal et al, 2018;Wang et al, 2009). Images display Cohen's D effect sizes, and the positive (hot) and negative (winter) color maps range from the absolute value corresponding to an uncorrected p < .05 to an absolute value of 1.…”

“…At medium functional distance (five link-step distance), adults with ADHD exhibited reduced degree of functional connectivity with, predominantly, the DMN, and with the frontoparietal and limbic net- in the DMN , and distributed hypo-connectivity within the DMN . Additionally, children with ADHD have been found to exhibit decreased short and long-range functional connectivity density in regions of the DMN (Tomasi & Volkow, 2012) and increased local functional connectivity in the boundaries of the DMN (Marcos-Vidal et al, 2018). In adults with ADHD weaker segregation has been found between the DMN and cognitive control networks (Lin, Cocchi, et al, 2018).…”