Functional Connectivity based Brain Signatures of Behavioral Regulation in Children with ADHD, DCD and ADHD-DCD

Abstract

1Background: Children with neurodevelopmental disorders such as Attention Deficit Hyperactivity 2 Disorder (ADHD) often struggle with behavioral self-regulation (BR), which is associated with daily-3 life challenges. ADHD sometimes presents with Developmental Coordination Disorder (DCD), but 4 little is known about BR in DCD. BR is thought to involve limbic, prefrontal, parietal and temporal 5 brain areas. Given the risk for negative outcomes, gaining a better understanding of the brain 6 mechanisms underlying BR in children with ADHD and/or DCD is imperative. 7Methods: Resting-state fMRI data collected from 115 children (31 typically developing (TD), 35 8 ADHD, 21 DCD, 28 ADHD-DCD) aged 7-17 years were preprocessed and motion was mitigated 9 using ICA-AROMA. Emotion control, inhibition, and shifting were assessed as subdomains of BR. 10Functional connectivity (FC) maps were computed for ten limbic, prefrontal, parietal and temporal 11 regions of interest and were investigated for associations with BR subdomains across all participants 12 as well as for significant group differences. 13 Results:Multiple FC patterns were associated with BR across all participants. Some FC patterns 14 were associated with multiple BR subdomains, while others were associated with only one. 15Differences in BR were found only between children with ADHD (i.e. ADHD and ADHD-DCD) and 16 those without ADHD (i.e. TD and DCD). FC differences were also found between children with and 17 without ADHD. 18 Conclusions:Our results show dimensional associations between BR subdomain scores and whole-19 brain FC and highlight the potential of these associative patterns as brain-based signatures of BR in 20 children with and without ADHD. 21

How does brain structure and function on MRI differ in children with autism spectrum disorder, developmental coordination disorder, and/or attention deficit hyperactivity disorder?

“…Quality assessment of 31 papers showed that 15 studies had an overall rating of high quality (Ameis et al, 2016; Aoki et al, 2017; Baribeau et al, 2019; Bethlehem et al, 2017; Boedhoe et al, 2020; Caeyenberghs et al, 2016; Dajani et al, 2019; Fine et al, 2014; Langevin et al, 2014; Qian et al, 2021; Shaw et al, 2016; Shook, 2015 × 3; Wan et al, 2019); and 16 papers were rated as a moderate quality (Albajara et al, 2020; Baribeau et al, 2019; Brieber et al, 2007; Di Martino et al, 2013; Henry et al, 2019; Jung et al, 2019; Langevin et al, 2015; Lim et al, 2015; Mahajan et al, 2016; McLeod et al, 2014, 2016; Mostofsky et al, 2007; Nickel et al, 2018; Ray et al, 2014; Rohr et al, 2021; Vasa et al, 2012). There were 15 structural studies, six of which were rated as high quality (Bethlehem et al, 2017; Boedhoe et al, 2020; Caeyenberghs et al, 2016; Fine et al, 2014; Shaw et al, 2016; Shook, 2015).…”

“…Rohr et al (2021) stated that children with ADHD and those with DCD + ADHD had more behavioral self‐regulation problems compared with children with DCD alone. Accordingly, children with ADHD and DCD + ADHD showed weaker positive functional connectivity around the subgenual anterior cingulate cortex, putamen, pallidum, insula, orbitofrontal cortex, and ventromedial prefrontal cortex compared children with DCD alone.…”

“…These findings highlighted the similar neural substrates of self‐regulation in children with ADHD and DCD + ADHD, which is different from that of children with DCD. They concluded that the self‐regulation problems and associated brain differences in children with DCD + ADHD are due to the ADHD diagnosis rather than DCD (Rohr et al, 2021).…”

“…Both DCD + ADHD and ADHD showed functional connectivity alterations between primary cortex and left postcentral gyrus (McLeod et al, 2014). Rohr et al (2021) found decreased functional connectivity in the basal ganglia (i.e., putamen and pallidum), corpus callosum, and frontal lobe (i.e., orbitofrontal cortex and ventromedial prefrontal cortex) in both children with DCD + ADHD and those with ADHD, suggesting impaired behavior self‐regulation in these two groups. Another shared neural correlate in DCD + ADHD and ADHD in basal ganglia was the stronger connection between right putamen and right primary and sensory motor cortex, compared to the left side (McLeod et al, 2016).…”

Effects of prolonged methylphenidate treatment on amygdala reactivity and connectivity: a randomized controlled trial in stimulant treatment-naive, male participants with ADHD

“…For example, more emotional problems, particularly externalizing symptoms, were associated with a hyperconnectivity of the cortico-amygdalar network, including the anterior cingulate cortex, both in children and adolescents (Hulvershorn et al, 2014;Hafeman et al, 2017;Damiani et al, 2020). Furthermore, different self-regulation problem dimensions were associated with stronger negative whole-brain functional connectivity patterns in children (Rohr et al, 2020). Additionally, in adolescents with ADHD (aged 11-16 years), hyperreactivity and -connectivity of the amygdala were reported in response to fearful faces, which was notably increased further after MPH abstinence (Posner et al, 2011b).…”