Tracking Inhibitory Control in Youth With ADHD: A Multi-Modal Neuroimaging Approach

Abstract

Background: A decreased ability to inhibit a speeded motor response is a well-studied deficit in Attention Deficit Hyperactivity Disorder (ADHD), and has been proposed as an endophenotype. Inhibitory control has been assessed reliably with the Stop Signal Task (SST) and is associated with prior documented differences in regional brain function using f-MRI. Here, we advance on these findings by examining their structural connectivity and white matter integrity with the goal of identifying a network underlying a core cognitive deficit in ADHD. Methods: Healthy controls (N=16) and youth diagnosed with ADHD (N=60) were recruited through the Province of Ontario Neurodevelopmental Disorders Network (POND) and the Hospital for Sick Children. An f-MRI activation difference map was coregistered with each participant's white matter imaging data, representing the specific network nodes where ADHD youth diverged significantly from controls while performing the SST. Probabilistic tractography was applied from these nodes, and white matter integrity indices such as fractional anisotropy (FA) within the tracts of interest were contrasted between the groups and correlated with SST output measures, including the measure of inhibitory control, the stop signal reaction time (SSRT). Results: The tracts that connected the network nodes belonged primarily to the inferior fronto-occipital fasciculus (IFOF) and cingulum. ADHD subjects showed trend differences in FA compared to controls between right inferior frontal gyrus (IFG) and right superior temporal gyrus (P= 0.09), right IFG and right posterior cingulate (P= 0.01), right anterior cingulate to posterior cingulate (p= 0.08), and between left middle temporal gyrus (BA 39) and left posterior cingulate (P=0.02). A trend correlation was found between radial diffusivity within IFG to STG white matter (IFOF) and SSRT. Conclusions: We identified potential white matter tracts related to deficient inhibitory control, elucidating the brain mechanisms of an important cognitive deficit in ADHD. These

Frontal interhemispheric structural connectivity, attention, and executive function in children with perinatal stroke

“…This finding is consistent with previous literature investigating frontal white matter in unilateral cerebral palsy reporting lower FA values in anterior cingulate cortex and superior frontal gyrus (Scheck et al, 2015). This is also consistent with the wider ADHD literature that demonstrates lower FA values and higher diffusivity values in frontal white matter of children with ADHD (Konrad & Eickhoff, 2010;Liston et al, 2011;Tremblay et al, 2020;van Ewijk et al, 2012).…”

“…Previous research using diffusion imaging metrics has shown an association between microstructural characteristics of frontal white matter, symptomology of ADHD, and executive function (Ashtari et al., 2005; Hong et al., 2014; Konrad & Eickhoff, 2010; Liston et al., 2011; Makris et al., 2009; Wu et al., 2020). Specifically, FA has been found to be lower in the frontal white matter of children with ADHD compared to peers (Konrad & Eickhoff, 2010; Liston et al., 2011; Tremblay et al., 2020; van Ewijk et al., 2012). Elevated MD in the anterior forceps of those with ADHD is a consistent finding across literature examining frontal tracts (Lawrence et al., 2013; van Ewijk et al., 2012).…”

Electrocorticography to Investigate Age-Related Brain Lateralization on Pediatric Motor Inhibition

“…In an MRI study, decreasing WM tracts over right IFG was observed in the patients with Attention Deficit Hyperactivity Disorder, compared with the normal population. For the motor inhibition, the results identified the pathogenesis of WM tracts over IFG potentially related to deficient inhibitory control ( 59 ). Our study indicated that both IFG played a role in motor inhibition in the pediatric population, but with age, lateralization to the right IFG becomes dominant.…”

Structural and diffusion weighted brain imaging biomarkers for ADHD and its symptomology in very young (4–7-year-old) children

“…Another relevant and related context that implicates the right inferior frontal cortex has been inhibitory control operations identified in Go-No Go paradigms such as the Stop Signal Task (Hannah & Aron, 2021). Notably, previous research has identified this region as a potential modulatory neural measure for ADHD-related performance deficits in this task (Chevrier & Schachar, 2020;Tremblay et al, 2020). Given that inhibitory control and working memory deficits are commonly observed in ADHD (Hammer et al, 2015;Karalunas et al, 2017;Palladino & Ferrari, 2013;Raiker et al, 2019;Raiker et al, 2012), it will be important for future research to clarify whether its potential role in ADHD is via its modulatory role in controlled working memory processes.…”

“…Our assessment of neurobiology using a machine learning approach leverages structural brain imaging measures, as well as diffusion-weighted imaging measures of neurite density and fractional anisotropy in three fiber pathways of importance to ADHD in this ange range (Cooper et al, 2015;Frodl & Skokauskas, 2012;Garic et al, 2019;Graziano et al, 2021;Jones et al, 2013;Konrad & Eickhoff, 2010;Nagel et al, 2011;Peterson et al, 2011;van Ewijk et al, 2012), namely the frontal aslant tract (FAT), cingulum, and the uncinate fasciculus (UF). In addition to assessing the predictive performance of the target measures, we further evaluated their relative importance.…”