Resting state functional connectivity correlates of inhibitory control in children with attention-deficit/hyperactivity disorder

Abstract

Motor inhibition is among the most commonly studied executive functions in attention-deficit/hyperactivity disorder (ADHD). Imaging studies using probes of motor inhibition such as the stop signal task (SST) consistently demonstrate ADHD-related dysfunction within a right-hemisphere fronto-striatal network that includes inferior frontal gyrus and pre-supplementary motor area. Beyond findings of focal hypo- or hyper-function, emerging models of ADHD psychopathology highlight disease-related changes in functional interactions between network components. Resting state fMRI (R-fMRI) approaches have emerged as powerful tools for mapping such interactions (i.e., resting state functional connectivity, RSFC), and for relating behavioral and diagnostic variables to network properties. We used R-fMRI data collected from 17 typically developing controls (TDC) and 17 age-matched children with ADHD (aged 8-13years) to identify neural correlates of SST performance measured outside the scanner. We examined two related inhibition indices: stop signal reaction time (SSRT), indexing inhibitory speed, and stop signal delay (SSD), indexing inhibitory success. Using 11 fronto-striatal seed regions-of-interest, we queried the brain for relationships between RSFC and each performance index, as well as for interactions with diagnostic status. Both SSRT and SSD exhibited connectivity-behavior relationships independent of diagnosis. At the same time, we found differential connectivity-behavior relationships in children with ADHD relative to TDC. Our results demonstrate the utility of RSFC approaches for assessing brain/behavior relationships, and for identifying pathology-related differences in the contributions of neural circuits to cognition and behavior. © 2012 Mennes, Vega Potler, Kelly, Di Martino, Castellanos and Milham.