Abstract

Attention Deficit Hyperactivity Disorder (ADHD) is associated with pervasive impairments in attention and cognitive control. Although brain circuits underlying these impairments have been extensively investigated with resting-state fMRI, little is known about task-evoked functional brain circuits and their relation to cognitive control deficits and inattention symptoms in children with ADHD. Children with ADHD and age, gender and head motion matched typically-developing (TD) children completed a Go/NoGo fMRI task. We used multivariate and dimensional analyses to investigate impairments in two core cognitive control systems: (i) cingulo-opercular “salience” network (SN) anchored in the right anterior insula, dorsal anterior cingulate cortex (rdACC), and ventrolateral prefrontal cortex (rVLPFC) and (ii) dorsal fronto-parietal “central executive” (FPN) network anchored in right dorsolateral prefrontal cortex (rDLPFC) and posterior parietal cortex (rPPC). We found that multivariate patterns of task-evoked effective connectivity between brain regions in SN and FPN distinguished the ADHD and control groups, with rDLPFC–rPPC connectivity emerging as the most distinguishing link. Task-evoked rdACC–rVLPFC connectivity was positively correlated with NoGo accuracy, and negatively correlated with severity of inattention symptoms. Brain-behavior relationships were robust against potential age, gender and head motion confounds. Our findings highlight aberrancies in task-evoked modulation of SN and FPN connectivity in children with ADHD. Crucially, cingulo-frontal connectivity was a common locus of deficits in cognitive control and clinical measures of inattention symptoms. Our study provides insights into a parsimonious systems neuroscience model of cognitive control deficits in ADHD, and suggests specific circuit biomarkers for predicting treatment outcomes in childhood ADHD.

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