BOLD differences normally attributed to inhibitory control predict symptoms, not task-directed inhibitory control in ADHD

Abstract

BackgroundAltered brain activity that has been observed in attention deficit hyperactivity disorder (ADHD) while performing cognitive control tasks like the stop signal task (SST), has generally been interpreted as reflecting either weak (under-active) or compensatory (over-active) versions of the same functions as in healthy controls. If so, then regional activities that correlate with the efficiency of inhibitory control (i.e. stop signal reaction time, SSRT) in healthy subjects should also correlate with SSRT in ADHD. Here we test the alternate hypothesis that BOLD differences might instead reflect the redirection of neural processing resources normally used for task-directed inhibitory control, toward actively managing symptomatic behavior. If so, then activities that correlate with SSRT in TD should instead correlate with inattentive and hyperactive symptoms in ADHD.\n\nMethodsWe used fMRI in 14 typically developing (TD) and 14 ADHD adolescents performing the SST, and in a replication sample of 14 healthy adults. First we identified significant group BOLD differences during all phases of activity in the SST (i.e. warning, response, reactive inhibition, error detection and post-error slowing). Next, we correlated these phases of activity with SSRT in TD, and with SSRT, inattentive and hyperactive symptom scores in ADHD. We then identified whole brain significant correlations in regions of significant group difference in activity.\n\nResultsOnly three regions of significant group difference were correlated with SSRT in TD and replication groups (left and right inferior frontal gyri (IFG) during error detection, and hypothalamus during post-error slowing). Consistent with regions of altered activity managing symptomatic behavior instead of task-directed behavior, left IFG correlated with greater inattentive score, right IFG correlated with lower hyperactive score, and hypothalamus correlated with greater inattentive score and oppositely correlated with SSRT compared to TD.\n\nConclusionsResults are consistent with stimuli that elicit task-directed integration of neural processing in healthy subjects, instead directing integrated function towards managing symptomatic behavior in ADHD. The ability of the current approach to determine whether altered neural activities reflect comparable functions in ADHD and control groups has broad implications for the development and monitoring of therapeutic interventions.