Neural activation during response inhibition in adult attention-deficit/hyperactivity disorder: preliminary findings on the effects of medication and symptom severity

Abstract

Studies of adults with attention-deficit/hyperactivity disorder (ADHD) have suggested that they have deficient response inhibition, but findings concerning the neural correlates of inhibition in this patient population are inconsistent. We used the Stop-Signal task and functional magnetic resonance imaging (fMRI) to compare neural activation associated with response inhibition between adults with ADHD (N=35) and healthy comparison subjects (N=62), and in follow-up tests to examine the effect of current medication use and symptom severity. There were no differences in Stop-Signal task performance or neural activation between ADHD and control participants. Among the ADHD participants, however, significant differences were associated with current medication, with individuals taking psychostimulants (N=25) showing less stopping-related activation than those not currently receiving psychostimulant medication (N=10). Follow-up analyses suggested that this difference in activation was independent of symptom severity. These results provide evidence that deficits in inhibition-related neural activation persist in a subset of adult ADHD individuals, namely those individuals currently taking psychostimulants. These findings help to explain some of the disparities in the literature, and advance our understanding of why deficits in response inhibition are more variable in adult, as compared with child and adolescent, ADHD patients.

Keywords: Adults; Functional magnetic resonance imaging (fMRI); Hyperactivity; Inhibitory control; Psychostimulants; Stop-Signal task.

Fig. 1

Schematic of the Stop-Signal task. Participants were shown a series of go stimuli (left- and right-wards pointing arrows), to which participants were told to respond with left and right button presses, respectively (Go trials); on a subset of trials, a stop-signal (a 500-Hz tone presented through headphones) was presented at a variable delay after the onset of the go stimulus (duration indicated by stop-signal delay (SSD)) and lasted for 250 ms (Stop trials), indicating that participants should withhold the go response.

Fig. 2

Consort diagram of data collection and exclusion.

Fig. 3

Separate group maps of StopInhibit-Go activation. Stopping-related activation in controls (A) and adult ADHD (B) groups alone. Statistical maps are corrected for whole-brain multiple comparisons and were projected onto an average cortical surface using CARET (R = Right). The color represents the z-score.

Fig. 4

Differences in StopInhibit-Go activation as a function of symptom severity and medication use. While controlling for psychostimulant use, positive correlation between StopInhibit-Go activation and Hyperactivity symptoms in ADHD participants alone (A). While controlling for Hyperactivity symptoms, greater stopping-related activation seen in ADHD participants Off vs. On psychostimulant medication (B) and in controls vs. ADHD participants On psychostimulant medication (C). Multiple contrasts overlaid on a single image to illustrate overlap (D), with ADHD group mean in red, greater stopping-related activation seen in ADHD participants Off vs. On psychostimulant medication in blue, and the positive correlation between stopping-related activation and Hyperactivity symptoms in yellow. Statistical maps are corrected for whole-brain multiple comparisons and were projected onto an average cortical surface using CARET; in D, axial slices are included to illustrate the overlap of activation with coordinated in MNI space (R = Right). The color represents the z-score.