Methylphenidate Normalizes Frontocingulate Underactivation During Error Processing in Attention-Deficit/Hyperactivity Disorder

Background: Children with attention-deficit/hyperactivity disorder (ADHD) have deficits in performance monitoring often improved with the indirect catecholamine agonist methylphenidate (MPH). We used functional magnetic resonance imaging to investigate the effects of single-dose MPH on activation of error processing brain areas in medication-naive boys with ADHD during a stop task that elicits 50% error rates. Methods: Twelve medication-naive boys with ADHD were scanned twice, under either a single clinical dose of MPH or placebo, in a randomized, double-blind design while they performed an individually adjusted tracking stop task, designed to elicit 50% failures. Brain activation was compared within patients under either drug condition. To test for potential normalization effects of MPH, brain activation in ADHD patients under either drug condition was compared with that of 13 healthy age-matched boys. Results: During failed inhibition, boys with ADHD under placebo relative to control subjects showed reduced brain activation in performance monitoring areas of dorsomedial and left ventrolateral prefrontal cortices, thalamus, cingulate, and parietal regions. MPH, relative to placebo, upregulated activation in these brain regions within patients and normalized all activation differences between patients and control subjects. During successful inhibition, MPH normalized reduced activation observed in patients under placebo compared with control subjects in parietotemporal and cerebellar regions. Conclusions: MPH normalized brain dysfunction in medication-naive ADHD boys relative to control subjects in typical brain areas of performance monitoring, comprising left ventrolateral and dorsomedial frontal and parietal cortices. This could underlie the amelioration of MPH of attention and academic performance in ADHD.