Methylphenidate normalizes frontocingulate underactivation during error processing in attention-deficit/hyperactivity
Katya Rubia1, Rozmin Halari, Abdul-Majeed Mohammad
1Department of Child Psychiatry, Institute of Psychiatry, King's College London, London, United Kingdom. katya.rubia@kcl.ac.uk.
Insights
Methylphenidate (MPH) normalized brain activity in children with attention-deficit/hyperactivity disorder (ADHD) during error monitoring tasks. This suggests MPH may improve attention and academic performance by correcting brain dysfunction.
Area of Science:
- Neuroscience
- Child Psychology
- Pharmacology
Background:
- Attention-deficit/hyperactivity disorder (ADHD) is associated with performance monitoring deficits.
- Methylphenidate (MPH), a catecholamine agonist, often improves ADHD symptoms.
- Functional magnetic resonance imaging (fMRI) can investigate brain activity related to error processing.
Purpose of the Study:
- To examine the effects of a single dose of MPH on brain activation in medication-naive boys with ADHD during a stop task.
- To compare brain activation in ADHD patients with and without MPH to that of healthy controls.
Main Methods:
- A randomized, double-blind, placebo-controlled design was used.
- Twelve medication-naive boys with ADHD underwent fMRI scans twice, receiving either MPH or placebo.
- An individually adjusted stop task was employed to elicit a 50% error rate.
Main Results:
- Boys with ADHD showed reduced activation in prefrontal, thalamic, cingulate, and parietal regions during failed inhibition compared to controls.
- MPH upregulated activation in these areas in ADHD patients, normalizing differences with controls.
- MPH also normalized reduced activation in parietotemporal and cerebellar regions during successful inhibition.
Conclusions:
- MPH normalized brain dysfunction in key performance monitoring areas in medication-naive ADHD boys.
- This normalization of brain activity may explain the improvement in attention and academic performance observed with MPH treatment.
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.
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