Methylphenidate normalises fronto-striatal underactivation during interference inhibition in medication-naive boys with Attention-Deficit Hyperactivity Disorder

Katya Rubia (1) , Rozmin Halari (1) , Ana Cubillo (1) , Anna Smith (1) , Abdul-Majeed Mohammad (1) , Michael Brammer (1) , Eric Taylor (1)

1 Child Psychiatry

Youth with Attention Deficit Hyperactivity Disorder (ADHD) have deficits in interference inhibition, which can be improved with the indirect catecholamine agonist Methylphenidate (MPH). Functional magnetic resonance imaging (fMRI) was used to investigate the effects of a single dose of MPH on brain activation during interference inhibition in medication-naïve ADHD boys. Medication-naïve boys with ADHD were scanned twice, in a randomised, double-blind design, under either a single clinical dose of MPH or Placebo, while performing a Simon task that measures interference inhibition and controls for the oddball effect of low frequency appearance of incongruent trials. Brain activation was compared within patients under either drug condition. To test for potential normalisation effects of MPH, brain activation in ADHD patients under either drug condition was compared to that of healthy age-matched comparison boys. During incongruent trials compared to congruent oddball trials, boys with ADHD under placebo relative to controls showed reduced brain activation in typical areas of interference inhibition, including right inferior prefrontal cortex, left striatum and thalamus, mid-cingulate/Supplementary Motor Area and left superior temporal lobe. MPH relative to placebo upregulated brain activation in right inferior prefrontal and premotor cortices. Under the MPH condition, patients relative to controls no longer showed the reduced activation in right inferior prefrontal and striato-thalamic regions. Effect size comparison furthermore showed that these normalisation effects were significant. MPH significantly normalised the fronto-striatal underfunctioning in ADHD patients relative to controls during interference inhibition, but did not affect medial frontal or temporal dysfunction. MPH therefore appears to have a region-specific upregulation effect on fronto-striatal activation.

Mots clés: Methylphenidate; Development; Developmental Disorders; Biological Psychiatry; Neuropharmacology; Psychostimulants; fMRI; Attention Deficit Hyperactivity Disorder; Interference inhibition

Katya Rubia, Rozmin Halari, Ana Cubillo, Anna Smith, Abdul-Majeed Mohammad, et al.. Methylphenidate normalises fronto-striatal underactivation during interference inhibition in medication-naive boys with Attention-Deficit Hyperactivity Disorder. Neuropsychopharmacology, 2011, ⟨10.1038/npp.2011.30⟩. ⟨hal-00627924⟩