Functional magnetic resonance imaging of methylphenidate and placebo in attention-deficit/hyperactivity disorder during the multi-source interference task

Arch Gen Psychiatry. 2008 Jan;65(1):102-14. doi: 10.1001/archgenpsychiatry.2007.16.

Abstract

Context: Previous studies have reported hypofunction, structural abnormalities, and biochemical abnormalities of the dorsal anterior midcingulate cortex (daMCC) in attention-deficit/hyperactivity disorder (ADHD). Stimulant medications are effective treatments for ADHD, but their neural effects have not been fully characterized.

Objective: To determine whether the methylphenidate hydrochloride osmotic-release oral system (OROS) would increase functional magnetic resonance imaging (fMRI) activation, compared with placebo, in the daMCC and other frontoparietal regions subserving attention during the Multi-Source Interference Task (MSIT).

Design: Randomized, placebo-controlled, 6-week, before-after fMRI study.

Setting: Academic medical center ambulatory clinic.

Patients: Twenty-one adults with ADHD randomized to 6 weeks of treatment with methylphenidate OROS (n = 11) or placebo (n = 10).

Interventions: Patients underwent fMRI twice while performing the MSIT (scan 1 at baseline and scan 2 at 6 weeks).

Main outcome measures: Group-averaged, random-effects, repeated-measures, general linear model analyses were used to compare daMCC (and whole-brain) fMRI activation during the MSIT. Individual-based daMCC volume-of-interest confirmatory analyses and behavioral data are also presented.

Results: Performance and baseline fMRI measures in the daMCC and other a priori brain regions did not differ between groups. Group comparisons showed a group x scan interaction and t test confirmation of higher activation in the daMCC at 6 weeks in the methylphenidate OROS group than in the placebo group (P < 1 x 10(-4), cluster corrected for multiple comparisons). Individual daMCC volume-of-interest analyses confirmed group-averaged findings and suggested that daMCC activity might be related to clinical response. Methylphenidate OROS also produced higher activation in the dorsolateral prefrontal cortex and the parietal cortex at 6 weeks.

Conclusion: Methylphenidate OROS increased daMCC activation during the MSIT and may act, in part, by normalizing daMCC hypofunction in ADHD.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Attention Deficit Disorder with Hyperactivity / drug therapy*
  • Attention Deficit Disorder with Hyperactivity / pathology
  • Attention Deficit Disorder with Hyperactivity / physiopathology*
  • Central Nervous System Stimulants / administration & dosage
  • Central Nervous System Stimulants / pharmacology*
  • Double-Blind Method
  • Female
  • Frontal Lobe / drug effects*
  • Frontal Lobe / physiopathology
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Methylphenidate / administration & dosage
  • Methylphenidate / pharmacology*
  • Parietal Lobe / drug effects*
  • Parietal Lobe / physiopathology
  • Reaction Time
  • Task Performance and Analysis

Substances

  • Central Nervous System Stimulants
  • Methylphenidate