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Bush G, Spencer TJ, Holmes J, et al. Functional Magnetic Resonance Imaging of Methylphenidate and Placebo in Attention-Deficit/Hyperactivity Disorder During the Multi-Source Interference Task. Arch Gen Psychiatry. 2008;65(1):102–114. doi:10.1001/archgenpsychiatry.2007.16
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.
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).
Randomized, placebo-controlled, 6-week, before-after fMRI study.
Academic medical center ambulatory clinic.
Twenty-one adults with ADHD randomized to 6 weeks of treatment with methylphenidate OROS (n = 11) or placebo (n = 10).
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.
Performance and baseline fMRI measures in the daMCC and other a priori brain regions did not differ between groups. Group comparisons showed a group × 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 × 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.
Methylphenidate OROS increased daMCC activation during the MSIT and may act, in part, by normalizing daMCC hypofunction in ADHD.
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