RT Journal A1 Bush G, Spencer TJ, Holmes J, et al T1 FUnctional magnetic resonance imaging of methylphenidate and placebo in attention-deficit/hyperactivity disorder during the multi-source interference task JF Archives of General Psychiatry JO Archives of General Psychiatry YR 2008 FD January 1 VO 65 IS 1 SP 102 OP 114 DO 10.1001/archgenpsychiatry.2007.16 UL http://dx.doi.org/10.1001/archgenpsychiatry.2007.16 AB 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 × 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.Conclusion  Methylphenidate OROS increased daMCC activation during the MSIT and may act, in part, by normalizing daMCC hypofunction in ADHD.