title: Functional magnetic resonance imaging of methylphenidate and placebo in attention-deficit/hyperactivity disorder during the multi-source interference task.
abstract: BACKGROUND
  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).
  
  
  METHODS
  Randomized, placebo-controlled, 6-week, before-after fMRI study.
  
  
  METHODS
  Academic medical center ambulatory clinic.
  
  
  METHODS
  Twenty-one adults with ADHD randomized to 6 weeks of treatment with methylphenidate OROS (n = 11) or placebo (n = 10).
  
  
  METHODS
  Patients underwent fMRI twice while performing the MSIT (scan 1 at baseline and scan 2 at 6 weeks).
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  Methylphenidate OROS increased daMCC activation during the MSIT and may act, in part, by normalizing daMCC hypofunction in ADHD.
authors.affiliation: Departments of Psychiatry, Harvard Medical School, Boston, Massachusetts, USA. geo@nmr.mgh.harvard.edu
authors.forename: George
authors.initials: G
authors.lastname: Bush
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Spencer
authors.forename: Jennifer
authors.initials: J
authors.lastname: Holmes
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Shin
authors.forename: Eve M
authors.initials: EM
authors.lastname: Valera
authors.forename: Larry J
authors.initials: LJ
authors.lastname: Seidman
authors.forename: Nikos
authors.initials: N
authors.lastname: Makris
authors.forename: Craig
authors.initials: C
authors.lastname: Surman
authors.forename: Megan
authors.initials: M
authors.lastname: Aleardi
authors.forename: Eric
authors.initials: E
authors.lastname: Mick
authors.forename: Joseph
authors.initials: J
authors.lastname: Biederman
mesh_terms: D000284:Administration, Oral; D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000494:pharmacology*; D004311:Double-Blind Method; D005260:Female; D005625:Frontal Lobe / Q000187:drug effects* / Q000503:physiopathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008774:Methylphenidate / Q000008:administration & dosage / Q000494:pharmacology*; D010296:Parietal Lobe / Q000187:drug effects* / Q000503:physiopathology; D011930:Reaction Time; D013647:Task Performance and Analysis
chemical_list: D000697:Central Nervous System Stimulants; D008774:Methylphenidate