Functional magnetic resonance imaging of methylphenidate and placebo in attention-deficit/hyperactivity disorder during the multi-source interference task.
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.
Bush
George
G
Departments of Psychiatry, Harvard Medical School, Boston, Massachusetts, USA. geo@nmr.mgh.harvard.edu
Spencer
Thomas J
TJ
Holmes
Jennifer
J
Shin
Lisa M
LM
Valera
Eve M
EM
Seidman
Larry J
LJ
Makris
Nikos
N
Surman
Craig
C
Aleardi
Megan
M
Mick
Eric
E
Biederman
Joseph
J
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
D000697:Central Nervous System Stimulants; D008774:Methylphenidate