Functional Magnetic Resonance Imaging of Methylphenidate and Placebo in Attention-Deficit/Hyperactivity Disorder During the Multi-Source Interference Task

Departments of Psychiatry, Harvard Medical School, Boston, Massachusetts, USA.
Archives of general psychiatry (Impact Factor: 14.48). 01/2008; 65(1):102-14. DOI: 10.1001/archgenpsychiatry.2007.16
Source: PubMed


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

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Available from: Craig B Surman, Oct 17, 2015
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    • "Our finding is in agreement with findings from Bush et al. (2008) that utilized interference task that requires numbering process as well. Despite a consistently reported increase of striatal activation among patients with ADHD by a single dose methylphenidate treatment (Cubillo et al., 2014b; Rubia et al., 2011), present results lacking of striatal activation changes are not surprising because our results are in agreement with studies addressing effect of weeks of methylphenidate treatment (Bush et al., 2008; Schulz et al., 2012). Similar observations were reported in rodent models following 14-day treatment of methylphenidate. "
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    • "However, the degree to which the brain 0 s response curve follows the plasma concentration curve is entirely unknown. We chose 75 min because this is when the slope of the plasma concentration curve begins to flatten out, and because most prior studies of behavior and/or neuroimaging have used between 60 and 90 min from dosage to testing as the delay period (Barry et al., 2009; Chamberlain et al., 2009; Dodds et al., 2008; Peterson et al., 2009; Rubia et al., 2009a, 2009b; Wienbruch et al., 2005; Wilson et al., 2012; for an exception, see Bush et al. (2008)). Thus, 75 min was near the middle of the " standard " window. "
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