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Functional Magnetic Resonance Imaging of Methylphenidate and Placebo in Attention-Deficit/Hyperactivity Disorder During the Multi-Source Interference Task
Abstract
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 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. CONCLUSION: Methylphenidate OROS increased daMCC activation during the MSIT and may act, in part, by normalizing daMCC hypofunction in ADHD.
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“Indeed, imaging studies have shown that methylphenidate enhances the efficiency of PFC activity both in healthy college students (Mehta et al., 2000) and in subjects with ADHD (Bush et al., 2008).”
From Catecholamine influences on prefrontal cortical function: Relevance to treatment of attention deficit/hyperactivity disorder and related disorders (2011) · cites this paper as Bush et al., 2008
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Metadata
- Authors
- Bush, G., Spencer, T. J., Holmes, J., Shin, L. M., Valera, E. M., Seidman, L. J., Makris, N., Surman, C., Aleardi, M., Mick, E., & Biederman, J.
- Affiliations
- Harvard University (US)
- Massachusetts General Hospital (US)
- ORCID
- Venue
- Archives of General Psychiatry
- Publisher
- American Medical Association (AMA)
- Published
- 2008-01-01
- Volume
- 65
- Issue
- 1
- Pages
- 102
- ISSN
- 0003-990X (ISSN-L)
- OpenAlex
- W2113225772
- Cited by
- 201
- References
- 119
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 5 · 2023: 4 · 2022: 7 · 2021: 7 · 2020: 4 · 2019: 8 · 2018: 1 · 2017: 10 · 2016: 5 · 2015: 14 · 2014: 15 · 2013: 20 · 2012: 27
- FWCI
- 16.16
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Archives of General Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (1f32mh065040-01a1)
- National Institute of Mental Health (F32 MH065040-01A1, MH 16259, R01MH064019, 5 RO1 MH064019, T32MH016259)
- National Center for Research Resources (P41-RR-14075, P41RR014075)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (MH/HD 62152)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- attention deficit hyperactivity disorder, methylphenidate, OROS methylphenidate, Multi-Source Interference Task, stimulant medication effects, brain activation, dorsolateral prefrontal cortex, parietal cortex, attention, treatment response, adult ADHD
- MeSH terms
- Administration, Oral, Adult, Central Nervous System Stimulants, Attention Deficit Disorder with Hyperactivity, Double-Blind Method, Female, Frontal Lobe, Humans, Magnetic Resonance Imaging, Male, Methylphenidate, Parietal Lobe, Reaction Time, Task Performance and Analysis
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