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Methylphenidate Normalizes Frontocingulate Underactivation During Error Processing in Attention-Deficit/Hyperactivity Disorder
Open accessAbstract
BACKGROUND: Children with attention-deficit/hyperactivity disorder (ADHD) have deficits in performance monitoring often improved with the indirect catecholamine agonist methylphenidate (MPH). We used functional magnetic resonance imaging to investigate the effects of single-dose MPH on activation of error processing brain areas in medication-naive boys with ADHD during a stop task that elicits 50% error rates. METHODS: Twelve medication-naive boys with ADHD were scanned twice, under either a single clinical dose of MPH or placebo, in a randomized, double-blind design while they performed an individually adjusted tracking stop task, designed to elicit 50% failures. Brain activation was compared within patients under either drug condition. To test for potential normalization effects of MPH, brain activation in ADHD patients under either drug condition was compared with that of 13 healthy age-matched boys. RESULTS: During failed inhibition, boys with ADHD under placebo relative to control subjects showed reduced brain activation in performance monitoring areas of dorsomedial and left ventrolateral prefrontal cortices, thalamus, cingulate, and parietal regions. MPH, relative to placebo, upregulated activation in these brain regions within patients and normalized all activation differences between patients and control subjects. During successful inhibition, MPH normalized reduced activation observed in patients under placebo compared with control subjects in parietotemporal and cerebellar regions. CONCLUSIONS: MPH normalized brain dysfunction in medication-naive ADHD boys relative to control subjects in typical brain areas of performance monitoring, comprising left ventrolateral and dorsomedial frontal and parietal cortices. This could underlie the amelioration of MPH of attention and academic performance in ADHD.
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“the cerebellum during attention, TD, and interference inhibition 4, 16, 18”
From Effects of stimulants on brain function in attention-deficit/hyperactivity disorder: a systematic review and meta-analysis (2014) · cites this paper as [18]
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“and striatum during reward and response inhibition 16, 18.”
From Effects of stimulants on brain function in attention-deficit/hyperactivity disorder: a systematic review and meta-analysis (2014) · cites this paper as [18]
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“Randomized placebo-controlled fMRI studies of acute methylphenidate effects in medication-naïve ADHD boys using whole-brain image analyses found increased activation in predominantly right, but also left, IFC during tasks of sustained attention, inhibition, and time discrimination (TD) 4, 16, 17, 18”
From Effects of stimulants on brain function in attention-deficit/hyperactivity disorder: a systematic review and meta-analysis (2014) · cites this paper as [18]
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“Ten datasets compared methylphenidate with placebo on brain function in medication-naïve patients in randomized controlled designs 4, 16, 17, 18”
From Effects of stimulants on brain function in attention-deficit/hyperactivity disorder: a systematic review and meta-analysis (2014) · cites this paper as [18]
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“in parietal regions during sustained attention, error monitoring, and interference inhibition 16, 17, 18”
From Effects of stimulants on brain function in attention-deficit/hyperactivity disorder: a systematic review and meta-analysis (2014) · cites this paper as [18]
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“While most fMRI studies found methylphenidate to have a positive effect on brain activation, only some studies observed performance improvement 18, 21, 24, 25, 26, 74, 75, likely reflecting the superior sensitivity of fMRI relative to behavior to detect pharmacologic effects or the relatively small subject numbers of fMRI studies, underpowered for performance effects.”
From Effects of stimulants on brain function in attention-deficit/hyperactivity disorder: a systematic review and meta-analysis (2014) · cites this paper as [18]
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Research works printed but not linked: 2
- Rubia, 2010, “Cool” inferior frontostriatal dysfunction in attention deficit hyperactivity disorder (ADHD) versus “hot” ventromedial orbitofronto-limbic dysfunction in conduct disorder: A review [published online ahead of print November 20]
- Rubia, 2010, Disorder-specific inferior frontal dysfunction in boys with pure attention-deficit/hyperactivity disorder compared to boys with pure CD during cognitive flexibility, Hum Brain Mapp, 31, 1823, 10.1002/hbm.20975 · DOI · Paper page
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Hart, H., Radua, J., Nakao, T., Mataix-Cols, D., & Rubia, K. (2013) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2013.277 · Cited by 764
Self-citationNeuroimaging of child abuse: a critical review
Hart, H., & Rubia, K. (2012) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2012.00052 · Cited by 660
Self-citationRubia, K. (2018) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2018.00100 · Cited by 384
“Thus, during cognitive control tasks, IFC was found to be disorder-specifically reduced compared to OCD patients in individual fMRI studies (Rubia et al., 2010a, 2011a), as well as in a comparative fMRI meta-analysis of cognitive control functions, including motor and interference inhibition and…”
Self-citationNoreika, V., Falter, C. M., & Rubia, K. (2013) · Neuropsychologia · doi:10.1016/j.neuropsychologia.2012.09.036 · Cited by 339
Self-citationRubia, K., Alegria, A. A., Cubillo, A. I., Smith, A. B., Brammer, M. J., & Radua, J. (2014) · Biological Psychiatry · doi:10.1016/j.biopsych.2013.10.016 · Cited by 315
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Metadata
- Authors
- Rubia, K., Halari, R., Mohammad, A.-M., Taylor, E., & Brammer, M.
- Affiliations
- King's College London (GB)
- Corresponding author
- Rubia, Katya
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2011-08
- Volume
- 70
- Issue
- 3
- Pages
- 255-262
- ISSN
- 0006-3223 (ISSN-L)
- PMC
- PMC3139835
- OpenAlex
- W2050444644
- Cited by
- 171
- References
- 92
- Citations by year
- 2026: 7 · 2025: 7 · 2024: 8 · 2023: 7 · 2022: 5 · 2021: 10 · 2020: 8 · 2019: 5 · 2018: 8 · 2017: 14 · 2016: 12 · 2015: 14 · 2014: 19 · 2013: 20 · 2012: 25
- FWCI
- 14.53
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Biological Psychiatry (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- Medical Research Council (G9900839)
- PPP Healthcare UK (1206/1140)
- 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
- methylphenidate, attention deficit hyperactivity disorder, error processing, performance monitoring, ventrolateral prefrontal cortex, dorsomedial prefrontal cortex, stop-signal task, inhibition, catecholamine agonists
- MeSH terms
- Adolescent, Central Nervous System Stimulants, Attention, Attention Deficit Disorder with Hyperactivity, Child, Double-Blind Method, Frontal Lobe, Gyrus Cinguli, Humans, Magnetic Resonance Imaging, Male, Methylphenidate, Neuropsychological Tests, Psychomotor Performance
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