Drug-specific laterality effects on frontal lobe activation of atomoxetine and methylphenidate in attention deficit hyperactivity disorder boys during working memory
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Background The catecholamine reuptake inhibitors methylphenidate (MPH) and atomoxetine (ATX) are the most common treatments for attention deficit hyperactivity disorder (ADHD). This study compares the neurofunctional modulation and normalization effects of acute doses of MPH and ATX within medication-naive ADHD boys during working memory (WM). Method A total of 20 medication-naive ADHD boys underwent functional magnetic resonance imaging during a parametric WM n-back task three times, under a single clinical dose of either MPH, ATX or placebo in a randomized, double-blind, placebo-controlled, cross-over design. To test for normalization effects, brain activations in ADHD under each drug condition were compared with that of 20 age-matched healthy control boys. Results Relative to healthy boys, ADHD boys under placebo showed impaired performance only under high WM load together with significant underactivation in the bilateral dorsolateral prefrontal cortex (DLPFC). Both drugs normalized the performance deficits relative to controls. ATX significantly enhanced right DLPFC activation relative to MPH within patients, and significantly normalized its underactivation relative to controls. MPH, by contrast, both relative to placebo and ATX, as well as relative to controls, upregulated the left inferior frontal cortex (IFC), but only during 2-back. Both drugs enhanced fronto-temporo-striatal activation in ADHD relative to control boys and deactivated the default-mode network, which w…
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Testing single dose effects is valuable because they could be less confounded by longer-term purely developmental effects, side effects and clinical improvements that could indirectly affect cognition.
“While testing longer-term effects on cognition is clinically relevant, testing single dose effects is also valuable because they could be less confounded by longer-term purely developmental effects, side effects and clinical improvements that could indirectly affect cognition (45).”
From Differential effects of a single dose of Lisdexamfetamine and Guanfacine on cognitive function in children with ADHD (2025) · cites this paper as [45]
In the authors' four fMRI studies comparing single dosages of methylphenidate and atomoxetine versus placebo on brain activation in children and adolescents with ADHD, reduced activation in frontal, parietal, temporal, and insular-striatal regions during cognitive tasks can be increased (and even normalized) by both stimulant and non-stimulant medications.
“Thus, in our four fMRI studies comparing the effects of single dosages of methylphenidate and atomoxetine versus placebo on brain activation in children and adolescents with ADHD (45, 85–87), we found that reduced activation in frontal, parietal, temporal, and insular-striatal regions during cognitive tasks can be increased (and even normalized) by both stimulant and non-stimulant medications.”
From Differential effects of a single dose of Lisdexamfetamine and Guanfacine on cognitive function in children with ADHD (2025) · cites this paper as [45]
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- Authors
- Cubillo, A., Smith, A. B., Barrett, N., Giampietro, V., Brammer, M., Simmons, A., & Rubia, K.
- Affiliations
- King's College London (GB)
- Corresponding author
- Rubia, K.
- Venue
- Psychological Medicine
- Publisher
- Cambridge University Press (CUP)
- Published
- 2013-04-19
- Volume
- 44
- Issue
- 3
- Pages
- 633-646
- ISSN
- 0033-2917 (ISSN-L)
- 1469-8978
- OpenAlex
- W1976271649
- Cited by
- 88
- References
- 22
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 6 · 2023: 5 · 2022: 3 · 2021: 4 · 2020: 4 · 2019: 6 · 2018: 4 · 2017: 10 · 2016: 13 · 2015: 11 · 2014: 12 · 2013: 4
- FWCI
- 9.45
- Type
- journal article
- Language
- en
- Open access
- green
- www.zora.uzh.ch
- Licence
- Locations
- Psychological Medicine (publishedVersion)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, other-oa)
- Research Portal (King's College London) (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- National Institute for Health and Care Research
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- attention deficit hyperactivity disorder, atomoxetine, methylphenidate, working memory, dorsolateral prefrontal cortex, inferior frontal cortex, default mode network
- MeSH terms
- Atomoxetine Hydrochloride, Adolescent, Analysis of Variance, Attention Deficit Disorder with Hyperactivity, Basal Ganglia, Brain Mapping, Child, Double-Blind Method, Frontal Lobe, Humans, Functional Laterality, Magnetic Resonance Imaging, Male, Memory, Short-Term, Methylphenidate, Neuropsychological Tests, Placebos, Propylamines, Neurotransmitter Uptake Inhibitors, Prefrontal Cortex, Cross-Over Studies
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