Methylphenidate and atomoxetine normalise fronto-parietal underactivation during sustained attention in ADHD adolescents
Abstract
Problems with sustained attention are a key clinical feature of Attention Deficit/Hyperactivity Disorder (ADHD) which also manifests in poor performance and abnormal fronto-striato-parietal activation during sustained attention. Methylphenidate and atomoxetine improve attention functions and upregulate abnormal fronto-cortical activation during executive function tasks in ADHD patients. Despite this, no functional Magnetic Resonance Imaging (fMRI) study has compared the effects of methylphenidate and atomoxetine on the neurofunctional substrates of sustained attention in ADHD. This randomised, double-blind, placebo-controlled, cross-over study investigated the comparative normalisation effects of methylphenidate and atomoxetine on fMRI correlates and performance in 14 ADHD adolescents relative to 27 age-matched healthy controls during a parametric sustained attention/vigilance task with progressively increasing load of sustained attention. ADHD patients were scanned three times under a single clinical dose of either methylphenidate, atomoxetine, or placebo in pseudo-randomised order. Healthy controls were scanned once and compared to patients under each drug condition to test for potential drug-normalisation effects. Relative to controls, ADHD boys under placebo were impaired in performance and had underactivation in predominantly right-hemispheric fronto-parietal, and striato-thalamic regions. Both drugs normalised all underactivations, while only methylphenidate improved pe…
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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 [86]
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- Authors
- Kowalczyk, O. S., Cubillo, A. I., Smith, A., Barrett, N., Giampietro, V., Brammer, M., Simmons, A., & Rubia, K.
- Affiliations
- King's College London (GB)
- Corresponding author
- Kowalczyk, Olivia S
- ORCID
- Venue
- European Neuropsychopharmacology
- Publisher
- Elsevier BV
- Published
- 2019-10
- Volume
- 29
- Issue
- 10
- Pages
- 1102-1116
- ISSN
- 0924-977X (ISSN-L)
- OpenAlex
- W2966093564
- Cited by
- 63
- References
- 21
- Citations by year
- 2026: 5 · 2025: 14 · 2024: 12 · 2023: 7 · 2022: 11 · 2021: 7 · 2020: 6 · 2019: 1
- FWCI
- 5.00
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Neuropsychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- National Institute for Health 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
- methylphenidate, atomoxetine, attention deficit hyperactivity disorder, sustained attention, adolescents, executive function, ventrolateral prefrontal cortex, temporal cortex, posterior cingulate cortex, precuneus, stimulant medication effects
- MeSH terms
- Atomoxetine Hydrochloride, Adolescent, Central Nervous System Stimulants, Attention, Attention Deficit Disorder with Hyperactivity, Brain, Child, Double-Blind Method, Humans, Magnetic Resonance Imaging, Male, Methylphenidate, Neural Pathways, Neuropsychological Tests, Cross-Over Studies, Adrenergic Uptake Inhibitors, Functional Neuroimaging
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