Methylphenidate enhances brain activation and deactivation responses to visual attention and working memory tasks in healthy controls
Open accessAbstract
Methylphenidate (MPH) is a stimulant drug that amplifies dopamineric and noradrenergic signaling in the brain, which is believed to underlie its cognition enhancing effects. However, the neurobiological effects by which MPH improves cognition are still poorly understood. Here, functional magnetic resonance imaging (fMRI) was used together with working memory (WM) and visual attention (VA) tasks to test the hypothesis that 20mg oral MPH would increase activation in the dorsal attention network (DAN) and deactivation in the default mode network (DMN) as well as improve performance during cognitive tasks in healthy men. The group of subjects that received MPH (MPH group; N=16) had higher activation than the group of subjects who received no medication (control group: N=16) in DAN regions (parietal and prefrontal cortex, regions increasingly activated with increased cognitive load) and had increased deactivation in the insula and posterior cingulate cortex (regions increasingly deactivated with increased cognitive load) and these effects did not differ for the VA and the WM tasks. These findings provide the first evidence that MPH enhances activation of the DAN whereas it alters DMN deactivation. This suggests that MPH (presumably by amplifying dopamine and noradrenergic signaling) modulates cognition in part through its effects on DAN and DMN.
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Both stimulants and nonstimulants may act on brain frontoparietal circuitry to ameliorate the dysfunction of cognitive control and attention in ADHD individuals.
“Taken together, both stimulants and nonstimulants may act on brain frontoparietal circuity to ameliorate the dysfunction of cognitive control and attention in ADHD individuals (Cubillo et al., 2014; Fu et al., 2022; Tomasi et al., 2011)”
From Overlapping and differential neuropharmacological mechanisms of stimulants and nonstimulants for attention-deficit/hyperactivity disorder: A comparative neuroimaging analysis (2024) · cites this paper as Tomasi et al., 2011
The Results and Discussion (page numbers unavailable) report that methylphenidate, a stimulant, increased activation in frontal and parietal attention-network regions during attention and working-memory tasks. The study tested healthy controls, not people with ADHD; it did not test nonstimulants or show that either drug class ameliorates cognitive-control dysfunction in ADHD. (LLM, conf=0.88)
Experimental — accuracy not yet measuredMethylphenidate increases activation of parietal and prefrontal cortices and increases deactivation of insula and posterior cingulate cortex during visual attention and working memory tasks.
“Using fMRI, it has been shown that MPH increases activation of the parietal and prefrontal cortices and increases deactivation of the insula and posterior cingulate cortex during visual attention and working memory tasks (180).”
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“…given the massive presence in DAT and NET expression in the motor cortex, while also being associated with indirect and down-stream effects modulated by responses of the prefrontal cortex (Lewis et al., 2001; Peterson et al., 2009; Schulz et al., 2012; Seneca et al., 2006; Tomasi et al., 2011).”
- Authors
- Tomasi, D., Volkow, N. D., Wang, G. J., Wang, R., Telang, F., Caparelli, E. C., Wong, C., Jayne, M., & Fowler, J. S.
- Affiliations
- National Institute on Alcohol Abuse and Alcoholism (US)
- Brookhaven National Laboratory (US)
- Corresponding author
- Tomasi, D.
- Venue
- NeuroImage
- Publisher
- Elsevier BV
- Published
- 2011-02
- Volume
- 54
- Issue
- 4
- Pages
- 3101-3110
- ISSN
- 1053-8119 (ISSN-L)
- PMC
- PMC3020254
- OpenAlex
- W2027473195
- Cited by
- 145
- References
- 51
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 8 · 2023: 7 · 2022: 4 · 2021: 9 · 2020: 5 · 2019: 6 · 2018: 5 · 2017: 8 · 2016: 17 · 2015: 5 · 2014: 11 · 2013: 26 · 2012: 19
- FWCI
- 11.15
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- NeuroImage (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Alcohol Abuse and Alcoholism (2RO1AA09481)
- National Center for Research Resources (GCRC 5-MO1-RR-10710)
- 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, stimulants, cognitive enhancement, dorsal attention network, default mode network, brain deactivation, visual attention, working memory, cognitive load, parietal cortex, prefrontal cortex, insula, posterior cingulate cortex, dopamine, norepinephrine
- MeSH terms
- Adult, Central Nervous System Stimulants, Attention, Brain, Humans, Image Interpretation, Computer-Assisted, Magnetic Resonance Imaging, Male, Memory, Short-Term, Methylphenidate, Photic Stimulation
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