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Methylphenidate Enhances Working Memory by Modulating Discrete Frontal and Parietal Lobe Regions in the Human Brain
Open accessAbstract
The indirect catecholamine agonist methylphenidate (Ritalin) is the drug treatment of choice in attention deficit/hyperactivity disorder (AD/HD), one of the most common behavioral disorders of childhood (DSM-IV), although symptoms may persist into adulthood. Methylphenidate can enhance cognitive performance in adults and children diagnosed with AD/HD (Kempton et al., 1999; Riordan et al., 1999) and also in normal human volunteers on tasks sensitive to frontal lobe damage, including aspects of spatial working memory (SWM) performance (Elliott et al., 1997). The present study investigated changes in regional cerebral blood flow (rCBF) induced by methylphenidate during performance of a self-ordered SWM task to define the neuroanatomical loci of the beneficial effect of the drug. The results show that the methylphenidate-induced improvements in working memory performance occur with task-related reductions in rCBF in the dorsolateral prefrontal cortex and posterior parietal cortex. The beneficial effects of methylphenidate on working memory were greatest in the subjects with lower baseline working memory capacity. This is to our knowledge the first demonstration of a localization of a drug-induced improvement in SWM performance in humans and has relevance for understanding the treatment of AD/HD.
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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 Mehta et al., 2000
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“Research additionally shows that ADHD is associated with decreased activity in frontal brain areas and increased activity in posterior (parietal and occipital) brain areas (Durston, 2003), and that MPH affects not only frontal but also posterior areas (Mehta et al., 2000).”
From Implementation Intentions Facilitate Response Inhibition in Children with ADHD (2008) · cites this paper as Mehta et al., 2000
In the citing paper
“Based on accumulating evidence that effects of methylphenidate and related drugs on cognition are baseline performance-dependent (Kimberg et al., 1997; Mattay et al., 2000; Mehta et al., 2000; Gibbs and D’Esposito, 2005; Tipper et al., 2005; Finke et al., 2010), changes in sustained attention following methylphenidate were assessed as a function of baseline A’ scores, independent of group.”
From A positron emission tomography study of nigro-striatal dopaminergic mechanisms underlying attention: implications for ADHD and its treatment (2013) · cites this paper as Mehta et al., 2000
In the citing paper
“The effects of methylphenidate and related stimulant drugs in healthy individuals have been shown to be baseline-dependent; i.e. those subjects with relatively low performance levels exhibit greater benefit after the drug (Naylor et al., 1985; Rogers et al., 1999; Mehta et al., 2000; Turner et al., 2003; Clatworthy et al., 2009).”
From A positron emission tomography study of nigro-striatal dopaminergic mechanisms underlying attention: implications for ADHD and its treatment (2013) · cites this paper as Mehta et al., 2000
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The effects of acute dopamine reuptake inhibition on cognitive function during passive hyperthermia
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Cosmetic psychopharmacology: drugs that enhance wellbeing, performance, and creativity
Rosenthal, R. N., & Westreich, L. M. (2010) · Cambridge University Press eBooks · doi:10.1017/cbo9780511782107.009 · Cited by 3
Effect of Methylphenidate on Learning in Normal Population
Na, K., & Lee, S. I. (2012) · Journal of korean Academy of Child and Adolescent Psychiatry · doi:10.5765/jkacap.2012.23.2.49 · Cited by 3
Arzi, A., Hemmati, A. A., Karampour, N. S., & Khorasgani, Z. N. (2014) · Jundishapur Journal of Health Sciences · doi:10.5812/jjhs.23465 · Cited by 3
“For example, improvement in spatial working memory in healthy adults was reported by Mehta (9).”
BackgroundContext, goals, and behavioral regulation in schizophrenia: Psychological and neural mechanisms.
Barch, D. M., & Braver, T. S. (2009) · American Psychological Association eBooks · doi:10.1037/11884-002 · Cited by 3
Cools, R., & Roberts, A. (2006) · Kluwer Academic Publishers eBooks · doi:10.1007/1-4020-7949-4_10 · Cited by 3
“flow, possibly reflecting increased cortical ‘efficiency’ (see also Mattay et al., 2000, 2002a,b; Mehta et al., 2000).”
BackgroundResultCONTRIBUTION OF CATECHOLAMINES TO VISUAL WORKING MEMORY IN THE MACAQUE MONKEY
Oemisch, M. (2012) · QSpace (Queen's University Library) · Cited by 3
Functional Imaging of Cognitive Psychopharmacology
(2004) · Elsevier eBooks · doi:10.1016/b978-012264841-0/50018-4 · Cited by 3
Fogelson, N., Lopez, E. M., Gonzalez, M. R., Fernández‐del‐Olmo, M., Gurevich, T., & Desojo, L. V. (2025) · Clinical Neurophysiology · doi:10.1016/j.clinph.2025.2110781 · Cited by 2
Methylphenidate (Ritalin) does not improve exam performance in an experimental setting
Sambeth, A., Tóth, M., & Blokland, A. (2025) · Psychopharmacology · doi:10.1007/s00213-025-06864-1 · Cited by 3
“Since the effects of MPH on cognition have been shown to be dependent on baseline dopamine levels, previous studies included a working memory task to control for individual differences in baseline levels (Mattay et al. 2000 ; Mehta et al. 2000 ; van der Schaaf et al. 2013 ).”
Dynamics of a Neuromodulator – II. Dopaminergic Balance and Cognition
Aboitiz, F. (2008) · Springer eBooks · doi:10.1007/978-3-540-70573-4_11 · Cited by 2
DesRuisseaux, L. A., Williams, V. J., McManus, A. J., Gupta, A. S., Carlyle, B. C., Azami, H., Gerber, J. A., Bolling, A. M., Cook, C. L., Betensky, R. A., et al. (2020) · Trials · doi:10.1186/s13063-020-04752-x · Cited by 2
“Usefulness of MPH has also been suggested for depression [14–16], neuroprotection against Parkinson’s disease [17], and general memory and attentional cognitive enhancement [18, 19].”
BackgroundSpencer, R. C., Martin, A. J., Devilbiss, D. M., & Berridge, C. W. (2023) · Neuropsychopharmacology · doi:10.1038/s41386-023-01738-6 · Cited by 2
“Currently, the role of non-catecholamine neuromodulators in the cognitive actions of high-dose psychostimulants remain to be determined.”
Nootropics for Healthy Individuals
Jeon, J. P. (2015) · Trinity College Digital Repository (Trinity College, Hartford CT) · Cited by 2
Wider die Begrenzung der Enhancement-Debatte auf angewandte Ethik
Coenen, C., Ferrari, A., & Grünwald, A. (2018) · Springer eBooks · doi:10.1007/978-3-658-03683-6_4 · Cited by 2
Responding to requests from adult patients for neuroenhancements
Racine, É., & Forlini, C. (2021) · Cited by 2
Chapter VII Role of cortical and striatal dopamine in cognitive function
Robbins, T. W. (2005) · Handbook of chemical neuroanatomy · doi:10.1016/s0924-8196(05)80011-9 · Cited by 2
Self-citationSeeking more than health: Using medicine for enhancement
Gligorov, N. (2012) · Filozofija i drustvo · doi:10.2298/fid1202079g · Cited by 1
Alpha power oscillation in the frontal cortex under Bromazepam and Modafinil effects
Alves, D. D. P. A., Adolfo, W., Bittencourt, J., Gongora, M., Teixeira, S. S., Basile, L., Budde, H., Cagy, M., Ribeiro, P. F. M., & Velasques, B. (2015) · Arquivos de Neuro-Psiquiatria · doi:10.1590/0004-282x20150140 · Cited by 2
Clinical relevance of cognitive dysfunction in major depressive disorder
Cha, D. S. (2015) · Cambridge University Press eBooks · doi:10.1017/cbo9781139860567.002 · Cited by 2
Pharmacological Treatment of ADHD
Yadav, P. (2020) · Advances in medical diagnosis, treatment, and care (AMDTC) book series · doi:10.4018/978-1-7998-5495-1.ch008 · Cited by 2
Molecular Genetic Research on Temperament in Infancy and Early Childhood
Sheese, B. E. (2020) · Springer eBooks · doi:10.1007/978-1-0716-0933-0_3 · Cited by 2
Nogami, T., Arakawa, R., Sakayori, T., Ikeda, Y., Okubo, Y., & Tateno, A. (2022) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2022.799319 · Cited by 2
“Methylphenidate, used for treatment of attention deficit hyperactivity disorder (ADHD), is also used for the enhancement of cognitive performance (39).”
Method
Metadata
- Authors
- Mehta, M. A., Owen, A. M., Sahakian, B. J., Mavaddat, N., Pickard, J. D., & Robbins, T. W.
- Affiliations
- University of Cambridge (GB)
- MRC Cognition and Brain Sciences Unit (GB)
- Addenbrooke's Hospital (GB)
- ORCID
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2000-03-15
- Volume
- 20
- Issue
- 6
- Pages
- RC65-RC65
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6772505
- OpenAlex
- W2170595219
- Cited by
- 608
- References
- 31
- Citations by year
- 2026: 7 · 2025: 9 · 2024: 16 · 2023: 8 · 2022: 9 · 2021: 14 · 2020: 26 · 2019: 21 · 2018: 13 · 2017: 15 · 2016: 27 · 2015: 29 · 2014: 26 · 2013: 34 · 2012: 42
- FWCI
- 11.63
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- Wellcome Trust
- Medical Research Council
- 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, working memory, spatial working memory, attention deficit hyperactivity disorder, regional cerebral blood flow, dorsolateral prefrontal cortex, posterior parietal cortex, catecholamine agonists, working memory capacity
- MeSH terms
- Adult, Central Nervous System Stimulants, Cerebrovascular Circulation, Frontal Lobe, Humans, Functional Laterality, Male, Memory, Short-Term, Methylphenidate, Parietal Lobe, Tomography, Emission-Computed, Adrenergic Uptake Inhibitors, Dopamine Uptake Inhibitors
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