Cited by 610Attention Deficit Hyperactivity DisorderNeural and Behavioral Psychology StudiesNeurotransmitter Receptor Influence on Behavior

Methylphenidate enhances working memory by modulating discrete frontal and parietal lobe regions in the human brain

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Mehta, Mitul A., Owen, Adrian M., Sahakian, Barbara J., Mavaddat, Nahal, Pickard, John D., Robbins, Trevor W.·2000·The Journal of Neuroscience

Abstract

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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Crossref · 10.1523/jneurosci.20-06-j0004.2000

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  • Imaging studies have shown that methylphenidate enhances the efficiency of PFC activity both in healthy college students and in subjects with ADHD.

    “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

    The Discussion reports improved working-memory accuracy alongside reduced blood flow in the dorsolateral prefrontal cortex, consistent with more efficient task-related activity. The Materials and Methods identify the participants as 10 healthy male volunteers (mean age 34.8), but do not identify them as college students. The ADHD portion of the citing sentence is attributed to a different source. (LLM, conf=0.88)

    Experimental — accuracy not yet measured
  • ADHD is associated with decreased activity in frontal brain areas and increased activity in posterior brain areas, and MPH affects not only frontal but also posterior areas.

    “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

  • Effects of methylphenidate and related drugs on cognition are baseline performance-dependent.

    “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.”
  • 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.

    “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).”

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Research works printed but not linked: 2

  1. Baddeley AD (1986) Working memory. Oxford: Clarendon.
  2. Cochran WG, Cox GM (1957) Experimental designs. New York: Wiley.

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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)
Venue
The Journal of Neuroscience
Published
2000-03-15
Volume
20
Issue
6
Pages
RC65-RC65
ISSN
  • 0270-6474 (ISSN-L)
  • 1529-2401
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
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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