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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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In the citing paper
“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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Stimulants improve theory of mind in children with attention deficit/hyperactivity disorder
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MethodResultInfluentialThe ethics of elective psychopharmacology
Mohamed, A. D., & Sahakian, B. J. (2011) · The International Journal of Neuropsychopharmacology · doi:10.1017/s146114571100037x · Cited by 56
“Consistent with this hypothesis, methylphenidate improves cognitive performance in individuals with greater impairment (Konrad et al. 2004 ; Mehta et al. 2000) while guanfacine (Tenex(1)), an a2-adrenergic receptor agonist, has beneficial effects on WM and attentional functions in patients with ADHD, but does not impr…”
BackgroundSelf-citationMäkelä, P., Wakeley, J., Gijsman, H. J., Robson, P. J., Bhagwagar, Z., & Rogers, R. D. (2005) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300871 · Cited by 62
Wolff, W., & Brand, R. (2013) · Substance Abuse Treatment Prevention and Policy · doi:10.1186/1747-597x-8-23 · Cited by 59
“Enhancers have shown to be more effective in novel situations [31] and for participants with poor memory capacity [32] for example.”
BackgroundPDE and cognitive processing: Beyond the memory domain
Heckman, P. R. A., Blokland, A., Ramaekers, J. G., & Prickaerts, J. (2014) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2014.10.011 · Cited by 55
“Stimulant drugs such as methylphenidate (Ritalin) and amphetamine (Adderall) improve the attention of individuals with ADHD and can enhance attention in healthy people as well (Lakhan & Kirchgessner, 2012; Mehta et al., 2000).”
From Clinical Application to Cognitive Enhancement: The Example of Methylphenidate
Busardò, F. P., Kyriakou, C., Cipolloni, L., Zaami, S., & Frati, P. (2016) · Current Neuropharmacology · doi:10.2174/1570159x13666150407225902 · Cited by 59
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Association of the COMT Met158 allele with trait impulsivity in healthy young adults
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BackgroundPeripheral biomarkers of cognitive response to dopamine receptor agonist treatment
Ersche, K. D., Roiser, J. P., Lucas, M., Domenici, E., Robbins, T. W., & Bullmore, E. T. (2010) · Psychopharmacology · doi:10.1007/s00213-010-2087-1 · Cited by 55
“Performance on such tests is amenable to dopaminergic modulation (Mehta et al. 2000).”
BackgroundSelf-citationMiklós, M., Futó, J., Komáromy, D., & Balázs, J. (2019) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph16203822 · Cited by 64
“Partly supporting our findings, previous studies have shown that psychostimulant medication alters performance on EF tests in children with ADHD [61,92,93].”
ResultKim, J., Whyte, J., Patel, S., Europa, E., Wang, J., Coslett, H. B., & Detre, J. A. (2011) · Psychopharmacology · doi:10.1007/s00213-011-2622-8 · Cited by 52
Wolff, W., Brand, R., Baumgarten, F., Lösel, J., & Ziegler, M. D. (2014) · BioPsychoSocial Medicine · doi:10.1186/1751-0759-8-12 · Cited by 64
“on the enhancing individuals’ side [7,8].”
Gilleen, J., Yakub, F., Davison, C., Kerins, S., Valdearenas, L., Uz, T., Lahu, G., Tsai, M. C., Ogrinc, F., Reichenberg, A., et al. (2018) · Psychopharmacology · doi:10.1007/s00213-018-5134-y · Cited by 52
Self-citationMüller, U., Suckling, J., Zelaya, F. O., Honey, G. D., Faessel, H. M., Williams, S., Routledge, C. A., Brown, J. R., Robbins, T. W., & Bullmore, E. T. (2005) · Psychopharmacology · doi:10.1007/s00213-005-2264-9 · Cited by 52
“Mehta et al. (2000) studied ten healthy male volunteers (mean age, 34.8 years) using PET in a placebo-controlled design.”
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Dopaminergic genotype biases spatial attention in healthy children
Bellgrove, M. A., Chambers, C., Johnson, K. A., Dáibhis, A., Daly, M., Hawi, Z., Lambert, D., Gill, M., & Robertson, I. H. (2007) · Molecular Psychiatry · doi:10.1038/sj.mp.4002022 · Cited by 52
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“It can also be used for the enhancement of cognitive and attention task performance in the human (Mehta et al., 2000; Linssen et al., 2012), monkey (Gamo et al., 2010; Rajala et al., 2012, 2015), and rat (Berridge et al., 2006; Spencer et al., 2012).”
BackgroundInfluentialAssessment of Working Memory in Children
Pickering, S. J. (2006) · Elsevier eBooks · doi:10.1016/b978-012554465-8/50011-9 · Cited by 55
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“This phenomenon has also been described in pharmacological studies as an inverted-U response function (18, 27, 29).”
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Cao, A., Yu, L., Wang, Y., Wang, J.-M., Yang, L., & Lei, G.-F. (2012) · Behavioral and Brain Functions · doi:10.1186/1744-9081-8-10 · Cited by 52
“Imaging studies have shown that more efficient dorsolateral PFC activity can be found following MPH treatment which is considered to improve PFC cognitive function [17].”
BackgroundVerbal working memory impairments following traumatic brain injury: an fNIRS investigation
Merzagora, A. C., İzzetoğlu, M., Onaral, B., & Schultheis, M. T. (2013) · Brain Imaging and Behavior · doi:10.1007/s11682-013-9258-8 · Cited by 50
Munro, B. A., Weyandt, L. L., Marraccini, M. E., & Oster, D. R. (2016) · Addictive Behaviors · doi:10.1016/j.addbeh.2016.08.023 · Cited by 52
“Those with EF deficits might benefit from prescription stimulants, yet healthy individuals that do not have EF deficits might not benefit from prescription stimulants (Mehta et al., 2000; Smith and Farah, 2011).”
BackgroundAlkam, T., Mamiya, T., Kimura, N., Yoshida, A., Kihara, D., Tsunoda, Y., Aoyama, Y., Hiramatsu, M., Kim, H.-C., & Nabeshima, T. (2017) · Psychopharmacology · doi:10.1007/s00213-017-4591-z · Cited by 50
“…medications such as ATX and MPH that block the reuptake of DA and NE are found most effective in reduction of ADHD symptoms by increasing DAergic and NAergic neurotransmission in fronto-striato-cerebellar circuitry (Chamberlain et al. 2007a; Mehta et al. 2000; Prince 2008; Volkow et al. 2011).”
BackgroundModulation of Social Influence by Methylphenidate
Campbell-Meiklejohn, D. K., Simonsen, A., Jensen, M., Wohlert, V., Gjerløff, T., Scheel‐Krüger, J., Møller, A., Frith, C., & Roepstorff, A. (2012) · Neuropsychopharmacology · doi:10.1038/npp.2011.337 · Cited by 54
“In contrast, previous studies (Elliott et al, 1997; Mehta et al, 2000) have found that MPH can affect spatial working memory in healthy volunteers.”
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“The behavioral and cognitive actions of MPH also occur in both normal human subjects and animal models; thus, comparative studies can be performed on normal, healthy rats (Arnsten & Dudley, 2005; Berridge et al., 2006; Kuczenski & Segal, 2002; Mehta et al., 2000).”
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1H MRSI of Middle Frontal Gyrus in Pediatric ADHD
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“…Spatial working memory is a neurocognitive function that is impaired in pediatric ADHD (Gau et al., 2009), correlates with pediatric ADHD core symptoms (Barnett et al., 2009) and is affected by stimulants in pediatric ADHD patients (Gau et al., 2009) and adult healthy controls (Mehta et al., 2000).”
BackgroundInfluentialEffect of ADHD medication in male C57BL/6J mice performing the rodent Continuous Performance Test
Caballero-Puntiverio, M., Lerdrup, L., Grupe, M., Larsen, C., Dietz, A. G., & Andreasen, J. T. (2019) · Psychopharmacology · doi:10.1007/s00213-019-5167-x · Cited by 48
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“Verbal working memory load affects regional brain activation as measured by PET.”
BackgroundDopaminergic Neuromodulation of Semantic Processing: A 4-T fMRI Study with Levodopa
Copland, D. A., McMahon, K. L., Silburn, P. A., & de Zubicaray, G. I. (2009) · Cerebral Cortex · doi:10.1093/cercor/bhp017 · Cited by 47
“…Results Drug-by-condition interactions were investigated for each priming comparison (see Table 4 and Figs 1 and 2) using a threshold of P 0.001 uncorrected for regions where we had reasonable a priori expectations of DAergic modulation of priming (see Introduction), as per Mehta et al (2000).”
InfluentialExpectations regarding cognitive enhancement create substantial challenges
Racine, É., & Forlini, C. (2009) · Journal of Medical Ethics · doi:10.1136/jme.2009.030460 · Cited by 47
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“Second, stimulants are known to act on areas of the brain that are important for directed attention, including the striatum and frontal and parietal cortices (Mehta et al, 2000; Volkow et al, 1998).”
BackgroundDifferential optimal dopamine levels for set-shifting and working memory in Parkinson's disease
Fallon, S. J., Smulders, K., Esselink, R. A. J., van de Warrenburg, B. P. C., Bloem, B. R., & Cools, R. (2015) · Neuropsychologia · doi:10.1016/j.neuropsychologia.2015.07.031 · Cited by 50
“…cognitive functions of attentional set-shifting and spatial working memory, both strongly associated with frontal dopamine (Crofts et al., 2001; Mehta et al., 2000; Owen et al., 1993; Robbins and Roberts, 2007; Roberts et al., 1994; Sawaguchi and Goldman-Rakic, 1991, 1994; Vijayraghavan et…”
Manktelow, A. E., Menon, D. K., Sahakian, B. J., & Stamatakis, E. A. (2017) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2017.00058 · Cited by 46
“, 1997) and WM (Mehta et al., 2000) where volunteers with a lower baseline WM capacity demonstrated greater performance improvement.”
BackgroundSelf-citation5.4 Dopaminergic Modulation of Flexible Cognitive Control in Humans
Cools, R., & D’Esposito, M. (2009) · Dopamine Handbook · doi:10.1093/acprof:oso/9780195373035.003.0017 · Cited by 46
Does gender influence cognitive outcome after traumatic brain injury?
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“Cognition was assessed through the Cambridge Neuropsychological Test Automated Battery (CANTAB), a brief computerised test battery (Morris, Evenden, Sahakian, & Robbins, 1986) that has been established as reliable, valid, and sensitive to cognitive changes in neurological and normal populations (De Luca et al., 2008;…”
BackgroundMethodDopamine and the Development of Executive Dysfunction in Autism Spectrum Disorders
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Catecholaminergic modulation of the avoidance of cognitive control.
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“Conversely, our hypothesis with regard to working memory capacity was bidirectional, given prior reports of positive, but also negative associations between working memory capacity and cognitive effects of MPH (Mehta et al., 2000; van der Schaaf et al., 2013).”
Cho, S.-C., Hwang, J., Kim, B., Lee, H., Kim, H., Lee, J.-S., Shin, M., & Lee, D.-S. (2006) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2006.05.011 · Cited by 44
“Although various brain areas on which MPH may have influences have been suggested (Gustafsson et al., 2000; Langleben et al., 2002; Lee et al., 2005; Mehta et al., 2000; Schweitzer et al., 2000; Shafritz et al., 2004; Szobot et al., 2003; Teicher et al., 1996; Vaidya et al., 1998; Volkow et al., 1997), there has been…”
BackgroundResultMetilfenidato e aprimoramento cognitivo farmacológico: representações sociais de universitários
Barros, D., & Ortega, F. (2011) · Saúde e Sociedade · doi:10.1590/s0104-12902011000200008 · Cited by 44
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“A previous PET study has demonstrated methylphenidate-induced improvements in working memory performance in association with task-related reductions in rCBF in the DLPFC and posterior parietal cortex (Mehta et al., 2000).”
BackgroundForlini, C., & Racine, É. (2010) · Public Understanding of Science · doi:10.1177/0963662510385062 · Cited by 43
“…contend that it is premature to declare CE beneficial given existing knowledge gaps (Racine and Forlini, 2009) including limited evidence of its safety and its efficacy in enhancing cognition of healthy people (Barch and Carter, 2005; Bray et al., 2004; Elliott et al., 1997; Mehta et al., 2000).”
BackgroundSleep Deprivation Impairs and Caffeine Enhances My Performance, but Not Always Our Performance
Faber, N. S., Häusser, J. A., & Kerr, N. L. (2015) · Personality and Social Psychology Review · doi:10.1177/1088868315609487 · Cited by 46
“Similarly, methylphenidate can enhance working memory and planning (Elliott et al., 1997; Mehta et al., 2000).”
BackgroundFrancis, S., Fine, J. B., & Tannock, R. (2001) · Journal of Child and Adolescent Psychopharmacology · doi:10.1089/10445460152595540 · Cited by 44
“In that stimulant medication (methylphenidate; MPH), which is used to treat the behavioral symptoms of ADHD, has been shown to improve some executive functions (Mehta et al. 2000), it may also enhance narrative performance.”
Attentional blink in adults with attention-deficit hyperactivity disorder
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“Mehta et al. (2000) showed that methylphenidate, a drug known to enhance cognitive performance and commonly prescribed for people diagnosed with ADHD, reduced blood flow to the dorsolateral prefrontal cortex and to the posterior parietal cortex.”
BackgroundCornforth, C., Sonuga-Barke, E., & Coghill, D. (2010) · Current Pharmaceutical Design · doi:10.2174/138161210791959827 · Cited by 41
“Whilst several studies have reported that MPH is associated with enhanced executive functioning [26] others using a double-blind randomised controlled”
BackgroundGarasic, M. D., & Lavazza, A. (2016) · BMC Medical Ethics · doi:10.1186/s12910-016-0102-8 · Cited by 41
“First of all, large doses of caffeine and nicotine do not provide the high level of focus that would be typical of specific modern CE – in other words, the “peak” of the performance is not comparable to that sought through the use of methylphenidate and Modafinil, for instance [15–17].”
BackgroundMethylphenidate improves performance on the radial arm maze in periadolescent rats
Dow-Edwards, D. L., Weedon, J. C., & Hellmann, E. (2008) · Neurotoxicology and Teratology · doi:10.1016/j.ntt.2008.04.001 · Cited by 41
Effects of Acute Aerobic Exercise on Response Inhibition in Adult Patients with ADHD
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“Furthermore, in healthy adults, methylphenidate-induced enhancement of SWM performance is accompanied by regional cerebral blood flow decreases in the DLPFC and posterior parietal cortex ( Mehta et al. 2000 ).”
BackgroundMethodInfluentialBecker, M., Repantis, D., Dresler, M., & Kühn, S. (2022) · Human Brain Mapping · doi:10.1002/hbm.25949 · Cited by 46
“Importantly, ADHD is successfully treated with MPH by increasing the extracellular concentration of catecholamines in prefrontal, striatal, and other brain areas (Mehta et al., 2000).”
BackgroundFocusing effects of L ‐dopa in Parkinson's disease
Ng, B., Palmer, S., Rafeef Abugharbieh, A., & McKeown, M. J. (2009) · Human Brain Mapping · doi:10.1002/hbm.20847 · Cited by 39
“Similar findings were observed in a working memory study by Mattay et al. [2002] and similar effects were seen in healthy controls given methylphenidate [Mehta et al., 2000].”
Sources of Working Memory Deficits in Children and Possibilities for Remediation
Minear, M. E., & Shah, P. (2006) · Elsevier eBooks · doi:10.1016/b978-012554465-8/50012-0 · Cited by 39
Pharmacological Strategies for Enhancing Cognition in Schizophrenia
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“Methylphenidate (Clark et al. 1986; Elliott et al. 1997; Mehta et al. 2000), amphetamine (Mattay et al.”
Non-medical use of methylphenidate: a review
Freese, L., Signor, L., Machado, C. A., Ferigolo, M., & Barros, H. M. T. (2012) · Trends in Psychiatry and Psychotherapy · doi:10.1590/s2237-60892012000200010 · Cited by 38
The Neurocognitive Enhancement of Surgeons: An Ethical Perspective
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“However, in one study, healthy volunteers performed a novel neuropsychological test of planning more accurately after being given methylphenidate than after being given a placebo [16].”
BackgroundTian, T., Qin, W., Liu, B., Jiang, T., & Yu, C. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.2163-13.2013 · Cited by 37
Dopaminergic Influences on Emotional Decision Making in Euthymic Bipolar Patients
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“…cognitive effects of pro-dopaminergic agents on measures of attention and working memory (Costa et al, 2009; Granon et al, 2000; Mattay et al, 2000; Mehta et al, 2000), there have also been reports of rare but concerning side effects, including induced impulse-control disorders in individuals with…”
BackgroundImaging Genomics Applied to Anxiety, Stress Response, and Resiliency
Xu, K., Ernst, M., & Goldman, D. A. (2006) · Neuroinformatics · doi:10.1385/ni:4:1:51 · Cited by 38
“Both too much and too little dopamine may impair frontal cognitive performance (Goldman-Rakic et al., 1992; Granon et al., 2000; Mehta et al., 2000).”
BackgroundMultilevel models from biology to psychology: Mission impossible?
Bilder, R. M., Howe, A. G., & Sabb, F. W. (2013) · Journal of Abnormal Psychology · doi:10.1037/a0032263 · Cited by 37
Network Structure among Brain Systems in Adult ADHD is Uniquely Modified by Stimulant Administration
Cary, R. P., Ray, S., Grayson, D. S., Painter, J. G., Carpenter, S. D., Maron, L. M., Sporns, O., Stevens, A. A., Nigg, J. T., & Fair, D. A. (2016) · Cerebral Cortex · doi:10.1093/cercor/bhw209 · Cited by 34
Effects of methylphenidate on basic and higher-order oculomotor functions
Allman, A.-A., Ettinger, U., Joober, R., & O’Driscoll, G. A. (2012) · Journal of Psychopharmacology · doi:10.1177/0269881112446531 · Cited by 35
“An inverted-U relationship between baseline performance and MPH effects on cognition has been suggested in some studies (Engert et al., 2009; Mehta et al., 2000).”
Backgroundde Haes, J. I. U., Maguire, R. P., Jager, P. L., Paans, A. M. J., & den Boer, J. A. (2006) · Human Brain Mapping · doi:10.1002/hbm.20293 · Cited by 37
“Increases in (right) cerebellar rCBF have also been reported in previous studies using psychoactive drugs [Gamma et al., 2000; Gouzoulis et al., 1999; Mehta et al., 2000; Volkow et al., 1997].”
BackgroundResultMichaelides, M., Pascau, J., Gispert, J. D., Delis, F., Grandy, D. K., Wang, G., Desco, M., Rubinstein, M., Volkow, N. D., & Thanos, P. K. (2010) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2010.07319.x · Cited by 35
“It is also consistent with findings from imaging studies in non-ADHD humans that showed MP-induced decreases in PFC cerebral blood flow in controls (Mehta et al., 2000) and with cerebral blood flow increases in the PFC in children with ADHD (Teicher et al., 1996; Vaidya et al., 1998).”
MethodResultSzobot, C. M., Ketzer, C. R., Cunha, R. D., Parente, M. A. D. M. P., Langleben, D. D., Acton, P. D., Kapczinski, F. P., & Rohde, L. A. (2003) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-002-1082-0 · Cited by 35
“The duration of treatment has ranged from several weeks [4, 13] to a single dose [6, 7 , 8, 9]. Also, studies have varied in the extent of prior MPH exposure, with some including drug-naive subjects [4] and others enrolling patients chronically treated with stimulants [5].”
BackgroundResultInfluentialStimulant Medication and Prefrontal Functional Connectivity During Working Memory in ADHD
Sheridan, M. A., Hinshaw, S. P., & D’Esposito, M. (2010) · Journal of Attention Disorders · doi:10.1177/1087054709347444 · Cited by 34
“…of the PFC was identified in more than one region (ACC, middle frontal gyrus), consistent with previous literature identifying multiple areas of dysfunction in the PFC for individuals with ADHD (Durston et al., 2003; Mehta et al., 2000; Schulz et al., 2004; Schweitzer et al., 2003, 2004, 2005).”
InfluentialCreativity and executive function across manic, mixed and depressive episodes in bipolar I disorder
Soeiro‐de‐Souza, M. G., Dias, V. V., Bio, D. S., Post, R. M., & Moreno, R. A. (2011) · Journal of Affective Disorders · doi:10.1016/j.jad.2011.06.024 · Cited by 33
Is Methylphenidate Beneficial and Safe in Pharmacological Cognitive Enhancement?
Kapur, A. (2020) · CNS Drugs · doi:10.1007/s40263-020-00758-w · Cited by 36
Brignell, C. M., Rosenthal, J., & Curran, H. V. (2007) · Journal of Psychopharmacology · doi:10.1177/0269881107077351 · Cited by 33
Moses, M., Tiego, J., Demontis, D., Bragi Walters, G., Stefansson, H., Stefansson, K., Børglum, A. D., Arnatkeviciute, A., & Bellgrove, M. A. (2022) · Molecular Psychiatry · doi:10.1038/s41380-022-01775-5 · Cited by 31
“Moreover, methylphenidate-induced improvements in working memory performance occur with task-related reductions in regional cerebral blood flow in the dorsolateral prefrontal cortex and posterior parietal cortex [98].”
BackgroundAbelman, D. D. (2017) · Harm Reduction Journal · doi:10.1186/s12954-017-0194-6 · Cited by 32
Honarmand, K., Malik, S., Wild, C. J., González-Lara, L. E., McIntyre, C. W., Owen, A. M., & Slessarev, M. (2019) · PLoS ONE · doi:10.1371/journal.pone.0215203 · Cited by 40
Self-citationGoldstein, R. Z., & Volkow, N. D. (2010) · Neuropsychopharmacology · doi:10.1038/npp.2010.145 · Cited by 32
“…disorder and other prefrontal psychopathologies (eg, frontotemporal dementia); indeed MPH has been suggested to improve signal-to-noise ratio (SNR) and optimize activity (eg, processing efficiency) in brain regions that modulate executive functions (Mehta et al, 2000; Volkow et al, 2008).”
BackgroundAgay, N., Yechiam, E., Carmel, Z., & Levkovitz, Y. (2014) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0000000000000076 · Cited by 32
Murray, D. W., Childress, A. C., Giblin, J., Williamson, D., Armstrong, R., & Starr, H. L. (2011) · Clinical Pediatrics · doi:10.1177/0009922810394832 · Cited by 33
“Concurrent diagnoses, n (%) Anxiety 9 (11) 6 (9) Depression 1 (1) 1 (1) Learning disability 33 (39) 26 (38) Baseline ADHD-RS-IV score Hyperactivity- impulsivity score Mean 17.”
Housden, C. R., Morein‐Zamir, S., & Sahakian, B. J. (2011) · Wiley eBooks · doi:10.1002/9781444393552.ch7 · Cited by 33
Self-citationMethylphenidate alters selective attention by amplifying salience
ter Huurne, N., Fallon, S. J., van Schouwenburg, M., van der Schaaf, M., Buitelaar, J., Jensen, O., & Cools, R. (2015) · Psychopharmacology · doi:10.1007/s00213-015-4059-y · Cited by 31
“Improved working memory (Clatworthy et al. 2009; Elliott et al. 1997; Mehta et al. 2000) and enhanced sustained attention (Agay et al.”
InfluentialPetrovsky, N., Ettinger, U., Quednow, B. B., Walter, H., Schnell, K., Kessler, H., Mößner, R., Maier, W., & Wagner, M. (2011) · Psychopharmacology · doi:10.1007/s00213-011-2540-9 · Cited by 31
“The influence of baseline performance on subsequent response to a drug challenge has been previously discussed by a number of other authors (Kimberg et al. 1997; Mattay et al. 2000; Mehta 2002; Mehta et al. 2000; Robbins and Sahakian 1979) demonstrating that despite the absence of an overall effect of a drug, the drug…”
BackgroundSeu, E., & Jentsch, J. D. (2009) · Neuropharmacology · doi:10.1016/j.neuropharm.2009.08.007 · Cited by 32
“…cognitive dysfunction and behavioral symptoms of ADHD (Aron et al., 2003; Chamberlain et al., 2007; Faraone et al., 2005a; Faraone et al., 2005b; Frank et al., 2007; Kempton et al., 1999; Mehta et al., 2000a; Mehta et al., 2000b; Scheres et al., 2003; Spencer et al., 2001; Tannock et al., 1989).”
BackgroundBurden, M. J., & Mitchell, D. B. (2005) · Developmental Neuropsychology · doi:10.1207/s15326942dn2803_3 · Cited by 31
Wacker, J., & Gatt, J. M. (2010) · Neuroscience Letters · doi:10.1016/j.neulet.2010.04.071 · Cited by 33
Oral methylphenidate improves spatial learning and memory in pre- and periadolescent rats.
Zhu, N. W., Weedon, J., & Dow-Edwards, D. L. (2007) · Behavioral Neuroscience · doi:10.1037/0735-7044.121.6.1272 · Cited by 31
Leussis, M. P., Brown, R. E., & CARREY, N. J. (2002) · Developmental Psychobiology · doi:10.1002/dev.10059 · Cited by 31
“For example, the passive avoidance paradigm could be used to examine differences in behavioral inhibition, and tests of working memory such as the delayed match/nonmatch to sample paradigm should be used as MPH has recently been found to enhance working memory in humans (Mehta et al., 2000).”
MethodWhat do experts think we should do to achieve brain health?
Sahakian, B. J. (2014) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2014.04.002 · Cited by 31
“In studies using positron emission tomography (PET), methylphenidate has also been shown to increase efficiency in the brain network activated during performance of a working memory task by healthy people (Mehta et al., 2000).”
BackgroundSelf-citationReceptor and circuit mechanisms underlying differential procognitive actions of psychostimulants
Spencer, R. C., & Berridge, C. W. (2019) · Neuropsychopharmacology · doi:10.1038/s41386-019-0314-y · Cited by 31
Sequential neural processes of tactile–visual crossmodal working memory
Ohara, S., Lenz, F. A., & Zhou, Y.-D. (2005) · Neuroscience · doi:10.1016/j.neuroscience.2005.05.058 · Cited by 30
Keage, H. A. D., Clark, C. R., Hermens, D. F., Williams, L. M., Kohn, M. R., Clarke, S. P., Lamb, C., Crewther, D. P., & Gordon, E. (2008) · Journal of Clinical Neurophysiology · doi:10.1097/wnp.0b013e318163ccc0 · Cited by 30
“…medication-related improvements seen for the AD/HD-com groups that displayed the greatest number of abnormalities premedication, is similar to the findings of Mehta et al. (2000), who reported that methylphenidate improved working memory performance most in groups with the lowest baseline capacity.”
ResultPsychostimulants As Cognitive Enhancers in Adolescents: More Risk than Reward?
Urban, K. R., & Gao, W. (2017) · Frontiers in Public Health · doi:10.3389/fpubh.2017.00260 · Cited by 30
The modulatory effects of dopamine D1 and D2 receptor function on object working memory in humans
Bartholomeusz, C. F., Box, G., Rooy, C. V., & Nathan, P. J. (2003) · Journal of Psychopharmacology · doi:10.1177/0269881103017001688 · Cited by 32
Wanke, N., & Schwabe, L. (2020) · Cerebral Cortex · doi:10.1093/cercor/bhz298 · Cited by 28
“Although this negative correlation might be surprising at first glance, a negative relationship between dlPFC activities and working memory performance has been reported before (Mehta et al. 2000; Karlsgodt et al. 2009) and might reflect increased neural efficiency or suppression of distracting processes.”
BackgroundHernaus, D., Santa, M. M. C., Offermann, J. S., & van Amelsvoort, T. (2017) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2017.02.004 · Cited by 33
“, 2004) and correlates with working memory-related frontal cortical brain function (Mehta et al., 2000).”
Pharmaceutical cognitive doping in students: A chimeric way to get-a-head?
Carton, L., Cabé, N., Ménard, O., Deheul, S., Caous, A., Devos, D., Cottencin, O., & Bordet, R. (2018) · Therapies · doi:10.1016/j.therap.2018.02.005 · Cited by 29
How pills undermine skills: Moralization of cognitive enhancement and causal selection
Mihailov, E., López, B. R., Cova, F., & Hannikainen, I. R. (2021) · Consciousness and Cognition · doi:10.1016/j.concog.2021.103120 · Cited by 28
COMT and ANKK1 gene–gene interaction modulates contextual updating of mental representations
García-García, M., Barceló, F., Clemente, I. C., & Escera, C. (2011) · NeuroImage · doi:10.1016/j.neuroimage.2011.02.053 · Cited by 32
“This crucial function involves the DA system (Cools, 2008; Garcia-Garcia et al., 2010a; Garcia-Garcia et al., 2010b; Kaplan and Oudeyer, 2007; DA Lewis et al., 2001; Mehta et al., 2000; Sawaguchi and Goldman-Rakic, 1994) putatively through a reciprocal relationship between PFC and striatal DA (Akil et al.”
Brain perfusion and dopaminergic genes in boys with attention‐deficit/hyperactivity disorder
Szobot, C. M., Roman, T., Cunha, R. D., Acton, P. D., Hutz, M. H., & Rohde, L. A. (2004) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30096 · Cited by 29
Luman, M., Goos, V., & Oosterlaan, J. (2014) · Research on Child and Adolescent Psychopathology · doi:10.1007/s10802-014-9934-1 · Cited by 30
“The finding that MPH took performance of children with ADHD to a higher level is line with the idea that MPH is a cognitive enhancer, effective at improving cognitive functions, such as working memory (Elliott et al. 1997; Mehta et al. 2000).”
BackgroundRacine, É., & Illes, J. (2006) · Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques · doi:10.1017/s0317167100005138 · Cited by 28
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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