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The Journal of Neuroscience, 2000, 20:RC65:1-6

RAPID COMMUNICATION
Methylphenidate Enhances Working Memory by Modulating Discrete Frontal and Parietal Lobe Regions in the Human Brain

Mitul A. Mehta¹, Adrian M. Owen³, Barbara J. Sahakian¹, Nahal Mavaddat¹, John D. Pickard², and Trevor W. Robbins⁴

¹ University of Cambridge, Department of Psychiatry, and ² Wolfson Brain Imaging Centre, Addenbrooke's Hospital, Cambridge, CB2 2QQ, United Kingdom, ³ Medical Research Council Cognition and Brain Sciences Unit, Cambridge, CB2 2EF, United Kingdom, and ⁴ University of Cambridge, Department of Experimental Psychology, Downing Site, Cambridge CB2 3EB, United Kingdom

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.

Key words: cognition; dopamine; humans; methylphenidate; neuroimaging; Ritalin; stimulant; working memory

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Copyright © 2000 Society for Neuroscience  0270-6474/00/$05.00/0

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