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

The indirect catecholamine agonist methylphenidate (Ritalin) is the drug tr eatment of choice in attention deficit/hyperactivity disorder (AD/HD), one of the most common behavioral disorders of childhood (DSM-IV), although sym ptoms may persist into adulthood. Methylphenidate can enhance cognitive per formance in adults and children diagnosed with AD/HD (Kempton et al., 1999; Riordan et al., 1999) and also in normal human volunteers on tasks sensiti ve to frontal lobe damage, including aspects of spatial working memory (SWM ) performance (Elliott et al., 1997). The present study investigated change s in regional cerebral blood flow (rCBF) induced by methylphenidate during performance of a self-ordered SWM task to define the neuroanatomical loci o f the beneficial effect of the drug. The results show that the methylphenid ate-induced improvements in working memory performance occur with task-rela ted reductions in rCBF in the dorsolateral prefrontal cortex and posterior parietal cortex. The beneficial effects of methylphenidate on working memor y were greatest in the subjects with lower baseline working memory capacity . This is to our knowledge the first demonstration of a localization of a d rug-induced improvement in SWM performance in humans and has relevance for understanding the treatment of AD/HD.