Working memory capacity predicts effects of methylphenidate on reversal learning.

Increased use of stimulant medication, such as methylphenidate, by healthy college students has raised questions about its cognitive-enhancing effects. Methylphenidate acts by increasing extracellular catecholamine levels and is generally accepted to remediate cognitive and reward deficits in patients with attention deficit hyperactivity disorder. However, the cognitive-enhancing effects of such 'smart drugs' in the healthy population are still unclear. Here, we investigated effects of methylphenidate (Ritalin, 20  mg) on reward and punishment learning in healthy students (N=19) in a within-subject, double-blind, placebo-controlled cross-over design. Results revealed that methylphenidate effects varied both as a function of task demands and as a function of baseline working memory capacity. Specifically, methylphenidate improved reward vs punishment learning in high-working memory subjects, whereas it impaired reward vs punishment learning in low-working memory subjects. These results contribute to our understanding of individual differences in the cognitive-enhancing effects of methylphenidate in the healthy population. Moreover, they highlight the importance of taking into account both inter- and intra-individual differences in dopaminergic drug research.