OBJECTIVE:Functional near-infrared spectroscopy (fNIRS) is a non-invasive optical technique for bedside evaluation of cerebral metabolism that has clinical potential for monitoring the efficacy of pharmacological treatment. In this pilot study, we investigated the cognitive effects of methylphenidate (MP) on prefrontal function using fNIRS in healthy subjects. METHODS:Thirteen right-handed healthy subjects underwent working memory tasks (0-back and 2-back) after a single oral dose of MP (20 mg) or placebo administered in a double-blind crossover design on two different days separated by 1-3 days. We measured changes in oxyhemoglobin (oxy-Hb) and deoxyhemoglobin (deoxy-Hb) concentrations during the tasks in bilateral prefrontal regions after MP or placebo administration using two-channel fNIRS. RESULTS:There were significantly more correct responses and fewer missed responses during the 2-back task performance after MP treatment as compared with placebo. Baseline-corrected oxy-Hb was significantly decreased after MP treatment compared with the placebo in the 2-back task in the right frontal region but was not different in the 0-back task. Baseline-corrected deoxy-Hb and total-Hb concentrations were not significant between MP and placebo conditions in either of the cognitive tasks. CONCLUSIONS:These data are consistent with previous positron emission tomography findings of MP-mediated reduction in lateral prefrontal activity accompanied by improved cognitive performance.