Modafinil activates cortical and subcortical sites in the sleep-deprived state

Subject Objectives: To assess the effect of the wake-promoting drug modafinil on working memory and brain activation in the executive network, following a single night of sleep deprivation. Design: Randomized, placebo-controlled, 4-arm, double-blind evaluation of a single 200-mg dose of modafinil on working memory (1-, 2-, and 3-back)-related functional brain activation and performance following overnight sleep deprivation. Setting: General Clinical Research Center, Biomedical Imaging Center. Subjects: Eight medication-free men, aged 21 to 35 years. Interventions: Overnight sleep deprivation, single-dose 200-mg modafinil, functional magnetic resonance imaging Measurements and Results: Brain activation patterns and regional signal intensity based on the blood-oxygen level-dependent signal were assessed. The following reaction times were used as measures of performance: (1) attention in the scanner before functional scanning, (2) back responses during the active-task block, and (3) attention during the base-line task block. Contrast of activation maps among conditions revealed sleep-deprivation and drug effects, and their interactions. Performance in the deprived state was enhanced by modafinil only at an intermediate (2-back) level of task difficulty and was associated with the recruitment of increased cortical activation volumes. Strong and consistent individual differences in performance were noted on the working memory tasks. Conclusions: Modafinil effectively counters the adverse effects of overnight sleep deprivation on working memory but only when task difficulty is moderate, recruiting extensive areas in the executive network to do so. Interindividual differences in working-memory performance are stable trait characteristics.