Human memory is susceptible to manipulation in many respects. While consolidation is well known to be prone to disruption, there is also growing evidence for the enhancement of memory function. Beside cognitive strategies and mnemonic training, the use of stimulants may improve memory processing in healthy adults. In this single-dose, double-blind, within-subject, randomized, placebo-controlled pilot study, 20 mg methylphenidate (N = 13) or 200 mg modafinil (N = 12) or 200 mg caffeine (N = 14) were administrated to in total 39 healthy participants while performing a declarative memory task. Each participant received only one substance and functional magnetic resonance imaging (fMRI) was used to assess drug-dependent memory effects of the substance for encoding and recognition compared to task-related activation under placebo. While methylphenidate showed some behavioral effect regarding memory recall performance, on the neural level, methylphenidate-dependent deactivations were found in fronto-parietal and temporal regions during recognition of previously learned words. No BOLD alterations were seen during encoding. Caffeine led to deactivations in the precentral gyrus during encoding whereas modafinil did not show any BOLD signal alterations at all. These results should be interpreted with caution since this a pilot study with several limitations, most importantly the small number of participants per group. However, our main finding of task-related deactivations may point to a drug-dependent increase of efficiency in physiological response to memory processing.
