Brain Activity during Working Memory Tasks after Daily Caffeine Intake: a randomized double-blind placebo-controlled trial

Abstract Caffeine has been reported to acutely increase working memory (WM)-related brain activity without a significant enhancement in performances in healthy adults. As a ritual in the society, however, the impacts of daily caffeine intake on WM-related brain activities remain unknown. This double-blind randomized crossover study aimed to investigate the blood-oxygen-level-dependent (BOLD) activity in 20 young healthy non-smokers (age: 26.4 ± 4.0 years; body mass index: 22.7 ± 1.4 kg/m2; and self-report habitual caffeine intake: 474.1 ± 107.5 mg/day) during WM tasks (consisting high and low workloads) after 10-day caffeine intake (150 mg x 3/day) and after 36h withdrawal (9-day caffeine & 1-day placebo) compared to 10-day placebo intake (150 mg x 3/day). In caffeine condition, participants showed more errors and longer reaction times (RTs) in WM tasks, without significant changes in the workload-dependent BOLD activities. Worse WM performance remained after acute withdrawal. Furthermore, independent of workloads, BOLD activity was reduced in hippocampus in caffeine but partially mitigated in withdrawal condition. No significant differences in simple attention tasks were observed between caffeine and placebo, while withdrawal showed longer RTs than the other two. Taken together with the earlier evidence, caffeine might acutely increase the demands of cerebral metabolic activities for WM, which however could no longer be fulfilled after daily intake and results in compromised performances. The reduced hippocampal activities additionally echoed the caffeine-reduced grey matter volume previously reported. This study is funded by Swiss National Science Foundation (grant 320030 − 163058).