Caffeine and modafinil counteract sleep deprivation through distinct neurocognitive pathways: an ERP study of object working memory

Background: Sleep deprivation impairs core cognitive functions, such as working memory. Previous studies focused on global working memory performance, and direct comparisons of how different cognitive enhancers mitigate sleep deprivation-induced deficits in object working memory remain limited, particularly regarding the underlying neurophysiological mechanisms. This study compared the counteractive effects of caffeine and modafinil after 36 h of total sleep deprivation and elucidated their stage-specific neural mechanisms during object working memory processing. Methods: A randomized, double-blind, crossover design was used with 14 healthy male participants. Participants completed a 2-back object working memory task at baseline and after 36 h of sleep deprivation under caffeine and modafinil conditions. Event-related potentials were recorded to assess key component changes, including P2, N2, P3, and LPC. Results: Behaviorally, modafinil significantly improved accuracy after sleep deprivation, surpassing baseline performance, with an exploratory trend toward shorter reaction times. In contrast, caffeine maintained behavioral performance at baseline levels without significant change. Neurophysiologically, caffeine markedly increased P2 amplitude but significantly decreased LPC amplitude after sleep deprivation, reflecting enhanced early perceptual processing alongside a decline in late-stage cognitive maintenance resources. However, modafinil stabilized P2 and LPC responses, suggesting improved neural efficiency and sustained top-down cognitive control during stimulus evaluation. Conclusion: Although caffeine and modafinil mitigate sleep deprivation induced decline in object working memory, they operate through distinct neural mechanisms. Caffeine relies on generalized compensatory arousal mechanisms, whereas modafinil exerts a more efficient and targeted enhancement of executive control. These findings provide electrophysiological evidence supporting the differential application of cognitive enhancers under extreme sleep loss.