Purpose: The cognitive effects of total sleep deprivation on the brain remain poorly understood. Electroencephalography is a very useful tool for detecting spontaneous brain activity in the resting state. Quasi-stable electrical distributions, known as microstates, carry useful information about the dynamics of large-scale brain networks. In this study, microstate analysis was used to study changes in brain activity after 24 h of total sleep deprivation.Participants and Methods: Twenty-seven healthy volunteers were recruited and underwent EEG scans before and after 24 h (...) of TSD. Microstate analysis was applied, and six microstate classes were identified. Topographies and temporal parameters of the microstates were compared between the rested wakefulness and TSD conditions.Results: Microstate class A showed lower global explained variance, frequency of occurrence, and time coverage in TSD than RW, whereas microstate class D displayed higher GEV, frequency of occurrence, and time coverage in TSD compared to RW. Moreover, subjective sleepiness was significantly negatively correlated with the microstate parameters of class A and positively correlated with the microstate parameters of class D. Transition analysis revealed that class B exhibited a higher probability of transition than did classes D and F in TSD compared to RW.Conclusion: The observation suggests alterations of the dynamic brain-state properties of TSD in healthy young male subjects, which may serve as system-level neural underpinnings for cognitive declines in sleep-deprived subjects. (shrink)