Frequency Analysis of EEG Microstate Sequences in Wakefulness and NREM Sleep

The majority of EEG microstate analyses concern wakefulness, and the existing sleep studies have focused on changes in spatial microstate properties and on microstate transitions between adjacent time points, the shortest available time scale. We present a more extensive time series analysis of unsmoothed EEG microstate sequences in wakefulness and non-REM sleep stages across many time scales. Very short time scales are assessed with Markov tests, intermediate time scales by the entropy rate and long time scales by a spectral analysis which identifies characteristic microstate frequencies. During the descent from wakefulness to sleep stage N3, we find that the increasing mean microstate duration is a gradual phenomenon explained by a continuous slowing of microstate dynamics as described by the relaxation time of the transition probability matrix. The finite entropy rate, which considers longer microstate histories, shows that microstate sequences become more predictable (less random) with decreasing vigilance level. Accordingly, the Markov property is absent in wakefulness but in sleep stage N3, 10/19 subjects have microstate sequences compatible with a second-order Markov process. A spectral microstate analysis is performed by comparing the time-lagged mutual information coefficients of microstate sequences with the autocorrelation function of the underlying EEG. We find periodic microstate behavior in all vigilance states, linked to alpha frequencies in wakefulness, theta activity in N1, sleep spindle frequencies in N2, and in the delta frequency band in N3. In summary, we show that EEG microstates are a dynamic phenomenon with oscillatory properties that slow down in sleep and are coupled to specific EEG frequencies across several sleep stages.