Frequency modulations of cortical synchronization in human cortex during wakefulness and sleep

Abstract

Vigilance states are associated with reproducible reconfigurations of large-scale brain dynamics, reflected in changes in inter-areal phase synchronization and cross-frequency phase-amplitude coupling. Here, we characterized how these two forms of phase-based coordination jointly organize across sleep and wakefulness in the human brain at local and regional levels. We analysed phase-locking value (PLV) and phase-amplitude coupling (PAC) from intracranial stereo-electroencephalography (SEEG) recordings in 46 individuals with drug-resistant focal epilepsy, focusing on contacts outside the epileptogenic zone (non-epileptogenic zone, nEZ) to define physiological coupling profiles and comparing them with contacts within the EZ. For each subject, representative epochs of wakefulness, NREM sleep stages N2 and N3, and REM sleep were examined. Across vigilance states, large-scale phase synchronization exhibited distinct spectral fingerprints. Theta and sigma synchronization predominated during NREM sleep, beta synchronization increased during REM sleep, and theta interactions characterized wakefulness. PAC showed complementary state-dependent reorganizations: N3 was characterized by delta-driven modulation of broadband high-frequency activity; N2 additionally exhibited theta- and spindle-phase modulation of beta-gamma amplitudes; REM sleep showed reduced coupling; and wakefulness was marked by theta-to-beta interactions. Within vigilance states, epileptogenic regions displayed increased delta and gamma synchronization and enhanced delta-to-beta/gamma PAC, most prominently during N2 sleep and wakefulness, whereas differences between EZ and nEZ tissue were attenuated during REM sleep. Using partial least squares analysis, we further identified system-specific patterns of PLV-PAC covariation, with prominent involvement of temporal networks during NREM sleep and visual and limbic systems during REM sleep. Together, these findings delineate a frequency-specific, state-dependent architecture linking phase synchronization and phase-amplitude coupling in the human brain and describe how epileptogenic networks deviate from physiological coupling profiles across vigilance states.