Abstract Introduction Sleep is a highly stereotyped phenomenon that is ubiquitous across species. Although behaviorally appearing as a homogeneous process, sleep has been recognized as cortically heterogenous and locally dynamic. PET/fMRI studies have provided key insights into regional activation and deactivation with sleep onset, but they lack the high temporal resolution and electrophysiology for understanding neural interactions. Using simultaneous electrocorticography (EEG) and magnetoencephalography (MEG) imaging, we systematically characterize whole-brain neural oscillations and identify frequency specific, cortically-based patterns associated with sleep onset. Methods In this study, 14 healthy subjects underwent simultaneous EEG and MEG imaging. Sleep states were determined by scalp EEG. Eight 15s artifact-free epochs, e.g. 120s sensor time series, were selected to represent each behavioral state: N1, N2 and wake. Atlas-based source reconstruction was performed using adaptive beamforming methods. Functional connectivity measures were computed using imaginary coherence and across regions of interests (ROIs, segmentation of 210 cortical regions with Brainnetome Atlas) in multiple frequency bands, including delta (1-4Hz), theta (4-8Hz), alpha (8-12Hz), sigma (12-15Hz), beta (15-30Hz), and gamma (30-50Hz). Directional phase transfer entropy (PTE) was also evaluated to determine the direction of information flow with transition to sleep. Results We show that the transition to sleep is encoded in a spatially and temporally specific dynamic pattern of whole-brain functional connectivity. With sleep onset, there is increased functional connectivity diffusely within the delta frequency, while spatially specific profiles in other frequency bands, e.g. increased fronto-temporal connectivity in the alpha frequency band and fronto-occipital connectivity in the theta band. In addition, rather than a decoupling of anterior-posterior regions with transition to sleep, there is a spectral shift to delta frequencies observed in the synchrony and information flow of neural activity. Conclusion Sleep onset is cortically heterogeneous, composed of spatially and temporally specific patterns of whole-brain functional connectivity, which may play an essential role in the transition to sleep. Support (if any) Research reported in this publication was supported by the National Center for Advancing Translational Sciences of the NIH under Award Number (5TL1TR001871-05 to JMF). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.
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