Normal brain function requires interactions between spatially separated, and functionally specialized, macroscopic regions, yet the directionality of these interactions in large-scale functional networks is unknown. Magnetoencephalography was used to determine the directionality of these interactions, where directionality was inferred from time series of beamformer-reconstructed estimates of neuronal activation, using a recently proposed measure of phase transfer entropy. We observed well-organized posterior-to-anterior patterns of information flow in the higher-frequency bands (alpha1, alpha2, and beta band), dominated by regions in the visual cortex and posterior default mode network. Opposite patterns of anterior-toposterior flow were found in the theta band, involving mainly regions in the frontal lobe that were sending information to a more distributed network. Many strong information senders in the theta band were also frequent receivers in the alpha2 band, and vice versa. Our results provide evidence that large-scale resting-state patterns of information flow in the human brain form frequencydependent reentry loops that are dominated by flow from parietooccipital cortex to integrative frontal areas in the higher-frequency bands, which is mirrored by a theta band anterior-to-posterior flow.information flow | phase transfer entropy | resting-state networks | magnetoencephalography | atlas-based beamforming T he brain is an extremely complex system (1-3) containing, at the macroscopic scale, interconnected functional units (4) with more-or-less specific information processing capabilities (5). However, cognitive functions require the coordinated activity of these spatially separated units, where the oscillatory nature of neuronal activity may provide a possible mechanism (6-9). A complete description of these interactions, in terms of both strength and directionality, is therefore necessary for the understanding of both normal and abnormal brain functioning.Functional interactions may be inferred from statistical dependencies between the time series of neuronal activity at different sites, so-called functional connectivity (10). Indeed, interactions in large-scale functional networks have been observed using Electroencephalography, Magnetoencephalography (EEG/MEG) and functional Magnetic Resonance Imaging (fMRI) (e.g., refs. 11-14). However, as yet, little is known about the directionality of these interactions in large-scale functional networks during the resting state. Estimating directionality from fMRI is challenging due to its limited temporal resolution and indirect relation to neuronal activity (15, 16). In contrast, EEG studies in healthy controls have revealed a front-to-back pattern of directed connectivity, particularly in the alpha band (17-22), consistent with modeling studies that have shown that such patterns may arise due to differences in the number of anatomical connections (the degree) of anterior and posterior regions (22, 23). However, modeled patterns of information flow depend on the a...