Graph theoretical analysis of functional magnetic resonance imaging (fMRI) time series has revealed a small-world organization of slow-frequency blood oxygen level-dependent (BOLD) signal fluctuations during wakeful resting. In this study, we used graph theoretical measures to explore how physiological changes during sleep are reflected in functional connectivity and small-world network properties of a large-scale, low-frequency functional brain network. Twenty-five young and healthy participants fell asleep during a 26.7 min fMRI scan with simultaneous polysomnography. A maximum overlap discrete wavelet transformation was applied to fMRI time series extracted from 90 cortical and subcortical regions in normalized space after residualization of the raw signal against unspecific sources of signal fluctuations; functional connectivity analysis focused on the slow-frequency BOLD signal fluctuations between 0.03 and 0.06 Hz. We observed that in the transition from wakefulness to light sleep, thalamocortical connectivity was sharply reduced, whereas corticocortical connectivity increased; corticocortical connectivity subsequently broke down in slow-wave sleep. Local clustering values were closest to random values in light sleep, whereas slow-wave sleep was characterized by the highest clustering ratio (gamma). Our findings support the hypothesis that changes in consciousness in the descent to sleep are subserved by reduced thalamocortical connectivity at sleep onset and a breakdown of general connectivity in slow-wave sleep, with both processes limiting the capacity of the brain to integrate information across functional modules.
We investigated human hippocampal functional connectivity in wakefulness and throughout non-rapid eye movement sleep. Young healthy subjects underwent simultaneous EEG and functional magnetic resonance imaging (fMRI) measurements at 1.5 T under resting conditions in the descent to deep sleep. Continuous 5 min epochs representing a unique sleep stage (i.e., wakefulness, sleep stages 1 and 2, or slow-wave sleep) were extracted. fMRI time series of subregions of the hippocampal formation (HF) (cornu ammonis, dentate gyrus, and subiculum) were extracted based on cytoarchitectonical probability maps. We observed sleep stage-dependent changes in HF functional coupling. The HF was integrated to variable strength in the default mode network (DMN) in wakefulness and light sleep stages but not in slow-wave sleep. The strongest functional connectivity between the HF and neocortex was observed in sleep stage 2 (compared with both slow-wave sleep and wakefulness). We observed a strong interaction of sleep spindle occurrence and HF functional connectivity in sleep stage 2, with increased HF/neocortical connectivity during spindles. Moreover, the cornu ammonis exhibited strongest functional connectivity with the DMN during wakefulness, while the subiculum dominated hippocampal functional connectivity to frontal brain regions during sleep stage 2. Increased connectivity between HF and neocortical regions in sleep stage 2 suggests an increased capacity for possible global information transfer, while connectivity in slow-wave sleep is reflecting a functional system optimal for segregated information reprocessing. Our data may be relevant to differentiating sleep stage-specific contributions to neural plasticity as proposed in sleep-dependent memory consolidation.