Infra-slow (<0.1 Hz) Modulation of Human Brain Pulsations in Awake and Sleep States

The human brain exhibits three propagating pulsations, namely, cardiovascular, respiratory, and infra-slow fluctuations (ISFs <0.1 Hz), which are thought to contribute to the flow of intracranial fluids. While their pulsation characteristics have been extensively studied, their mutual dependencies have not been systematically investigated. Using ultrafast whole-brain magnetic resonance encephalography fMRI sequence, we analyzed the frequency domain up to 5 Hz for cross-frequency oscillatory interactions in awake and NREM sleep states of 23 (13 F, 10 M) healthy volunteers. Using phase transfer entropy analysis, we found that in the awake state the resting-state network (RSN) activity largely predicted the neurofluid (NF) signal changes. NREM sleep was associated with increased power of ISF and with altered directed coupling patterns between RSN and NF components. Importantly, within these independent signal sources, we found three distinct cross-frequency coupling frequency ranges occurring at ISF (<0.1 Hz), respiratory (∼0.25 Hz), and cardiovascular (∼1 Hz) frequencies, where the slower pulsations generally predicted the faster ones, except for a finding of inverted cardiorespiratory coupling in NREM-2 sleep. These results suggest the presence of directional ISF mediated mechanisms underlying brain pulsations that contribute to driving the intracranial fluid transfer processes.