Human brain exhibits three propagating pulsations, namely cardiovascular, respiratory, and infra-slow fluctuations (ISF <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 (MREG) fMRI sequence, we analysed 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 (TE) 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. Significance statement Cerebrospinal fluid (CSF) flow is essential for brain fluid homeostasis and interstitial metabolite clearance. Human brain exhibits three types of intracranial pulsations linked to CSF flow, which are particularly distinct during sleep, when fluid clearance processes are most active. We hypothesized that these pulsations, despite their independent sources, interact with each other to facilitate CSF flow. Using functional magnetic resonance imaging (fMRI) during wakefulness and non-rapid eye movement sleep (NREM), we investigated cross-frequency coupling patterns up to 5 Hz within the brain. The results revealed novel cross-frequency coupling bands in the human brain, in which infra-slow fluctuation (ISF) dynamics predicted faster brain pulsations, potentially contributing to increased perivascular clearance during sleep.
Väyrynen et al. (Fri,) studied this question.