Infra-slow (<0.1 Hz) modulation of human brain pulsations in awake and sleep states

Human brain exhibits three propagating pulsations, namely cardiovascular, respiratory, and vasomotor waves, which together propel the flow of intracranial fluids. While their pulsation characteristics have been extensively studied, their causal interconnections have not been systematically investigated. Using ultrafast whole brain magnetic resonance encephalography (MREG), we analysed the frequency domain up to 5 Hz for cross-frequency oscillatory interactions in awake and NREM-sleep states of 23 healthy volunteers. Using transfer entropy (TE) analysis, we found that in the awake state the infra-slow (ISF < 0.1 Hz) oscillations of statistically independent resting state networks (RSN) largely drove the neurofluid (NF) pulsatility. NREM-sleep was associated with increased power of infra-slow fluctuation (ISF) vasomotor oscillations and with altered driving patterns between RSN and NF networks in the direction of a causally chained pattern. 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 modulated the faster ones, except for a finding of inverted cardiorespiratory drive in NREM-2 sleep. These results indicate the presence of directional ISF-coordinated mechanisms underlying brain pulsations that contribute to driving the intracranial fluid transfer processes. Significance statementCerebrospinal 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 predicted that these pulsations, despite their independent sources, interact with each other to coordinate 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. Results revealed a novel mechanism in human brain whereby infra-slow (ISF) vasomotor oscillations coordinated faster brain pulsation dynamics, which could be a factor mediating the increased perivascular clearance during sleep.