Sleep specific changes in infra-slow and respiratory frequency drivers of cortical EEG rhythms

Infra-slow fluctuations (ISFs, 0.008-0.1 Hz) characterize hemodynamic and electric potential signals from the human brain. ISFs are known to correlate with the amplitude dynamics of fast (> 1 Hz) neuronal oscillations, and may arise from permeability fluctuations of the blood-brain barrier (BBB). Slow physiological pulsations such as respiration may also influence the amplitude dynamics of fast oscillations, but it remains uncertain if these processes track the fluctuations of fast cortical oscillations or act as their drivers. Moreover, possible effects of sleep and associated BBB permeability changes on such coupling are unknown. Here, we used non-invasive high-density full-band electroencephalography (EEG) in healthy human volunteers (N=21) to measure concurrently the ISFs, respiratory pulsations, and fast neuronal oscillations during periods of wakefulness and sleep, and to assess the strength and direction of their phase-amplitude coupling. The phases of ISFs and respiration were both coupled with the amplitude of fast neuronal oscillations, with stronger ISF coupling evident during sleep. Causality analysis robustly showed that the phase of ISF and respiration drove the amplitude dynamics of fast oscillations in sleeping and waking states. However, the net direction of modulation was stronger during the awake state, despite the stronger power and phase-amplitude coupling of slow signals during sleep. These findings show that the ISFs in slow cortical potentials and respiration together significantly determine the dynamics of fast cortical oscillations. We propose that these slow physiological phases are involved in coordinating cortical excitability, which is a fundamental aspect of brain function. ### Competing Interest Statement The authors have declared no competing interest.