Background.

Background. Sleep increases brain solute convection, and this has been related to increased power of physiological brain pulsations^1,2,3. In this study we investigated how the causal connection between the brain water concentrations (wNIRS) and dcEEG derived blood-brain-barrier (BBBEEG) potential dynamics⁴ is altered with respect to venous vasomotor BOLD fluctuations. We hypothesized that the increased brain solute transport is driven by increased vasomotor BOLD waves. To test the hypothesis, we statistically compared the causal relations of the brain water wNIRS and electrodynamic BBBEEG signals during normal awake and increased glymphatic convection in NREM sleep.
Methods. After approved informed consent, healthy subjects (n=21 awake, n=19 EEG verified sleep) were scanned with: a) water sensitized near-infrared spectroscopy (wNIRS) to measure brain water concentration⁵ in synchrony with b) ultrafast MREG scanning (TR 100 ms, 3D whole brain, flip angle 5°) reflecting brain non-aliased venous BOLD fluctuations⁶,and c) 256 ch dcEEG recording (EGI) for BBBEEG. Standard FSL pre-processing was used on MREG BOLD data, dcEEG was corrected also with standard fMRI artifact removal. Water concentration wNIRS was calculated using Beer-Lambert law from 3 NIR wavelengths (690 nm, 830 nm and water sensitive 980 nm). The simultaneous dcEEG, wNIRS and MREG data were segmented into 2 min EEG-verified sleep segments and bandpass filtered to very low frequency (VLF, 0.01-0.08 Hz). Hilbert transformation was applied for both VLF traces to extract instantaneous phase time-series. Phase transfer entropy (PTE)⁷ was then used to study the causal directional interactions with differential form (dPTE). FSL randomise (TFCE) with 5k permutations p < 0.05 was used for statistical inferences in brain images of altered dPTE causal drive.
Results. In awake state the brain H₂O-signal and dcEEG reflecting BBB_EEG potential causally precede and drive VLF BOLD signal wave amplitude and phase transitions over the whole brain, blue color c.f. Fig 1-2. However, in N1 and N2 sleep this interaction inverts; the VLF BOLD waves starts to causally drive both H₂O signal and BBB potential regionally, c.f. Fig’s 1-2 hot colors in cortex. In especially the BBBEEG the spatial extent in N2 > N1 and co-localizes with sensory and parasagittal areas known to have increased glymphatic slow delta activity^1,2. Deeper areas of the brain seem to maintain the normal causal drive of BOLD in even in N1-N2 sleep.
Conclusion: Vasomotor waves causal relation to electro/hydrodynamic signals inverts in NREM sleep in parasagittal areas of slow delta sleep. Vasomotor waves start to drive glymphatic water and electrolyte convection over BBB.

Acknowledgements

JAES-Foundation, Aivosäätiö, VTR & Research Council of Finland are cordially acknowledged for their grant support.