Deep NREM sleep lowers the amplitude of global cerebral hemodynamic oscillations

2572 

Abstract Submission 

Vidhya Vijayakrishnan Nair¹, Brianna R. Kish¹, Hideyuki Oshima², A.J Schwichtenberg¹, Yunjie Tong¹

¹Purdue University, West Lafayette, IN, ²Shibaura Institute of Technology, Tokyo, Japan

Vidhya Vijayakrishnan Nair  
Purdue University
West Lafayette, IN

Brianna R. Kish  
Purdue University
West Lafayette, IN

Hideyuki Oshima  
Shibaura Institute of Technology
Tokyo, Japan

A.J Schwichtenberg  
Purdue University
West Lafayette, IN

Yunjie Tong  
Purdue University
West Lafayette, IN

A recently postulated function of slow-wave Non-Rapid Eye Movement (NREM) sleep is brain-metabolic waste clearance via the glymphatic system. The cerebrospinal fluid (CSF) flow through the brain's perivascular pathways and further exchange with interstitial fluid, as described in the glymphatic model, increases dramatically during slow-wave NREM sleep in live mice(Nedergaard, 2013; Xie et al., 2013). In agreement with this observation, recent functional magnetic resonance imaging (fMRI) studies in humans report large amplitude CSF fluctuations moving craniad into the brain during light NREM (NREM-1 and NREM-2) sleep(Fultz et al., 2019; Picchioni et al., 2022). Similar increases in the amplitude of cerebral hemodynamic oscillations are reported during light NREM sleep(Vijayakrishnan Nair et al., 2023). These large CSF movements have also been shown to be mechanistically driven by low-frequency changes in cerebral hemodynamic oscillations(Fultz et al., 2019; Vijayakrishnan Nair et al., 2023; Yang et al., 2022). However, it is unknown if the amplitude of cerebral hemodynamic oscillations also exhibits a similar increase during deep (slow-wave) NREM sleep (NREM-3). Here, we investigate the amplitude variations in both cerebral hemodynamic oscillations and craniad CSF movement, as well as the strength of coupling between them during NREM-3.

All participants' structural and functional MRI data were acquired using a 3T SIEMENS MRI scanner (Magnetom Prisma, Siemens Medical Solutions, Erlangen, Germany) with a 64-channel head coil. The scans included structural T1-weighted MPRAGE and fMRI. 32-channel Electroencephalography (EEG) was also concurrently acquired using an MRI-compatible EEG system (BrainAmp MR, Brain Products GmbH, Gilching, Germany) during fMRI scans for sleep scoring. The fMRI scans employed here were carefully designed to concurrently capture the craniad CSF movement at the fourth ventricle utilizing the inflow effect(Fultz et al., 2019; Vijayakrishnan Nair et al., 2022, 2023; Yang et al., 2022) and the global cerebral hemodynamic oscillations across the entire brain (see Figure 1 for an overview of the experimental design). To quantify the variations in amplitude, the standard deviations of detrended (MATLAB detrend) global signal (GS) and CSF signals were calculated across continuous segments (at least 3 minutes in duration) of wakefulness, NREM-1, NREM-2, and NREM-3 for each participant. Similarly, the cross-correlations between changes in GS and CSF movement signals (in the low-frequency range of 0.01 – 0.1 Hz) were also quantified across continuous segments of wakefulness, NREM-1, NREM-2 and NREM-3.

The time series plots of detrended GS and CSF signals clearly illustrate that the amplitude of both GS and CSF increase during light NREM sleep states compared to wakefulness. However, the amplitude of only the GS lowers and resembles wakefulness patterns, whereas CSF movement remains elevated during NREM sleep (figure 2A & 2B). Group results also reveal the same pattern with no statistically significant changes across wake and sleep states (figure 2C). In terms of mechanistic coupling between low-frequency changes in the GS and craniad CSF movement, a strong coupling is apparent (Correlations < -0.3) regardless of the wake/sleep states with change in GS temporally leading/driving CSF movement into the brain with delays of ~2 seconds during wakefulness and ~3-4 seconds during NREM sleep (figure 2D, 2E and 2F).

Data illustrate that deep NREM sleep lowers the amplitude of cerebral hemodynamic oscillations, whereas the CSF movement oscillation amplitudes stay elevated during all NREM sleep stages. This difference in amplitudes between cerebral hemodynamics and CSF movement during NREM-3 sleep does not affect their mechanistic coupling in the low-frequency range. This implies that mechanisms or forces capable of driving CSF movement without initiating changes in cerebral hemodynamics may be at play during deep NREM sleep.

Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s)

Neuroanatomy Other

Multi-Modal Imaging

Sleep and Wakefulness ¹

Neurophysiology of Imaging Signals ²

Cerebral Blood Flow

Cerebro Spinal Fluid (CSF)

Electroencephaolography (EEG)

FUNCTIONAL MRI

Sleep