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bioRxiv · 10.1101/2025.01.27.635032

Arousal State Control of Physiological Human Brain Pulsations

Järvelä, M.·Kananen, J.·Helakari, H.·Korhonen, V.·Huotari, N.·Raitamaa, L.·Tuunanen, J.·Kallio, M.·Piispala, J.·Ansakorpi, H.·Kiviniemi, V.
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Abstract

Sleep promotes cerebrospinal fluid (CSF) to interstitial fluid (ISF) exchange in brain facilitated by brain pulsations. Especially brain vasomotion and arterial pulsations modulated by noradrenaline drive the intracranial fluid dynamics. Narcolepsy type 1 (NT1) entails lessened hypocretinergic output to wake-promoting systems including the noradrenergic locus coeruleus. As arousal state and noradrenergic signaling affect CSF-ISF clearance, we chose patients with NT1 as a human hypocretin-targeted model of sleep-related pathology bridging the gap between healthy awake and sleep with respect to CSF flow pulsations. We also investigated the sensitivity of MREG to detect flow with a phantom model and sought to replicate earlier pulsation findings in sleep. In this case-control study, we used fast fMRI to map brain pulsations in groups of healthy sleeping controls (n=13), healthy awake controls (n=79) and awake NT1 (n=21) patients. We measured the very low frequency (0.008-0.1) and cardiorespiratory frequencies and calculated in each frequency band the coefficient of variation, spectral power, and full band spectral entropy to obtain brain pulsation maps. We uncovered a brain pulsation profile from healthy waking to sleep to a sleep-related pathology NT1 prominently affected in the vascular-related vasomotor and brain arterial pulsations. Our results established how drivers of brain hydrodynamics are affected by a specific loss of key neurotransmitter governing arousal compared to healthy sleep. We also showed with a phantom model that MREG is sensitive to flow-related signal changes and solidified evidence of brain pulsations in the healthy states of sleep and wakefulness. Significance statementThis study establishes how a specific depletion of arousal state controlling neurotransmitter hypocretin-1 affects brain fluid dynamics by comparing patients with narcolepsy type 1 (NT1) to healthy wake and sleeping controls. We used fast fMRI to reveal that reduced hypocretinergic activity and following postulated inconsistent noradrenergic signaling in NT1 leads to high vasomotor and low brain arterial pulsations compared to healthy wakefulness while healthy sleep produces brain arterial and respiratory pulsations that dominate over those observed in NT1. The water flow biometrics we verified in this study with a phantom model indicate that deficient hypocretin-noradrenaline axis in humans leads to opposing changes in vasomotor and arterial induced brain pulsation that may propagate to altered glymphatic solute transportation.

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Järvelä, M., Kananen, J., Helakari, H., Korhonen, V., Huotari, N., Raitamaa, L., Tuunanen, J., Kallio, M., Piispala, J., Ansakorpi, H., Kiviniemi, V.. 2025-01-28. Arousal State Control of Physiological Human Brain Pulsations. https://doi.org/10.1101/2025.01.27.635032

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