Biology subjects

Järvelä, M.

Publications and source records attributed to Järvelä, M..

2 recordsLinked to original sources

bioRxiv2025

Arousal State Control of Physiological Human Brain Pulsations

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.

neuroscience↗

bioRxiv2023

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. Significance StatementPreviously disregarded EEG infra-slow fluctuations (0.008-0.1 Hz) and slow physiological pulsations such as respiration have been attracting increasing research interest, which shows that both of these signals correlate with fast (> 1 Hz) neuronal oscillations. However, little has been known about the mechanisms underlying these interactions; for example, the direction of causality in this interaction has not hitherto been studied. Therefore, we investigated full-band EEG in healthy volunteers during wakefulness and sleep to determine if ISF and respiration phases drive neuronal amplitudes. Results showed that ISF and respiration are phase-amplitude coupled, and predict neuronal EEG rhythms. Thus, we conclude that fast neuronal rhythms in human brain are modulated by slower non-neural phenomena.

neuroscience↗