Biology subjects

Tuunanen, J.

Publications and source records attributed to Tuunanen, J..

5 recordsLinked to original sources

bioRxiv2025

Reduced harmonic complexity of brain parenchymal cardiovascular pulse waveforms in Alzheimer's disease

Alzheimers disease (AD) is characterized by specific neuropathologies, and is associated with arterial wall {beta}-amyloid accumulations, which lead to radiologically detectable amplitude increases and variable propagation speed of cardiovascular impulses in brain. In this study, we developed a fast frequency domain imaging method know as relative harmonic power of magnetic resonance encephalography (MREGRHP), aiming to investigate the configuration of the cardiovascular impulses independently of the mean magnetic resonance signal intensity and physiological impulse amplitude. In the initial analyses in healthy controls, we found that a wide 0.8 - 5Hz bandpass produced the most physiologically realistic cardiovascular waveforms. Whereas the data recorded in cerebrospinal fluid (CSF) from flip angle (FA) of 25{degrees} yielded up to 7-fold higher cardiac signal intensity as compared to FA of 5{degrees}, within the brain tissue recordings with FA of 5{degrees} were markedly more sensitive to cardiac waveform. We detected arterial impulses originating from major arteries and extending into the surrounding brain parenchyma, with simultaneous dampening of amplitude as a function of distance from source. Finally, we compared MREGRHP results in 34 AD patients (mean age: 60.7{+/-}4.7 years; 53% female) against 29 controls (mean age: 56.9{+/-}7.9 years; 66% female). We show that the harmonic power of cardiovascular brain pulses is significantly reduced in cortical frontoparietal areas of AD patients, indicating monotonous impulse patterns colocalizing with the previously reported areas of increased impulse propagation speed. In conclusion, the MREGRHP offers a fast Fourier transform (FFT)-based method to non-invasively quantify and locate human arterial blood vessel wall pathology.

neuroscience↗

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↗

bioRxiv2024

Sleep-Induced Vasomotor Pulsation is a Driver of Cerebrospinal Fluid and Blood-Brain Barrier Dynamics in the Human Brain

Sleep is essential for maintaining brain tissue homeostasis, which is facilitated by enhanced cerebrospinal fluid (CSF) solute transport. Infra-slow (<0.1 Hz) vasomotion, CSF flow, and electrophysiological potential all increase during sleep, but their contributions as potential drivers of CSF flow in human brain remain unknown. To investigate this, we recorded the three signals in healthy volunteers across sleep-wake states using 10 Hz functional magnetic resonance imaging (fMRI BOLD), electroencephalography (DC-EEG), and functional near-infrared spectroscopy (fNIRS). We then analyzed the directed coupling patterns using phase transfer entropy (TE). In the awake state, electrophysiological potential and water concentration changes both predicted vasomotor waves across the brain, possibly reflecting functional hyperemia. During sleep, this coupling reversed, with vasomotor waves instead predicting electrical changes and CSF flow in cortical areas. Furthermore, we found that the amplitude of these dynamics increased during sleep, highlighting the critical role of physiological oscillations in sleep-associated brain fluid flow.

neuroscience↗

bioRxiv2024

Cardiovascular and vasomotor pulsations in the brain and periphery during awake and NREM sleep in a multimodal fMRI study

The glymphatic brain clearance mechanism convects brain cerebrospinal fluid driven by physiological pulsations such as cardiovascular and very low-frequency (VLF < 0.1 Hz) vasomotor waves. Presently, ultrafast functional magnetic resonance imaging (fMRI) facilitates the measurement of these signals from both venous and arterial compartments. In this study, we compared the interaction of these two pulsations in awake and sleep using fMRI and peripheral fingertip photoplethysmography in both arterial and venous signals in ten subjects (5 female). Sleep increased the power of brain cardiovascular pulsations, decreased peripheral pulsation and desynchronized them. Vasomotor waves, however, increase in both power and synchronicity in brain and peripheral signals during sleep. Peculiarly, vasomotor lag reversed in sleep within the default mode network vs. peripheral signal. Finally, sleep synchronized cerebral arterial vasomotion measured with cardiovascular hemodynamic envelope (CHe) vs. venous blood oxygenation level dependent (BOLD) signals in parasagittal brain tissue. These changes in power and pulsation synchrony may reflect differential changes in vascular control between the periphery and brain vasculature, while the increased synchrony of arterial and venous compartments may reflect increased convection of neurofluids in parasagittal areas in sleep. Statement of SignificanceThis study shows that while sleep attenuated the cardiovascular synchrony and powers of pulsatility between the periphery and brain, it also increased brain tissue synchrony of venous and arterial vasomotor waves, specifically in the parasagittal regions. The study also shows that vasomotor waves increased in the human brain and the periphery during NREM sleep. Thus, sleep induces a whole-body vasomotor synchronization where the initiation of peripheral vasomotor waves is preceded within the default mode network area. Based on these results, we suggest that the synchronization of vasomotor waves may be a significant contributor to the enhancement of glymphatic fluid exchange in the human brain during sleep.

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↗