Biology subjects

Kiviniemi, V.

Publications and source records attributed to Kiviniemi, V..

10 recordsLinked to original sources

bioRxiv2025

Infra-slow (<0.1 Hz) modulation of human brain pulsations in awake and sleep states

Human brain exhibits three propagating pulsations, namely cardiovascular, respiratory, and vasomotor waves, which together propel the flow of intracranial fluids. While their pulsation characteristics have been extensively studied, their causal interconnections have not been systematically investigated. Using ultrafast whole brain magnetic resonance encephalography (MREG), we analysed the frequency domain up to 5 Hz for cross-frequency oscillatory interactions in awake and NREM-sleep states of 23 healthy volunteers. Using transfer entropy (TE) analysis, we found that in the awake state the infra-slow (ISF < 0.1 Hz) oscillations of statistically independent resting state networks (RSN) largely drove the neurofluid (NF) pulsatility. NREM-sleep was associated with increased power of infra-slow fluctuation (ISF) vasomotor oscillations and with altered driving patterns between RSN and NF networks in the direction of a causally chained pattern. Importantly, within these independent signal sources, we found three distinct cross-frequency coupling frequency ranges occurring at ISF (<0.1 Hz), respiratory ([~]0.25 Hz), and cardiovascular ([~]1 Hz) frequencies, where the slower pulsations generally modulated the faster ones, except for a finding of inverted cardiorespiratory drive in NREM-2 sleep. These results indicate the presence of directional ISF-coordinated mechanisms underlying brain pulsations that contribute to driving the intracranial fluid transfer processes. Significance statementCerebrospinal fluid (CSF) flow is essential for brain fluid homeostasis and interstitial metabolite clearance. Human brain exhibits three types of intracranial pulsations linked to CSF flow, which are particularly distinct during sleep, when fluid clearance processes are most active. We predicted that these pulsations, despite their independent sources, interact with each other to coordinate CSF flow. Using functional magnetic resonance imaging (fMRI) during wakefulness and non-rapid eye movement sleep (NREM), we investigated cross-frequency coupling patterns up to 5 Hz within the brain. Results revealed a novel mechanism in human brain whereby infra-slow (ISF) vasomotor oscillations coordinated faster brain pulsation dynamics, which could be a factor mediating the increased perivascular clearance during sleep.

neuroscience↗

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↗

bioRxiv2025

Sleep increases propagation speed of physiological brain pulsations

During sleep, there is an increase in the brain cerebrospinal fluid (CSF) solute convection driven by physiological pulsations. Although the main drivers of CSF flow, namely cardiac, respiratory, and vasomotor pulsations, become more powerful during sleep, there is relatively little information regarding their effects on CSF flow velocity across human brain during sleep. Here, we used functional magnetic resonance encephalography (MREG) to measure non-invasively changes in brain water flow during to sleep by tracking the propagating ultrafast signal changes induced by physiological brain pulsations. We first undertook a phantom study confirming that dense optical flow analysis of MREG data accurately detects water flow velocity, and reflects the power of the physiological pulsations. We then applied the method to quantify CSF water flow velocity in brain of healthy volunteers during EEG-verified awake and sleep recordings of ultrafast MREG data. Sleep induced an increase in CSF flow speed, as demonstrated by elevated vasomotor and respiratory pulsation speeds, while the speed of cardiovascular impulse propagation remained unchanged. The speed increases match previous findings of respective pulsation power changes, and correlated with slow delta EEG power. The sleep-induced CSF flow speed increases occurred dynamically over both pulsation cycles, without the large effects on flow directions reported previously in several neurological conditions. In conclusion, sleep increases 3D water flow speed dynamically in human brain regions showing concomitant pulse power increases, supporting a porous media model of hydrodynamics in brain cortex.

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

Blood pressure lowering enhances cerebrospinal fluid efflux primarily via the lymphatic vasculature

BackgroundInside the incompressible cranium, the volume of cerebrospinal fluid (CSF) is directly linked to blood volume: a change in either will induce a compensatory change in the other. Vasodilatory lowering of blood pressure has been shown to result in an increase of intracranial pressure, which, in normal circumstances should return to equilibrium by increased fluid efflux. In this study, we investigated the effect of blood pressure lowering (BPL) on fluorescent CSF tracer absorption into the systemic blood circulation. MethodsBPL was performed by an i.v. administration of nitric oxide donor sodium nitroprusside (5 {micro}g kg-1 min-1) or the Ca2+-channel blocker nicardipine hydrochloride (0.5 {micro}g kg-1 min-1) for 10 and 15 to 40 mins, respectively. The effect of BPL on CSF clearance was investigated by measuring the efflux of fluorescent tracers (40 kDa FITC-dextran, 45 kDa Texas Red-conjugated ovalbumin) into blood and deep cervical lymph nodes. ResultsNicardipine and sodium nitroprusside reduced blood pressure by 32.0 {+/-} 19.6% and 22.0 {+/-} 2.5%, while temporarily elevating in intracranial pressure by 14.0 {+/-} 6.0% and 11.6 {+/-} 2.0%, respectively. BPL significantly increased tracer accumulation into deep cervical lymph nodes and systemic circulation, but reduced perivascular inflow along penetrating arteries in the brain. The enhanced tracer efflux by BPL into the systemic circulation was markedly reduced (-66.7%) by ligation of lymphatic vessels draining into deep cervical lymph nodes. ConclusionsThis is the first study showing that CSF clearance can be improved with acute hypotensive treatment and that the effect of the treatment is reduced by ligation of a lymphatic drainage pathway. Enhanced CSF clearance by BPL may have therapeutic potential in diseases with dysregulated CSF flow.

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↗

bioRxiv2020

Sleep-specific changes in physiological brain pulsations

Sleep is known to increase the convection of interstitial brain metabolites along with cerebrospinal fluid (CSF). We used ultrafast magnetic resonance encephalography (MREGBOLD) to quantify the effect of sleep on physiological (vasomotor, respiratory and cardiac) brain pulsations driving the CSF convection in humans. Transition to electroencephalography verified sleep occurred in conjunction with power increase and reduced spectral entropy (SE) of physiological brain pulsations. During sleep, the greatest increase in spectral power was in very-low frequency (VLF < 0.1 Hz) waves, followed by respiratory and cardiac brain pulsations. SE reduction coincided with decreased vigilance in awake state and could robustly (ROC 0.88, p < 0.001) differentiate between sleep vs. awake states, indicating the sensitivity of SE of the MREGBOLD signal as a marker for sleep level. In conclusion, the three physiological brain pulsation contribute to the sleep-associated increase in glymphatic CSF convective flow in an inverse frequency order. HighlightsO_LIBrain tissue contains almost no connective tissue, this enabling pressure waves to initiate long-distance brain pulsations C_LIO_LIBrain pulsations are induced by vasomotion, respiration, and the cardiac cycle C_LIO_LISleep strikingly increases spectral power and decreases spectral entropy of brain pulsations, especially for the very low frequency vasomotor waves C_LIO_LISpectral entropy of brain pulsations detected by MREG is a sensitive measure of vigilance, resembling the corresponding entropy changes detected by scalp EEG C_LI

neuroscience↗

bioRxiv2018

Altered BOLD signal variation in Alzheimer’s disease and frontotemporal dementia

Recently discovered glymphatic brain clearance mechanisms utilizing physiological pulsations have been shown to fail at removing waste materials such as amyloid and tau plaques in neurodegenerative diseases. Since cardiovascular pulsations are a main driving force of the clearance, this research investigates if commonly available blood oxygen level-dependent (BOLD) signals at 1.5 and 3 T could detect abnormal physiological pulsations in neurodegenerative diseases. Coefficient of variation in BOLD signal (CVBOLD) was used to estimate contribution of physiological signals in Alzheimers disease (AD) and behavioural variant frontotemporal dementia (bvFTD). 17 AD patients and 18 bvFTD patients were compared to 24 control subjects imaged with a 1.5 T setup from a local institute. AD results were further verified with 3 T data from the Alzheimers disease neuroimaging initiative (ADNI) repository with 30 AD patients and 40 matched controls. Effect of motion and gray matter atrophy was evaluated and receiver operating characteristic (ROC) analyses was performed.\n\nThe CVBOLD was higher in both AD and bvFTD groups compared to controls (p < 0.0005). The difference was not explained by head motion or gray matter atrophy. In AD patients, the CVBOLD alterations were localized in overlapping structures in both 1.5 T and 3 T data. Localization of the CVBOLD alterations was different in AD than in bvFTD. Areas where CVBOLD is higher in patient groups than in control group involved periventricular white matter, basal ganglia and multiple cortical structures. Notably, a robust difference between AD and bvFTD groups was found in the CVBOLD of frontal poles. In the analysis of diagnostic accuracy, the CVBOLD metrics area under the ROC for detecting disease ranged 0.85 - 0.96.\n\nConclusionsThe analysis of brain physiological pulsations measured using CVBOLD reveals disease-specific alterations in both AD and bvFTD.

neuroscience↗