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Objective: The default mode network (DMN) is active in the brain at rest and de-activated during cognitive tasks. Abnormal function in the DMN has been reported in people with schizophrenia but it is not known whether this applies also to people with a familial risk for psychosis (FR). We compared the activity of the DMN between FR participants and controls.Methods: We conducted a resting state functional MRI (R-fMRI) in 72 young adults without psychosis and with a history of psychosis in one or both parents (FR group) and 72 age matched controls without parental psychosis, and without current psychosis or a current prodromal syndrome. Both groups were drawn from the Northern Finland Birth Cohort 1986 (Oulu Brain and Mind study). Parental psychosis was established using the Finnish hospital discharge register. We pre-processed R-fMRI data using independent component analysis followed by a dual regression approach to assess differences between the groups. The FR vs. Control group differences were assessed using non-parametric permutation tests utilizing threshold-free cluster enhancement and correcting for multiple comparisons (p<0.05).Results: FR participants demonstrated significantly lower activity compared with controls in the posterior cingulate cortex, the central node of the DMN. The size of the region was 41 mm(3).Conclusion: The activity of the DMN differed between FR and control groups. This suggests that familial risk for psychotic disorders may be mediated through genetic effects on connectivity in the posterior cingulate cortex. [ABSTRACT FROM AUTHOR]

Aim: The aim of the present study was to assess the relationship between patient-toregistered nurse (RN) ratios and nursing outcomes: job satisfaction and stress, nursing care quality, control of own practise, intent to leave, adequacy of material resources and attitudes towards technical equipment.Background: Although there is a growing body of evidence showing that higher levels of RN staffing are linked to better outcomes, it still is unclear how nurse staffing produces these effects.Method: A survey of data of RNs (n = 854) in 46 inpatient units at five university hospitals in Finland was used to create a Bayesian network (BN) model of connections between the variables.Results: A BN model constructed showed that the quality of nursing care is influenced by multifaceted work environment measures. RNs\'02 possibility to control their own practice and the quality of care are mediation between patient-to-RN ratio and other variables examined.Conclusions: New insight was given to the complex theme of the nursing practice environment and its connections to nursing outcomes.Implications for nursing management: Work environment should be developed with consideration of many factors, including adequate staffing levels and the ability for nurses to control their own work. This could increase nurses\'02 work satisfaction, retention and patient care quality outcomes. [ABSTRACT FROM AUTHOR]

This study aimed to develop a theoretical basis for the promotion of school staff's occupational well-being. The 'Content Model for the Promotion of School Community Staff's Occupational Well-being' describes the four aspects of the promotion of occupational well-being ('working conditions', 'worker and work', 'working community' and 'professional competence') as well as the functionality and structure of the model. The content model was examined empirically by means of a structural equation model. The project was developed with school staff and occupational health nurses and implemented in 2001-2004. The target group consisted of the staff of 12 comprehensive schools in Eastern Finland in 2002 (n = 211) and 2004 (n = 266). The data were collected using a 'well-being at your work index' questionnaire at both times. A structural equation model for the school staff's occupational well-being, i.e. the 'Occupational Well-being of School Staff Model' (baseline OWSS Model: Study I in the year 2002), was produced. The model was tested with the 2004 data. Based on this, the model was further developed into the final OWSS Model (Study II). The theoretical Content Model for the Promotion of School Community Staff's Occupational Well-being can be used as a framework for planning, implementing and evaluating school staff's occupational well-being. [ABSTRACT FROM AUTHOR]

Objective: We studied the association of maximum oxygen uptake (Vo(2max)) with the development and resolution of metabolic syndrome (MetS) for 2 years in older individuals.Research Design and Methods: Subjects were a population sample of 1,226 men and women aged 57-78 years. We assessed Vo(2max) directly by respiratory gas analysis during maximum exercise testing and used dichotomous and continuous variables for MetS.Results: One SD increase in baseline Vo(2max) associated with 44% (95% CI 24-58) decreased risk of developing MetS. Individuals in the highest third of baseline Vo(2max) were 68% (37-84) less likely to develop MetS than those in the lowest third. One SD increase in Vo(2max) increased the likelihood to resolve MetS 1.8 (1.2-2.8) times. Individuals in the highest Vo(2max) third were 3.9 (1.5-9.9) times more likely to resolve MetS than those in the lowest third.Conclusions: Higher levels of cardiorespiratory fitness protect against MetS and may resolve it in older individuals. [ABSTRACT FROM AUTHOR]

Abstract Background There is a permanent need to evaluate and develop the ethical quality of scientific research and to widen knowledge about the effects of ethical issues. Therefore we evaluated whether informed consent is related to implementation and success in a lifestyle intervention study with older research participants. There is little empirical research into this topic. Methods The subjects (n = 597) are a subgroup of a random population sample of 1410 men and women aged 57-78 years who are participating in a 4-year randomized controlled intervention trial on the effects of physical exercise and diet on atherosclerosis, endothelial function and cognition. Data were collected in two steps: A questionnaire about informed consent was given to all willing participants (n = 1324) three months after the randomization. Data on implementation and success in the exercise and diet interventions were evaluated at 12 months by intervention-group personnel. The main purpose of the analysis procedure performed in this study was to identify and examine potential correlates for the chosen dependent variables and to generate future hypotheses for testing and confirming the independent determinants for implementation and success. The nature of the analysis protocol is exploratory at this stage. Results About half of the participants (54%) had achieved good results in the intervention. Nearly half of the participants (47%) had added to or improved their own activity in some sector of exercise or diet. Significant associations were found between performance in the interventions and participants' knowledge of the purpose of the study (p < 0.001), and between success in interventions and working status (p = 0.02), and the participants' knowledge of the purpose of the study (p = 0.04). Conclusion The main finding of this study was that those participants who were most aware or had understood the purpose of the study at an early stage had also attained better results at their 12-month intervention evaluation. Therefore, implementation and success in intervention is related to whether subjects receive a sufficient amount and are able to comprehend the information provided i.e. the core principles of informed consent. Trial Registration (ISRCTN 45977199)

Abstract Background Calcium antagonist overdose can cause severe deterioration of hemodynamics unresponsible to treatment with beta adrenergic inotropes. The aim of the study was to evaluate in an experimental model the effects of levosimendan during severe calcium antagonist intoxication. Methods Twelve landrace-pigs were intoxicated with intravenous verapamil at escalating infusion rates. The infusion containing 2.5 mg/ml verapamil was used aiming to a reduction of cardiac output by 40% from the baseline value. Intoxicated pigs were randomized into two groups: control (saline) and levosimendan (intravenous bolus). Inotropic effect was measured as a change in a maximum of the positive slope of the left ventricular pressure (LV dP/dt). The survival and hemodynamics of the animals were followed for 120 min after the targeted reduction of cardiac output. Results In the control group, five out of six pigs died during the experiment. In the levosimendan group, one pig died before completion of the experiment (p = 0.04). In the levosimendan group a change in LV dP/dt was positive in four out of six pigs compared to one out of six pigs in the control group (p = ns). Conclusions In this experimental model, the use of levosimendan was associated with improved survival.

Optical techniques, such as functional near-infrared spectroscopy (fNIRS), contain high potential for the development of non-invasive wearable systems for evaluating cerebral vascular condition in aging, due to their portability and ability to monitor real-time changes in cerebral hemodynamics. In this study, thirty-six healthy adults were measured by single channel fNIRS to explore differences between two age groups using machine learning (ML). The subjects, measured during functional magnetic resonance imaging (fMRI) at Oulu University Hospital, were divided into young (age ≤ 32) and elderly (age ≥ 57) groups. Brain pulses were extracted from fNIRS using a single 830 nm wavelength. Four feature sets were derived from log-normal parameters estimated by pulse decomposition algorithm. ML experiments utilized support vector machines and random forest learners, along with maximum relevance minimum redundancy and principal component analysis for feature selection. Performance with increasing sample size was estimated using learning curve method. The best mean balanced accuracies for each feature set were over 75% (75.9%, 76.4%, 79.3%, 76.9%), indicating the pulse features containing age related information. Learning curves indicated stable classification performance with increasing sample size. The results demonstrate the potential of using single channel fNIRS in the analysis of aging., Competing Interests: Declarations. Ethics approval and consent to participate: The study protocol was approved by the regional medical research ethics committee of the Wellbeing services county of North Ostrobothnia (53/2012, 274/2020). All participants of the study signed informed consent letters before the measurements. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

There is an ongoing search for a reliable and continuous method of noninvasive blood pressure (BP) tracking. In this study, we investigate the feasibility of utilizing seismocardiogram (SCG) signals, i.e., chest motion caused by cardiac activity, for this purpose. This research is novel in examining the temporal relationship between the SCG-measured isovolumic moment and the electrocardiogram (PEP IM ). Additionally, we compare these results with the traditionally measured pre-ejection period with the aortic opening marked as an endpoint (PEP AO ). The accuracy of the BP estimation was evaluated beat to beat against invasively measured arterial BP. Data were collected on separate days as eighteen sets from nine subjects undergoing a medical procedure with anesthesia. Results for PEP IM showed a correlation of 0.67 ± 0.18 ( p < 0.001), 0.66 ± 0.17 ( p < 0.001), and 0.67 ± 0.17 ( p < 0.001) when compared to systolic BP, diastolic BP, and mean arterial pressure (MAP), respectively. Corresponding results for PEP AO were equal to 0.61 ± 0.22 ( p < 0.001), 0.61 ± 0.21 ( p < 0.001), and 0.62 ± 0.22 ( p < 0.001). Values of PEP IM were used to estimate MAP using two first-degree models, the linear regression model (achieved RMSE of 11.7 ± 4.0 mmHg) and extended model with HR (RMSE of 10.8 ± 4.2 mmHg), and two corresponding second-degree models (RMSE of 10.8 ± 3.7 mmHg and RMSE of 8.5 ± 3.4 mmHg for second-degree polynomial and second-degree extended, respectively). In the intrasubject testing of the second-degree model extended with HR based on PEP IM values, the mean error of MAP estimation in three follow-up measurements was in the range of 7.5 to 10.5 mmHg, without recalibration. This study demonstrates the method's potential for further research, particularly given that both proximal and distal pulses are measured in close proximity to the heart and cardiac output. This positioning may enhance the method's capacity to more accurately reflect central blood pressure compared to peripheral measurements.

Overlapping symptoms between Alzheimer's disease (AD), behavioral variant of frontotemporal dementia (bvFTD), and schizophrenia (SZ) can lead to misdiagnosis and delays in appropriate treatment, especially in cases of early-onset dementia. To determine the potential of brain signal variability as a diagnostic tool, we assessed the coefficient of variation of the BOLD signal (CV BOLD ) in 234 participants spanning bvFTD (n = 53), AD (n = 17), SZ (n = 23), and controls (n = 141). All underwent functional and structural MRI scans. Data unveiled a notable increase in CV BOLD in bvFTD patients across both datasets (local and international, p < 0.05), revealing an association with clinical scores (CDR and MMSE, r = 0.46 and r = -0.48, p < 0.0001). While SZ and control group demonstrated no significant differences, a comparative analysis between AD and bvFTD patients spotlighted elevated CV BOLD in the frontopolar cortices for the latter (p < 0.05). Furthermore, CV BOLD not only presented excellent diagnostic accuracy for bvFTD (AUC 0.78-0.95) but also showcased longitudinal repeatability. During a one-year follow-up, the CV BOLD levels increased by an average of 35% in the bvFTD group, compared to a 2% increase in the control group (p < 0.05). Our findings suggest that CV BOLD holds promise as a biomarker for bvFTD, offering potential for monitoring disease progression and differentiating bvFTD from AD and SZ., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: The cerebrospinal fluid dynamics in the human brain are driven by physiological pulsations, including cardiovascular pulses and very low-frequency (< 0.1 Hz) vasomotor waves. Ultrafast functional magnetic resonance imaging (fMRI) facilitates the simultaneous measurement of these signals from venous and arterial compartments independently with both classical venous blood oxygenation level dependent (BOLD) and faster arterial spin-phase contrast., Methods: 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 10 healthy subjects (5 female)., Results: Sleep increased the power of brain cardiovascular pulsations, decreased peripheral pulsation, and desynchronized them. However, vasomotor waves increase power and synchronicity in both brain and peripheral signals during sleep. Peculiarly, lag between brain and peripheral vasomotor signals reversed in sleep within the default mode network. Finally, sleep synchronized cerebral arterial vasomotor waves with venous BOLD waves within distinct parasagittal brain tissue., Discussion: These changes in power and pulsation synchrony may reflect systemic sleep-related changes in vascular control between the periphery and brain vasculature, while the increased synchrony of arterial and venous compartments may reflect increased convection of regional neurofluids in parasagittal areas in sleep., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Tuunanen, Helakari, Huotari, Väyrynen, Järvelä, Kananen, Kivipää, Raitamaa, Ebrahimi, Kallio, Piispala, Kiviniemi and Korhonen.)

Background/objective: Obesity is a risk factor for several brain-related health issues, and high body-mass index (BMI) is associated with an increased risk for several neurological conditions, including cognitive decline and dementia. Cardiovascular, respiratory, and vasomotor brain pulsations have each been shown to drive intracranial cerebrovascular fluid (CSF) flow, which is linked to the brain metabolite efflux that sustains homeostasis. While these three physiological pulsations are demonstrably altered in numerous brain diseases, there is no previous investigation of the association between physiological brain pulsations and BMI., Subjects/methods: We measured the amplitudes of the physiological brain pulsations using amplitude of low frequency fluctation (ALFF) based method with resting-state functional magnetic resonance imaging via high temporal resolution whole-brain magnetic resonance encephalography (MREG) in 115 healthy subjects. We next undertook multiple linear regression to model the BMI effect voxel-wise whole-brain on very low frequency (VLF), respiration, cardiovascular, and respiratory induced modulation of cardiovascular pulsation amplitudes with age, pulse pressure, and gender as nuisance variables., Results: In our study population, BMI was positively associated with the amplitudes of vasomotor, respiratory, and respiratory induced modulations of cardiovascular pulsations (p < 0.05), while negatively associated with the amplitudes of cardiovascular pulsations (p < 0.05)., Conclusions: The findings suggest that BMI is a significant factor in alterations of cardiovascular pulsation of neurofluids. As physiological pulsations are the drivers of CSF flow and subsequent metabolite clearance, these results emphasize the need for further research into the mechanisms through which obesity affects brain clearance., (© 2024. The Author(s).)

The eye possesses a paravascular solute transport pathway that is driven by physiological pulsations, resembling the brain glymphatic pathway. We developed synchronous multimodal imaging tools aimed at measuring the driving pulsations of the human eye, using an eye-tracking functional eye camera (FEC) compatible with magnetic resonance imaging (MRI) for measuring eye surface pulsations. Special optics enabled integration of the FEC with MRI-compatible video ophthalmoscopy (MRcVO) for simultaneous retinal imaging along with functional eye MRI imaging (fMREye) of the BOLD (blood oxygen level dependent) contrast. Upon optimizing the fMREye parameters, we measured the power of the physiological (vasomotor, respiratory, and cardiac) eye and brain pulsations by fast Fourier transform (FFT) power analysis. The human eye pulsated in all three physiological pulse bands, most prominently in the respiratory band. The FFT power means of physiological pulsation for two adjacent slices was significantly higher than in one-slice scans (RESP1 vs. RESP2; df = 5, p = 0.045). FEC and MRcVO confirmed the respiratory pulsations at the eye surface and retina. We conclude that in addition to the known cardiovascular pulsation, the human eye also has respiratory and vasomotor pulsation mechanisms, which are now amenable to study using non-invasive multimodal imaging of eye fluidics., (© 2024. The Author(s).)

Background: Inside the incompressible cranium, the volume of cerebrospinal fluid 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 on fluorescent cerebrospinal fluid tracer absorption into the systemic blood circulation., Methods: Blood pressure lowering was performed by an i.v. administration of nitric oxide donor (sodium nitroprusside, 5 µg kg -1  min -1 ) or the Ca 2+ -channel blocker (nicardipine hydrochloride, 0.5 µg kg -1  min -1 ) for 10, and 15 to 40 min, respectively. The effect of blood pressure lowering on cerebrospinal fluid 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. The effect of nicardipine on cerebral hemodynamics was investigated by near-infrared spectroscopy. The distribution of cerebrospinal fluid tracers (40 kDa horse radish peroxidase,160 kDa nanogold-conjugated IgG) in exit pathways was also analyzed at an ultrastructural level using electron microscopy., Results: Nicardipine and sodium nitroprusside reduced blood pressure by 32.0 ± 19.6% and 24.0 ± 13.3%, while temporarily elevating intracranial pressure by 14.0 ± 7.0% and 18.2 ± 15.0%, respectively. Blood pressure lowering significantly increased tracer accumulation into dorsal dura, deep cervical lymph nodes and systemic circulation, but reduced perivascular inflow along penetrating arteries in the brain. The enhanced tracer efflux by blood pressure lowering into the systemic circulation was markedly reduced (- 66.7%) by ligation of lymphatic vessels draining into deep cervical lymph nodes., Conclusions: This is the first study showing that cerebrospinal fluid 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 cerebrospinal fluid clearance by blood pressure lowering may have therapeutic potential in diseases with dysregulated cerebrospinal fluid  flow., (© 2024. The Author(s).)

In-vivo microscopical studies indicate that brain cerebrospinal fluid (CSF) transport driven by blood vessel pulsations is reduced in the early stages of Alzheimer's disease (AD). We hypothesized that the coupling pattern between cerebrovascular pulsations and CSF is altered in AD, and this can be measured using multi-wavelength functional near-infrared spectroscopy (fNIRS). To study this, we quantified simultaneously cerebral hemo- and CSF hydrodynamics in early AD patients and age-matched healthy controls. Physiological pulsations were analysed in the vasomotor very low frequency (VLF 0.008-0.1 Hz), respiratory (Resp. 0.1-0.6 Hz), and cardiac (Card. 0.6-5 Hz) bands. A sliding time window cross-correlation approach was used to estimate the temporal stability of the cerebrovascular-CSF coupling. We investigated how the lag time series variation of the coupling differs between AD patients and control. The couplings involving deoxyhemoglobin (HbR) and CSF water, along with their first derivative, in the cardiac band demonstrated significant difference between AD patients and controls. Furthermore, the lag time series variation of HbR-CSF in the cardiac band provided a significant relationship, p-value = 0.04 and r 2  = 0.16, with the mini-mental state exam (MMSE) score. In conclusion, the coupling pattern between hemodynamics and CSF is reduced in AD and it correlates with MMSE score., (© 2023. The Author(s).)

Introduction: Sleep increases brain fluid transport and the power of pulsations driving the fluids. We investigated how sleep deprivation or electrophysiologically different stages of non-rapid-eye-movement (NREM) sleep affect the human brain pulsations., Methods: Fast functional magnetic resonance imaging (fMRI) was performed in healthy subjects ( n  = 23) with synchronous electroencephalography (EEG), that was used to verify arousal states (awake, N1 and N2 sleep). Cardiorespiratory rates were verified with physiological monitoring. Spectral power analysis assessed the strength, and spectral entropy assessed the stability of the pulsations., Results: In N1 sleep, the power of vasomotor (VLF < 0.1 Hz), but not cardiorespiratory pulsations, intensified after sleep deprived vs. non-sleep deprived subjects. The power of all three pulsations increased as a function of arousal state (N2 > N1 > awake) encompassing brain tissue in both sleep stages, but extra-axial CSF spaces only in N2 sleep. Spectral entropy of full band and respiratory pulsations decreased most in N2 sleep stage, while cardiac spectral entropy increased in ventricles., Discussion: In summary, the sleep deprivation and sleep depth, both increase the power and harmonize the spectral content of human brain pulsations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Helakari, Järvelä, Väyrynen, Tuunanen, Piispala, Kallio, Ebrahimi, Poltojainen, Kananen, Elabasy, Huotari, Raitamaa, Tuovinen, Korhonen, Nedergaard and Kiviniemi.)

Objective: Infra-slow fluctuations (ISF, 0.008-0.1 Hz) characterize hemodynamic and electric potential signals of human brain. ISFs correlate with the amplitude dynamics of fast (>1 Hz) neuronal oscillations, and may arise from permeability fluctuations of the blood-brain barrier (BBB). It is unclear if physiological rhythms like respiration drive or track fast cortical oscillations, and the role of sleep in this coupling is unknown., Methods: We used 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., Results: The phases of ISFs and respiration were both coupled with the amplitude of fast neuronal oscillations, with stronger ISF coupling being evident during sleep. Phases of ISF and respiration drove the amplitude dynamics of fast oscillations in sleeping and waking states, with different contributions., Conclusions: ISFs in slow cortical potentials and respiration together significantly determine the dynamics of fast cortical oscillations., Significance: We propose that these slow physiological phases play a significant role in coordinating cortical excitability, which is a fundamental aspect of brain function., Competing Interests: Conflict of interest statement The authors declare no conflicting interest., (Copyright © 2023 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Respiratory brain pulsations pertaining to intra-axial hydrodynamic solute transport are markedly altered in focal epilepsy. We used optical flow analysis of ultra-fast functional magnetic resonance imaging (fMRI) data to investigate the velocity characteristics of respiratory brain impulse propagation in patients with focal epilepsy treated with antiseizure medication (ASM) (medicated patients with focal epilepsy; ME, n = 23), drug-naïve patients with at least one seizure (DN, n = 19) and matched healthy control subjects (HC, n = 75). We detected in the two patient groups (ME and DN) several significant alterations in the respiratory brain pulsation propagation velocity, which showed a bidirectional change dominated by a reduction in speed. Furthermore, the respiratory impulses moved more in reversed or incoherent directions in both patient groups vs. the HC group. The speed reductions and directionality changes occurred in specific phases of the respiratory cycle. In conclusion, irrespective of medication status, both patient groups showed incoherent and slower respiratory brain impulses, which may contribute to epileptic brain pathology by hindering brain hydrodynamics., (© 2023. The Author(s).)

Respiratory brain pulsations have recently been shown to drive electrophysiological brain activity in patients with epilepsy. Furthermore, functional neuroimaging indicates that respiratory brain pulsations have increased variability and amplitude in patients with epilepsy compared to healthy individuals. To determine whether the respiratory drive is altered in epilepsy, we compared respiratory brain pulsation synchronicity between healthy controls and patients. Whole brain fast functional magnetic resonance imaging was performed on 40 medicated patients with focal epilepsy, 20 drug-naïve patients and 102 healthy controls. Cerebrospinal fluid associated respiratory pulsations were used to generate individual whole brain respiratory synchronization maps, which were compared between groups. Finally, we analyzed the seizure frequency effect and diagnostic accuracy of the respiratory synchronization defect in epilepsy. Respiratory brain pulsations related to the verified fourth ventricle pulsations were significantly more synchronous in patients in frontal, periventricular and mid-temporal regions, while the seizure frequency correlated positively with synchronicity. The respiratory brain synchronicity had a good diagnostic accuracy (ROC AUC  = 0.75) in discriminating controls from medicated patients. The elevated respiratory brain synchronicity in focal epilepsy suggests altered physiological effect of cerebrospinal fluid pulsations possibly linked to regional brain water dynamics involved with interictal brain physiology.

Background: Narcolepsy is a chronic neurological disease characterized by daytime sleep attacks, cataplexy, and fragmented sleep. The disease is hypothesized to arise from destruction or dysfunction of hypothalamic hypocretin-producing cells that innervate wake-promoting systems including the ascending arousal network (AAN), which regulates arousal via release of neurotransmitters like noradrenalin. Brain pulsations are thought to drive intracranial cerebrospinal fluid flow linked to brain metabolite transfer that sustains homeostasis. This flow increases in sleep and is suppressed by noradrenalin in the awake state. Here we tested the hypothesis that narcolepsy is associated with altered brain pulsations, and if these pulsations can differentiate narcolepsy type 1 from healthy controls., Methods: In this case-control study, 23 patients with narcolepsy type 1 (NT1) were imaged with ultrafast fMRI (MREG) along with 23 age- and sex-matched healthy controls (HC). The physiological brain pulsations were quantified as the frequency-wise signal variance. Clinical relevance of the pulsations was investigated with correlation and receiving operating characteristic analysis., Results: We find that variance and fractional variance in the very low frequency (MREG vlf ) band are greater in NT1 compared to HC, while cardiac (MREG card ) and respiratory band variances are lower. Interestingly, these pulsations differences are prominent in the AAN region. We further find that fractional variance in MREG vlf shows promise as an effective bi-classification metric (AUC = 81.4%/78.5%), and that disease severity measured with narcolepsy severity score correlates with MREG card variance (R = -0.48, p = 0.0249)., Conclusions: We suggest that our novel results reflect impaired CSF dynamics that may be linked to altered glymphatic circulation in narcolepsy type 1., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s) 2022.)

Primary central nervous system lymphoma (PCNSL) is an aggressive brain disease where lymphocytes invade along perivascular spaces of arteries and veins. The invasion markedly changes (peri)vascular structures but its effect on physiological brain pulsations has not been previously studied. Using physiological magnetic resonance encephalography (MREG BOLD ) scanning, this study aims to quantify the extent to which (peri)vascular PCNSL involvement alters the stability of physiological brain pulsations mediated by cerebral vasculature. Clinical implications and relevance were explored. In this study, 21 PCNSL patients (median 67y; 38% females) and 30 healthy age-matched controls (median 63y; 73% females) were scanned for MREG BOLD signal during 2018-2021. Motion effects were removed. Voxel-by-voxel Coefficient of Variation (CV) maps of MREG BOLD signal was calculated to examine the stability of physiological brain pulsations. Group-level differences in CV were examined using nonparametric covariate-adjusted tests. Subject-level CV alterations were examined against control population Z-score maps wherein clusters of increased CV values were detected. Spatial distributions of clusters and findings from routine clinical neuroimaging were compared [contrast-enhanced, diffusion-weighted, fluid-attenuated inversion recovery (FLAIR) data]. Whole-brain mean CV was linked to short-term mortality with 100% sensitivity and 100% specificity, as all deceased patients revealed higher values (n = 5, median 0.055) than surviving patients (n = 16, median 0.028) (p < .0001). After adjusting for medication, head motion, and age, patients revealed higher CV values (group median 0.035) than healthy controls (group median 0.024) around arterial territories (p ≤ .001). Abnormal clusters (median 1.10 × 10 5 mm 3 ) extended spatially beyond FLAIR lesions (median 0.62 × 10 5 mm 3 ) with differences in volumes (p = .0055)., (© 2022 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

We review theoretical and numerical models of the glymphatic system, which circulates cerebrospinal fluid and interstitial fluid around the brain, facilitating solute transport. Models enable hypothesis development and predictions of transport, with clinical applications including drug delivery, stroke, cardiac arrest, and neurodegenerative disorders like Alzheimer's disease. We sort existing models into broad categories by anatomical function: Perivascular flow, transport in brain parenchyma, interfaces to perivascular spaces, efflux routes, and links to neuronal activity. Needs and opportunities for future work are highlighted wherever possible; new models, expanded models, and novel experiments to inform models could all have tremendous value for advancing the field., Competing Interests: We declare no conflicts of interest., (© 2022 The Author(s).)

The physiological underpinnings of the necessity of sleep remain uncertain. Recent evidence suggests that sleep increases the convection of cerebrospinal fluid (CSF) and promotes the export of interstitial solutes, thus providing a framework to explain why all vertebrate species require sleep. Cardiovascular, respiratory and vasomotor brain pulsations have each been shown to drive CSF flow along perivascular spaces, yet it is unknown how such pulsations may change during sleep in humans. To investigate these pulsation phenomena in relation to sleep, we simultaneously recorded fast fMRI, magnetic resonance encephalography (MREG), and electroencephalography (EEG) signals in a group of healthy volunteers. We quantified sleep-related changes in the signal frequency distributions by spectral entropy analysis and calculated the strength of the physiological (vasomotor, respiratory, and cardiac) brain pulsations by power sum analysis in 15 subjects (age 26.5 ± 4.2 years, 6 females). Finally, we identified spatial similarities between EEG slow oscillation (0.2-2 Hz) power and MREG pulsations. Compared with wakefulness, nonrapid eye movement (NREM) sleep was characterized by reduced spectral entropy and increased brain pulsation intensity. These effects were most pronounced in posterior brain areas for very low-frequency (≤0.1 Hz) vasomotor pulsations but were also evident brain-wide for respiratory pulsations, and to a lesser extent for cardiac brain pulsations. There was increased EEG slow oscillation power in brain regions spatially overlapping with those showing sleep-related MREG pulsation changes. We suggest that reduced spectral entropy and enhanced pulsation intensity are characteristic of NREM sleep. With our findings of increased power of slow oscillation, the present results support the proposition that sleep promotes fluid transport in human brain. SIGNIFICANCE STATEMENT We report that the spectral power of physiological brain pulsation mechanisms driven by vasomotor, respiration, and cardiac rhythms in human brain increase during sleep, extending previous observations of their association with glymphatic brain clearance during sleep in rodents. The magnitudes of increased pulsations follow the rank order of vasomotor greater than respiratory greater than cardiac pulsations, with correspondingly declining spatial extents. Spectral entropy, previously known as vigilance and as an anesthesia metric, decreased during NREM sleep compared with the awake state in very low and respiratory frequencies, indicating reduced signal complexity. An EEG slow oscillation power increase occurring in the early sleep phase (NREM 1-2) spatially overlapped with pulsation changes, indicating reciprocal mechanisms between those measures., (Copyright © 2022 Helakari et al.)

The physiological pulsations that drive tissue fluid homeostasis are not well characterized during brain activation. Therefore, we used fast magnetic resonance encephalography (MREG) fMRI to measure full band (0-5 Hz) blood oxygen level-dependent (BOLD FB ) signals during a dynamic visual task in 23 subjects. This revealed brain activity in the very low frequency (BOLD VLF ) as well as in cardiac and respiratory bands. The cardiovascular hemodynamic envelope (CHe) signal correlated significantly with the visual BOLD VLF response, considered as an independent signal source in the V1-V2 visual cortices. The CHe preceded the canonical BOLD VLF response by an average of 1.3 (± 2.2) s. Physiologically, the observed CHe signal could mark increased regional cardiovascular pulsatility following vasodilation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Huotari, Tuunanen, Raitamaa, Raatikainen, Kananen, Helakari, Tuovinen, Järvelä, Kiviniemi and Korhonen.)

Physiological pulsations have been shown to affect the global blood oxygen level dependent (BOLD) signal in human brain. While these pulsations have previously been regarded as noise, recent studies show their potential as biomarkers of brain pathology. We used the extended 5 Hz spectral range of magnetic resonance encephalography (MREG) data to investigate spatial and frequency distributions of physiological BOLD signal sources. Amplitude spectra of the global image signals revealed cardiorespiratory envelope modulation (CREM) peaks, in addition to the previously known very low frequency (VLF) and cardiorespiratory pulsations. We then proceeded to extend the amplitude of low frequency fluctuations (ALFF) method to each of these pulsations. The respiratory pulsations were spatially dominating over most brain structures. The VLF pulsations overcame the respiratory pulsations in frontal and parietal gray matter, whereas cardiac and CREM pulsations had this effect in central cerebrospinal fluid (CSF) spaces and major blood vessels. A quasi-periodic pattern (QPP) analysis showed that the CREM pulsations propagated as waves, with a spatiotemporal pattern differing from that of respiratory pulsations, indicating them to be distinct intracranial physiological phenomenon. In conclusion, the respiration has a dominant effect on the global BOLD signal and directly modulates cardiovascular brain pulsations., (© 2021 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)