The relative brain signal variability increases in the behavioral variant of frontotemporal dementia and Alzheimer's disease but not in schizophrenia.

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 (CVBOLD) 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 CVBOLD 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 CVBOLD in the frontopolar cortices for the latter (p < 0.05). Furthermore, CVBOLD 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 CVBOLD 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 CVBOLD holds promise as a biomarker for bvFTD, offering potential for monitoring disease progression and differentiating bvFTD from AD and SZ.

Effect of sleep deprivation and NREM sleep stage on physiological brain pulsations.

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.

eHealth competence building for future doctors and nurses - Attitudes and capabilities.

BACKGROUND: Digitalisation is rapidly changing health care processes and the health care sector, thus increasing the need to improve the digital competence of future health care professionals. PURPOSE: The aim of this study was to describe the attitudes of medical and nursing students towards digital health based on self-evaluation as well as to compare the differences in perceptions between the two student groups. METHODS: A cross-sectional study was conducted as an online survey using the Webropol in April 2021 at the University of Oulu and Oulu University of Applied Sciences in Finland. The survey questionnaire consisted of seven background questions and 16 statements on a five-point Likert scale (fully disagree to fully agree) to survey student attitudes towards eHealth, and their digital capabilities. RESULTS: A total of 250 medical and nursing students were invited to participate in the study and 170 of them took the survey (response rate 68 %). Of those answered, 38 % (n = 64) were nursing and 32 % (n = 106) medical students. Students generally had a positive attitude towards eHealth and health care digitalisation. The differences in perceptions and preparedness between medical and nursing students were surprisingly small in the two student groups. There was a statistically significant difference between the two groups in three out of 16 statements: these were related to changes in the roles of health care professionals and patients as well as the students' knowledge of information contained in the national patient portal. CONCLUSIONS: The results of this study provide a good starting point for further harmonisation of the curriculum for both health professional groups regarding the teaching of eHealth and telemedicine.

National Development and Regional Differences in eHealth Maturity in Finnish Public Health Care: Survey Study.

BACKGROUND: eHealth increasingly affects the delivery of health care around the world and the quest for more efficient health systems. In Finland, the development of eHealth maturity has been systematically studied since 2003, through surveys conducted every 3 years. It has also been monitored in several international studies. The indicators used in these studies examined the availability of the electronic patient record, picture archiving and communication system, health information exchange, and other key eHealth functionalities. OBJECTIVE: The first aim is to study the national development in the maturity level of eHealth in primary health care and specialized care between 2011 and 2020 in Finland. The second aim is to clarify the regional differences in the maturity level of eHealth among Finnish hospital districts in 2020. METHODS: Data for this study were collected in 2011, 2014, 2017, and 2020, using web-based questionnaires from the Use of information and communication technology surveys in Finnish health care project. In total, 16 indicators were selected to describe the status of eHealth, and they were based on international eHealth studies and Finnish eHealth surveys in 3 areas: applications, regional integration, and data security and information and communications technology skills. The indicators remain the same in all the study years; therefore, the results are comparable. RESULTS: All the specialized care organizations (21/21, 100%) in 2011, 2014, 2017, and 2020 participated in the study. The response rate among primary health care organizations was 86.3% (139/161) in 2011, 88.2% (135/153) in 2014, 85.8% (121/141) in 2017, and 95.6% (130/136) in 2020. At the national level, the biggest developments in eHealth maturity occurred between 2011 and 2014. The development has since continued, and some indicators have been saturated. Primary health care lags behind specialized care organizations, as measured by all the indicators and throughout the period under review. Regionally, there are differences among different types of organizations. CONCLUSIONS: eHealth maturity has steadily progressed in Finland nationally, and its implementation has also been promoted through various national strategies and legislative changes. Some eHealth indicators have already been saturated and achieved an intensity of use rate of 100%. However, the scope for development remains, especially in primary health care. As Finland has long been a pioneer in the digitalization of health care, the results of this study show that the functionalities of eHealth will be adopted in stages, and deployment will take time; therefore, national eHealth strategies and legislative changes need to be implemented in a timely manner. The comprehensive sample size used in this study allows a regional comparison in the country, compared with previous country-specific international studies.

Physiological instability is linked to mortality in primary central nervous system lymphoma: A case-control fMRI study.

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 (MREGBOLD ) 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 MREGBOLD signal during 2018-2021. Motion effects were removed. Voxel-by-voxel Coefficient of Variation (CV) maps of MREGBOLD 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 × 105 mm3 ) extended spatially beyond FLAIR lesions (median 0.62 × 105 mm3 ) with differences in volumes (p = .0055).

Increased interictal synchronicity of respiratory related brain pulsations in epilepsy.

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 (ROCAUC = 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.

Cardiovascular Pulsatility Increases in Visual Cortex Before Blood Oxygen Level Dependent Response During Stimulus.

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 (BOLDFB) signals during a dynamic visual task in 23 subjects. This revealed brain activity in the very low frequency (BOLDVLF) as well as in cardiac and respiratory bands. The cardiovascular hemodynamic envelope (CHe) signal correlated significantly with the visual BOLDVLF response, considered as an independent signal source in the V1-V2 visual cortices. The CHe preceded the canonical BOLDVLF response by an average of 1.3 (± 2.2) s. Physiologically, the observed CHe signal could mark increased regional cardiovascular pulsatility following vasodilation.

Human NREM Sleep Promotes Brain-Wide Vasomotor and Respiratory Pulsations.

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.

Cardiovascular brain impulses in Alzheimer's disease.

Accumulation of amyloid-ß is a key neuropathological feature in brain of Alzheimer's disease patients. Alterations in cerebral haemodynamics, such as arterial impulse propagation driving the (peri)vascular CSF flux, predict future Alzheimer's disease progression. We now present a non-invasive method to quantify the three-dimensional propagation of cardiovascular impulses in human brain using ultrafast 10 Hz magnetic resonance encephalography. This technique revealed spatio-temporal abnormalities in impulse propagation in Alzheimer's disease. The arrival latency and propagation speed both differed in patients with Alzheimer's disease. Our mapping of arterial territories revealed Alzheimer's disease-specific modifications, including reversed impulse propagation around the hippocampi and in parietal cortical areas. The findings imply that pervasive abnormality in (peri)vascular CSF impulse propagation compromises vascular impulse propagation and subsequently glymphatic brain clearance of amyloid-ß in Alzheimer's disease.

The variability of functional MRI brain signal increases in Alzheimer's disease at cardiorespiratory frequencies.

Biomarkers sensitive to prodromal or early pathophysiological changes in Alzheimer's disease (AD) symptoms could improve disease detection and enable timely interventions. Changes in brain hemodynamics may be associated with the main clinical AD symptoms. To test this possibility, we measured the variability of blood oxygen level-dependent (BOLD) signal in individuals from three independent datasets (totaling 80 AD patients and 90 controls). We detected a replicable increase in brain BOLD signal variability in the AD populations, which constituted a robust biomarker for clearly differentiating AD cases from controls. Fast BOLD scans showed that the elevated BOLD signal variability in AD arises mainly from cardiovascular brain pulsations. Manifesting in abnormal cerebral perfusion and cerebrospinal fluid convection, present observation presents a mechanism explaining earlier observations of impaired glymphatic clearance associated with AD in humans.

Respiratory-related brain pulsations are increased in epilepsy-a two-centre functional MRI study.

Resting-state functional MRI has shown potential for detecting changes in cerebral blood oxygen level-dependent signal in patients with epilepsy, even in the absence of epileptiform activity. Furthermore, it has been suggested that coefficient of variation mapping of fast functional MRI signal may provide a powerful tool for the identification of intrinsic brain pulsations in neurological diseases such as dementia, stroke and epilepsy. In this study, we used fast functional MRI sequence (magnetic resonance encephalography) to acquire ten whole-brain images per second. We used the functional MRI data to compare physiological brain pulsations between healthy controls (n = 102) and patients with epilepsy (n = 33) and furthermore to drug-naive seizure patients (n = 9). Analyses were performed by calculating coefficient of variation and spectral power in full band and filtered sub-bands. Brain pulsations in the respiratory-related frequency sub-band (0.11-0.51 Hz) were significantly (P < 0.05) increased in patients with epilepsy, with an increase in both signal variance and power. At the individual level, over 80% of medicated and drug-naive seizure patients exhibited areas of abnormal brain signal power that correlated well with the known clinical diagnosis, while none of the controls showed signs of abnormality with the same threshold. The differences were most apparent in the basal brain structures, respiratory centres of brain stem, midbrain and temporal lobes. Notably, full-band, very low frequency (0.01-0.1 Hz) and cardiovascular (0.8-1.76 Hz) brain pulses showed no differences between groups. This study extends and confirms our previous results of abnormal fast functional MRI signal variance in epilepsy patients. Only respiratory-related brain pulsations were clearly increased with no changes in either physiological cardiorespiratory rates or head motion between the subjects. The regional alterations in brain pulsations suggest that mechanisms driving the cerebrospinal fluid homeostasis may be altered in epilepsy. Magnetic resonance encephalography has both increased sensitivity and high specificity for detecting the increased brain pulsations, particularly in times when other tools for locating epileptogenic areas remain inconclusive.

The relationship of genetic susceptibilities for psychosis with physiological fluctuation in functional MRI data.

Previously, schizophrenia is found to be related to the variability of the functional magnetic resonance imaging (fMRI) signal in the white matter. However, evidence about the relationship between genetic vulnerabilities and physiological fluctuation in the brain is lacking. We investigated whether familial risk for psychosis (FR) and polygenic risk score for schizophrenia (PRS) are linked with physiological fluctuation in fMRI data. We used data from the Oulu Brain and Mind study (n = 140-149, aged 20-24 years) that is a substudy of the Northern Finland Birth Cohort 1986. The participants underwent a resting-state fMRI scan. Coefficient of variation (CV) of blood oxygen level dependent (BOLD) signal (CVBOLD) was used as a proxy of physiological fluctuation in the brain. Familial risk was defined to be present if at least one parent had been diagnosed with psychosis previously. PRS was computed based on the results of the prior GWAS by the Schizophrenia Working Group. FR or PRS were not associated with CVBOLD in cerebrospinal fluid, white matter, or grey matter. The findings did not provide evidence for the previous suggestions that genetic vulnerabilities for schizophrenia become apparent in alterations of the variation of the BOLD signal in the brain.

Symptomatic psychosis risk and physiological fluctuation in functional MRI data.

BACKGROUND: Physiological brain pulsations have been shown to play a critical role in maintaining interstitial homeostasis in the glymphatic brain clearance mechanism. We investigated whether psychotic symptomatology is related to the physiological variation of the human brain using fMRI. METHODS: The participants (N = 277) were from the Northern Finland Birth Cohort 1986. Psychotic symptoms were evaluated with the Positive Symptoms Scale of the Structured Interview for Prodromal Syndromes (SIPS). We used the coefficient of variation of BOLD signal (CVBOLD) as a proxy for physiological brain pulsatility. The CVBOLD-analyses were controlled for motion, age, sex, and educational level. The results were also compared with fMRI and voxel-based morphometry (VBM) meta-analyses of schizophrenia patients (data from the Brainmap database). RESULTS: At the global level, participants with psychotic-like symptoms had higher CVBOLD in cerebrospinal fluid (CSF) and white matter (WM), when compared to participants with no psychotic symptoms. Voxel-wise analyses revealed that CVBOLD was increased, especially in periventricular white matter, basal ganglia, cerebellum and parts of the cortical structures. Those brain regions, which included alterations of physiological fluctuation in symptomatic psychosis risk, overlapped <6% with the regions that were found to be affected in the meta-analyses of previous fMRI and VBM studies in schizophrenia patients. Motion did not vary as a function of SIPS. CONCLUSIONS: Psychotic-like symptoms were associated with elevated CVBOLD in a variety of brain regions. The CVBOLD findings may produce new information about cerebral physiological fluctuations that have been out of reach in previous fMRI and VBM studies.

Sampling Rate Effects on Resting State fMRI Metrics.

Low image sampling rates used in resting state functional magnetic resonance imaging (rs-fMRI) may cause aliasing of the cardiorespiratory pulsations over the very low frequency (VLF) BOLD signal fluctuations which reflects to functional connectivity (FC). In this study, we examine the effect of sampling rate on currently used rs-fMRI FC metrics. Ultra-fast fMRI magnetic resonance encephalography (MREG) data, sampled with TR 0.1 s, was downsampled to different subsampled repetition times (sTR, range 0.3-3 s) for comparisons. Echo planar k-space sampling (TR 2.15 s) and interleaved slice collection schemes were also compared against the 3D single shot trajectory at 2.2 s sTR. The quantified connectivity metrics included stationary spatial, time, and frequency domains, as well as dynamic analyses. Time domain methods included analyses of seed-based functional connectivity, regional homogeneity (ReHo), coefficient of variation, and spatial domain group level probabilistic independent component analysis (ICA). In frequency domain analyses, we examined fractional and amplitude of low frequency fluctuations. Aliasing effects were spatially and spectrally analyzed by comparing VLF (0.01-0.1 Hz), respiratory (0.12-0.35 Hz) and cardiac power (0.9-1.3 Hz) FFT maps at different sTRs. Quasi-periodic pattern (QPP) of VLF events were analyzed for effects on dynamic FC methods. The results in conventional time and spatial domain analyses remained virtually unchanged by the different sampling rates. In frequency domain, the aliasing occurred mainly in higher sTR (1-2 s) where cardiac power aliases over respiratory power. The VLF power maps suffered minimally from increasing sTRs. Interleaved data reconstruction induced lower ReHo compared to 3D sampling (p < 0.001). Gradient recalled echo-planar imaging (EPI BOLD) data produced both better and worse metrics. In QPP analyses, the repeatability of the VLF pulse detection becomes linearly reduced with increasing sTR. In conclusion, the conventional resting state metrics (e.g., FC, ICA) were not markedly affected by different TRs (0.1-3 s). However, cardiorespiratory signals showed strongest aliasing in central brain regions in sTR 1-2 s. Pulsatile QPP and other dynamic analyses benefit linearly from short TR scanning.

3D Multi-Resolution Optical Flow Analysis of Cardiovascular Pulse Propagation in Human Brain.

The brain is cleaned from waste by glymphatic clearance serving a similar purpose as the lymphatic system in the rest of the body. Impairment of the glymphatic brain clearance precedes protein accumulation and reduced cognitive function in Alzheimer's disease (AD). Cardiovascular pulsations are a primary driving force of the glymphatic brain clearance. We developed a method to quantify cardiovascular pulse propagation in the human brain with magnetic resonance encephalography (MREG). We extended a standard optical flow estimation method to three spatial dimensions, with a multi-resolution processing scheme. We added application-specific criteria for discarding inaccurate results. With the proposed method, it is now possible to estimate the propagation of cardiovascular pulse wavefronts from the whole brain MREG data sampled at 10 Hz. The results show that on average the cardiovascular pulse propagates from major arteries via cerebral spinal fluid spaces into all tissue compartments in the brain. We present an example, that cardiovascular pulsations are significantly altered in AD: coefficient of variation and sample entropy of the pulse propagation speed in the lateral ventricles change in AD. These changes are in line with the theory of glymphatic clearance impairment in AD. The proposed non-invasive method can assess a performance indicator related to the glymphatic clearance in the human brain.

Altered physiological brain variation in drug-resistant epilepsy.

INTRODUCTION: Functional magnetic resonance imaging (fMRI) combined with simultaneous electroencephalography (EEG-fMRI) has become a major tool in mapping epilepsy sources. In the absence of detectable epileptiform activity, the resting state fMRI may still detect changes in the blood oxygen level-dependent signal, suggesting intrinsic alterations in the underlying brain physiology. METHODS: In this study, we used coefficient of variation (CV) of critically sampled 10 Hz ultra-fast fMRI (magnetoencephalography, MREG) signal to compare physiological variance between healthy controls (n = 10) and patients (n = 10) with drug-resistant epilepsy (DRE). RESULTS: We showed highly significant voxel-level (p < 0.01, TFCE-corrected) increase in the physiological variance in DRE patients. At individual level, the elevations range over three standard deviations (σ) above the control mean (µ) CVMREG values solely in DRE patients, enabling patient-specific mapping of elevated physiological variance. The most apparent differences in group-level analysis are found on white matter, brainstem, and cerebellum. Respiratory (0.12-0.4 Hz) and very-low-frequency (VLF = 0.009-0.1 Hz) signal variances were most affected. CONCLUSIONS: The CVMREG increase was not explained by head motion or physiological cardiorespiratory activity, that is, it seems to be linked to intrinsic physiological pulsations. We suggest that intrinsic brain pulsations play a role in DRE and that critically sampled fMRI may provide a powerful tool for their identification.

Real-time monitoring of human blood-brain barrier disruption.

Chemotherapy aided by opening of the blood-brain barrier with intra-arterial infusion of hyperosmolar mannitol improves the outcome in primary central nervous system lymphoma. Proper opening of the blood-brain barrier is crucial for the treatment, yet there are no means available for its real-time monitoring. The intact blood-brain barrier maintains a mV-level electrical potential difference between blood and brain tissue, giving rise to a measurable electrical signal at the scalp. Therefore, we used direct-current electroencephalography (DC-EEG) to characterize the spatiotemporal behavior of scalp-recorded slow electrical signals during blood-brain barrier opening. Nine anesthetized patients receiving chemotherapy were monitored continuously during 47 blood-brain barrier openings induced by carotid or vertebral artery mannitol infusion. Left or right carotid artery mannitol infusion generated a strongly lateralized DC-EEG response that began with a 2 min negative shift of up to 2000 µV followed by a positive shift lasting up to 20 min above the infused carotid artery territory, whereas contralateral responses were of opposite polarity. Vertebral artery mannitol infusion gave rise to a minimally lateralized and more uniformly distributed slow negative response with a posterior-frontal gradient. Simultaneously performed near-infrared spectroscopy detected a multiphasic response beginning with mannitol-bolus induced dilution of blood and ending in a prolonged increase in the oxy/deoxyhemoglobin ratio. The pronounced DC-EEG shifts are readily accounted for by opening and sealing of the blood-brain barrier. These data show that DC-EEG is a promising real-time monitoring tool for blood-brain barrier disruption augmented drug delivery.

Ultra-fast magnetic resonance encephalography of physiological brain activity - Glymphatic pulsation mechanisms?

The theory on the glymphatic convection mechanism of cerebrospinal fluid holds that cardiac pulsations in part pump cerebrospinal fluid from the peri-arterial spaces through the extracellular tissue into the peri-venous spaces facilitated by aquaporin water channels. Since cardiac pulses cannot be the sole mechanism of glymphatic propulsion, we searched for additional cerebrospinal fluid pulsations in the human brain with ultra-fast magnetic resonance encephalography. We detected three types of physiological mechanisms affecting cerebral cerebrospinal fluid pulsations: cardiac, respiratory, and very low frequency pulsations. The cardiac pulsations induce a negative magnetic resonance encephalography signal change in peri-arterial regions that extends centrifugally and covers the brain in ≈1 Hz cycles. The respiratory ≈0.3 Hz pulsations are centripetal periodical pulses that occur dominantly in peri-venous areas. The third type of pulsation was very low frequency (VLF 0.001-0.023 Hz) and low frequency (LF 0.023-0.73 Hz) waves that both propagate with unique spatiotemporal patterns. Our findings using critically sampled magnetic resonance encephalography open a new view into cerebral fluid dynamics. Since glymphatic system failure may precede protein accumulations in diseases such as Alzheimer's dementia, this methodological advance offers a novel approach to image brain fluid dynamics that potentially can enable early detection and intervention in neurodegenerative diseases.

The Effect of Gray Matter ICA and Coefficient of Variation Mapping of BOLD Data on the Detection of Functional Connectivity Changes in Alzheimer's Disease and bvFTD.

Resting-state fMRI results in neurodegenerative diseases have been somewhat conflicting. This may be due to complex partial volume effects of CSF in BOLD signal in patients with brain atrophy. To encounter this problem, we used a coefficient of variation (CV) map to highlight artifacts in the data, followed by analysis of gray matter voxels in order to minimize brain volume effects between groups. The effects of these measures were compared to whole brain ICA dual regression results in Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD). 23 AD patients, 21 bvFTD patients and 25 healthy controls were included. The quality of the data was controlled by CV mapping. For detecting functional connectivity (FC) differences whole brain ICA (wbICA) and also segmented gray matter ICA (gmICA) followed by dual regression were conducted, both of which were performed both before and after data quality control. Decreased FC was detected in posterior DMN in the AD group and in the Salience network in the bvFTD group after combining CV quality control with gmICA. Before CV quality control, the decreased connectivity finding was not detectable in gmICA in neither of the groups. Same finding recurred when exclusion was based on randomization. The subjects excluded due to artifacts noticed in the CV maps had significantly lower temporal signal-to-noise ratio than the included subjects. Data quality measure CV is an effective tool in detecting artifacts from resting state analysis. CV reflects temporal dispersion of the BOLD signal stability and may thus be most helpful for spatial ICA, which has a blind spot in spatially correlating widespread artifacts. CV mapping in conjunction with gmICA yields results suiting previous findings both in AD and bvFTD.

Mental health and well-being in a 6-year follow-up of patients with depression: assessments of patients and clinicians.

BACKGROUND: Psychiatric patients have the right to strive for well-being and not only be confined to symptom reduction. Studies are needed to assess global well-being during recovery from depression by comparing the assessments of patients and clinicians. METHOD: A 6-year natural follow-up of 185 depressive out-patients was carried out with health questionnaires at baseline, 0.5, 1, 2 and 6 years, including scales on depression (BDI, HDRS), general psychopathology (SCL), functional capacity (GAF, SOFAS) and life satisfaction (LS). A structured diagnostic interview was carried out at baseline, 2 and 6 years. Complete follow-up data were obtained from 121 patients. RESULTS: In general, depressive patients mainly attained a normal mood, adequate functional capacity and life satisfaction. Those with a slow recovery improved with successive treatment contacts, eventually reaching levels of mental health not significantly different from the others. Throughout the follow-up, recovery was similarly shown with the self-reported BDI-21, SCL-90 and LS-4, while intercorrelations between clinician ratings were low at baseline. CONCLUSIONS: Adequate mental health and global well-being can be reached among depressive patients, but it may take time in treatment. Subjective assessments are reliable. The 4-item life satisfaction scale is a global well-being indicator and a valid treatment outcome measure.