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.

Association of body-mass index with physiological brain pulsations across adulthood - a fast fMRI study.

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.

Synchronous functional magnetic resonance eye imaging, video ophthalmoscopy, and eye surface imaging reveal the human brain and eye pulsation mechanisms.

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.

Blood pressure lowering enhances cerebrospinal fluid efflux to the systemic circulation primarily via the lymphatic vasculature.

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 Ca2+-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.

Altered cerebrovascular-CSF coupling in Alzheimer's Disease measured by functional near-infrared spectroscopy.

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 r2 = 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.

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.