Network analysis identifies consensus physiological measures of neurovascular coupling in humans.
Ontology highlight
ABSTRACT:
SUBMITTER: Squair JW
PROVIDER: S-EPMC7026847 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Significance: Functional brain imaging in awake animal models is a popular and powerful technique that allows the investigation of neurovascular coupling (NVC) under physiological conditions. However, ubiquitous facial and body motions (fidgeting) are prime drivers of spontaneous fluctuations in neural and hemodynamic signals. During periods without movement, animals can rapidly transition into sleep, and the hemodynamic signals tied to arousal state changes can be several times larger than sensory-evoked responses. Given the outsized influence of facial and body motions and arousal signals in neural and hemodynamic signals, it is imperative to detect and monitor these events in experiments with un-anesthetized animals. Aim: To cover the importance of monitoring behavioral state in imaging experiments using un-anesthetized rodents, and describe how to incorporate detailed behavioral and physiological measurements in imaging experiments. Approach: We review the effects of movements and sleep-related signals (heart rate, respiration rate, electromyography, intracranial pressure, whisking, and other body movements) on brain hemodynamics and electrophysiological signals, with a focus on head-fixed experimental setup. We summarize the measurement methods currently used in animal models for detection of those behaviors and arousal changes. We then provide a guide on how to incorporate this measurements with functional brain imaging and electrophysiology measurements. Results: We provide a how-to guide on monitoring and interpreting a variety of physiological signals and their applications to NVC experiments in awake behaving mice. Conclusion: This guide facilitates the application of neuroimaging in awake animal models and provides neuroscientists with a standard approach for monitoring behavior and other associated physiological parameters in head-fixed animals.
| S-EPMC8802326 | biostudies-literature
Project description:Local changes in cerebral blood flow are thought to match changes in neuronal activity, a phenomenon termed neurovascular coupling. Hypoxia increases global resting cerebral blood flow, but regional cerebral blood flow (rCBF) changes are non-uniform. Hypoxia decreases baseline rCBF to the default mode network (DMN), which could reflect either decreased neuronal activity or altered neurovascular coupling. To distinguish between these hypotheses, we characterized the effects of hypoxia on baseline rCBF, task performance, and the hemodynamic (BOLD) response to task activity. During hypoxia, baseline CBF increased across most of the brain, but decreased in DMN regions. Performance on memory recall and motion detection tasks was not diminished, suggesting task-relevant neuronal activity was unaffected. Hypoxia reversed both positive and negative task-evoked BOLD responses in the DMN, suggesting hypoxia reverses neurovascular coupling in the DMN of healthy adults. The reversal of the BOLD response was specific to the DMN. Hypoxia produced modest increases in activations in the visual attention network (VAN) during the motion detection task, and had no effect on activations in the visual cortex during visual stimulation. This regional specificity may be particularly pertinent to clinical populations characterized by hypoxemia and may enhance understanding of regional specificity in neurodegenerative disease pathology.
| S-EPMC7983511 | biostudies-literature
Project description:Neurovascular coupling is typically considered as a master-slave relationship between the neurons and the cerebral vessels: the neurons demand energy which the vessels supply in the form of glucose and oxygen. In the recent past, both theoretical and experimental studies have suggested that the neurovascular coupling is a bidirectional system, a loop that includes a feedback signal from the vessels influencing neural firing and plasticity. An integrated model of bidirectionally connected neural network and the vascular network is hence required to understand the relationship between the informational and metabolic aspects of neural dynamics. In this study, we present a computational model of the bidirectional neurovascular system in the whisker barrel cortex and study the effect of such coupling on neural activity and plasticity as manifest in the whisker barrel map formation. In this model, a biologically plausible self-organizing network model of rate coded, dynamic neurons is nourished by a network of vessels modeled using the biophysical properties of blood vessels. The neural layer which is designed to simulate the whisker barrel cortex of rat transmits vasodilatory signals to the vessels. The feedback from the vessels is in the form of available oxygen for oxidative metabolism whose end result is the adenosine triphosphate (ATP) necessary to fuel neural firing. The model captures the effect of the feedback from the vascular network on the neuronal map formation in the whisker barrel model under normal and pathological (Hypoxia and Hypoxia-Ischemia) conditions.
| S-EPMC8241226 | biostudies-literature
Project description:A numerical model of neurovascular coupling (NVC) is presented based on neuronal activity coupled to vasodilation/contraction models via the astrocytic mediated perivascular K(+) and the smooth muscle cell (SMC) Ca(2+) pathway termed a neurovascular unit (NVU). Luminal agonists acting on P2Y receptors on the endothelial cell (EC) surface provide a flux of inositol trisphosphate (IP3) into the endothelial cytosol. This concentration of IP3 is transported via gap junctions between EC and SMC providing a source of sarcoplasmic derived Ca(2+) in the SMC. The model is able to relate a neuronal input signal to the corresponding vessel reaction (contraction or dilation). A tissue slice consisting of blocks, each of which contain an NVU is connected to a space filling H-tree, simulating a perfusing arterial tree (vasculature) The model couples the NVUs to the vascular tree via a stretch mediated Ca(2+) channel on both the EC and SMC. The SMC is induced to oscillate by increasing an agonist flux in the EC and hence increased IP3 induced Ca(2+) from the SMC stores with the resulting calcium-induced calcium release (CICR) oscillation inhibiting NVC thereby relating blood flow to vessel contraction and dilation following neuronal activation. The coupling between the vasculature and the set of NVUs is relatively weak for the case with agonist induced where only the Ca(2+) in cells inside the activated area becomes oscillatory however, the radii of vessels both inside and outside the activated area oscillate (albeit small for those outside). In addition the oscillation profile differs between coupled and decoupled states with the time required to refill the cytosol with decreasing Ca(2+) and increasing frequency with coupling. The solution algorithm is shown to have excellent weak and strong scaling. Results have been generated for tissue slices containing up to 4096 blocks.
| S-EPMC4569750 | biostudies-literature
Project description:Birth asphyxia constitutes a major global public health burden for millions of infants, despite hypothermia therapy. There is a critical need for real time surrogate markers of therapeutic success, to aid in patient selection and/or modification of interventions in neonatal encephalopathy (NE). This is a proof of concept study aiming to quantify neurovascular coupling (NVC) using wavelet analysis of the dynamic coherence between amplitude-integrated electroencephalography (aEEG) and near-infrared spectroscopy in NE. NVC coupling is assessed by a wavelet metric estimation of percent time of coherence between NIRS SctO2 and aEEG for 78 hours after birth. An abnormal outcome was predefined by a Bayley III score <85 by 18-24 m. We observed high coherence, intact NVC, between the oscillations of SctO2 and aEEG in the frequency range of 0.00025-0.001 Hz in the non-encephalopathic newborns. NVC coherence was significantly decreased in encephalopathic newborns who were cooled vs. non-encephalopathic controls (median IQR 3[2-9] vs.36 [33-39]; p < 0.01), and was significantly lower in those with abnormal 24 months outcomes relative to those with normal outcomes (median IQR 2[1-3] vs 28[19-26], p = 0.04). Wavelet coherence analysis of neurovascular coupling in NE may identify infants at risk for abnormal outcomes.
| S-EPMC5385531 | biostudies-literature
Project description:The coupling of cerebral blood flow (CBF) to neuronal activity is well preserved during evolution. Upon changes in the neuronal activity, an incompletely understood coupling mechanism regulates diameter changes of supplying blood vessels, which adjust CBF within seconds. The physiologic brain tissue oxygen content would sustain unimpeded brain function for only 1 second if continuous oxygen supply would suddenly stop. This suggests that the CBF response has evolved to balance oxygen supply and demand. Surprisingly, CBF increases surpass the accompanying increases of cerebral metabolic rate of oxygen (CMRO2). However, a disproportionate CBF increase may be required to increase the concentration gradient from capillary to tissue that drives oxygen delivery. However, the brain tissue oxygen content is not zero, and tissue pO2 decreases could serve to increase oxygen delivery without a CBF increase. Experimental evidence suggests that CMRO2 can increase with constant CBF within limits and decreases of baseline CBF were observed with constant CMRO2. This conflicting evidence may be viewed as an oxygen paradox of neurovascular coupling. As a possible solution for this paradox, we hypothesize that the CBF response has evolved to safeguard brain function in situations of moderate pathophysiological interference with oxygen supply.
| S-EPMC3887356 | biostudies-other
Project description:BackgroundAltered cerebral blood flow (CBF) and amplitude of low-frequency fluctuation (ALFF) have been reported in hemodialysis patients. However, neurovascular coupling impairments, which provide a novel insight into the human brain, have not been reported in hemodialysis patients.MethodsWe combined arterial spin labeling (ASL) and blood oxygen level dependent (BOLD) techniques to investigate neurovascular coupling alterations and its relationships with demographic and clinical data in 46 hemodialysis patients and 47 healthy controls. To explore regional neuronal activity, ALFF was obtained from resting-state functional MRI. To measure cerebral vascular response, CBF was calculated from ASL. The across-voxel CBF-ALFF correlations for global neurovascular coupling and CBF/ALFF ratio for regional neurovascular coupling were compared between hemodialysis patients and healthy controls. Two-sample t-tests were used to compare the intergroup differences in CBF and ALFF. Multiple comparisons were corrected using a voxel-wise false discovery rate (FDR) method (P < 0.05).ResultsAll hemodialysis patients and healthy controls showed significant across-voxel correlations between CBF and ALFF. Hemodialysis patients showed a significantly reduced global CBF-ALFF coupling (P = 0.0011) compared to healthy controls at the voxel-level. Of note, decreased CBF/ALFF ratio was exclusively located in the bilateral amygdala involved in emotional regulation and cognitive processing in hemodialysis patients. In hemodialysis patients, the decreased CBF (right olfactory cortex, anterior cingulate gyrus and bilateral insula) and ALFF (bilateral precuneus and superior frontal gyrus) were mainly located in the default mode network and salience network-related regions as well as increased CBF in the bilateral thalamus.ConclusionsThese novel findings reveal that disrupted neurovascular coupling may be a potential neural mechanism in hemodialysis patients.
| S-EPMC7166048 | biostudies-literature
Project description:Mice with insulin receptor (IR)-deficient astrocytes (GFAP-IR knockout [KO] mice) show blunted responses to insulin and reduced brain glucose uptake, whereas IR-deficient astrocytes show disturbed mitochondrial responses to glucose. While exploring the functional impact of disturbed mitochondrial function in astrocytes, we observed that GFAP-IR KO mice show uncoupling of brain blood flow with glucose uptake. Since IR-deficient astrocytes show higher levels of reactive oxidant species (ROS), this leads to stimulation of hypoxia-inducible factor-1α and, consequently, of the vascular endothelial growth factor angiogenic pathway. Indeed, GFAP-IR KO mice show disturbed brain vascularity and blood flow that is normalized by treatment with the antioxidant N-acetylcysteine (NAC). NAC ameliorated high ROS levels, normalized angiogenic signaling and mitochondrial function in IR-deficient astrocytes, and normalized neurovascular coupling in GFAP-IR KO mice. Our results indicate that by modulating glucose uptake and angiogenesis, insulin receptors in astrocytes participate in neurovascular coupling.
| S-EPMC9304019 | biostudies-literature
Project description:We describe methodology for joint reconstruction of physiological-survival networks from observational data capable of identifying key survival-associated variables, inferring a minimal physiological network structure, and bridging this network to the Gompertzian survival layer. Using synthetic network structures, we show that the method is capable of identifying aging variables in cohorts as small as 5,000 participants. Applying the methodology to the observational human cohort, we find that interleukin-6, vascular calcification, and red-blood distribution width are strong predictors of baseline fitness. More important, we find that red blood cell counts, kidney function, and phosphate level are directly linked to the Gompertzian aging rate. Our model therefore enables discovery of processes directly linked to the aging rate of our species. We further show that this epidemiological framework can be applied as a causal inference engine to simulate the effects of interventions on physiology and longevity.
| S-EPMC9795372 | biostudies-literature
Project description:Idiopathic pulmonary fibrosis (IPF) is a severe fibrotic lung disease characterized by irreversible scarring of the lung parenchyma leading to dyspnea, progressive decline in lung function, and respiratory failure. We analyzed lung transcriptomic data from independent IPF cohorts using weighted gene co-expression network analysis (WGCNA) to identify gene modules based on their preservation status in these cohorts. The consensus gene modules were characterized by leveraging existing clinical and molecular data such as lung function, biological processes, pathways, and lung cell types. From a total of 32 consensus gene modules identified, two modules were found to be significantly correlated with the disease, lung function, and preserved in other IPF datasets. The upregulated gene module was enriched for extracellular matrix, collagen metabolic process, and BMP signaling while the downregulated module consisted of genes associated with tube morphogenesis, blood vessel development, and cell migration. Using a combination of connectivity-based and trait-based significance measures, we identified and prioritized 103 "hub" genes (including 25 secretory candidate biomarkers) by their similarity to known IPF genetic markers. Our validation studies demonstrate the dysregulated expression of CRABP2, a retinol-binding protein, in multiple lung cells of IPF, and its correlation with the decline in lung function.
| S-EPMC9141193 | biostudies-literature