Coupling Of Cerebral Blood Flow Research Articles

Neurovascular Correlates of Cobalamin, Folate, and Homocysteine in Dementia.

Cobalamin (Cbl) and folate are common supplements clinicians prescribe as an adjuvant therapy for dementia patients, on the presumption of their neurotrophic and/or homocysteine (Hcy) lowering effect. However, the treatment efficacy has been found mixed and the effects of Cbl/folate/Hcy on the human brain remain to be elucidated. To explore the neurovascular correlates of Cbl/folate/Hcy in Alzheimer's disease (AD) and subcortical ischemic vascular dementia (SIVD). Sixty-seven AD patients and 57 SIVD patients were prospectively and consecutively recruited from an outpatient clinic. Multimodal 3-Tesla magnetic resonance imaging was performed to quantitatively evaluate cerebral blood flow (CBF) and white matter integrity. The relationship between neuroimaging metrics and the serum levels of Cbl/folate/Hcy was examined by using the Kruskal-Wallis test, partial correlation analysis, and moderation analysis, at a significance level of 0.05. As a whole, CBF mainly associated with Cbl/folate while white matter hyperintensities exclusively associated with Hcy. As compared with AD, SIVD exhibited more noticeable CBF correlates (spatially widespread with Cbl and focal with folate). In SIVD, a bilateral Cbl-moderated CBF coupling was found between medial prefrontal cortex and ipsilateral basal ganglia, while in the fronto-subcortical white matter tracts, elevated Hcy was associated with imaging metrics indicative of increased injury in both axon and myelin sheath. We identified the neurovascular correlates of previously reported neurotrophic effect of Cbl/folate and neurotoxic effect of Hcy in dementia. The correlates exhibited distinct patterns in AD and SIVD. The findings may help improving the formulation of supplemental Cbl/folate treatment for dementia.

Dysfunctional Coupling of Cerebral Blood Flow and Susceptibility Value in the Bilateral Hippocampus is Associated with Cognitive Decline in Nondialysis Patients with CKD.

Patients with end stage CKD often develop cognitive decline, but whether this is related to the underlying disease or to hemodialysis remains unclear. We performed three-dimensional pseudocontinuous arterial spin labeling and quantitative susceptibility mapping prospectively in 40 patients with stage 1-4 CKD, 47 nondialysis patients with stage 5 CKD, and 44 healthy controls. Our magnetic resonance imaging data demonstrate that changes in cerebral blood flow-susceptibility coupling might underlie this cognitive decline, perhaps in the hippocampus and thalamus. These results suggest that magnetic resonance imaging parameters are potential biomarkers of cognitive decline in patients with CKD. Moreover, our findings may lead to discovery of novel therapeutic targets to prevent cognitive decline in patients with CKD. Cerebral blood flow (CBF) and susceptibility values reflect vascular and iron metabolism, providing mechanistic insights into conditions of health and disease. Nondialysis patients with CKD show a cognitive decline, but the pathophysiological mechanisms underlying this remain unclear. Three-dimensional pseudocontinuous arterial spin labeling and quantitative susceptibility mapping were prospectively performed in 40 patients with stage 1-4 CKD (CKD 1-4), 47 nondialysis patients with stage 5 CKD (CKD 5ND), and 44 healthy controls (HCs). Voxel-based global and regional analyses of CBF, susceptibility values, and vascular-susceptibility coupling were performed. Furthermore, the association between clinical performance and cerebral perfusion and iron deposition was analyzed. For CBF, patients with CKD 5ND had higher normalized CBF in the hippocampus and thalamus than HCs. Patients with CKD 5ND had higher normalized CBF in the hippocampus and thalamus than those with CKD 1-4. The susceptibility values in the hippocampus and thalamus were lower in patients with CKD 5ND than in HCs. Patients with CKD 5ND had higher susceptibility value in the caudate nucleus than those with CKD 1-4. More importantly, patients with CKD 5ND had lower CBF-susceptibility coupling than HCs. In addition, CBF and susceptibility values were significantly associated with clinical performance. Our findings demonstrate a new neuropathological mechanism in patients with CKD, which leads to regional changes in CBF-susceptibility coupling. These changes are related to cognitive decline, providing potential imaging markers for assessing clinical disability and cognitive decline in these patients.

Reversal of neurovascular decoupling and cognitive impairment in patients with end-stage renal disease during a hemodialysis session: Evidence from a comprehensive fMRI analysis.

Neurovascular (NV) decoupling is a potential neuropathologic mechanism of cognitive impairment in patients with end-stage renal disease (ESRD). Hemodialysis improves cognitive impairment at 24 h post-dialysis, which suggests a potential neuroprotective effect of hemodialysis treatment on the brain. We investigated the effects of hemodialysis treatment on the reversal of NV decoupling associated with cognitive improvement. A total of 39 patients with ESRD and 39 healthy controls were enrolled. All patients were imaged twice during a dialysis session: before hemodialysis (T1pre-dialysis ) and at 24 h after dialysis (T2post-dialysis ). The healthy controls were imaged once. NV coupling was characterized based on correlation coefficients between four types of blood oxygen level-dependent signals and cerebral blood flow (CBF). A battery of neuropsychological and blood tests was performed before the imaging. Patients with ESRD showed improvements in memory and executive function at T2post-dialysis compared with that at T1pre-dialysis . At both T1pre-dialysis and T2post-dialysis , patients with ESRD had lower amplitude of low-frequency fluctuation (ALFF)-CBF coupling than healthy controls. Additionally, patients with ESRD had higher ALFF-CBF coupling at T2post-dialysis than at T1pre-dialysis . Higher memory scores, higher hemoglobin level, lower total plasma homocysteine level, lower systolic blood pressure variance, and lower ultrafiltration volume were associated with higher ALFF-CBF coupling in patients with ESRD after a hemodialysis session. These findings indicate that partial correction of anemia and hyperhomocysteinemia, stable systolic blood pressure, and fluid restriction may be closely linked to the reversal of NV decoupling and improvement in cognition in patients with ESRD.

The Relationship Between Resting Cerebral Blood Flow, Neurometabolites, Cardio-Respiratory Fitness and Aging-Related Cognitive Decline.

Older adults typically experience a decline in cognitive function, but improvements in physical health and lifestyle can be neuroprotective across the human lifespan. The primary objective of this study is to advance our basic understanding of how cardiorespiratory fitness and neurophysiological attributes relate to cognitive decline. While cerebral blood flow (CBF) is critical for the supply of nutrients to the tissue, the brain’s major neurotransmitters (i.e., gamma-aminobutyric acid, GABA, and glutamate-glutamine complex, Glx) are closely linked to oxidative metabolism. Within the context of flow-metabolism coupling, the critical question is how these neurophysiological parameters interplay, resulting in cognitive decline. Further, how cardiorespiratory fitness may impact aging neurophysiology and cognition is not well understood. To address these questions, we recruited 10 younger and 12 older cognitively intact participants to collect GABA and Glx using magnetic resonance spectroscopy (MRS), CBF using pseudo-continuous arterial spin labeling Magnetic Resonance Imaging (MRI), VO2max as a measure of cardiorespiratory fitness using the YMCA submax test, and cognitive and motor-cognitive measures using a battery of behavioral assessments. We observed expected differences in GABA+, Glx, and CBF between younger and older participants in pre-SMA, a frontal domain-general region. When GABA+ and Glx were related to CBF via multiple linear regression, Glx was identified as the main contributor to the model. For higher-order executive function (i.e., inhibition versus color naming), GABA*Glx*CBF interaction was critical in younger, while only Glx was involved in older participants. For unimanual motor dexterity, GABA*Glx interaction was the common denominator across both groups, but younger participants’ brain also engages CBF. In terms of selective motor inhibition, CBF from younger participants was the only major neurophysiological factor. In terms of fitness, cardiorespiratory fitness was significantly related to GABA, Glx, and motor performance when combining cohorts, but no group-specific relationships were observed. Taken together, our results indicate that Glx and CBF coupling decreases with aging, perhaps due to altered glial oxidative metabolism. Our data suggest that GABA, Glx, and CBF are engaged and weighted differently for different cognitive measures sensitized to aging, and higher fitness allows for a more efficient metabolic shift that facilitates improved performance on cognitive-motor tasks.

Developmental Coupling of Cerebral Blood Flow and fMRI Fluctuations in Youth

To support brain development during youth, the brain must balance energy delivery and consumption. Previous studies in adults have demonstrated high coupling between cerebral blood flow and brain function as measured using functional neuroimaging, but how this relationship evolves over adolescence is unknown.

Altered Coupling of Cerebral Blood Flow and Functional Connectivity Strength in First-Episode Schizophrenia Patients With Auditory Verbal Hallucinations.

ObjectiveAuditory verbal hallucinations (AVHs) are a major symptom of schizophrenia and are connected with impairments in auditory and speech-related networks. In schizophrenia with AVHs, alterations in resting-state cerebral blood flow (CBF) and functional connectivity have been described. However, the neurovascular coupling alterations specific to first-episode drug-naïve schizophrenia (FES) patients with AVHs remain unknown.MethodsResting-state functional MRI and arterial spin labeling (ASL) was performed on 46 first-episode drug-naïve schizophrenia (FES) patients with AVHs (AVH), 39 FES drug-naïve schizophrenia patients without AVHs (NAVH), and 48 healthy controls (HC). Then we compared the correlation between the CBF and functional connection strength (FCS) of the entire gray matter between the three groups, as well as the CBF/FCS ratio of each voxel. Correlation analyses were performed on significant results between schizophrenia patients and clinical measures scale.ResultsThe CBF/FCS ratio was reduced in the cognitive and emotional brain regions in both the AVH and NAVH groups, primarily in the crus I/II, vermis VI/VII, and cerebellum VI. In the AVH group compared with the HC group, the CBF/FCS ratio was higher in auditory perception and language-processing areas, primarily the left superior and middle temporal gyrus (STG/MTG). The CBF/FCS ratio in the left STG and left MTG positively correlates with the score of the Auditory Hallucination Rating Scale in AVH patients.ConclusionThese findings point to the difference in neurovascular coupling failure between AVH and NAVH patients. The dysfunction of the forward model based on the predictive and computing role of the cerebellum may increase the excitability in the auditory cortex, which may help to understand the neuropathological mechanism of AVHs.

Developmental coupling of cerebral blood flow and fMRI fluctuations in youth.

SUMMARYThe functions of the human brain are metabolically expensive and reliant on coupling between cerebral blood flow (CBF) and neural activity, yet how this coupling evolves over development remains unexplored. Here, we examine the relationship between CBF, measured by arterial spin labeling, and the amplitude of low-frequency fluctuations (ALFF) from resting-state magnetic resonance imaging across a sample of 831 children (478 females, aged 8–22 years) from the Philadelphia Neurodevelopmental Cohort. We first use locally weighted regressions on the cortical surface to quantify CBF-ALFF coupling. We relate coupling to age, sex, and executive functioning with generalized additive models and assess network enrichment via spin testing. We demonstrate regionally specific changes in coupling over age and show that variations in coupling are related to biological sex and executive function. Our results highlight the importance of CBF-ALFF coupling throughout development; we discuss its potential as a future target for the study of neuropsychiatric diseases.

Cerebrovascular Diseases and Autonomic Failure

Cerebral vessels are innervated by sympathetic and parasympathetic nerves, as well as the trigeminal nerve. Under physiological conditions, neural regulation contributes to coupling of cerebral blood flow (CBF) and metabolism and autoregulation of CBF against systemic blood pressure. It also plays a key role in vasodilatation distal to narrowed vascular lesions associated with atherosclerosis, hyperperfusion syndrome that occurs after vascular reconstruction in patients with chronic ischemic diseases, reversible cerebral vasoconstriction syndrome, and migraine. Moreover, cerebrovascular disease can cause autonomic dysfunction; frontal lobe and brain stem lesions are known to result in urinary incontinence, mydriasis, and Horner's syndrome.

Acute cerebral blood flow response to lipid ingestion in older adults: A pilot study

AbstractBackgroundHigh fat feeding (HFF) is a risk factor for Alzheimer’s disease (AD), and acute meal studies including lipid tolerance tests can be used to understand mechanisms by which diet affects disease processes. This study seeks to describe cerebral blood flow (CBF) response using arterial spin labeling (ASL) MRI, given the tight coupling of CBF to brain metabolism.MethodAfter fasting, 16 older adults (age 66.3±2.9) underwent baseline and 1, 2, 3‐hour ASL MRI after ingestion of 1/2 cup heavy cream with comparable total and saturated fat to a high fat breakfast. We used pCASL MRI with background suppression to measure CBF in ml/100g/min. Imaging parameters were in accordance with the recommendations of ISMRM: label duration = 1.8 s, post‐labeling delay = 2 s, labeling offset = 25‐30 mm, slices = 20, resolution = 3.5×3.5×5 mm3, SENSE‐factor = 2, TR/TE= 5000/18 ms. Finally, we acquired a reference scan (M0, 1 minute) identical to the above scan but with TR = 10,000 ms and no labeling or background suppression. Statistical analyses included paired t tests and ANOVA for group comparisons.ResultGlobal CBF decreased at 1, 2, and 3 hours post‐lipid drink, compared to time 0 (1h:‐2.12±4.1, 2h:‐1.9±3.2, 3h:‐2.9±3.1); only 2 and 3 hours were statistically lower. No group differences by sex or APOE status were noted in baseline or change CBF for this small pilot sample.ConclusionGlobal CBF decreased after lipid ingestion, similar to what has been reported with glucose and fructose ingestion. Sustained decreases in CBF were still detectable at 3 hours. Future studies include investigation of pre‐post CBF in various regions known to be affected by AD.

Developmental Coupling of Cerebral Blood Flow and fMRI Fluctuations in Youth

To support brain development during youth, the brain must balance energy delivery and consumption. Previous studies in adults have demonstrated high coupling between cerebral blood flow and brain function as measured using functional neuroimaging, but how this relationship evolves over adolescence is unknown. To address this gap, we studied a sample of 831 children and adolescents (478 females, ages 8-22) from the Philadelphia Neurodevelopmental Cohort who were scanned at 3T with both arterial spin-labeled (ASL) MRI and resting-state functional MRI (fMRI). Local coupling between cerebral blood flow (CBF, from ASL) and the amplitude of low frequency fluctuations (ALFF, from fMRI) was first quantified using locally weighted regressions on the cortical surface. We then used generalized additive models to evaluate how CBF-ALFF coupling was associated with age, sex, and executive function. Enrichment of effects within canonical functional networks was evaluated using spin-based permutation tests. Our analyses revealed tight CBF-ALFF coupling across the brain. Whole-brain CBF-ALFF coupling decreased with age, largely driven by coupling decreases in the inferior frontal cortex, precuneus, visual cortex, and temporoparietal cortex (pfdr<0.05). Furthermore, we found that females had stronger coupling in the frontoparietal network than males (pfdr<0.05) and that better executive function was associated with decreased coupling in the somatomotor network (pfdr<0.05). These results emphasize that CBF-ALFF coupling undergoes development in youth and is linked to individual differences in cognition. As such, this relationship may be a valuable marker of both normal brain development and abnormalities associated with neuropsychiatric illness in youth.

Altered coupling of cerebral blood flow and functional connectivity strength in visual and higher order cognitive cortices in primary open angle glaucoma

Primary open-angle glaucoma (POAG) has been suggested to be a neurodegenerative disease associated with altered cerebral vascular hemodynamics and widespread disruption of neuronal activity within the visual, working memory, attention and executive networks. We hypothesized that disturbed neurovascular coupling in visual and higher order cognitive cortices exists in POAG patients and correlates with glaucoma stage and visual field defects. Through multimodal magnetic resonance imaging, we evaluated the cerebral blood flow (CBF)-functional connectivity strength (FCS) correlations of the whole gray matter and CBF/FCS ratio per voxel for all subjects. Compared with normal controls, POAG patients showed reduced global CBF-FCS coupling and altered CBF/FCS ratios, predominantly in regions in the visual cortex, salience network, default mode network, and dorsal attentional network. The CBF/FCS ratio was negatively correlated with glaucoma stage, and positively correlated with visual field defects in the lingual gyrus in POAG patients. Moreover, early brain changes were detected in early POAG. These findings indicate neurovascular coupling dysfunction might exist in the visual and higher order cognitive cortices in POAG patients and its clinical relevance. The results may contribute to the monitoring of POAG progression and provide insight into the pathophysiology of the neurodegenerative process in POAG.

Coupling of cerebral blood flow and functional connectivity is decreased in healthy aging.

Aging leads to cerebral perfusion and functional connectivity changes that have been assessed using various neuroimaging techniques. In addition, a link between these two parameters has been demonstrated in healthy young adults. In this work, we employed arterial spin labeling (ASL) fMRI to measure global and voxel-wise differences in cerebral blood flow (CBF) and intrinsic connectivity contrast (ICC) in the resting state in a group of cognitively normal elderly subjects and a group of cognitively normal young subjects, in order to assess the effects of aging on CBF-ICC coupling, which had not been previously evaluated. Our results showed age-related global and regional CBF decreases in prefrontal mesial areas, lateral frontal regions, insular cortex, lateral parietal areas, precuneus and occipital regions. Subcortically, perfusion was reduced in the medial thalamus and caudate nucleus. ICC was also found reduced with age in prefrontal cortical areas and insular cortex, affecting key nodes of the default mode and salience networks. Areas of ICC and CBF decrease partially overlapped, however, the CBF reduction was more extensive and encompassed more areas. This dissociation was accompanied by a decrease in CBF-ICC coupling. These results suggest that aging leads to a disruption in the relationship between CBF and intrinsic functional connectivity that could be due to neurovascular dysregulation.

Aberrant Coupling Between Resting-State Cerebral Blood Flow and Functional Connectivity in Wilson's Disease.

Both abnormalities of resting-state cerebral blood flow (CBF) and functional connectivity in Wilson’s disease (WD) have been identified by several studies. Whether the coupling of CBF and functional connectivity is imbalanced in WD remains largely unknown. To assess this possibility, 27 patients with WD and 27 sex- and age-matched healthy controls were recruited to acquire functional MRI and arterial spin labeling imaging data. Functional connectivity strength (FCS) and CBF were calculated based on standard gray mask. Compared to healthy controls, the CBF–FCS correlations of patients with WD were significantly decreased in the basal ganglia and the cerebellum and slightly increased in the prefrontal cortex and thalamus. In contrast, decreased CBF of patients with WD occurred predominately in subcortical and cognitive- and emotion-related brain regions, including the basal ganglia, thalamus, insular, and inferior prefrontal cortex, whereas increased CBF occurred primarily in the temporal cortex. The FCS decrease in WD patients was predominately in the basal ganglia and thalamus, and the increase was primarily in the prefrontal cortex. These findings suggest that aberrant neurovascular coupling in the brain may be a possible neuropathological mechanism underlying WD.

Oxygen therapy improves cerebral oxygen delivery and neurovascular function in hypoxaemic chronic obstructive pulmonary disease patients.

What is the central question of this study? How does oxygen therapy influence cerebral blood flow, cerebral oxygen delivery and neurovascular function in chronic obstructive pulmonary disease patients? What is the main finding and its importance? Oxygen therapy improves cerebral oxygen delivery and neurovascular function in chronic obstructive pulmonary disease patients. This improvement in cerebral oxygen delivery and neurovascular function might provide a physiological link between oxygen therapy and a reduced risk of cerebrovascular disease (e.g. stroke, mild cognitive impairment and dementia) in chronic obstructive pulmonary disease. We investigated the role of hypoxaemia in cerebral blood flow (CBF), oxygen delivery (CDO2 ) and neurovascular coupling (coupling of CBF to neural activity; NVC) in hypoxaemic chronic obstructive pulmonary disease (COPD) patients (n=14). Resting CBF (duplex ultrasound), peripheral oxyhaemoglobin saturation (SpO2; pulse-oximetry) and NVC (transcranial Doppler) were assessed before and after a 20min wash-in of supplemental oxygen (∼3lmin-1 ). The peripheral oxyhaemoglobin saturation increased from 91.0±3.3 to 97.4±3.0% (P<0.01), whereas CBF was unaltered (593.0±162.8 versus 590.1±138.5mlmin-1 ; P=0.91) with supplemental O2 . In contrast, both CDO2 (98.1±25.7versus 108.7±28.4mldl-1 ; P=0.02) and NVC were improved. Specifically, the posterior cerebral artery cerebrovascular conductance was increased to a greater extent after O2 normalization (+40%, from 20.4±9.9 to 28.0±10.4% increase in conductance; P=0.04), whereas the posterior cerebral artery cerebrovascular resistance decreased to a greater extent during O2 normalization (+22%, from -16.7±7.3 to -21.4±6.6% decrease in resistance; P=0.04). The cerebral vasculature of COPD patients appears insensitive to oxygen, because CBF was unaltered in response to O2 supplementation leading to improved CDO2 . In patients, the improvements in CDO2 and neurovascular function with supplemental O2 may underlie the cognitive benefits associated with O2 therapy.

Transcranial Doppler combined with quantitative EEG brain function monitoring and outcome prediction in patients with severe acute intracerebral hemorrhage

BackgroundNeurological deterioration after intracerebral hemorrhage (ICH) is thought to be closely related to increased intracranial pressure (ICP), decreased cerebral blood flow (CBF), and brain metabolism. Transcranial Doppler (TCD) is increasingly used as an indirect measure of ICP, and quantitative EEG (QEEG) can reflect the coupling of CBF and metabolism. We aimed to combine TCD and QEEG to comprehensively assess brain function after ICH and provide prognostic diagnosis.MethodsWe prospectively enrolled patients with severe acute supratentorial (SAS)-ICH from June 2015 to December 2016. Mortality was assessed at 90-day follow-up. We collected demographic data, serological data, and clinical factors, and performed neurophysiological tests at study entry. Quantitative brain function monitoring was performed using a TCD-QEEG recording system at the patient’s bedside (NSD-8100; Delica, China). Univariate and multivariable analyses and receiver operating characteristic (ROC) curves were employed to assess the relationships between variables and outcome.ResultsForty-seven patients (67.3 ± 12.6 years; 23 men) were studied. Mortality at 90 days was 55.3%. Statistical results showed there were no significant differences in brain symmetry index between survivors and nonsurvivors, nor between patients and controls (all p > 0.05). Only TCD indicators of the pulsatility index from unaffected hemispheres (UPI) (OR 2.373, CI 1.299–4.335, p = 0.005) and QEEG indicators of the delta/alpha ratio (DAR) (OR 5.306, CI 1.533–18.360, p = 0.008) were independent predictors for clinical outcome. The area under the ROC curve after the combination of UPI and DAR was 0.949, which showed better predictive accuracy compared to individual variables.ConclusionsIn patients with SAS-ICH, multimodal neuromonitoring with TCD combined with QEEG indicated that brain damage caused diffuse changes, and the predictive accuracy after combined use of TCD-QEEG was statistically superior in performance to any single variable, whether clinical or neurophysiological.

Simultaneous Voltammetric Measurements of Glucose and Dopamine Demonstrate the Coupling of Glucose Availability with Increased Metabolic Demand in the Rat Striatum.

Cerebral blood flow ensures delivery of nutrients, such as glucose, to brain sites with increased metabolic demand. However, little is known about rapid glucose dynamics at discrete locations during neuronal activation in vivo. Acute exposure to many substances of abuse elicits dopamine release and neuronal activation in the striatum; however, the concomitant changes in striatal glucose remain largely unknown. Recent developments have combined fast-scan cyclic voltammetry with glucose oxidase enzyme modified carbon-fiber microelectrodes to enable the measurement of glucose dynamics with subsecond temporal resolution in the mammalian brain. This work evaluates several waveforms to enable the first simultaneous detection of endogenous glucose and dopamine at single recording sites. These molecules, one electroactive and one nonelectroactive, were found to fluctuate in the dorsal striatum in response to electrical stimulation of the midbrain and systemic infusion of cocaine/raclopride. The data reveal the second-by-second dynamics of these species in a striatal microenvironment, and directly demonstrate the coupling of glucose availability with increased metabolic demand. This work provides a foundation that will enable detailed investigation of local mechanisms that regulate the coupling of cerebral blood flow with metabolic demand under normal conditions, and in animal studies of drug abuse and addiction.

The pitfalls of bedside regional cerebral oxygen saturation in the early stage of post cardiac arrest.

It remains uncertain whether neuromonitoring reliably predicts outcome in adult post-cardiac arrest patients in the early stage treated with therapeutic hypothermia. Recent reports demonstrated a regional cerebral oxygen saturation of cardiac arrest patients on hospital arrival could predict their neurological outcome. There has been little discussion about the significance of regional cerebral oxygen saturation in patients with post-cardiac arrest syndrome. Amplitude-integrated electroencephalography monitoring may also provide early prognostic information for post-cardiac arrest syndrome. However, even when the initial electroencephalography is flat after the return of spontaneous circulation, good neurological outcome may still be obtainable if the electroencephalography shifts to a continuous pattern. The electroencephalography varied from flat to various patterns, such as flat, epileptic, or continuous during the first 24 h, while regional cerebral oxygen saturation levels varied even when the electroencephalography was flat. It is therefore difficult to estimate whether regional cerebral oxygen saturation accurately indicates the coupling of cerebral blood flow and metabolism in the early stage after cardiac arrest. Careful assessment of prognosis is necessary when relying solely on regional cerebral oxygen saturation as a single monitoring modality.

Coupling of cerebral blood flow and oxygen consumption during hypothermia in newborn piglets as measured by time-resolved near-infrared spectroscopy: a pilot study.

Hypothermia (HT) is a potent neuroprotective therapy that is now widely used in following neurological emergencies, such as neonatal asphyxia. An important mechanism of HT-induced neuroprotection is attributed to the associated reduction in the cerebral metabolic rate of oxygen ([Formula: see text]). Since cerebral circulation and metabolism are tightly regulated, reduction in [Formula: see text] typically results in decreased cerebral blood flow (CBF); it is only under oxidative stress, e.g., hypoxia-ischemia, that oxygen extraction fraction (OEF) deviates from its basal value, which can lead to cerebral dysfunction. As such, it is critical to measure these key physiological parameters during therapeutic HT. This report investigates a noninvasive method of measuring the coupling of [Formula: see text] and CBF under HT and different anesthetic combinations of propofol/nitrous-oxide ([Formula: see text]) that may be used in clinical practice. Both CBF and [Formula: see text] decreased with decreasing temperature, but the OEF remained unchanged, which indicates a tight coupling of flow and metabolism under different anesthetics and over the mild HT temperature range (38°C to 33°C).

The cerebral blood flow response dependency on stimulus pulse width is affected by stimulus current amplitude - a study of activation flow coupling.

The coupling of cerebral blood flow (CBF) to neuronal activation, referred to as activation flow coupling (AFC), has been a fundamental brain physiology property. The stimulus-evoked CBF response was usually considered as a surrogate marker for neuronal activity in AFC studies. The selection of appropriate stimulation parameters, e.g., current amplitude and pulse width, is of great importance yet the effect of pulse width changes remained contradictory in previous studies. In this work, we use laser speckle contrast imaging (LSCI) to study the spatiotemporal CBF response to hindpaw somatosensory stimulation of different pulse widths (0.3 ms vs 1 ms) and current amplitudes (3 mA vs 6 mA) in a rodent experiment. The results showed that the change of pulse width significantly affected the CBF peak value at a lower current level (p<;0.05). In addition, the duration for observing significantly different average CBF response, denoted as td, at various pulse widths, was dependent on stimulus current amplitude. At a lower amplitude (3 mA), td was 6.5 s; While at a higher amplitude (6 mA), td was 2.5 s. It was indicated that the changes of pulse width had longer influence on the average CBF response at a lower current amplitude. Our findings may help to understand and explain the inconsistent AFC with different stimulation parameters in fundamental brain physiology.

Neurovascular coupling during cortical spreading depolarization and -depression.

Cortical spreading depolarizations (CSDs) are self-propagating waves of transient loss of neuronal transmembrane ion gradients, followed by prolonged suppression of neuronal activity (spreading depression). CSDs emerge spontaneously in animal models of traumatic brain injury,1 subarachnoid hemorrhage,2 and in focal ischemia3 where they are associated with infarct growth.4 In humans, CSDs have been demonstrated in traumatic brain injury,5 subarachnoid hemorrhage,6,7 and malignant hemispheric stroke,8 and they are believed to be the brain mechanism underlying migraine aura.9 CSDs are associated with dramatic changes in cerebral blood flow (CBF). During the depolarization phase of CSDs induced in healthy and well-perfused brain tissue in animal models, an early hyperemic response is observed, typically followed by prolonged oligemia after the neuronal repolarization. Despite the initial CBF increase, tissue hypoxia may develop in more distant territories of capillary supply.10,11 Similar CBF changes have been observed in patients with migraine aura.12–14 In the injured brain, CSDs can be accompanied by severe initial CBF reduction instead of a CBF increase during the depolarization phase, termed spreading ischemia.15 When this inverse hemodynamic response is observed, the energy-dependent recovery from CSD is delayed in a characteristic fashion, indicating a severe mismatch between oxygen supply and demand2 and a high risk of tissue damage.16 In rat and cat models of focal ischemia, CSD-related CBF transients range from monophasic, positive CBF responses in peri-ischemic tissue, over biphasic transients in mildly ischemic tissue, to negative CBF transients in more severe ischemia.17–19 During CSD in animal models, capillary flow patterns become severely disturbed.10,20,21 The passage of a CSD causes erythrocytes in some capillaries to reduce their speed, whereas other capillaries reveal 4-fold increases in flow or higher. …