Cerebral Blood Velocity Research Articles

Dynamic cerebral carbon dioxide reactivity at rest and during exercise

The cerebral vasculature is highly sensitive to direct arterial carbon dioxide tension (PaCO2) changes. Hypocapnia causes cerebral vasoconstriction, while hypercapnia causes cerebral vasodilation to maintain the brain tissue PCO2 within narrow limits. The cerebral blood flow (CBF) responses to PaCO2 changes should be quick, but the cerebral vasculature sensitivity as cerebral CO2 is measured during steady‐state vascular responses. Therefore, the CBF time response to PaCO2 changes remains unknown. The purpose of this study was to examine dynamic cerebral CO2 reactivity at rest and during exercise using the frequency domain analysis.Seven healthy young subjects participated in the study. At rest and during exercise (30% VO2max and cycling exercise), the dynamic CO2 reactivity was calculated based on the transfer function analysis between the end‐tidal CO2 (PETCO2) and the middle cerebral artery mean blood velocity (MCAvm), using a binary white‐noise sequence (0%–7% inspired CO2 fraction). Dynamic characteristics of the respiratory controller showed a low‐pass filter characteristic for regulating ventilation, and the dynamic gain was decreased gradually to 0.7 at 0.02 Hz. However, the gain from PETCO2 to MCAvm (dynamic CO2 reactivity) remained reasonably constant up to 0.02 Hz. Moreover, it did not change during exercise.These findings suggest that the dynamic cerebral CO2 reactivity is reflected in slow to fast PaCO2 changes, and does not change during exercise. In terms of CO2 homeostasis, the cerebral CO2 reactivity may be a more important physiological mechanism to adapt to fast CO2 changes than the ventilatory response to PaCO2 changes.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Morning exercise mitigates the impact of prolonged sitting on cerebral blood flow in older adults.

Preventing declines in cerebral blood flow is important for maintaining optimal brain health with aging. We compared the effects of a morning bout of moderate-intensity exercise, with and without subsequent light-intensity walking breaks from sitting, on cerebral blood velocity over 8 h in older adults. In a randomized crossover trial, overweight/obese older adults ( n = 12, 70 ± 7 yr; 30.4 ± 4.3 kg/m2), completed three acute conditions (6-day washout); SIT: prolonged sitting (8 h, control); EX+SIT: sitting (1 h), moderate-intensity walking (30 min), followed by uninterrupted sitting (6.5 h); and EX + BR: sitting (1 h), moderate-intensity walking (30 min), followed by sitting (6.5 h) interrupted with 3 min of light-intensity walking every 30 min. Bilateral middle cerebral artery velocities (MCAv) were determined using transcranial Doppler at 13 time points across the day. The temporal pattern and average MCAv over 8 h was determined. The pattern of MCAv over 8 h was a negative linear trend in SIT ( P < 0.001), but a positive quadratic trend in EX + SIT ( P < 0.001) and EX + BR ( P < 0.01). Afternoon time points in SIT were lower than baseline within condition ( P ≤ 0.001 for all). A morning dip in MCAv was observed in EX + SIT and EX + BR ( P < 0.05 relative to baseline), but afternoon time points were not significantly lower than baseline. The average MCAv over 8 h was higher in EX + SIT than SIT ( P = 0.007) or EX + BR ( P = 0.024). Uninterrupted sitting should be avoided, and moderate-intensity exercise should be encouraged for the daily maintenance of cerebral blood flow in older adults. The clinical implications of maintaining adequate cerebral blood flow include the delivery of vital oxygen and nutrients to the brain. NEW & NOTEWORTHY This is the first study to measure the combined effects of an exercise bout with breaks in sitting on cerebral blood velocity in older adults. Using frequent recordings over an 8-h period, we have performed a novel analysis of the pattern of cerebral blood velocity, adjusting for concurrent measures of mean arterial pressure and other potential confounders in a linear mixed effects regression.

Dynamic Cerebral Autoregulation Is Maintained during High-Intensity Interval Exercise.

High-intensity interval exercise (HIIE) is more effective at increasing metabolic and cardiovascular health compared with moderate-intensity continuous exercise for patients with cardiovascular disease, but exhaustive high-intensity continuous exercise attenuates dynamic cerebral autoregulation (CA). This study assessed the effect of HIIE on dynamic CA. Nine healthy men (age, 24 ± 3 yr; mean ± SD) warmed up at 50%-60% maximal workload (Wmax) for 5 min before HIIE including four 4-min bouts of exercise at 80%-90% Wmax interspaced by four 3-min bouts at 50% to 60% Wmax. Transcranial Doppler determined middle cerebral artery mean blood velocity (MCA Vmean), and brachial artery catheterization determined mean arterial pressure (MAP). Dynamic CA was evaluated by transfer function analysis of changes in MAP and MCA Vmean. The HIIE increased MAP (from 92 ± 9 to 104 ± 10 mm Hg; P < 0.0125), whereas MCA Vmean did not change. Transfer function phase increased and coherence decreased during HIIE (P < 0.0125 vs rest, respectively), whereas gain was unchanged. The results suggest that dynamic CA is unaffected during HIIE, indicating that the brain is protected from fluctuations in MAP. Thus, we propose that HIIE may be beneficial for brain-related health as maintenance of cerebral perfusion in contrast to high-intensity continuous exercise.

Transfer Learning for a Multimodal Hybrid EEG-fTCD Brain–Computer Interface

Humans can transfer knowledge previously acquired from a specific task to new and unknown ones. Recently, transfer learning (TL) has been extensively used in brain–computer interface (BCI) research to reduce the training/calibration requirements. BCI systems have been designed to provide alternative communication or control access through computers to individuals with limited speech and physical abilities (LSPA). These systems generally require a calibration session in order to train the BCI before each usage. Such a calibration session may be burdensome for the individuals with LSPA. In this article, we introduce a multimodal hybrid BCI based on electroencephalography (EEG) and functional transcranial Doppler ultrasound (fTCD) and present a TL approach to reduce the calibration requirements. In the hybrid BCI, EEG, and fTCD are used simultaneously to measure the electrical brain activity and cerebral blood velocity, respectively, in response to motor imagery (MI) tasks. Using the data we collected from ten healthy individuals, we perform dimensionality reduction utilizing regularized discriminant analysis (RDA). Using the scores from RDA, we learn class conditional probabilistic distributions for each individual. We use these class conditional distributions to perform TL across different participants. More specifically, in order to reduce the calibration requirements for each individual, we choose the recorded data from other individuals to augment the training data for that specific individual. We choose the data for augmentation based on the probabilistic similarities between the class conditional distributions. For the final classification, we use the RDA scores after TL as features input to three different classifiers: quadratic discriminant analysis (QDA), linear discriminant analysis (LDA), and support vector machines (SVMs). Using our experimental data, we show that TL decreases the calibration requirements up to $87.5\%$ . Also by comparing SVM, LDA, and QDA, we observe that the SVM provides the best classification performance.

Dynamic cerebral autoregulation measurement using rapid changes in head positioning: experiences in acute ischemic stroke and healthy control populations.

The ideal technique for dynamic cerebral autoregulation (dCA) assessment in critically ill patients should provide considerable variability in blood pressure (BP) but without the need for patient cooperation. We proposed using rapid head positioning (RHP) over spontaneous BP fluctuations for dCA assessment in patients with acute ischemic stroke (AIS). Cerebral blood velocity (transcranial Doppler), beat-to-beat BP (Finometer), and end-tidal CO2 (capnography) were recorded during 5-min baseline and RHP in 16 controls (8 women and 8 men, mean age: 57 ± 16 yr) and 15 patients with AIS (7 women and 8 men, mean age: 69 ± 8 yr) at two (12 ± 8 days) and three visits (13.3 ± 6.9 h, 4.8 ± 3.2 days, and 93.9 ± 11.5 days from the symptom onset), respectively. All participants were able to complete the RHP protocol without difficulty. Compared with controls, patients with AIS were hypocapnic (all visits, P < 0.0024) and hypertensive ( visit 1, P = 0.011), although BP gradually reduced after the acute phase. RHP demonstrated greater beat-to-beat BP variability (BPV) in controls ( visits 1 and 2, P < 0.001) but not in patients with AIS at any visit. Compared with controls, a reduced autoregulation index (ARI) was demonstrated in patients with AIS, at visit 2 for the baseline recording but not at other visits or during RHP. The area under the receiver-operating curve was 0.53 and 0.54 for baseline and RHP, respectively. The RHP paradigm required minimal patient cooperation and could be considered a feasible alternative for assessing dCA, mainly in conditions leading to increased BPV. The lack of BPV increase in AIS with RHP deserves further investigation. NEW & NOTEWORTHY This study used rapid head positioning (RHP) to enhance blood pressure (BP) variability (BPV) to improve BP signal-to-noise ratio and reliability of dynamic cerebral autoregulation (dCA). RHP was well accepted by controls and acute ischemic stroke (AIS); the increased BPV induced in controls was not observed in AIS, suggesting BPV at rest was already elevated. RHP did not improve detection of impaired CA in AIS; further work is needed to understand the different responses observed.

Transcranial Doppler-based modeling of hemodynamics using delay differential equations

Approximately 40,000 people suffer brain aneurysm rupture and 2.5 million suffer a traumatic brain injury (TBI) each year in the USA. Cerebral vasospasm (CV) occurs as a complication of brain hemorrhage resulting from cerebral aneurysm rupture and TBI. CV causes further cerebral injury and is the primary cause of death and disability in aneurysmal hemorrhage and TBI. Consequently, it is critical to design a model for diagnosing and analyzing the abnormal cerebral blood flow velocity hemodynamics associated with CV. By generating such a model, it would be possible to design machine learning mechanisms for earlier prediction of CV. In previous studies, cerebrovascular models of blood flow behavior for different disorders were established. Unfortunately, those models are disorder specific and have too many parameters to tune. We have established a model for the signal envelope of the cerebral blood flow velocity that was produced by transcranial Doppler (TCD). We have applied it to simulate CV behavior, and it is general enough to be applied to other cerebrovascular disorders. The model is based on the delay differential equation as a representative modeling equation for three diagnostic categories: control (no CV or hyperemia), hyperemia, and CV. The model has only four tunable parameters and allows switching from one case to another by changing those parameters. After validation of the model, the generated envelope signals compared to spectrograms recorded by transcranial Doppler, demonstrated good concordance in all three categories between the model and signals acquired with TCD. This result could be used for modeling cerebral blood velocity abnormalities and lead to early detection of CV in TBI and aneurysmal hemorrhage.

Associations of transcranial doppler velocity, age, and gender with cognitive function in children with sickle cell anemia in Nigeria

ABSTRACTChildren with sickle cell anemia (SCA) have elevated cerebral blood velocity relative to healthy peers. The primary aim of this study was to evaluate the association between cerebral blood velocity, measured by transcranial Doppler (TCD) ultrasound, age, and gender with cognitive function in children with SCA in Nigeria. Eighty-three children (Mage = 9.10, SD = 1.90 years; 55% female) with SCA in Nigeria completed cognitive assessments and a TCD ultrasound. The association between TCD velocity and measures of perceptual reasoning (Raven’s Progressive Matrices), working memory (WISC-IV Digit Span), and executive planning (Tower of London, TOL) were assessed. Results showed that elevated TCD velocity significantly predicted lower scores on TOL Time Violations and Total Problem-Solving Time when controlling for BMI, hemoglobin level, and parent education, suggesting that TCD velocity is related to the efficiency of executive function. Further, age was negatively related to children’s performance on the Ravens Matrices and TOL Total Correct, and boys showed greater deficits on the TOL Total Correct relative to girls. Moderation analyses for gender showed that there was a conditional negative association between TCD velocity and Digit Span for boys, but not for girls. Findings suggest that children with SCA in Nigeria with elevated TCD velocity are at risk for deficits in efficiency of executive planning, and boys with elevated TCD velocity are particularly at increased risk for deficits in auditory working memory. Implications of this study are important for interventions to reduce cerebral blood velocity and the use of TCD in this population.

Towards optimal visual presentation design for hybrid EEG—fTCD brain–computer interfaces

Objective. In this paper, we introduce a novel hybrid brain–computer interface (BCI) system that measures electrical brain activity as well as cerebral blood velocity using electroencephalography (EEG) and functional transcranial Doppler ultrasound (fTCD) respectively in response to flickering mental rotation (MR) and flickering word generation (WG) cognitive tasks as well as a fixation cross that represents the baseline. This work extends our previous approach, in which we showed that motor imagery induces simultaneous changes in EEG and fTCD to enable task discrimination; and hence, provides a design approach for a hybrid BCI. Here, we show that instead of using motor imagery, the proposed visual stimulation technique enables the design of an EEG-fTCD based BCI with higher accuracy. Approach. Features based on the power spectrum of EEG and fTCD signals were calculated. Mutual information and support vector machines were used for feature selection and classification purposes. Main results. EEG-fTCD combination outperformed EEG by 4.05% accuracy for MR versus baseline problem and by 5.81% accuracy for WG versus baseline problem. An average accuracy of 92.38% was achieved for MR versus WG problem using the hybrid combination. Average transmission rates of 4.39, 3.92, and 5.60 bits min−1 were obtained for MR versus baseline, WG versus baseline, and MR versus WG problems respectively. Significance. In terms of accuracy, the current visual presentation outperforms the motor imagery visual presentation we designed before for the EEG-fTCD system by 10% accuracy for task versus task problem. Moreover, the proposed system outperforms the state of the art hybrid EEG-fNIRS BCIs in terms of accuracy and/or information transfer rate. Even though there are still limitations of the proposed system, such promising results show that the proposed hybrid system is a feasible candidate for real-time BCIs.

Directional sensitivity of dynamic cerebral autoregulation in squat-stand maneuvers.

Dynamic cerebral autoregulation (CA), the transient response of cerebral blood flow (CBF) to rapid changes in arterial blood pressure (BP), is usually modeled as a linear mechanism. We tested the hypothesis that dynamic CA can display nonlinear behavior resulting from differential efficiency dependent on the direction of BP changes. Cerebral blood velocity (CBV) (transcranial Doppler), heart rate (HR) (three-lead ECG), continuous BP (Finometer), and end-tidal CO2 (capnograph) were measured in 10 healthy young subjects during 15 squat-stand maneuvers (SSM) with a frequency of 0.05 Hz. The protocol was repeated with a median (interquartile range) of 44 (35-64) days apart. Dynamic CA was assessed with the autoregulation index (ARI) obtained from CBV step responses estimated with an autoregressive moving-average model. Mean BP, HR, and CBV were different (all P < 0.001) between squat and stand, regardless of visits. ARI showed a strong interaction ( P < 0.001) of SSM with the progression of transients; in general, the mean ARI was higher for the squat phase compared with standing. The changes in ARI were partially explained by concomitant changes in CBV ( P = 0.023) and pulse pressure ( P < 0.001), but there was no evidence that ARI differed between visits ( P = 0.277). These results demonstrate that dynamic CA is dependent on the direction of BP change, but further work is needed to confirm if this finding can be generalized to other physiological conditions and also to assess its dependency on age, sex and pathology.

Evaluating the methods used for measuring cerebral blood flow at rest and during exercise in humans.

The first accounts of measuring cerebral blood flow (CBF) in humans were made by Angelo Mosso in ~1880, who recorded brain pulsations in patients with skull defects. In 1890, Charles Roy and Charles Sherrington determined in animals that brain pulsations-assessed via a similar method used by Mosso-were altered during a variety of stimuli including sensory nerve stimulation, asphyxia, and pharmacological interventions. Between 1880 and 1944, measurements for CBF were typically relied on skull abnormalities in humans. Thereafter, Kety and Schmidt introduced a new methodological approach in 1945 that involved nitrous oxide dilution combined with serial arterial and jugular venous blood sampling. Less than a decade later (1950's), several research groups employed the Kety-Schmidt technique to assess the effects of exercise on global CBF and metabolism; these studies demonstrated an uncoupling of CBF and metabolism during exercise, which was contrary to early hypotheses. However, there were several limitations to this technique related to low temporal resolution and the inability to measure regional CBF. These limitations were overcome in the 1960's when transcranial Doppler ultrasound (TCD) was developed as a method to measure beat-by-beat cerebral blood velocity. Between 1990 and 2010, TCD further progressed our understanding of CBF regulation and allowed forinsight into other mechanistic factors, independent of local metabolism, involved in regulating CBF during exercise. Recently, it was discovered that TCD may not be accurate under several physiological conditions. Other measures of indexing CBF such as Duplex ultrasound and magnetic resonance imaging, although not without some limitations, may be more applicable for future investigations.

Dynamic cerebral autoregulation is impaired during submaximal isometric handgrip in patients with heart failure.

The incidence of neurological complications, including stroke and cognitive dysfunction, is elevated in patients with heart failure (HF) with reduced ejection fraction. We hypothesized that the cerebrovascular response to isometric handgrip (iHG) is altered in patients with HF. Adults with HF and healthy volunteers were included. Cerebral blood velocity (CBV; transcranial Doppler, middle cerebral artery) and arterial blood pressure (BP; Finometer) were continuously recorded supine for 6 min, corresponding to 1 min of baseline and 3 min of iHG exercise, at 30% maximum voluntary contraction, followed by 2 min of recovery. The resistance-area product was calculated from the instantaneous BP-CBV relationship. Dynamic cerebral autoregulation (dCA) was assessed with the time-varying autoregulation index estimated from the CBV step response derived by an autoregressive moving-average time-domain model. Forty patients with HF and 23 BP-matched healthy volunteers were studied. Median left ventricular ejection fraction was 38.5% (interquartile range: 0.075%) in the HF group. Compared with control subjects, patients with HF exhibited lower time-varying autoregulation index during iHG, indicating impaired dCA ( P < 0.025). During iHG, there were steep rises in CBV, BP, and heart rate in control subjects but with different temporal patterns in HF, which, together with the temporal evolution of resistance-area product, confirmed the disturbance in dCA in HF. Patients with HF were more likely to have impaired dCA during iHG compared with age-matched control subjects. Our results also suggest an impairment of myogenic, neurogenic, and metabolic control mechanisms in HF. The relationship between impaired dCA and neurological complications in patients with HF during exercise deserves further investigation. NEW & NOTEWORTHY Our findings provide the first direct evidence that cerebral blood flow regulatory mechanisms can be affected in patients with heart failure during isometric handgrip exercise. As a consequence, eventual blood pressure modulations are buffered less efficiently and metabolic demands may not be met during common daily activities. These deficits in cerebral autoregulation are compounded by limitations of the systemic response to isometric exercise, suggesting that patients with heart failure may be at greater risk for cerebral events during exercise.

The Influence of Aging on Central Artery Stiffness and Cerebral Vascular Function Following an Acute Hypertensive Stimulus

Aging decreases cerebral blood flow and increases cerebral pulsatility. High‐intensity resistance exercise (RE) has been shown to acutely increase blood pressure (BP) and reduce cerebral blood velocity (CBv), resulting in greater flow pulsatility in the cerebral circulation, potentially injuring cerebral microvasculature. Understanding the relationship between aging and cerebral blood flow regulation in response to a hypertensive physiological stress (e.g. RE), is important due to its association with increased risk of cerebrovascular events in older adults.ObjectiveTo examine the effect of age on cerebral blood flow dynamics following acute RE in young and older adults.MethodsYoung (n=35, 26 yrs, BMI: 23.8 kg/m2) and older (n=26, 60 yrs, BMI: 30.1 kg/m2) adults performed maximal leg‐extension/flexion RE (3×10 rep), with hemodynamic measurements obtained pre and post‐RE (immediate, 5‐, 30‐min). CBv was measured via transcranial Doppler. Central pulse wave velocity (PWV) was acquired by an automated ambulatory BP cuff. Common carotid artery beta‐stiffness index (β) and blood flow pulsatility were measured by ultrasonography. Continuous beat‐to‐beat heart rate (HR), cardiac output (Q), blood pressure (SBP, DBP, MAP, PP) and end‐tidal CO2 were also measured.ResultsMean and diastolic CBv increased immediately post‐RE in the young (interaction, p&lt;0.05) and decreased below baseline at 5‐min post‐RE (p&lt;0.05) in both groups. Older adults had a greater increase in CBv pulsatility immediate post‐RE (interaction, p&lt;0.05) compared to the young, but continued to rise at 5‐min post‐RE only in the young (interaction, p&lt;0.05). MAP was higher and carotid pulsatility was lower in the older group and increased immediate post‐RE (p&lt;0.05) in both groups. PWV increased immediate post‐RE (p&lt;0.05), and remained elevated at 5‐min post‐RE in the young (interaction, p&lt;0.05). There were no changes in β.ConclusionsImmediately following the cessation of the hypertensive stimulus, an increase in aortic arterial stiffness and BP occurred, accompanied by an increase in carotid and cerebral pulsatility. Despite obtaining higher BP during the stimulus in the older group, mean and diastolic CBv did not increase post‐RE, resulting in greater cerebral pulsatility in older adults. This differential age response indicates reduced cerebral hemodynamic responsiveness to an acute increase in BP with aging.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Ling-Yang-Gou-Teng-decoction prevents vascular dementia through inhibiting oxidative stress induced neurovascular coupling dysfunction

Ethnopharmacological relevanceVascular dementia (VaD) is the common cognitive disorder derived mainly from lacunar stroke (LS). The oxidative stress induced neurovascular coupling (NVC) dysfunction involves in the pathogenesis of VaD. Currently, there is no specific drug for VaD. Ling-Yang-Gou-Teng -Decoction (LG), a well-known traditional Chinese formula, has been used for preventing VaD in clinic. Aim of the studyIn this study, we aimed to investigate the underlying mechanism of LG on VaD in rats. Materials and methodVaD was replicated with autologous micro-thrombi against the background of hypercholesterolemia induced with high fatty diet. PTX (68.90 mg/kg/day), LG with three dosages (2.58, 8.14, 25.80 g/kg/day) was orally administrated to VaD rats, respectively. The NVC sensitivity was defined as the ratio of the microcirculative cerebral blood velocity (CBV) to the electroencephalograph (EEG) before and after penicillin stimulation. Behavioral performance, pathological changes of brain and oxidation related molecules were detected to assess the effects of LG on VaD. ResultsLG exhibited beneficial effects on the VaD, which was demonstrated as improved exploratory, learning and memory abilities, relieved vascular or neural pathological changes in cerebral cortex or hippocampus. LG maintained NVC sensitivity, which was confirmed as significantly increased ΔCBV and the elevated ratio of ΔCBV/ΔqEEG. The underlying mechanisms of LG was associated with antioxidant effects, which was confirmed as significantly decreased nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) expression, and increased superoxide dismutase 3 (SOD3) expression. LG also reduced iNOS, increased nNOS and eNOS expression to restore NO bioavailability. ConclusionsThe results suggested that LG prevented VaD may associate with inhibiting oxidative stress, protecting NO bioavailability, and then maintaining NVC sensitivity.

Feasibility of Improving Cerebral Autoregulation in Acute Intracerebral Haemorrhage (BREATHE-ICH) study: a protocol for an experimental interventional study

IntroductionCerebral autoregulation (CA) is impaired in a multitude of neurological conditions. Increasingly, clinical studies are correlating the nature of this impairment with prognostic markers. In acute intracerebral haemorrhage (ICH), impairment...

Severity-dependent influence of isocapnic hypoxia on reaction time is independent of neurovascular coupling

With exposure to acute normobaric hypoxia, global cerebral oxygen delivery is maintained via increases in cerebral blood flow (CBF); therefore, regional and localized changes in oxygen tension may explain neurocognitive impairment. Neurovascular coupling (NVC) is the close temporal and regional relationship of CBF to changes in neural activity and may aid in explaining the localized CBF response with cognitive activation. High-altitude related cognitive impairment is likely affected by hypocapnic cerebral vasoconstriction that may influence regional CBF regulation independent of hypoxia. We assessed neurocognition and NVC following 30 min of acute exposure to isocapnic hypoxia (decreased partial pressure of end-tidal oxygen; PETO2) during moderate hypoxia (MOD HX; 55 mm Hg PETO2), and severe hypoxia (SEV HX; 45 mm Hg PETO2) in 10 healthy individuals (25.5 ± 3.3 yrs). Transcranial Doppler ultrasound was used to assess mean posterior and middle cerebral blood velocity (PCAv and MCAv, respectively) and neurocognitive performance was assessed via validated computerized tests. The main finding was that reaction time (i.e., kinesthetic and visual-motor ability via Stroop test) was selectively impaired in SEV HX (−4.6 ± 5.2%, P = 0.04), but not MOD HX, while complex cognitive performance (e.g., psychomotor speed, cognitive flexibility, processing speed, executive function, and motor speed) was unaffected with hypoxia (P > 0.05). Additionally, severity of hypoxia had no effect on NVC (PCAv CON vs. SEV HX relative peak response 13.7 ± 6.4% vs. 16.2 ± 11.5%, P = 0.71, respectively). In summary, severe isocapnic hypoxia impaired reaction time, but not complex cognitive performance or NVC. These findings have implications for recreational and military personnel who may experience acute hypoxia.

Does gradual change in head positioning affect cerebrovascular physiology?

We studied cerebral blood velocity (CBV), and associated hemodynamic parameters during gradual changes in head positioning in a nonstroke group. CBV (transcranial Doppler ultrasound), beat‐to‐beat blood pressure (BP, Finometer), and end‐tidal carbon dioxide (ETCO 2, capnography) were recorded between lying flat (0°) and sitting up (30°) head positions, in 18 volunteers (10 female, mean age, 57 ± 16 years), at two visits (12 ± 8 days). A significant reduction was found between 5‐min FLAT (0°) and 5‐min SIT (30°) positions in CBV (visit 1: 4.5 ± 3.3%, P = 0.006; visit 2: 4.1 ± 3.5%, P = 0.003), critical closing pressure (CrCP; visit 1: 15.5 ± 14.0%, P = 0.0002; visit 2: 14.1 ± 7.8%, P = 0.009) and BP (visit 1: 8.3 ± 7.4%, P = 0.001; visit 2: 11.0 ± 11.3%, P < 0.001). For 5 min segments of data, the autoregulation index and other hemodynamic parameters did not show differences either due to head position or visit. For 30 sec time intervals, significant differences were observed in the following: (BP, P < 0.001; dominant hemisphere (DH) CBV, P < 0.005; nondominant hemisphere (NDH) CBV, P < 0.005; DH CrCP, P < 0.001; NDH CrCP, P < 0.001; DH resistance area product (RAP), P = 0.002; NDH RAP, P = 0.033). Significant static changes in BP, CBV and CrCP, and large transient changes in key hemodynamic parameters occur during 0° to 30°, and vice versa, with reproducible results. Further studies are needed following acute ischemic stroke to determine if a similar responses is present.

Differential Systolic and Diastolic Regulation of the Cerebral Pressure-Flow Relationship During Squat-Stand Manoeuvres.

Cerebral pressure-flow dynamics are typically reported between mean arterial pressure and mean cerebral blood velocity. However, by reporting only mean responses, potential differential regulatory properties associated with systole and diastole may have been overlooked. Twenty young adults (16 male, age: 26.7 ± 6.6 years, BMI: 24.9 ± 3.0 kg/m2) were recruited for this study. Middle cerebral artery velocity was indexed via transcranial Doppler. Cerebral pressure-flow dynamics were assessed using transfer function analysis at both 0.05 and 0.10 Hz using squat-stand manoeuvres. This method provides robust and reliable measures for coherence (correlation index), phase (timing buffer) and gain (amplitude buffer) metrics. There were main effects for both cardiac cycle and frequency for phase and gain metrics (p < 0.001). The systolic phase (mean ± SD) was elevated at 0.05 (1.07 ± 0.51 radians) and 0.10 Hz (0.70 ± 0.46 radians) compared to the diastolic phase (0.05 Hz: 0.59 ± 0.14 radians; 0.10 Hz: 0.33 ± 0.11 radians). Conversely, the systolic normalized gain was reduced (0.05 Hz: 0.49 ± 0.12%/%; 0.10 Hz: 0.66 ± 0.20%/%) compared to the diastolic normalized gain (0.05 Hz: 1.46 ± 0.43%/%; 0.10 Hz: 1.97 ± 0.48%/%). These findings indicate there are differential systolic and diastolic aspects of the cerebral pressure-flow relationship. The oscillations associated with systole are extensively buffered within the cerebrovasculature, whereas diastolic oscillations are relatively unaltered. This indicates that the brain is adapted to protect itself against large increases in systolic blood pressure, likely as a mechanism to prevent cerebral haemorrhages.

The cerebrocardiovascular response to periodic squat-stand maneuvers in healthy subjects: a time-domain analysis.

Squat-stand maneuvers (SSMs) have been used to improve the coherence of transfer function analysis (TFA) estimates during the assessment of dynamic cerebral autoregulation (dCA). There is a need to understand the influence of peripheral changes resulting from SSMs on cerebral blood flow, which might confound estimates of dCA. Healthy subjects ( n = 29) underwent recordings at rest (5-min standing) and 15 SSMs (0.05 Hz). Heart rate (three-lead ECG), end-tidal CO2 (capnography), blood pressure (Finometer), cerebral blood velocity (CBV; transcranial Doppler, middle cerebral artery), and the angle of the thigh (tilt sensor) were measured continuously. The response of CBV to SSMs was decomposed into the relative contributions of mean arterial pressure (MAP), resistance-area product (RAP), and critical closing pressure (CrCP). Upon squatting, a rise in MAP (83.6 ± 21.1% contribution) was followed by increased CBV. A dCA response could be detected, determined by adjustments in RAP and CrCP (left hemisphere) with peak contributions of 24.8 ± 12.7% and 27.4 ± 22.8%, respectively, at different times during SSMs. No interhemispheric differences were detected. During standing, the contributions of MAP, RAP, and CrCP changed considerably. In conclusion, the changes of CBV subcomponents during repeated SSMs indicate a complex response of CBV to SSMs that can only be partially explained by myogenic mechanisms. More work is needed to clarify the potential contribution of other cofactors, such as breath-to-breath changes in Pco2, heart rate, stroke volume, and the neurogenic component of dCA. NEW & NOTEWORTHY Here, we describe the different contributions to the cerebral blood flow response after squat-stand maneuvers. Furthermore, we demonstrate the complex interaction of peripheral and cerebral parameters for the first time. Moreover, we show that the cerebral blood velocity response to squatting is likely to include a significant metabolic component.

Blunted cerebral vascular responsiveness to hypercapnia in obese individuals.

What is the central question of this study? Is there a difference in the cerebral vascular response to rebreathing-induced hypercapnia between obese and lean individuals? What is the main finding and its importance? The main finding is that obese individuals have an attenuated increase in cerebral vascular conductance during hypercapnia relative to lean individuals. This finding suggests cerebral vascular dysfunction in this population, which might contribute to the greater prevalence of cerebral vascular and neurocognitive disease in this population. Obesity increases the risk of cardiovascular disease by >45%. Furthermore, obesity is a contributory factor to cognitive impairment and Alzheimer's disease. The mechanisms accounting for this increased disease risk have not been clarified. This study tested the hypothesis that the total range of change (a) in cerebral blood velocity (CBV) and cerebral vascular conductance (CVCI) and the maximal (y0) CBV and CVCI achieved during rebreathing-induced hypercapnia would be attenuated in obese individuals. Sixteen lean and 15 obese individuals participated. The magnitude of rebreathing-induced hypercapnia was similar between groups (lean, ∆15±3mmHg versus obese, ∆15±2mmHg; P=0.82). The total range of change in CBV during rebreathing (a; expressed as a percentage) was similar between groups (lean, 91±24% versus obese, 76±19%, P=0.07), whereas the total range of change in CVCI during rebreathing (a; expressed as a percentage) was attenuated in the obese individuals (lean, 71±20% versus obese, 51±15%, P<0.01). Likewise, the maximal increase in CBV during rebreathing (y0; expressed as a percentage) was similar between groups (lean, 189±22% versus obese, 179±20%, P=0.20), whereas the maximal increase in CVCI during rebreathing (y0; expressed as a percentage) was attenuated in the obese individuals (lean, 172±19% versus obese, 155±17 %, P=0.01). These data indicate that the cerebral vascular response to rebreathing-induced hypercapnia is attenuated in obese individuals. This impairment might be a factor contributing to the elevated cerebral vascular and neurocognitive disease risk in this population.

Cerebral Hemodynamics in Mild Cognitive Impairment: A Systematic Review.

The incidence of dementia is projected to rise over the coming decades, but with no sensitive diagnostic tests available. Vascular pathology precedes the deposition of amyloid and is an attractive early target. The aim of this review was to investigate the use of cerebral hemodynamics and oxygenation as a novel biomarker for mild cognitive impairment (MCI), focusing on transcranial Doppler ultrasonography (TCD) and near-infrared spectroscopy (NIRS). 2,698 articles were identified from Medline, Embase, PsychINFO, and Web of Science databases. 306 articles were screened and quality assessed independently by two reviewers; 26 met the inclusion criteria. Meta-analyses were performed for each marker with two or more studies and limited heterogeneity. Eleven studies were TCD, 8 NIRS, 5 magnetic resonance imaging, and 2 positron/single photon emission tomography. Meta-analyses showed reduced tissue oxygenation index, cerebral blood flow and velocity, with higher pulsatility index, phase and cerebrovascular resistance in MCI compared to controls. The majority of studies found reduced CO2 reactivity in MCI, with mixed findings in neuroactivation studies. Despite small sample sizes and heterogeneity, meta-analyses demonstrate clear abnormalities in cerebral hemodynamic and oxygenation parameters, even at an early stage of cognitive decline. Further work is required to investigate the use of cerebral hemodynamic and oxygenation parameters as a sensitive biomarker for dementia.