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Cerebral autoregulation (CA) refers to the control of cerebral tissue blood flow (CBF) in response to changes in perfusion pressure. Due to the challenges of measuring intracranial pressure, CA is often described as the relationship between mean arterial pressure (MAP) and CBF. Dynamic CA (dCA) can be assessed using multiple techniques, with transfer function analysis (TFA) being the most common. A 2016 white paper by members of an international Cerebrovascular Research Network (CARNet) that is focused on CA strove to improve TFA standardization by way of introducing data acquisition, analysis, and reporting guidelines. Since then, additional evidence has allowed for the improvement and refinement of the original recommendations, as well as for the inclusion of new guidelines to reflect recent advances in the field. This second edition of the white paper contains more robust, evidence-based recommendations, which have been expanded to address current streams of inquiry, including optimizing MAP variability, acquiring CBF estimates from alternative methods, estimating alternative dCA metrics, and incorporating dCA quantification into clinical trials. Implementation of these new and revised recommendations is important to improve the reliability and reproducibility of dCA studies, and to facilitate inter-institutional collaboration and the comparison of results between studies.

Currently, the standard approach for restricting exercise prior to cerebrovascular data collection varies widely between 6 and 24 h. This universally employed practice is a conservative approach to safeguard physiological alterations that could potentially confound one’s study design. Therefore, the purpose of this systematic review was to amalgamate the existing literature examining the extent and duration of postexercise alterations in cerebrovascular function, measured via transcranial Doppler ultrasound. Furthermore, an exploratory aim was to scrutinize and discuss common biases/limitations in the previous studies to help guide future investigations. Search strategies were developed and imported into PubMed, SPORTDiscus, and Medline databases. A total of 595 records were screened and 35 articles met the inclusion criteria in this review, which included assessments of basic cerebrovascular metrics ( n = 35), dynamic cerebral autoregulation (dCA; n = 9), neurovascular coupling (NVC; n = 2); and/or cerebrovascular reactivity (CVR-CO2; n = 1) following acute bouts of aerobic exercise. Across all studies, it was found that NVC was impacted for 1 h, basic cerebrovascular parameters and CVR-CO2 parameters for 2 h, and dCA metrics for 6 h postexercise. Therefore, future studies can provide participants with these evidence-based time restrictions, regarding the minimum time to abstain from exercise prior to data collection. However, it should be noted that other physiological mechanisms could still be altered (e.g., metabolic, hormonal, and/or autonomic influences), despite cerebrovascular function returning to baseline levels. Thus, future investigations should seek to control as many physiological influences when using cerebrovascular assessments, immediately following these time restraints. The main limitations/biases were lack of female participants, cardiorespiratory fitness, and consideration for vessel diameter.

The systematic review evaluated the evidence related to how physical activity affects recovery following a sport-related concussion (SRC) in adolescents. Databases indexed were PUBMED, MEDLINE, and SPORTDiscus. Inclusion criteria included 1) original research article, 2) ≥66% have an SRC diagnosed by a clinician, 3) human research, and 4) evaluated the effect of an SRC on physical activity in adolescents only (

Standard practices for quantifying neurovascular coupling (NVC) with transcranial Doppler ultrasound (TCD) require participants to complete one-to-ten repetitive trials. However, limited empirical evidence exists regarding how the number of trials completed influences the validity and reliability of temporally derived NVC metrics. Secondary analyses was performed on 60 young healthy participants (30 females/30 males) who completed eight cyclical eyes-closed (20-seconds), eyes-open (40-seconds) NVC trials, using the “Where’s Waldo?” visual paradigm. TCD data was obtained in posterior and middle cerebral arteries (PCA and MCA, respectively). The within-day (n = 11) and between-day ( n = 17) reliability were assessed at seven- and three-time points, respectively. Repeat testing from the reliability aims were also used for the concurrent validity analysis ( n = 160). PCA metrics (i.e., baseline, peak, percent increase, and area-under-the-curve) demonstrated five trials produced excellent intraclass correlation coefficient (ICC) 95% confidence intervals for validity and within-day reliability (>0.900), whereas between-day reliability was good-to-excellent (>0.750). Likewise, 95% confidence intervals for coefficient of variation (CoV) measures ranged from acceptable (

Cerebral hemodynamics, e.g., cerebral blood flow, can be measured and quantified using many different methods, with transcranial Doppler ultrasound (TCD) being one of the most commonly used approaches. In human physiology, the terminology used to describe metrics of cerebral hemodynamics are inconsistent and in some instances technically inaccurate; this is especially true when evaluating, reporting, and interpreting measures from TCD. Therefore, this perspective article presents recommended terminology when reporting cerebral hemodynamic data. We discuss the current use and misuse of the terminology in the context of using TCD to measure and quantify cerebral hemodynamics and present our rationale and consensus on the terminology that we recommend moving forward. For example, one recommendation is to discontinue the use of the term “cerebral blood flow velocity” in favor of “cerebral blood velocity” with precise indication of the vessel of interest. We also recommend clarity when differentiating between discrete cerebrovascular regulatory mechanisms, namely, cerebral autoregulation, neurovascular coupling, and cerebrovascular reactivity. This will be a useful guide for investigators in the field of cerebral hemodynamics research.

Accumulating evidence suggests asymmetrical responses of cerebral blood flow during large transient changes in mean arterial pressure. Specifically, the augmentation in cerebral blood flow is attenuated when mean arterial pressure acutely increases, compared with declines in cerebral blood flow when mean arterial pressure acutely decreases. However, common analytical tools to quantify dynamic cerebral autoregulation assume autoregulatory responses to be symmetric, which does not seem to be the case. Herein, we provide the rationale supporting the notion we need to consider the directional sensitivity of large and transient mean arterial pressure changes when characterizing dynamic cerebral autoregulation.

What is the central question of this study? Does habitual exercise modality affect the directionality of the cerebral pressure-flow relationship? What is the main finding and its importance? These data suggest the hysteresis-like pattern of dynamic cerebral autoregulation appears present in long-term sedentary and endurance-trained individuals, but absent in resistance-trained individuals. This is the first study to expand knowledge on the directional sensitivity of the cerebral pressure-flow relationship to trained populations.Evidence suggests the cerebrovasculature may be more efficient at dampening cerebral blood flow (CBF) variations when mean arterial pressure (MAP) transiently increases, compared to when it decreases. Despite divergent MAP and CBF responses to acute endurance and resistance training, the long-term impact of habitual exercise modality on the directionality of dynamic cerebral autoregulation (dCA) is currently unknown. Thirty-six young healthy participants (sedentary (n = 12), endurance-trained (n = 12), and resistance-trained (n = 12)) undertook a 5-min repeated squat-stand protocol at two forced MAP oscillation frequencies (0.05 and 0.10 Hz). Middle cerebral artery mean blood velocity (MCAv) and MAP were continuously monitored. We calculated absolute (ΔMCAv

Background While previous studies have demonstrated a complex visual scene search elicits a robust neurovascular coupling (NVC) response, it is unknown how the duration of visual stimuli presentation influences NVC metrics. This study examined how stimuli duration, in addition to biological sex and self‐reported engagement impact NVC responses. Methods Participants (n = 20, female = 10) completed four visual paradigms. Three involved simple visual shapes presented at 0.5‐, 2‐, and 4‐s intervals in randomized orders. The fourth paradigm was a complex visual scene search (“Where's Waldo?”). Participants completed eight cycles of 20‐s eyes‐closed followed by 40‐s eyes‐open. Transcranial Doppler ultrasound indexed posterior and middle cerebral artery velocities (PCA and MCA). Participants self‐reported their engagement following each task (1 [minimal] to 10 [maximal]). Results The “Where's Waldo?” task evoked greater PCA percent increase (all p, A simple shapes task elicited a modest neurovascular coupling (NVC) response, regardless of image presentation duration (4‐, 2‐, or 0.5‐s). Conversely, a complex “Where's Waldo?” search produced a robust response that maximized the NVC response. While absolute cerebral blood velocity metrics were higher in females, no differences were found between biological sexes regarding the NVC response. However, subjective task engagement had a greater correlation within males, highlighting the need for researchers to use more engaging tasks for males to elicit a similar NVC response compared to females.

We recently employed repeated squat-stands (RSS) to quantify directional sensitivity of the cerebral-pressure flow relationship (i.e. hysteresis) using a novel metric. Within-day reproducibility and diurnal variation impacts of this metric are unknown. We evaluated this metric for: 1) within-day reproducibility and the extent diurnal variation has in middle (MCA; ΔMCAvT/ΔMAPT) and posterior cerebral arteries (PCA; ΔPCAvT/ΔMAPT); 2) sex differences. Absolute (ΔMCAvT/ΔMAPT ; ΔPCAvT/ΔMAPT) and relative (%MCAvT/%MAPT, %PCAvT/%MAPT) metrics were calculated at seven time-points (08:00-17:00) in 18 participants (8 women; 24 ± 3 yrs) using the minimum-to-maximum MCAv/PCAv and MAP for each RSS at 0.05 Hz and 0.10 Hz. Reproducibility was evaluated with intraclass correlation coefficient (ICC). For all metrics, reproducibility was good (0.75-0.90) to excellent (>0.90). The metric in both arteries was impacted by MAP direction at 0.10 Hz (all p < 0.024). Time-of-day influenced ΔMCAvT/ΔMAPT (0.05 Hz: p = 0.0028; 0.10 Hz: p = 0.0009), %MCAvT/%MAPT (0.05 Hz: p = 0.035; 0.10 Hz: p = 0.0087), and ΔPCAvT/ΔMAPT (0.05 Hz: p = 0.0236). Sex differences in the MCA (p = 0.0028) vanished in relative terms and was absent in the PCA. These findings demonstrate within-day reproducibility of this metric in both arteries. Moreover, hysteresis is not impacted by sex.

This study examined cerebral blood flow (CBF) and its regulation before and after a short-term periodized aerobic exercise training intervention in patients with chronic obstructive pulmonary disease (COPD). Twenty-eight patients with COPD (forced expiratory volume in 1 s/forced vital capacity < 0.7 and −1·mmHg−1, P = 0.02). After aerobic training, absolute peak O2 consumption increased in both groups, with a greater improvement in control subjects (1.7 ± 0.4 vs. 4.1 ± 0.2 ml·kg−1·min−1, respectively, P = 0.001). Despite these improvements in peak O2 consumption, there were no significant alterations in CBF or any measures of cerebrovascular function after exercise training in either group. In conclusion, patients with COPD have a blunted cerebrovascular response to hypocapnia, and 8 wk of aerobic exercise training did not alter cerebrovascular function despite significant improvements in cardiorespiratory fitness. NEW & NOTEWORTHY No study to date has investigated whether exercise training can alter resting cerebral blood flow (CBF) regulation in patients with chronic obstructive pulmonary disease (COPD). This study is the first to assess CBF regulation at rest, before, and after aerobic exercise training in patients with COPD and healthy control subjects. This study demonstrated that while exercise training improved aerobic fitness, it had little effect on CBF regulation in patients with COPD or control subjects.

In 1959, Niels Lassen illustrated the cerebral autoregulation curve in the classic review article entitled Cerebral Blood Flow and Oxygen Consumption in Man. This concept suggested a relatively broad mean arterial pressure range (~60–150 mmHg) wherein cerebral blood flow remains constant. However, the assumption that this wide cerebral autoregulation plateau could be applied on a within‐individual basis is incorrect and greatly variable between individuals. Indeed, each data point on the autoregulatory curve originated from independent samples of participants and patients and represented interindividual relationships between cerebral blood flow and mean arterial pressure. Nonetheless, this influential concept remains commonly cited and illustrated in various high‐impact publications and medical textbooks, and is frequently taught in medical and science education without appropriate nuances and caveats. Herein, we provide the rationale and additional experimental data supporting the notion we need to lose this dogmatic view of cerebral autoregulation., In 1959, Niels Lassen illustrated the cerebral autoregulation curve in the classic review article entitled Cerebral Blood Flow and Oxygen Consumption in Man. This concept suggested a relatively broad mean arterial pressure range wherein cerebral blood flow remains constant. Herein, we provide the rationale and additional experimental data supporting the notion we need to lose this dogmatic view of cerebral autoregulation.

Hysteresis in the cerebral pressure-flow relationship describes the superior ability of the cerebrovasculature to buffer cerebral blood flow changes when mean arterial pressure (MAP) acutely increases compared to when MAP acutely decreases. This phenomenon can be evaluated by comparing the change in middle cerebral artery mean blood velocity (MCAv) per change in MAP during either acute increases or decreases in MAP induced by repeated squat-stands (RSS). However, no real baseline can be employed for this particular protocol as there is no true stable reference point. Herein, we characterized a novel metric using the greatest MAP oscillations induced by RSS without using an independent baseline value and adjusted for time intervals (ΔMCAvT/ΔMAPT). We also examined whether this metric during each RSS transition were comparable between each other over a 5-min period. ΔMCAvT/ΔMAPTwas calculated using the minimum to maximum MCAv and MAP for each RSS performed at 0.05 Hz and 0.10 Hz. We compared averaged ΔMCAvT/ΔMAPTduring MAP increases and decreases in 74 healthy subjects [9 women; 32 ± 13 years]. ΔMCAvT/ΔMAPTwas lower for MAP increases than MAP decreases at 0.10 Hz RSS only (0.91 ± 0.34 vs. 1.01 ± 0.44 cm·s-1/mmHg; p = 0.0013). For both frequency and MAP direction, time during RSS had no effect on ΔMCAvT/ΔMAPT. This novel analytical method supports the use of the RSS model to evaluate the directional sensitivity of the pressure-flow relationship. These results contribute to the importance of considering the direction of MAP changes when evaluating dynamic cerebral autoregulation.News & NoteworthyRepeated squat-stand maneuvers are able to examine the directional sensitivity of the cerebral pressure-flow relationship. These maneuvers induce stable physiological cyclic changes where brain blood flow changes with blood pressure increases are buffered more than decreases. These results highlight the importance of considering directional blood pressure changes within cerebral autoregulation.

While cardiac pulsations are widely present within physiological and neuroimaging data, it is unknown the extent this information can provide valid and reliable heart rate and heart rate variability (HRV) estimates. The objective of this study was to demonstrate how a slight temporal shift due to an insufficient sampling frequency can impact the validity/accuracy of deriving cardiac metrics.Twenty-two participants were instrumented with valid/reliable industry-standard or open-source electrocardiograms. Five-minute lead II recordings were collected at 1000 Hz in an upright orthostatic position. Following artifact removal, the 1000 Hz recording for each participant was downsampled to frequencies ranging 2-500 Hz. The validity of each participant's downsampled recording was compared against their 1000 Hz recording ("reference-standard") using Bland-Altman plots with 95 % limits of agreement (LOA), coefficient of variation (CoV), intraclass correlation coefficients, and adjusted r-squared values.Downsampled frequencies of ≥ 50 and ≥ 90 Hz produced highly robust measures with narrow log-transformed 95 % LOA (±0.01) and low CoV values (≤3.5 %) for heart rate and HRV metrics, respectively. Below these thresholds, the log-transformed 95 % LOA became wider (LOA range: ±0.1-1.9) and more variable (CoV range: 1.5-111.6 %).These results provide an important consideration for obtaining cardiac information from physiological data. Compared to the "reference-standard" ECG, a seemingly negligible temporal shift of the systolic contraction (R wave) greater than 11-milliseconds (90 Hz) away from its true value, lessened the validity of the HRV. Further research is warranted to determine the minimum sampling frequency required to obtain valid heart rate/HRV metrics from pulsatile waveforms.

A one size fits all methodological approach to quantify HRV metrics appears to be inappropriate, where study design considerations need to be conducted upon a variable-by-variable basis. The present results found 60 s (heart rate), 240 s (time-domain parameters), and 300 s (relative frequency-domain parameters) were required to obtain accurate and reproducible metrics. The lower validity/reliability of the ultra-short-term metrics was attributable to measurement error and/or confounding from extraneous physiological influences (i.e., respiratory and hemodynamic variables).

Context Current guidelines for recovery after sport-related concussion (SRC) recommend 24 to 48 hours of rest, followed by a gradual return to activity with heart rate (HR) maintained below the symptom threshold. In addition, monitoring physical activity (PA) after SRC using ActiGraph accelerometers can provide further objective insight into the amounts of activity associated with recovery trajectories. Cutpoint algorithms for these devices allow minute-by-minute PA to be classified into intensity domains; however, researchers have shown that different algorithms used to evaluate the same healthy participant dataset can produce various classifications. Objective To identify the more physiologically appropriate cutpoint algorithm (Evenson or Romanzini) to analyze ActiGraph data among concussed adolescents in comparison with their HR responses on the Buffalo Concussion Treadmill Test (BCTT). Design Prospective cohort study. Setting University sport concussion clinic. Patients or Other Participants Eleven high school students (5 boys, 6 girls; median [range] age = 16 years [15–17 years], height = 177.8 cm [157.5–198.1 cm], mass = 67 kg [52–98 kg], body mass index = 22 [17–31]) involved in high-risk sports who sustained a physician-diagnosed SRC. Main Outcome Measure(s) Evenson and Romanzini algorithm PA intensity domains via ActiGraph data and HR during the BCTT. Results We observed differences in PA time classified as moderate (P = .003) and vigorous (P = .004) intensities between algorithms but no difference in PA time classified as light intensity (P = .48). The Evenson algorithm classified most of the time as moderate-intensity PA (mean = 57.03%, range = 0.00%–94.12%), whereas the Romanzini algorithm classified virtually all PA as vigorous intensity (mean = 88.25%, range = 2.94%–97.06%]). Physical activity based on HR (stages 1–7 = 20%–39% HR reserve [HRR], stages 8–13 = 40%–59% HRR, stages ≥14 = 60%–85% HRR) indicated the BCTT primarily involved light to moderate intensity and, therefore, was better represented by the Evenson algorithm. Conclusions The Evenson algorithm better characterized the HR response during a standardized exercise test in concussed individuals and, thus, should be used to analyze ActiGraph PA data in pediatric populations with concussion.

Purpose Studies examining neurovascular coupling (NVC) require participants to refrain from exercise for 12–24 hours. However, there is a paucity of empirical evidence for this restriction. The objectives for this study were to delineate the time‐course recovery of NVC metrics following exercise and establish the NVC within‐ and between‐day reliability. Methods Nine participants completed a complex visual search paradigm to assess NVC via transcranial Doppler ultrasound of the posterior cerebral artery blood velocity (PCA). Measurements were performed prior to and throughout the 8‐hour recovery period following three randomized conditions: 45 minutes of moderate‐intensity exercise (at 50% heart‐rate reserve), 30 minutes high‐intensity intervals (10, 1‐minute intervals at 85% heart‐rate reserve), and control (30 minutes quiet rest). In each condition, baseline measures were collected at 8:00am with serial follow‐ups at hours zero, one, two, four, six, and eight. Results Area‐under‐the‐curve and time‐to‐peak PCA velocity during the visual search were attenuated at hour zero following high‐intensity intervals (all p 0.13). Conversely, baseline PCA velocity, peak PCA velocity, and the relative percent increase were not different following high‐intensity intervals compared to baseline (all p > 0.26). No NVC metrics differed from baseline following both moderate exercise and control conditions (all p > 0.24). The majority of the NVC parameters demonstrated high levels of reliability (intraclass correlation coefficient: >0.90). Conclusion Future NVC assessments can take place a minimum of one hour following exercise. Moreover, all metrics did not change across the control condition, therefore future studies using this methodology can reliably quantify NVC between 8:00am and 7:00 pm., Previous studies examining neurovascular coupling (NVC) metrics, required participants to refrain from exercise for 4‐24 hours prior to data collection, despite a lack of objective evidence for this time restriction. The results in the current investigation demonstrated that the NVC response was attenuated immediately following high‐intensity exercise within the posterior cerebral artery (PCA); however, the NVC response was comparable to baseline values one‐hour following exercise. Additionally, NVC metrics displayed high levels of within‐ and between‐day reliability across the control condition (8:00am – 7:00pm) when using a complex visual scene search paradigm (“Where’s Waldo”).

Presently, the literature describing the influence of diurnal variation on dynamic cerebral autoregulation (dCA) metrics is sparse. Additionally, there is little data with respect to dCA comparisons between anterior/posterior circulation beds and biological sexes using squat‐stand maneuvers. Eight male and eight female participants (n = 16) performed 5 min of spontaneous upright rest and squat‐stand maneuvers at 0.05 and 0.10 Hz across seven time points throughout the day. All testing sessions commenced at 8:00 a.m. each day and dCA parameters were quantified across the cardiac cycle (diastole, mean, and systole) using transcranial Doppler ultrasound to insonate cerebral blood velocity within the middle and posterior cerebral arteries (MCA, PCA). No cardiac cycle alternations were seen spontaneous (all p > .207) while a trend was noted in some driven (all p > .051) dCA metrics. Driven dCA produced much lower coefficient of variances (all .096). Between vessels, PCA absolute gain was reduced within all spontaneous and driven measures (all p .099). There appears to be little influence of diurnal variation on dCA measures across the day (8:00 a.m. to 6:00 p.m.). Absolute gain was blunted in the PCA relative to the MCA and consistent with previous literature, driven methods demonstrated vastly improved reproducibility metrics compared to spontaneous methods. Finally, no dCA differences were found between biological sexes, demonstrating that males and females regulate in a harmonious manner, when females are tested within the early follicular phase of the menstrual cycle., Driven dynamic dynamic cerebral autoregulation (dCA) metrics elicited more robust measures compared to spontaneous metrics across the day (8:00–18:00). Additionally, both the middle and posterior cerebral arteries regulated similarly across the day, as well did both males and female participants. Therefore, in the future when feasible, squat‐stand maneuvers should be used to assess dCA in participants, which can be performed in both vessels, across the cardiac cycle and in both biological sexes, as there is minimal influence of diurnal variation across the day within these measures.

A common inclusion criterion when assessing cerebrovascular (CVR) metrics is for individuals to abstain from exercise for 12–24 hr prior to data collections. While several studies have examined CVR during exercise, the literature describing CVR throughout post‐exercise recovery is sparse. The current investigation examined CVR measurements in nine participants (seven male) before and for 8 hr following three conditions: 45‐min moderate‐continuous exercise (at ~50% heart‐rate reserve), 25‐min high‐intensity intervals (ten, one‐minute intervals at ~85% heart‐rate reserve), and a control day (30‐min quiet rest). The hypercapnic (40–60 mmHg) and hypocapnic (25–40 mmHg) slopes were assessed via a modified rebreathing technique and controlled stepwise hyperventilation, respectively. All testing was initiated at 8:00a.m. with transcranial Doppler ultrasound measurements to index cerebral blood velocity performed prior to the condition (pre) with serial follow‐ups at zero, one, two, four, six, and eight hours within the middle and posterior cerebral artery (MCA, PCA). Absolute and relative MCA and PCA hypercapnic slopes were attenuated following high‐intensity intervals at hours zero and one (all p .13), aside from a reduced relative hypercapnic MCA slope at hours zero and one following moderate‐continuous exercise (all p, Absolute and relative MCA and PCA cerebrovascular reactivity hypercapnic slopes were attenuated following high‐intensity intervals at hours zero and one (all p .13), aside from a reduced relative hypercapnic MCA slope at hours zero and one following moderate‐continuous exercise (all p

Current protocols examining cerebral autoregulation (CA) parameters require participants to refrain from exercise for 12–24 hr, however there is sparse objective evidence examining the recovery trajectory of these measures following exercise across the cardiac cycle (diastole, mean, and systole). Therefore, this study sought to determine the duration acute exercise impacts CA and the within‐day reproducibility of these measures. Nine participants performed squat–stand maneuvers at 0.05 and 0.10 Hz at baseline before three interventions: 45‐min moderate‐continuous exercise (at 50% heart‐rate reserve), 30‐min high‐intensity intervals (ten, 1‐min at 85% heart‐rate reserve), and a control day (30‐min quiet rest). Squat–stands were repeated at hours zero, one, two, four, six, and eight after each condition. Transcranial doppler ultrasound of the middle cerebral artery (MCA) and the posterior cerebral artery (PCA) was used to characterize CA parameters across the cardiac cycle. At baseline, the systolic CA parameters were different than mean and diastolic components (ps 0.079). In the PCA, phase values were affected only following high‐intensity intervals until hour four (ps > 0.055). Normalized gain in all cardiac cycle domains remained different following both exercise protocols (ps, Nine participants performed squat‐stand maneuvers at 0.05 and 0.10 Hz at baseline before three interventions: 45‐min moderate‐continuous exercise (at 50% heart‐rate reserve), 30‐min high‐intensity intervals (ten, one minute at 85% heart‐rate reserve), and a control day (30‐min quiet rest). Squat‐stands were repeated at hours zero, one, two, four, six, and eight after each condition. exercise was shown to affect dynamic CA into recovery up to 4 hr following exercise, with HIIT demonstrating greater affects than MICT (each phase of the cardiac cycle responded differently to exercise, with the systolic component showing impairments for up to 4 hr, compared to diastolic and mean which recovered after 2 hr in all measures).

KEY POINTS: Chronic mountain sickness (CMS) is a maladaptation syndrome encountered at high altitude (HA) characterised by severe hypoxaemia that carries a higher risk of stroke and migraine and is associated with increased morbidity and mortality. We examined if exaggerated oxidative‐inflammatory‐nitrosative stress (OXINOS) and corresponding decrease in vascular nitric oxide bioavailability in patients with CMS (CMS+) is associated with impaired cerebrovascular function and adverse neurological outcome. Systemic OXINOS was markedly elevated in CMS+ compared to healthy HA (CMS−) and low‐altitude controls. OXINOS was associated with blunted cerebral perfusion and vasoreactivity to hypercapnia, impaired cognition and, in CMS+, symptoms of depression. These findings are the first to suggest that a physiological continuum exists for hypoxaemia‐induced systemic OXINOS in HA dwellers that when excessive is associated with accelerated cognitive decline and depression, helping identify those in need of more specialist neurological assessment and targeted support. ABSTRACT: Chronic mountain sickness (CMS) is a maladaptation syndrome encountered at high altitude (HA) characterised by severe hypoxaemia that carries a higher risk of stroke and migraine and is associated with increased morbidity and mortality. The present cross‐sectional study examined to what extent exaggerated systemic oxidative‐inflammatory‐nitrosative stress (OXINOS), defined by an increase in free radical formation and corresponding decrease in vascular nitric oxide (NO) bioavailability, is associated with impaired cerebrovascular function, accelerated cognitive decline and depression in CMS. Venous blood was obtained from healthy male lowlanders (80 m, n = 17), and age‐ and gender‐matched HA dwellers born and bred in La Paz, Bolivia (3600 m) with (CMS+, n = 23) and without (CMS−, n = 14) CMS. We sampled blood for oxidative (electron paramagnetic resonance spectroscopy, HPLC), nitrosative (ozone‐based chemiluminescence) and inflammatory (fluorescence) biomarkers. We employed transcranial Doppler ultrasound to measure cerebral blood flow (CBF) and reactivity. We utilised psychometric tests and validated questionnaires to assess cognition and depression. Highlanders exhibited elevated systemic OXINOS (P < 0.05 vs. lowlanders) that was especially exaggerated in the more hypoxaemic CMS+ patients (P < 0.05 vs. CMS−). OXINOS was associated with blunted cerebral perfusion and vasoreactivity to hypercapnia, impaired cognition and, in CMS+, symptoms of depression. Collectively, these findings are the first to suggest that a physiological continuum exists for hypoxaemia‐induced OXINOS in HA dwellers that when excessive is associated with accelerated cognitive decline and depression, helping identify those in need of specialist neurological assessment and support.

Young women exhibit higher prevalence of orthostatic hypotension with presyncopal symptoms compared to men. These symptoms could be influenced by an attenuated ability of the cerebrovasculature to respond to rapid blood pressure (BP) changes [dynamic cerebral autoregulation (dCA)]. The influence of sex on dCA remains unclear. dCA in 11 fit women (25 ± 2 years) and 11 age‐matched men (24 ± 1 years) was compared using a multimodal approach including a sit‐to‐stand (STS) and forced BP oscillations (repeated squat‐stand performed at 0.05 and 0.10 Hz). Prevalence of initial orthostatic hypotension (IOH; decrease in systolic ≥ 40 mmHg and/or diastolic BP ≥ 20 mmHg) during the first 15 sec of STS was determined as a functional outcome. In women, the decrease in mean middle cerebral artery blood velocity (MCAvmean) following the STS was greater (−20 ± 8 vs. −11 ± 7 cm sec−1; P = 0.018) and the onset of the regulatory change (time lapse between the beginning of the STS and the increase in the conductance index (MCAvmean/mean arterial pressure) was delayed (P = 0.007). Transfer function analysis gain during 0.05 Hz squat‐stand was ~48% higher in women (6.4 ± 1.3 vs. 3.8 ± 2.3 cm sec−1 mmHg−1; P = 0.017). Prevalence of IOH was comparable between groups (women: 4/9 vs. men: 5/9, P = 0.637). These results indicate the cerebrovasculature of fit women has an attenuated ability to react to rapid changes in BP in the face of preserved orthostasis, which could be related to higher resting cerebral blood flow allowing women to better face transient hypotension.

Women exhibit higher prevalence of orthostatic hypotension with presyncopal symptoms compared to men. These symptoms could be influenced by an attenuated ability of the cerebrovasculature to respond to rapid changes in blood pressure (BP) [dynamic cerebral autoregulation (dCA)]. However, the influence of sex on dCA remains equivocal. We compared dCA in 11 women (25 ± 2 y) and 11 age-matched men (24 ± 1 y) using a multimodal approach including a sit-to-stand maneuver and forced oscillations (5 min of squat-stand performed at 0.05 and 0.10 Hz). The prevalence of initial orthostatic hypotension (IOH; decrease in systolic ≥ 40 mmHg and/or diastolic BP ≥ 20 mmHg) during the first 15 sec of sit-to-stand was determined as a functional outcome. In women, the decrease in mean middle cerebral artery blood velocity (MCAvmean) following the sit-to-stand was greater (−20 ± 8 vs. -11 ± 7 cm sec-1; p=0.018) and the onset of the regulatory change (time lapse between the beginning of the sit-to-stand and the increase in the conductance index (MCAvmean/mean arterial pressure(MAP)) was delayed (p=0.007). Transfer function analysis gain during 0.05 Hz squat-stand was ∼48% higher in women (6.4 ± 1.3 vs. 3.8 ± 2.3 sec; p=0.017). The prevalence of IOH was comparable between groups (4/9 vs. 5/9, p=0.637). These results indicate the cerebrovasculature of healthy women has an attenuated ability to react to large and rapid changes in BP in the face of preserved orthostasis, which could be related to a higher cerebrovascular reserve to face a rapid transient hypotension.NEWS & NOTEWORTHYThe novel findings of this study are that healthy women have impaired dynamic cerebral autoregulation, although the prevalence of orthostatic intolerance was similar in women and men. These results indicate the cerebrovasculature of healthy women has an attenuated ability to react to large and rapid changes in blood pressure in the face of preserved orthostasis, which could be related to a higher cerebrovascular reserve to face a rapid transient hypotension.

ObjectivesTo determine the effect of heading a soccer ball on serum neurofilament light (NF-L) protein, plasma tau protein and symptom metrics including total number of symptoms reported and symptom severity scores on the Standardized Concussion Assessment Tool— 3rd edition (SCAT3).MethodsEleven male collegiate soccer players were recruited to take part in three experimental conditions including heading, sham and control conditions. Participants were required to perform 40 headers in 20 min in the heading condition, and control 40 soccer balls directed at them with their hands, chest or thigh in the sham condition. No ball contact was made during the control condition. Blood sampling and SCAT3 symptom assessments were completed prior to and 1 hour following conditions. A subset of participants returned 3 weeks following the heading condition for blood sampling.ResultsNF-L was elevated at 1 hour (p=0.004) and 1 month (p=0.04) following the heading condition, and at 1 hour (p=0.02) following the control condition. Tau levels remained unchanged following all conditions. The total number of symptoms (TS) and symptom severity (SS) scores from the SCAT3 were both elevated following the heading condition (p=0.01 and p=0.03, respectively). Both TS and SS decreased following sham (p=0.04 and p=0.04) and control conditions (p=0.04 and p=0.04).ConclusionAn acute bout of soccer heading is associated with increased NF-L concentrations at 1 hour and 1 month following the session and can lead to symptoms commonly reported following sport-related concussion.

We examined the between-day reproducibility of active (squat-stand maneuvers)- and passive [oscillatory lower-body negative pressure (OLBNP) maneuvers]-driven oscillations in blood pressure. These relationships were examined in both younger ( n = 10; 25 ± 3 yr) and older ( n = 9; 66 ± 4 yr) adults. Each testing protocol incorporated rest (5 min), followed by driven maneuvers at 0.05 (5 min) and 0.10 (5 min) Hz to increase blood-pressure variability and improve assessment of the pressure-flow dynamics using linear transfer function analysis. Beat-to-beat blood pressure, middle cerebral artery velocity, and end-tidal partial pressure of CO2 were monitored. The pressure-flow relationship was quantified in the very low (0.02-0.07 Hz) and low (0.07–0.20 Hz) frequencies (LF; spontaneous data) and at 0.05 and 0.10 Hz (driven maneuvers point estimates). Although there were no between-age differences, very few spontaneous and OLBNP transfer function metrics met the criteria for acceptable reproducibility, as reflected in a between-day, within-subject coefficient of variation (CoV) of

The cerebrovasculature is more efficient at compensating for pharmacologically induced transient hypertension versus transient hypotension. Whether this phenomenon exists during nonpharmacologically induced hypertension and hypotension is currently unknown. We compared the percent change in mean velocity in the middle cerebral artery (MCAvmean) per percent change in mean arterial pressure (MAP) (%ΔMCAVmean/%ΔMAP) during transient hypertension and hypotension induced during squat-stand maneuvers performed at 0.05 Hz (20-s cycles) and 0.10 Hz (10-s cycles) in 58 male volunteers. %ΔMCAvmean/%ΔMAP was attenuated by 25% ( P = 0.03, 0.05 Hz) and 47% ( P < 0.0001, 0.10 Hz) during transient hypertension versus hypotension. Thus, these findings indicate that the brain in healthy men is better adapted to compensate for physiologically relevant transient hypertension than hypotension. NEW & NOTEWORTHY The novel finding of this study is that the change in middle cerebral artery mean flow velocity is attenuated during hypertension compared with hypotension physiologically induced by oscillations in blood pressure in men. These results support that the human brain is more effective at compensating for transient hypertension than hypotension.