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Background: Although guidelines support aerobic exercise in sub-acute mild traumatic brain injury (mTBI), evidence for adults with persisting post-concussive symptoms (PPCS) after mTBI is lacking. The objective was to evaluate the impact of a sub-symptom threshold aerobic exercise intervention on overall symptom burden and quality of life in adults with PPCS. Methods: This prospective cohort study was nested within the ACTBI Trial (Aerobic Exercise for treatment of Chronic symptoms following mild Traumatic Brain Injury). A total of 50 adults with a diagnosis of mTBI, PPCS and exercise intolerance completed a 12-week sub-symptom threshold aerobic exercise intervention either immediately after enrollment (i-AEP group; n = 27) or following 6-weeks of stretching (d-AEP group; n = 23). Data from all participants (n = 50) were included in the combined AEP (c-AEP) group. The primary outcome was symptom burden on the Rivermead Post Concussion Symptoms Questionnaire (RPQ). Secondary outcomes included measures of quality of life and specific post-concussive symptoms (depressive and anxiety symptoms, functional impact of headache, fatigue, sleep, dizziness and exercise tolerance). Heart rate, blood pressure and heart rate variability were also assessed to understand autonomic function response to intervention. Results: Participants were a mean (SD) of 42.6 (10.9) years old (74% female) and 25.1 (14.1) months post-mTBI. Following 12-weeks of intervention participants had a significant improvement in symptom burden on the RPQ (i-AEP: mean change = −9.415, p < 0.001; d-AEP: mean change = −3.478, p = 0.034; c-AEP: mean change = −6.446, p < 0.001). Participants also had significant improvement in quality of life (i-AEP: mean change = 9.879, p < 0.001; d-AEP: mean change = 7.994, p < 0.001, c-AEP: mean change = 8.937, p < 0.001), dizziness (i-AEP: mean change = −11.159, p = 0.001; d-AEP: mean change = −6.516, p = 0.019; c-AEP: −8.837, p < 0.001) and exercise tolerance (i-AEP: mean change = 5.987, p < 0.001; d-AEP: mean change = 3.421, p < 0.001; c-AEP: mean change = 4.703, p < 0.001). Headache (mean change = −5.522, p < 0.001) and depressive symptoms (mean change = −3.032, p = 0.001) improved in the i-AEP group. There was no change in measures of autonomic function. Conclusion: A 12-week aerobic exercise intervention improves overall symptom burden, quality of life and specific symptom domains in adults with PPCS. Clinicians should consider prescription of progressive, individualized, sub-symptom threshold aerobic exercise for adults with PPCS even if presenting with exercise intolerance and months-to-years of symptoms. [ABSTRACT FROM AUTHOR]

This study applied alterations in partial pressure of end‐tidal carbon dioxide (PETCO2${{P}_{{\mathrm{ETC}}{{{\mathrm{O}}}_{\mathrm{2}}}}}$) to challenge dynamic cerebral autoregulation (dCA) responses across the cardiac cycle in both biological sexes. A total of 20 participants (10 females and 10 males; aged 19–34 years) performed 4‐min bouts of repeated squat–stand manoeuvres (SSMs) at 0.05 and 0.10 Hz (randomized orders) with PETCO2${{P}_{{\mathrm{ETC}}{{{\mathrm{O}}}_{\mathrm{2}}}}}$ clamped at ∼40 mmHg. The protocol was repeated for hypercapnic (∼55 mmHg) and hypocapnic (∼20 mmHg) conditions. Middle cerebral artery (MCA) and posterior cerebral artery (PCA) were insonated via transcranial Doppler ultrasound. Dynamic end‐tidal forcing clamped PETCO2${{P}_{{\mathrm{ETC}}{{{\mathrm{O}}}_{\mathrm{2}}}}}$, and finger photoplethysmography quantified beat‐to‐beat changes in blood pressure. Linear regressions were performed for transfer function analysis metrics including power spectrum densities, coherence, phase, gain and normalized gain (nGain) with adjustment for sex. During hypercapnic conditions, phase metrics were reduced from eucapnic levels (all P < 0.009), while phase increased during the hypocapnic stage during both 0.05 and 0.10 Hz SSMs (all P < 0.037). Sex differences were present with females displaying greater gain and nGain systole metrics during 0.10 Hz SSMs (all P < 0.041). Across PETCO2${{P}_{{\mathrm{ETC}}{{{\mathrm{O}}}_{\mathrm{2}}}}}$ stages, females displayed reduced buffering against systolic aspects of the cardiac cycle and augmented gain. Sex‐related variances in dCA could explain sex differences in the occurrence of clinical conditions such as orthostatic intolerance and stroke, though the effect of fluctuating sex hormones and contraceptive use on dCA metrics is not yet understood. What is the central question of this study?What is the influence partial pressure of end tidal carbon dioxide (PETCO2${{P}_{{\mathrm{ETC}}{{{\mathrm{O}}}_{\mathrm{2}}}}}$) on dynamic cerebral autoregulation (dCA) across all aspects of the cardiac cycle during hypocapnia, eucapnia and hypercapnia, and are biological sex differences observed in the responses?What is the main finding and its importance?There was delayed dCA response in hypercapnia and enhanced dCA during hypocapnia. Biological sex differences were most evident during 0.10 Hz squat–stand manoeuvres. Middle cerebral artery systolic gain and nGain were lower in males compared to females. [ABSTRACT FROM AUTHOR]

In this review, we have amalgamated the literature, taking a multimodal neuroimaging approach to quantify the relationship between neuronal firing and haemodynamics during a task paradigm (i.e., neurovascular coupling response), while considering confounding physiological influences. Original research articles that used concurrent neuronal and haemodynamic quantification in humans (n ≥ 10) during a task paradigm were included from PubMed, Scopus, Web of Science, EMBASE and PsychINFO. Articles published before 31 July 2023 were considered for eligibility. Rapid screening was completed by the first author. Two authors completed the title/abstract and full‐text screening. Article quality was assessed using a modified version of the National Institutes of Health Quality Assessment Tool for Observational Cohort and Cross‐Sectional Studies. A total of 364 articles were included following title/abstract and full‐text screening. The most common combination was EEG/functional MRI (68.7%), with cognitive (48.1%) and visual (27.5%) tasks being the most common. The majority of studies displayed an absence/minimal control of blood pressure, arterial gas concentrations and/or heart rate (92.9%), and only 1.3% monitored these factors. A minority of studies restricted or collected data pertaining to caffeine (7.4%), exercise (0.8%), food (0.5%), nicotine (2.7%), the menstrual cycle (0.3%) or cardiorespiratory fitness levels (0.5%). The cerebrovasculature is sensitive to numerous factors; thus, to understand the neurovascular coupling response fully, better control for confounding physiological influences of blood pressure and respiratory metrics is imperative during study‐design formulation. Moreover, further work should continue to examine sex‐based differences, the influence of sex steroid hormone concentrations and cardiorespiratory fitness. What is the topic of this review?This review examines literature using simultaneous multimodal neuroimaging to measure the relationship between neuronal firing and haemodynamics during task paradigms (i.e., neurovascular coupling). This review focuses on the control of physiological, psychological and lifestyle factors of the included articles.What advances does it highlight?The review underscores the critical need for improved control of physiological and lifestyle confounders, such as blood pressure, carbon dioxide levels, caffeine intake, exercise, menstrual cycle phase and sex comparisons, in study designs to ensure more accurate and reliable findings in neurovascular coupling research. [ABSTRACT FROM AUTHOR]

There are differences within the literature regarding the upper frequency cut‐off point of the dynamic cerebral autoregulation (CA) high‐pass filter. The projection pursuit regression approach has demonstrated that the upper frequency limit is ∼0.07 Hz, whereas another approach [transfer function analysis (TFA) phase approaching zero] indicated a theoretical upper frequency limit for the high‐pass filter of 0.24 Hz. We investigated how these limits accurately represent the CA upper frequency limit, in addition to extending earlier findings with respect to biological sexes and across the cardiac cycle. Sixteen participants (nine females and seven males) performed repeated squat–stand manoeuvres at frequencies of 0.05, 0.10, 0.15, 0.20 and 0.25 Hz, with insonation of the middle and posterior cerebral arteries. Linear regression modelling with adjustment for sex and order of squat completion was used to compared TFA gain and phase with 0.25 Hz (above the theoretical limit of CA). The upper frequency limit of CA with TFA gain was within the range of 0.05–0.10 Hz, whereas TFA phase was within the range of 0.20–0.25 Hz, and consistent between vessels, between sexes and across the cardiac cycle. Females displayed greater middle cerebral artery gain compared with males (all P < 0.047), and no phase differences were present (all P > 0.072). Although sex‐specific differences were present for specific TFA metrics at a given frequency, the upper frequency limit of autoregulation was similar between cerebral conduit vessels, cardiac cycle phase and biological sex. Future work is warranted to determine whether an upper frequency limit exists with respect to hysteresis analyses. What is the central question of this study?There is conflict in the current literature regarding the upper frequency limit of dynamic cerebral autoregulation, with proposed limits ranging from 0.07 to 0.24 Hz. The vast majority of previous work on the upper cerebral autoregulation frequency limit has been performed in males and with mean blood pressure and cerebral blood velocity.What is the main finding and its importance?The upper frequency limit for gain was 0.05–0.10 Hz and for phase it was 0.20–0.25 Hz. This occurred irrespective of cardiac cycle phase or biological sex. [ABSTRACT FROM AUTHOR]

Cerebral hemodynamics have been quantified during exercise via transcranial Doppler ultrasound, as it has high-sensitivity to movement artifacts and displays temporal superiority. Currently, limited research exists regarding how different exercise modalities and postural changes impact the cerebrovasculature across the cardiac cycle. Ten participants (4 females and 6 males) ages 20–29 completed three exercise tests (treadmill, supine, and upright cycling) to volitional fatigue. Physiological data collected included middle cerebral artery velocity (MCAv), blood pressure (BP), heart rate, and respiratory parameters. Normalized data were analyzed for variance and effect sizes were calculated to examine differences between physiological measures across the three exercise modalities. Systolic MCAv was greater during treadmill compared to supine and upright cycling (p < 0.001, (large) effect size), and greater during upright versus supine cycling (p < 0.017, (large)). Diastolic MCAv was lower during treadmill versus cycling exercise only at 60% maximal effort (p < 0.005, (moderate)) and no differences were observed between upright and supine cycling. No main effect was found for mean and diastolic BP (p > 0.05, (negligible)). Systolic BP was lower during treadmill versus supine cycling at 40% and 60% intensity (p < 0.05, (moderate–large)) and greater during supine versus upright at only 60% intensity (p < 0.003, (moderate)). The above differences were not explained by partial pressure of end-tidal carbon dioxide levels (main effect: p = 0.432). The current study demonstrates the cerebrovascular and cardiovascular systems respond heterogeneously to different exercise modalities and aspects of the cardiac cycle. As physiological data were largely similar between tests, differences associated with posture and modality are likely contributors. [ABSTRACT FROM AUTHOR]

Background: Sport-related concussions are a complex injury requiring multifaceted assessment, including physical exertion. Currently, concussion testing relies primarily on a treadmill-based protocol for assessing exertion-related symptoms in persons after concussion. This study compared a modified cycle protocol (Calgary Concussion Cycle Test [CCCT]) with the clinically adopted standard, the Buffalo Concussion Treadmill Test (BCTT), across multiple physiological parameters. Hypothesis: Treadmill and cycle matched workload protocols would produce similar results for cerebral blood velocity, mean arterial pressure (MAP), and end-tidal carbon dioxide partial pressure (PETCO2), but heart rate (HR) and oxygen consumption (VO2) would be higher on the treadmill than the cycle modality. Study Design: Crossover study design. Level of Evidence: Level 3. Methods: A total of 17 healthy adults (8 men, 9 women; age, 26 ± 3 years; body mass index, 23.8 ± 2.7 kg/m2) completed the BCTT and CCCT protocols, 7 days apart in a randomized order. During both exertional protocols, the physiological parameters measured were middle cerebral artery mean blood velocity (MCAv), MAP, PETCO2, VO2, and HR. Analysis of variance with effect size computations, coefficient of variation, and Bland-Altman plots with 95% limits of agreement were used to compare exercise tests. Results: The BCTT and CCCT produced comparable results for both male and female participants with no significant differences for average MCAv, MAP, and PETCO2 (all P > 0.05; all generalized eta squared [η2G] < 0.02 [negligible]; P value range, 0.29-0.99) between stages. When accounting for exercise stage and modality, VO2 (P < 0.01) and HR (P < 0.01) were higher on the treadmill compared with the cycle. Aside from the final few stages, all physiology measures displayed good-to-excellent agreeability/variability. Conclusion: The CCCT was physiologically similar to the BCTT in terms of MCAv, PETCO2, and MAP; however, HR and VO2 differed between modalities. Clinical Relevance: Providing a cycle-based modality to exertional testing after injury may increase accessibility to determine symptom thresholds in the future. [ABSTRACT FROM AUTHOR]

Highlights To examine the feasibility, utility and safety of superimposed lower body negative pressure (LBNP) and tilt during supine cycling in individuals suffering from persisting post‐concussive symptoms (PPCS). Eleven individuals aged 17–31 (6 females/5 males) participated in two randomized separate visits, 1 week apart. A ramp‐incremental test was performed during both visits until volitional failure. Visits included no pressure (control) or LBNP at −40 Torr (experimental) with head‐up tilt at 15 degrees (females) or 30 degrees (males). Transcranial Doppler ultrasound was utilized to quantify middle cerebral artery velocity (MCAv), while symptom reports were filled out before and 0, 10, and 60 min post‐exertion. Ratings of exertion and overall condition followed similar trends for participants across both tests. The relative increase in MCAv was blunted during the experimental condition (8%) compared to control (24%), while a greater heart rate (17 beats/min) was achieved during the LBNP condition (P = 0.047). Symptom severity at the 0 and 10 min post‐exertion time points displayed negligible‐to‐small effect sizes between conditions (Wilcoxon's r < 0.11). Symptom reporting was lower at the 60 min post‐exertion time point with these displaying a moderate effect size (Wilcoxon's r = 0.31). The combination of LBNP and tilt during supine cycling did not change the participants’ subjective interpretation of the exertional test but attenuated the hyperpnia‐induced vasodilatory MCAv response, while also enabling participants to achieve a higher heart rate during exercise and reduced symptoms 1 h later. As this protocol is safe and feasible, further research is warranted in this area for developing PPCS treatment options. What is the central question of this study? What are the feasibility, safety and utility of combining head‐up tilt with lower body negative pressure during supine cycling for blunting the increase in cerebral blood velocity seen during moderate‐intensity exercise in individuals experiencing persisting post‐concussion symptoms? What is the main finding and its importance? Although no differences were found in symptoms between conditions within the first 10 min following exertion, symptom severity scores showed a clinically meaningful reduction 60 min following the experimental condition compared to the non‐experimental control condition. What is the central question of this study?What are the feasibility, safety and utility of combining head‐up tilt with lower body negative pressure during supine cycling for blunting the increase in cerebral blood velocity seen during moderate‐intensity exercise in individuals experiencing persisting post‐concussion symptoms?What is the main finding and its importance?Although no differences were found in symptoms between conditions within the first 10 min following exertion, symptom severity scores showed a clinically meaningful reduction 60 min following the experimental condition compared to the non‐experimental control condition. [ABSTRACT FROM AUTHOR]

Numerous driven techniques have been utilized to assess dynamic cerebral autoregulation (dCA) in healthy and clinical populations. The current review aimed to amalgamate this literature and provide recommendations to create greater standardization for future research. The PubMed database was searched with inclusion criteria consisting of original research articles using driven dCA assessments in humans. Risk of bias were completed using Scottish Intercollegiate Guidelines Network and Methodological Index for Non-Randomized Studies. Meta-analyses were conducted for coherence, phase, and gain metrics at 0.05 and 0.10 Hz using deep-breathing, oscillatory lower body negative pressure (OLBNP), sit-to-stand maneuvers, and squat-stand maneuvers. A total of 113 studies were included, with 40 of these incorporating clinical populations. A total of 4126 participants were identified, with younger adults (18–40 years) being the most studied population. The most common techniques were squat-stands (n = 43), deep-breathing (n = 25), OLBNP (n = 20), and sit-to-stands (n = 16). Pooled coherence point estimates were: OLBNP 0.70 (95%CI:0.59–0.82), sit-to-stands 0.87 (95%CI:0.79–0.95), and squat-stands 0.98 (95%CI:0.98–0.99) at 0.05 Hz; and deep-breathing 0.90 (95%CI:0.81–0.99); OLBNP 0.67 (95%CI:0.44–0.90); and squat-stands 0.99 (95%CI:0.99–0.99) at 0.10 Hz. This review summarizes clinical findings, discusses the pros/cons of the 11 unique driven techniques included, and provides recommendations for future investigations into the unique physiological intricacies of dCA. [ABSTRACT FROM AUTHOR]

Sport-related concussion (SRC) can impair the cerebrovasculature both acutely and chronically. Transcranial Doppler (TCD) ultrasound assessment has the potential to illuminate the mechanisms of impairment and provide an objective evaluation of SRC. The current systematic review investigated studies employing TCD ultrasound assessment of intracranial arteries across three broad categories of cerebrovascular regulation: neurovascular coupling (NVC), cerebrovascular reactivity (CVR), and dynamic cerebral autoregulation (dCA). The current review was registered in the International Prospective Register of Systematic Reviews (PROSPERO) database (CRD42021275627). The search strategy was applied to PubMed, as this database indexes all biomedical journals. Original articles on TCD for athletes with medically diagnosed SRC were included. Title/abstract and full-text screening were completed by three authors. Two authors completed data extraction and risk of bias using the Methodological Index for Non-Randomized Studies and Scottish Intercollegiate Guideline Network checklists. Of the 141 articles identified, 14 met the eligibility criteria. One article used an NVC challenge, eight assessed CVR, and six investigated dCA. Methodologies varied widely among studies, and results were heterogeneous. There was evidence of cerebrovascular impairment in all three domains roughly 2 days post-SRC, but the magnitude and recovery of these impairments were not clear. There was evidence that clinical symptom resolution occurred before cerebrovascular function, indicating that physiological deficits may persist despite clinical recovery and return to play. Collectively, this emphasizes an opportunity for the use of TCD to illuminate the cerebrovascular deficits caused by SRC. It also highlights that there is need for consistent methodological rigor when employing TCD in a SRC population. [ABSTRACT FROM AUTHOR]

Introduction: Concussion is known to cause transient autonomic and cerebrovascular dysregulation that generally recovers; however, few studies have focused on individuals with an extensive concussion history. Method: The case was a 26-year-old male with a history of 10 concussions, diagnosed for bipolar type II disorder, mild attention-deficit hyperactivity disorder, and a history of migraines/headaches. The case was medicated with Valproic Acid and Escitalopram. Sensor-based baseline data were collected within six months of his injury and on days 1–5, 10, and 14 post-injury. Symptom reporting, heart rate variability (HRV), neurovascular coupling (NVC), and dynamic cerebral autoregulation (dCA) assessments were completed using numerous biomedical devices (i.e., transcranial Doppler ultrasound, 3-lead electrocardiography, finger photoplethysmography). Results: Total symptom and symptom severity scores were higher for the first-week post-injury, with physical and emotional symptoms being the most impacted. The NVC response showed lowered activation in the first three days post-injury, while autonomic (HRV) and autoregulation (dCA) were impaired across all testing visits occurring in the first 14 days following his concussion. Conclusions: Despite symptom resolution, the case demonstrated ongoing autonomic and autoregulatory dysfunction. Larger samples examining individuals with an extensive history of concussion are warranted to understand the chronic physiological changes that occur following cumulative concussions through biosensing devices. [ABSTRACT FROM AUTHOR]

Driven and spontaneous methods have been used to quantify the cerebral pressure-flow relationship via transfer function analysis (TFA). Commonly, TFA derived estimates are assessed using band averages within the very-low (0.02–0.07 Hz) and low (0.07–0.20 Hz) frequency during spontaneous oscillations but are quantified at frequencies of interest where blood pressure oscillations are driven (e.g., 0.05 and/or 0.10 Hz). Driven estimates more closely resemble the autoregulatory challenges individuals experience on a daily basis, while also eliciting higher levels of reliability. While driven estimates with point-estimates are not feasible for all clinical populations, these approaches increase the ability to understand pathophysiological changes. [ABSTRACT FROM AUTHOR]

Frequency-domain near-infrared spectroscopy (FD-NIRS) has been used for non-invasive assessment of cortical oxygenation since the late 1990s. However, there is limited research demonstrating clinical validity and general reproducibility. To address this limitation, recording duration for adequate validity and within- and between-day reproducibility of prefrontal cortical oxygenation was evaluated. To assess validity, a reverse analysis of 10-min-long measurements (n = 52) at different recording durations (1–10-min) was quantified via coefficients of variation and Bland–Altman plots. To assess within- and between-day within-subject reproducibility, participants (n = 15) completed 2-min measurements twice a day (morning/afternoon) for five consecutive days. While 1-min recordings demonstrated sufficient validity for the assessment of oxygen saturation (StO2) and total hemoglobin concentration (THb), recordings ≥4 min revealed greater clinical utility for oxy- (HbO) and deoxyhemoglobin (HHb) concentration. Females had lower StO2, THb, HbO, and HHb values than males, but variability was approximately equal between sexes. Intraclass correlation coefficients ranged from 0.50–0.96. The minimal detectable change for StO2 was 1.15% (95% CI: 0.336–1.96%) and 3.12 µM for THb (95% CI: 0.915–5.33 µM) for females and 2.75% (95%CI: 0.807–4.70%) for StO2 and 5.51 µM (95%CI: 1.62–9.42 µM) for THb in males. Overall, FD-NIRS demonstrated good levels of between-day reliability. These findings support the application of FD-NIRS in field-based settings and indicate a recording duration of 1 min allows for valid measures; however, data recordings of ≥4 min are recommended when feasible. [ABSTRACT FROM AUTHOR]

Wearable technology and neuroimaging equipment using photoplethysmography (PPG) have become increasingly popularized in recent years. Several investigations deriving pulse rate variability (PRV) from PPG have demonstrated that a slight bias exists compared to concurrent heart rate variability (HRV) estimates. PPG devices commonly sample at ~20–100 Hz, where the minimum sampling frequency to derive valid PRV metrics is unknown. Further, due to different autonomic innervation, it is unknown if PRV metrics are harmonious between the cerebral and peripheral vasculature. Cardiac activity via electrocardiography (ECG) and PPG were obtained concurrently in 54 participants (29 females) in an upright orthostatic position. PPG data were collected at three anatomical locations: left third phalanx, middle cerebral artery, and posterior cerebral artery using a Finapres NOVA device and transcranial Doppler ultrasound. Data were sampled for five minutes at 1000 Hz and downsampled to frequencies ranging from 20 to 500 Hz. HRV (via ECG) and PRV (via PPG) were quantified and compared at 1000 Hz using Bland–Altman plots and coefficient of variation (CoV). A sampling frequency of ~100–200 Hz was required to produce PRV metrics with a bias of less than 2%, while a sampling rate of ~40–50 Hz elicited a bias smaller than 20%. At 1000 Hz, time- and frequency-domain PRV measures were slightly elevated compared to those derived from HRV (mean bias: ~1–8%). In conjunction with previous reports, PRV and HRV were not surrogate biomarkers due to the different nature of the collected waveforms. Nevertheless, PRV estimates displayed greater validity at a lower sampling rate compared to HRV estimates. [ABSTRACT FROM AUTHOR]

To compare the construct validity and between‐day reliability of projection pursuit regression (PPR) from oscillatory lower body negative pressure (OLBNP) and squat‐stand maneuvers (SSMs). Nineteen participants completed 5 min of OLBNP and SSMs at driven frequencies of 0.05 and 0.10 Hz across two visits. Autoregulatory plateaus were derived at both point‐estimates and across the cardiac cycle. Between‐day reliability was assessed with intraclass correlation coefficients (ICCs), Bland–Altman plots with 95% limits of agreement (LOA), coefficient of variation (CoV), and smallest real differences. Construct validity between OLBNP‐SSMs were quantified with Bland–Altman plots and Cohen's d. The expected autoregulatory curve with positive rising and negative falling slopes were present in only ~23% of the data. The between‐day reliability for the ICCs were poor‐to‐good with the CoV estimates ranging from ~50% to 70%. The 95% LOA were very wide with an average spread of ~450% for OLBNP and ~350% for SSMs. Plateaus were larger from SSMs compared to OLBNPs (moderate‐to‐large effect sizes). The cerebral pressure‐flow relationship is a complex regulatory process, and the "black‐box" nature of this system can make it challenging to quantify. The current data reveals PPR analysis does not always elicit a clear‐cut central plateau with distinctive rising/falling slopes. [ABSTRACT FROM AUTHOR]

Purpose: Patients with dysautonomia often experience symptoms such as dizziness, syncope, blurred vision and brain fog. Dynamic cerebral autoregulation, or the ability of the cerebrovasculature to react to transient changes in arterial blood pressure, could be associated with these symptoms. Methods: In this narrative review, we go beyond the classical view of cerebral autoregulation to discuss dynamic cerebral autoregulation, focusing on recent advances pitfalls and future directions. Results: Following some historical background, this narrative review provides a brief overview of the concept of cerebral autoregulation, with a focus on the quantification of dynamic cerebral autoregulation. We then discuss the main protocols and analytical approaches to assess dynamic cerebral autoregulation, including recent advances and important issues which need to be tackled. Conclusion: The researcher or clinician new to this field needs an adequate comprehension of the toolbox they have to adequately assess, and interpret, the complex relationship between arterial blood pressure and cerebral blood flow in healthy individuals and clinical populations, including patients with autonomic disorders. [ABSTRACT FROM AUTHOR]

This article discusses a study that examined the influence of sex on the reliability of cerebral blood velocity regulation during lower body negative pressure (LBNP) and supine cycling, with considerations of the menstrual cycle. The study found that both males and females displayed high levels of reliability for cerebral blood velocity metrics during the LBNP cycling protocol, but there were sex differences in middle cerebral artery velocity, blood pressure, and heart rate. The study suggests that future LBNP studies can include females at any menstrual cycle stage. [Extracted from the article]

Moderate-intensity aerobic exercise increases cerebral blood velocity (CBv) primarily due to hyperpnea-induced vasodilation; however, the integrative control of cerebral blood flow (CBF) allows other factors to contribute to the vasodilation. Although lower body negative pressure (LBNP) can reduce CBv, the exact LBNP intensity required to blunt the aforementioned exercise-induced CBv response is unknown. This could hold utility for concussion recovery, allowing individuals to exercise at higher intensities without symptom exacerbation. Thirty-two healthy adults (age: 20–33 yr; 19 females/13 males) completed a stepwise maximal exercise test during a first visit to determine each participant’s wattage associated with their exercise-induced maximal CBv increase. During the second visit, following supine rest, participants completed moderate-intensity exercise at their determined threshold, while progressive LBNP was applied at 0, −20, −40, −60, −70, −80, and ∼88 Torr. Bilateral middle cerebral artery blood velocities (MCAvs), mean arterial pressure (MAP), heart rate, respiratory rate, and end-tidal carbon dioxide levels were measured continuously. Two-way analysis of variance with effect sizes compared between sexes and stages. Compared with resting supine baseline, averaged MCAv was elevated during 0 and −20 Torr LBNP (q value > 7.73; P < 0.001); however, no differences were noted between baseline and −40 to −70 Torr (q value < |4.24|; P > 0.262). Differences were present between females and males for absolute MCAv measures (q value > 11.2; P < 0.001), but not when normalized to baseline (q value < 0.03; P > 0.951). Supine cycling-elicited increases in MCAv are able to be blunted during the application of LBNP ranging from −40 to −70 Torr. The blunted CBv response demonstrates the potential benefit of allowing individuals to aerobically train (moderate-intensity supine cycling with LBNP) without exacerbating symptoms during the concussion recovery phase. NEW & NOTEWORTHY The current investigation demonstrated that moderate-intensity supine cycling-induced increases in cerebral blood velocities were balanced by the lower body negative pressure-induced decreases in cerebral blood velocity. Although performed in a healthy population, the results may lend themselves to a potential treatment option for individuals recovering from concussion or experience persistent concussion symptoms. [ABSTRACT FROM AUTHOR]

The article discusses the experience of graduate students in physiology-based programs in Canada, focusing on imposter syndrome as a common phenomenon. It explores how feelings of inadequacy and doubt can impact project advancement and personal development, emphasizing the importance of embracing rejection and failure as opportunities for growth. The author shares personal experiences and insights on navigating imposter syndrome, highlighting the transformative nature of graduate school and the significance of the defense process as a culmination of learning and growth. [Extracted from the article]

This investigation explored the impact of partial pressure of end-tidal carbon dioxide (PETCO2) alterations on temporal neurovascular coupling (NVC) responses across the cardiac cycle and the influence of biological sex via a complex visual scene-search task (“Where’s Waldo?”). 10 females and 10 males completed five puzzles, each with 40 seconds of eyes open and 20 seconds of eyes closed, under PETCO2 clamped at ∼40 mmHg (eucapnia), ∼55 mmHg (hypercapnia), and ∼25 mmHg (hypocapnia). Cerebral blood velocity (CBv) in the middle and posterior cerebral arteries (MCAv, PCAv) were measured via Transcranial Doppler ultrasound. Linear mixed-effects models with participants as a random effect analyzed NVC metrics, including baseline and peak CBv, relative increase, and area-under-the-curve (AUC30). During hypercapnic trials, reductions in PCAv and MCAv AUC30 were noted across the cardiac cycle (all p < 0.001). Hypocapnic PCAv AUC30 was reduced (all p < 0.012), as was systolic MCAv AUC30 (p = 0.003). Females displayed greater baseline PCA diastole (p = 0.048). No other biological sex differences were observed across conditions in baseline (all p > 0.050), peak (all p > 0.054), relative increase (all p > 0.511), and AUC30 metrics (all p > 0.514). Despite differences in responses to hypercapnic and hypocapnic stimuli, NVC responses to complex visual tasks remain robust, across the physiological CO2 range. [ABSTRACT FROM AUTHOR]

To determine the stability of the Sport Concussion Assessment Tool (SCAT) 5 between consecutive seasons in uninjured collision and combative varsity athletes. Thirty-six athletes (19 females) were recruited to participate (wrestling [n = 12], rugby [n = 14], and hockey [n = 10]). The SCAT5 was administration at the start of the 2017 and 2018 seasons. Median baseline demographics for 2017 were as follows: age (19 years [range: 17–24 years]), height (174 cm [range: 149–195 cm]), and weight (76 kg [range: 57–118 kg]). Outcome metrics included subcomponents of the SCAT5: symptom reporting, standardized assessment of concussion (SAC), neurological screening, and balance performance measured with the modified balance error scoring system (mBESS). Wilcoxon signed-rank tests and Cronbach's alpha (α) values were calculated to determine the stability between consecutive years for the SCAT5 variables in the same cohort of athletes. Bonferroni corrections were applied for Wilcoxon signed-rank tests, where alpha = 0.006 (0.05/9). Between the 2017 and 2018 seasons, no differences were noted in symptom reporting (p = 0.14), SAC (p = 0.32), neurological screening (p = 0.98), and balance performance on the mBESS (p = 0.01). The Cronbach's alpha displayed unacceptable to questionable levels of within-subject stability (range: α = 0.34–0.70) for all subcomponents, except months in reverse order (α = 0.92). While no statistical differences were present for all SCAT5 subcomponent metrics between 2017 and 2018 baselines, all but one displayed unacceptable to questionable stability (α ≤ 0.70) when retested one year later. Further research is needed to understand the appropriate time duration baseline SCAT5 values can reliably be utilized within longitudinal studies; as well as the normal variation of SCAT5 reporting/scoring. [ABSTRACT FROM AUTHOR]

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 (<20%) to excellent (<5%) with five-or-more trials. Employing fewer than five trials produced poor/unacceptable ICC and CoV metrics. Future NVC, TCD-based research should therefore have participants complete a minimum of five trials when quantifying the NVC response with TCD via a " Where's Waldo? " paradigm. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Sinusoidal squat‐stand maneuvers (SSM) without resistance have been shown to produce ~30–50 mmHg swings in mean arterial pressure which are largely buffered in the brain via dynamic cerebral autoregulation (dCA). This study aimed to further elucidate how this regulatory mechanism is affected during SSM with added resistance (~20% bodyweight). Twenty‐five participants (sex/gender: 13 females/12 males) completed two bouts of 5‐min SSM for both bodyweight and resistance conditions (10% bodyweight in each arm) at frequencies of 0.05 Hz (20‐s squat/stand cycles) and 0.10 Hz (10‐s squat/stand cycles). Middle and posterior cerebral artery (MCA/PCA) cerebral blood velocities were indexed with transcranial Doppler ultrasound. Beat‐to‐beat blood pressure (BP) was quantified via finger photoplesmography. Transfer function analysis was employed to quantify dCA in both cerebral arteries across the cardiac cycle (diastole, mean, and systole). Two‐by‐two Analysis of Variance with generalized eta squared effect sizes were utilized to determine differences between resistance vs. bodyweight squats and between sexes/genders. Absolute mean and diastolic BP were elevated during the resistance squats (p < 0.001); however, only the BP point‐estimate power spectrum densities were augmented at 0.10 Hz (p < 0.048). No differences were noted for phase and gain metrics between bodyweight and resistance SSM (p > 0.067); however, females displayed attenuated systolic regulation (p < 0.003). Despite augmented systemic BP during resistance SSM, the brain was effective at buffering the additional stress to mitigate overperfusion/pressure. Females displayed less dCA regulation within the systolic aspect of the cardiac cycle, which may be associated with physiological underpinnings related to various clinical conditions/presentations. [ABSTRACT FROM AUTHOR]

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 (<18 yr). Participants were seen within 1-2 wk after SRC for acute studies and 4 wk after SRC for studies focused on prolonged recoveries, which are standard timelines across the literature. Twenty-two studies met the inclusion criteria [i.e., 8 regarding physical activity (PA-daily aerobic activity including light and moderate intensities), 8 evaluating active rehabilitation/exercise programs (20 min of daily aerobic exercise below symptom threshold), 6 examining a single bout of exertion]. The methodological quality of the literature was assessed using the Downs and Black risk of bias (ROB) checklist. The ROB scores ranged from 7 to 24, with only two randomized controlled trials included. Studies demonstrated that single bouts of exertion testing were safe and feasible. Daily PA or active rehabilitation/exercise programs led to a reduction in symptoms present and a decrease in number of days to medical clearance. Following a brief period of rest (24-48 h), individuals may gradually and safely return to PA below their physical symptom exacerbation thresholds. Further research is warranted to delineate how to optimize the timing, intensity, duration, and modality of PA impacts symptom resolution and physiological recovery following different subtypes of SRC. [ABSTRACT FROM AUTHOR]

A simple bodyweight squat is sufficient to cause substantial stress on the autonomic nervous system (ANS) via ~30–50 mmHg blood pressure (BP) oscillations. However, it is unknown to the extent of the ANS is impacted during and immediately following bodyweight and resistance squat‐stand maneuvers (SSM) while considering chromosomal sex. Thirteen females and twelve males performed four, 5‐minute bouts of squat‐stand maneuvers (SSM); two at 0.05 Hz (10‐second squat/10‐second stand) and two at 0.10 Hz (5‐s squat/5‐s stand). The SSM were performed using bodyweight resistance and additional external resistance (~20% of bodyweight). Five‐minutes of quiet‐sitting and quiet‐standing were completed immediately following both bodyweight and resistance squats. Heart rate variability (HRV) and baroreceptor sensitivity metrics were extracted from beat‐to‐beat electrocardiography and systemic BP recordings. Repeated measure Analysis of Variance with generalized eta‐squared effect sizes assessed differences between SSM task type and chromosomal sex on ANS metrics. Despite added resistance eliciting greater elevations in blood pressure, no differences in ANS function were noted during competition and recovery between SSM tasks (all p > 0.050; negligible/small effect sizes). During recovery, females had an elevated heart rate (p = 0.017; small effect size), greater time‐domain HRV measures (p < 0.047; small effect size), greater high‐frequency domain HRV measures (p = 0.002; moderate effect size), and reduced low‐frequency domain HRV measures (p = 0.002; moderate effect size). A healthy ANS can modulate repetitive cardiovascular stressors via squat‐stand maneuvers in a harmonious manner irrespective of added low‐level resistance. Females were more parasympathetically driven following low‐level resistance exercise/stress, which may be a cardioprotective trait. [ABSTRACT FROM AUTHOR]

The cerebral pressure-flow relationship has directional sensitivity, meaning the augmentation in cerebral blood flow is attenuated when mean arterial pressure (MAP) increases versus MAP decreases. We used repeated squat-stands (RSS) to quantify it using a novel metric. However, its within-day reproducibility and the impacts of diurnal variation and biological sex are unknown. Study aims were to evaluate this metric for: 1) within-day reproducibility and diurnal variation in middle cerebral artery (MCA; ΔMCAvT/ ΔMAPT) and posterior cerebral artery (PCA; ΔPCAvT/ ΔMAPT) and 2) sex differences. ΔMCAvT/ ΔMAPT and ΔPCAvT/ ΔMAPT were calculated at 7 timepoints (08:00–17:00) in 18 participants (8 women; 24 ± 3 yr) using the minimum-to-maximum MCAv or PCAv and MAP for each RSS at 0.05 Hz and 0.10 Hz. Relative metric values were also calculated (%MCAvT/%MAPT, %PCAvT/%MAPT). Intraclass correlation coefficient (ICC) evaluated reproducibility, which was good (0.75–0.90) to excellent (>0.90). Time-of-day impacted ΔMCAvT/ ΔMAPT (0.05 Hz: P = 0.002; 0.10 Hz: P = 0.001), %MCAvT/%MAPT (0.05 Hz: P = 0.035; 0.10 Hz: P = 0.009), and ΔPCAvT/ ΔMAPT (0.05 Hz: P = 0.024), albeit with small/negligible effect sizes. MAP direction impacted both arteries’ metric at 0.10 Hz (all P < 0.024). Sex differences in the MCA only (P = 0.003) vanished when reported in relative terms. These findings demonstrate that this metric is reproducible throughout the day in the MCA and PCA and is not impacted by biological sex. [ABSTRACT FROM AUTHOR]

Previous research has highlighted that squat-stand maneuvers (SSMs) augment coherence values within the cerebral pressure- flow relationship to ~0.99. However, it is not fully elucidated if mean arterial pressure (MAP) leads to this physiological entrainment independently, or if heart rate (HR) and/or the partial pressure of carbon dioxide (PCO2) also have contributing influences. A 2:1 control-to-case model was used in the present investigation [participant number (n) = 40; n = 16 age-matched (AM); n = 16 donor control (DM); n = 8 heart transplant recipients (HTRs)]. The latter group was used to mechanistically isolate the extent to which HR influences the cerebral pressure-flow relationship. Participants completed 5 min of squat-stand maneuvers at 0.05 Hz (10 s) and 0.10 Hz (5 s). Linear transfer function analysis (TFA) examined the relationship between different physiological inputs (i.e., MAP, HR, and PCO2) and output [cerebral blood velocity (CBV)] during SSM; and cardiac baroreceptor sensitivity (BRS). Compared with DM, cardiac BRS was reduced in AM (P < 0.001), which was further reduced in HTR (P < 0.045). In addition, during the SSM, HR was elevated in HTR compared with both control groups (P < 0.001), but all groups had near-maximal coherence metrics ≥0.98 at 0.05 Hz and ≥0.99 at 0.10 Hz (P ≥0.399). In contrast, the mean HR-CBV/PCO2-CBV relationships ranged from 0.38 (HTR) to 0.81 (DM). Despite near abolishment of BRS and blunted HR following heart transplantation, long-term HTR exhibited near-maximal coherence within the MAP-CBV relationship, comparable with AM and DM. Therefore, these results show that the augmented coherence with SSM is driven by blood pressure, whereas elevations in TFA coherence as a result of HR contribution are likely correlational in nature. [ABSTRACT FROM AUTHOR]

After concussion, a multifaceted assessment is recommended, including tests of physical exertion. The current criterion standard for exercise testing after concussion is the Buffalo Concussion Treadmill Test (BCTT); however, validated tests that use alternative exercise modalities are lacking. To evaluate the feasibility and concurrent validity of a universal cycling test of exertion compared with the BCTT in adults who sustained a sport-related concussion. Crossover study. University sports medicine clinic. Twenty adults (age = 18–60 years) diagnosed with a sport-related concussion. Participants completed the BCTT and a cycling test of exertion in random order, approximately 48 hours apart. The primary outcome of interest was maximum heart rate (HRmax; beats per minute [bpm]). Secondary outcomes of interest were the total number of symptoms endorsed on the Post-Concussion Symptom Scale, whether the participant reached volitional fatigue (yes or no), the symptom responsible for test cessation (Post-Concussion Symptom Scale), maximum rating of perceived exertion, symptom severity on a visual scale (0–10), and the time to test cessation. Of the 20 participants, 19 (10 males, 9 females) completed both tests. One participant did not return for the second test and was excluded from the analysis. No adverse events were reported. The median HRmax for the BCTT (171 bpm; interquartile range = 139–184 bpm) was not different from the median HRmax for the cycle (173 bpm; interquartile range = 160–182 bpm; z = −0.63; P =.53). For both tests, the 3 most frequently reported symptoms responsible for test cessation were headache, dizziness, and pressure in the head. Of interest, most participants (64%) reported a different symptom responsible for cessation of each test. On the novel cycling test of exertion, participants achieved similar HRmax and test durations and, therefore, this test may be a suitable alternative to the BCTT. Future research to understand the physiological reason for the heterogeneity in symptoms responsible for test cessation is warranted. [ABSTRACT FROM AUTHOR]