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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]

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]

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]