A systematic review, meta-analysis, and meta-regression amalgamating the driven approaches used to quantify dynamic cerebral autoregulation.

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.

Transcranial Doppler Ultrasound and Concussion-Supplemental Symptoms with Physiology: A Systematic Review.

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.

Adolescent Sport-Related Concussion and the Associated Neurophysiological Changes: A Systematic Review.

BACKGROUND: Sport-related concussion (SRC) has been shown to induce cerebral neurophysiological deficits, quantifiable with electroencephalography (EEG). As the adolescent brain is undergoing rapid neurodevelopment, it is fundamental to understand both the short- and long-term ramifications SRC may have on neuronal functioning. The current systematic review sought to amalgamate the literature regarding both acute/subacute (≤28 days) and chronic (>28 days) effects of SRC in adolescents via EEG and the diagnostic accuracy of this tool. METHODS: The review was registered within the Prospero database (CRD42021275256). Search strategies were created and input into the PubMed database, where three authors completed all screening. Risk of bias assessments were completed using the Scottish Intercollegiate Guideline Network and Methodological Index for Non-Randomized Studies. RESULTS: A total of 128 articles were identified; however, only seven satisfied all inclusion criteria. The studies ranged from 2012 to 2021 and included sample sizes of 21 to 81 participants, albeit only ∼14% of the included athletes were females. The studies displayed low-to-high levels of bias due to the small sample sizes and preliminary nature of most investigations. Although heterogeneous methods, tasks, and analytical techniques were used, 86% of the studies found differences compared with control athletes, in both the symptomatic and asymptomatic phases of SRC. One study used raw EEG data as a diagnostic indicator demonstrating promise; however, more research and standardization are a necessity. CONCLUSIONS: Collectively, the findings highlight the utility of EEG in assessing adolescent SRC; however, future studies should consider important covariates including biological sex, maturation status, and development.

Time-course recovery of cerebral blood velocity metrics post aerobic exercise: a systematic review.

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.

Does oscillation size matter? Impact of added resistance on the cerebral pressure-flow Relationship in females and males.

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.

Sex differences in autonomic recovery following repeated sinusoidal resistance exercise.

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.

Long-term heart transplant recipients: heart rate-related effects on augmented transfer function coherence during repeated squat-stand maneuvers in males.

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.

Does task complexity impact the neurovascular coupling response similarly between males and females?

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 < 0.001) and area under the curve during the first 30-s of the task (all p < 0.001) compared to simple shapes. Females displayed greater absolute baseline and peak PCA and MCA velocities across all tasks (all p < 0.002). Subjective engagement displayed moderate correlation levels with PCA percent increase (Spearman ρ = 0.58) and area under the curve (Spearman ρ = 0.60) metrics in males, whereas these were weak for females (Spearman ρ = 0.43 and ρ = 0.38, respectively). CONCLUSIONS: The complex visual paradigm "Where's Waldo?" greatly augmented the signal-to-noise ratio within the PCA aspects of the NVC response compared to simple shapes. While both sexes had similar NVC responses, task engagement was more related to NVC metrics in males compared to females. Therefore, future NVC investigations should consider task engagement when designing studies.