Quantification of dynamic cerebral autoregulation: welcome to the jungle!

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.

Directional sensitivity of the cerebral pressure-flow relationship in young healthy individuals trained in endurance and resistance exercise.

NEW FINDINGS: 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. ABSTRACT: 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 (ΔMCAvT /ΔMAPT ) and relative (%MCAvT /%MAPT ) changes in MCAv and MAP with respect to the transition time intervals of both variables to compute a time-adjusted ratio in each MAP direction, averaged over the 5-min repeated squat-stand protocols. At 0.10 Hz repeated squat-stands, ΔMCAvT /ΔMAPT and %MCAvT /%MAPT were lower when MAP increased compared with when MAP decreased for sedentary (ΔMCAvT /ΔMAPT : P = 0.032; %MCAvT /%MAPT : P = 0.040) and endurance-trained individuals (ΔMCAvT /ΔMAPT : P = 0.012; %MCAvT /%MAPT P = 0.007), but not in the resistance-trained individuals (ΔMCAvT /ΔMAPT : P = 0.512; %MCAvT /%MAPT P = 0.666). At 0.05 Hz repeated squat-stands, time-adjusted ratios were similar for all groups (all P > 0.605). These findings suggest exercise training modality does influence the directionality of the cerebral pressure-flow relationship and support the presence of a hysteresis-like pattern during 0.10 Hz repeated squat-stands in sedentary and endurance-trained participants, but not in resistance-trained individuals. In future studies, assessment of elite endurance and resistance training habits may further elucidate modality-dependent discrepancies on directional dCA measurements.

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.

Directional sensitivity of the cerebral pressure-flow relationship during forced oscillations induced by oscillatory lower body negative pressure.

A directional sensitivity of the cerebral pressure-flow relationship has been described using repeated squat-stands. Oscillatory lower body negative pressure (OLBNP) is a reproducible method to characterize dynamic cerebral autoregulation (dCA). It could represent a safer method to examine the directional sensitivity of the cerebral pressure-flow relationship within clinical populations and/or during pharmaceutical administration. Therefore, examining the cerebral pressure-flow directional sensitivity during an OLBNP-induced cyclic physiological stress is crucial. We calculated changes in middle cerebral artery mean blood velocity (MCAv) per alterations to mean arterial pressure (MAP) to compute ratios adjusted for time intervals (ΔMCAvT/ΔMAPT) with respect to the minimum-to-maximum MCAv and MAP, for each OLBNP transition (0 to -90 Torr), during 0.05 Hz and 0.10 Hz OLBNP. We then compared averaged ΔMCAvT/ΔMAPT during OLBNP-induced MAP increases (INC) (ΔMCAvT/ΔMAPTINC) and decreases (DEC) (ΔMCAvT/ΔMAPTDEC). Nineteen healthy participants [9 females; 30 ± 6 years] were included. There were no differences in ΔMCAvT/ΔMAPT between INC and DEC at 0.05 Hz. ΔMCAvT/ΔMAPTINC (1.06 ± 0.35 vs. 1.33 ± 0.60 cm⋅s-1/mmHg; p = 0.0076) was lower than ΔMCAvT/ΔMAPTDEC at 0.10 Hz. These results support OLBNP as a model to evaluate the directional sensitivity of the cerebral pressure-flow relationship.

Impact of sex on the cerebrovascular response to incremental aerobic exercise in moderately trained endurance athletes.

The cerebrovascular response to incremental aerobic exercise is comparable between males and females. Whether this response can be found in moderately trained athletes remains unknown. We aimed to examine the effect of sex on the cerebrovascular response to incremental aerobic exercise until volitional exhaustion in this population. Twenty-two moderately trained athletes (11 M/11 F; age: 25 ± 5 vs. 26 ± 6 yr, P = 0.6478; peak oxygen consumption: 55.8 ± 5.2 vs. 48.3 ± 4 mL/kg/min; P = 0.0011; training volume: 532 ± 173 vs. 466 ± 151 min/wk, P = 0.3554) performed a maximal ergocycle exercise test. Systemic and cerebrovascular hemodynamics were measured. At rest, middle cerebral artery mean blood velocity (MCAvmean; 64.1 ± 12.7 vs. 72.2 ± 15.3 cm·s-1; P = 0.2713) was not different between groups, whereas partial pressure of end-tidal carbon dioxide ([Formula: see text], 42 ± 3 vs. 37 ± 2 mmHg, P = 0.0002) was higher in males. During the MCAvmean ascending phase, changes in MCAvmean (intensity: P < 0.0001, sex: P = 0.3184, interaction: P = 0.9567) were not different between groups. Changes in cardiac output ([Formula: see text]) (intensity: P < 0.0001, sex: P < 0.0001, interaction: P < 0.0001) and [Formula: see text] (intensity: P < 0.0001, sex: P < 0.0001, interaction: P < 0.0001) were higher in males. During the MCAvmean descending phase, changes in MCAvmean (intensity: P < 0.0001, sex: P = 0.5522, interaction: P = 0.4828) and [Formula: see text] (intensity: P = 0.0550, sex: P = 0.0003, interaction: P = 0.2715) were not different between groups. Changes in [Formula: see text] (intensity P < 0.0001, sex: P < 0.0001, interaction: P = 0.0280) were higher in males. These results suggest the MCAvmean response during exercise is comparable between moderately trained males and females notwithstanding differences in the response of key cerebral blood flow determinants.NEW & NOTEWORTHY The results of this study suggest the cerebrovascular response between moderately endurance-trained males and females is comparable in spite of a higher arterial carbon dioxide and cardiac output in males compared with females during incremental aerobic exercise until volitional exhaustion. This could help in providing a better understanding of the key differences in cerebral blood flow regulation between males and females during aerobic exercise.

Reproducibility and diurnal variation of the directional sensitivity of the cerebral pressure-flow relationship in men and women.

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.NEW & NOTEWORTHY The findings of the current study indicate that our time-adjusted metric to evaluate the directional sensitivity of the cerebral pressure-flow relationship is reproducible throughout the day in both the anterior and posterior cerebral circulations. Although a diurnal variation was noted across the day within this metric, this appeared to be of minimal physiological relevance. Finally, the metric is not impacted by biological sex.

Influence of high-intensity interval training to exhaustion on the directional sensitivity of the cerebral pressure-flow relationship in young endurance-trained men.

We previously reported subtle dynamic cerebral autoregulation (dCA) alterations following 6 weeks of high-intensity interval training (HIIT) to exhaustion using transfer function analysis (TFA) on forced mean arterial pressure (MAP) oscillations in young endurance-trained men. However, accumulating evidence suggests the cerebrovasculature better buffers cerebral blood flow changes when MAP acutely increases compared to when MAP acutely decreases. Whether HIIT affects the directional sensitivity of the cerebral pressure-flow relationship in these athletes is unknown. In 18 endurance-trained men (age: 27 ± 6 years, VO2 max: 55.5 ± 4.7 ml·kg-1 ·min-1 ), we evaluated the impact of 6 weeks of HIIT to exhaustion on dCA directionality using induced MAP oscillations during 5-min 0.05 and 0.10 Hz repeated squat-stands. We calculated time-adjusted changes in middle cerebral artery mean blood velocity (MCAv) per change in MAP (ΔMCAvT /ΔMAPT ) for each squat transition. Then, we compared averaged ΔMCAvT /ΔMAPT during MAP increases and decreases. Before HIIT, ΔMCAvT /ΔMAPT was comparable between MAP increases and decreases during 0.05 Hz repeated squat-stands (p = 0.518). During 0.10 Hz repeated squat-stands, ΔMCAvT /ΔMAPT was lower during MAP increases versus decreases (0.87 ± 0.17 vs. 0.99 ± 0.23 cm·s-1 ·mmHg-1 , p = 0.030). Following HIIT, ΔMCAvT /ΔMAPT was superior during MAP increases over decreases during 0.05 Hz repeated squat-stands (0.97 ± 0.38 vs. 0.77 ± 0.35 cm·s-1 ·mmHg-1 , p = 0.002). During 0.10 Hz repeated squat-stands, dCA directional sensitivity disappeared (p = 0.359). These results suggest the potential for HIIT to influence the directional sensitivity of the cerebral pressure-flow relationship in young endurance-trained men.