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

In 1959, Niels Lassen illustrated the cerebral autoregulation curve in the classic review article entitled Cerebral Blood Flow and Oxygen Consumption in Man. This concept suggested a relatively broad...

We assessed the convergent validity of commonly applied metrics of cerebral autoregulation (CA) to determine the extent to which the metrics can be used interchangeably. To examine between-subject relationships among low-frequency (LF; 0.07–0.2 Hz) and very-low-frequency (VLF; 0.02–0.07 Hz) transfer function coherence, phase, gain, and normalized gain, we performed retrospective transfer function analysis on spontaneous blood pressure and middle cerebral artery blood velocity recordings from 105 individuals. We characterized the relationships ( n = 29) among spontaneous transfer function metrics and the rate of regulation index and autoregulatory index derived from bilateral thigh-cuff deflation tests. In addition, we analyzed data from subjects ( n = 29) who underwent a repeated squat-to-stand protocol to determine the relationships between transfer function metrics during forced blood pressure fluctuations. Finally, data from subjects ( n = 16) who underwent step changes in end-tidal Pco₂ (PetCO₂) were analyzed to determine whether transfer function metrics could reliably track the modulation of CA within individuals. CA metrics were generally unrelated or showed only weak to moderate correlations. Changes in PetCO₂ were positively related to coherence [LF: β = 0.0065 arbitrary units (AU)/mmHg and VLF: β = 0.011 AU/mmHg, both P < 0.01] and inversely related to phase (LF: β = −0.026 rad/mmHg and VLF: β = −0.018 rad/mmHg, both P < 0.01) and normalized gain (LF: β = −0.042%/mmHg² and VLF: β = −0.013%/mmHg², both P < 0.01). However, PetCO₂ was positively associated with gain (LF: β = 0.0070 cm·s⁻¹·mmHg⁻², P < 0.05; and VLF: β = 0.014 cm·s⁻¹·mmHg⁻², P < 0.01). Thus, during changes in PetCO₂, LF phase was inversely related to LF gain (β = −0.29 cm·s⁻¹·mmHg⁻¹·rad⁻¹, P < 0.01) but positively related to LF normalized gain (β = 1.3% mmHg⁻¹/rad, P < 0.01). These findings collectively suggest that only select CA metrics can be used interchangeably and that interpretation of these measures should be done cautiously.

We examined the between-day reproducibility of active (squat-stand maneuvers)- and passive [oscillatory lower-body negative pressure (OLBNP) maneuvers]-driven oscillations in blood pressure. These relationships were examined in both younger ( n = 10; 25 ± 3 yr) and older ( n = 9; 66 ± 4 yr) adults. Each testing protocol incorporated rest (5 min), followed by driven maneuvers at 0.05 (5 min) and 0.10 (5 min) Hz to increase blood-pressure variability and improve assessment of the pressure-flow dynamics using linear transfer function analysis. Beat-to-beat blood pressure, middle cerebral artery velocity, and end-tidal partial pressure of CO₂ were monitored. The pressure-flow relationship was quantified in the very low (0.02-0.07 Hz) and low (0.07–0.20 Hz) frequencies (LF; spontaneous data) and at 0.05 and 0.10 Hz (driven maneuvers point estimates). Although there were no between-age differences, very few spontaneous and OLBNP transfer function metrics met the criteria for acceptable reproducibility, as reflected in a between-day, within-subject coefficient of variation (CoV) of <20%. Combined CoV data consist of LF coherence (15.1 ± 12.2%), LF gain (15.1 ± 12.2%), and LF normalized gain (18.5 ± 10.9%); OLBNP data consist of 0.05 (12.1 ± 15.%) and 0.10 (4.7 ± 7.8%) Hz coherence. In contrast, the squat-stand maneuvers revealed that all metrics (coherence: 0.6 ± 0.5 and 0.3 ± 0.5%; gain: 17.4 ± 12.3 and 12.7 ± 11.0%; normalized gain: 16.7 ± 10.9 and 15.7 ± 11.0%; and phase: 11.6 ± 10.2 and 17.3 ± 10.8%) at 0.05 and 0.10 Hz, respectively, were considered biologically acceptable for reproducibility. These findings have important implications for the reliable assessment and interpretation of cerebral pressure-flow dynamics in humans.

Cerebral autoregulation (CA) is a theoretical construct characterized by the relationship between mean arterial pressure (MAP) and cerebral blood flow (CBF). We performed a comprehensive literature search to provide an up-to-date review on the static relationship between MAP and CBF. The results are based on 40 studies (49 individual experimental protocols) in healthy subjects between 18 and 65 years. Exclusion criteria were: a ΔMAP <5%, hypoxia/hyperoxia or hypo/hypercapnia, and unstable levels (<2 min stages). The partial pressure of arterial CO2 (PaCO2) was measured in a subset of the included studies (n=28); therefore, CBF was also adjusted to account for small changes in PaCO2. The linear regression coefficient between MAP and CBF (or velocity) of 0.82±0.77%ΔCBF/%ΔMAP during decreases in MAP (n=23 experiments) was significantly different than the relationship of 0.21±0.47%ΔCBF/%ΔMAP during increases (n=26 experiments; p<0.001). After correction for increases/decreases in PaCO2, the slopes were not significantly different: 0.64±1.16%ΔCBF/%ΔMAP (n=16) and 0.39±0.30%ΔCBF/%ΔMAP (n=12) for increased vs. decreased MAP changes, respectively (p=0.60). The autoregulatory ability of the cerebral circulation appears to be more active in buffering increases in MAP as compared to reductions in MAP. However, the statistical finding of hysteresis is lost following an attempt to correct for PaCO2.