Examining the upper frequency limit of dynamic cerebral autoregulation: Considerations across the cardiac cycle during eucapnia.

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.

Effect of prolonged sitting on dynamic cerebral autoregulation in the anterior and posterior cerebral circulations.

Individuals who experience prolonged sitting daily are reported to be at risk of developing cerebrovascular disease, which is associated, in part, with attenuation in cerebral blood flow regulation. However, the effect of prolonged sitting on dynamic cerebral autoregulation (dCA), a crucial mechanism of cerebral blood flow regulation, remains unclear. Additionally, cerebrovascular disease occurs heterogeneously within cerebral arteries. The purpose of the present study was to examine the hypothesis that prolonged sitting attenuates dCA in the cerebral circulation heterogeneously. Twelve young, healthy participants were instructed to maintain a seated position for 4 h without moving their lower limbs. Mean arterial pressure and mean blood velocities of the middle cerebral artery (MCA Vm) and the posterior cerebral artery (PCA Vm) were measured continuously throughout the experiment. The dCA was assessed using transfer function analysis (TFA) with mean arterial pressure and either MCA Vm or PCA Vm. In the MCA, very low-frequency TFA-normalized gain decreased significantly during 4 h of prolonged sitting (P = 0.029), indicating an improvement rather than attenuation in dCA, despite a significant reduction in MCA Vm after 4 h of continuous sitting (P = 0.039). In the PCA, PCA Vm remained stable throughout the 4 h sitting period (P = 0.923), and all TFA parameters remained unchanged throughout the 4 h of sitting. Contrary to our hypothesis, these results suggest that the dCA in both the MCA and the PCA was well stabilized in healthy young individuals during acute prolonged sitting.

Is muscle sympathetic nerve activity associated with cerebral blood velocity? A partial coherence analysis.

Despite some evidence, the role of sympathetic nerve activity in the regulation of cerebral blood flow remains controversial. In humans, muscle sympathetic nervous activity (MSNA) is the only direct measure of sympathetic nerve activity that can be recorded with sufficient temporal resolution, to allow association with dynamic regulation of cerebral blood velocity (CBv). This study tested the hypothesis that MSNA is associated with the regulation of CBv at rest and during different physiological maneuvers. Nine healthy subjects underwent two sympathoexcitatory maneuvers: i) isometric handgrip exercise (HGR), and ii) cold pressor test (CPT). Mean arterial pressure (MAP, oscillometric method), CBv (transcranial Doppler ultrasound), and MSNA (microneurography) were measured continuously during experimental protocols. Ordinary and partial coherences of the MAP, CBv and MSNA time series were estimated by transfer function analysis in the low-frequency range (LF: 0.07-0.20 Hz), using MAP and MSNA as inputs and CBv as the output variable. When the influence of MSNA was taken into account, the partial coherences between MAP and CBv were considerably reduced at baseline (P<0.01), HGR (P=0.02), and CPT (P<0.01). Similarly, when the influence of MAP was taken into account, the coherence between MSNA and CBv was considerably reduced at baseline (P<0.01), HGR (P=0.02), and CPT (P=0.01), leading to the conclusion, that MSNA was associated to dynamic regulation of CBv. Partial coherence analysis is a promising method for assessing the influence of the sympathetic nervous system on cerebral hemodynamics.

Dynamic cerebral autoregulation during repeated handgrip exercise: comparisons with spontaneous rest and sit-stand maneuvers.

Induced arterial pressure oscillation may improve the assessment of dynamic cerebral autoregulation (dCA) with transfer function analysis (TFA). This study investigated dCA during repeated handgrip exercise (RHE) compared with spontaneous rest and sit-stand maneuvers (SSM), often used in cerebrovascular research. After a 5-min rest, 20 healthy young adults (10 women and 10 men) underwent 5 min of RHE (30% maximal voluntary contraction) and SSM at 0.05 Hz and 0.10 Hz each in random order. Power spectral density (PSD) and TFA gain, phase, coherence of mean arterial pressure (MAP), and blood velocity in the middle cerebral artery (MCAvmean) were measured in very low (VLF: 0.02-0.07 Hz) and low (LF: 0.07-0.20 Hz) frequencies. End-tidal CO2 (EtCO2) was continuously recorded throughout data collection. Compared with rest, RHE increased the PSD of MAP and MCAvmean in VLF (444% and 273%, respectively) and LF (1,571% and 1,765%, respectively) (all P < 0.001). Coherence increased during RHE (VLF: 131%, LF: 128%) and SSM (VLF: 166%, LF: 136%) compared with rest (all P < 0.05). TFA gain and phase were similar between RHE and rest, but VLF gain was higher, whereas VLF and LF phases were lower during SSM than RHE (all P < 0.05). EtCO2 was higher during SSM than rest and RHE (both P < 0.05), with the individual EtCO2 changes positively correlated with VLF gain (r = 0.538, P < 0.001). These results indicate that RHE significantly increases arterial pressure oscillation and TFA coherence and may improve dCA assessment in individuals unable to perform repeated postural changes.NEW & NOTEWORTHY This is the first study investigating dynamic cerebral autoregulation (dCA) during light-intensity repeated handgrip exercise (RHE) compared with rest and sit-stand maneuvers (SSM) using transfer function analysis (TFA). Compared with rest, RHE significantly increased oscillations of arterial blood pressure and cerebral blood velocity and coherence, whereas SSM exhibited the highest oscillations and coherence. These findings suggest that RHE may serve as an alternative method for assessing dCA in individuals unable to perform repeated postural changes.

Determinants of the dynamic cerebral critical closing pressure response to changes in mean arterial pressure.

Objective. Cerebral critical closing pressure (CrCP) represents the value of arterial blood pressure (BP) where cerebral blood flow (CBF) becomes zero. Its dynamic response to a step change in mean BP (MAP) has been shown to reflect CBF autoregulation, but robust methods for its estimation are lacking. We aim to improve the quality of estimates of the CrCP dynamic response.Approach. Retrospective analysis of 437 healthy subjects (aged 18-87 years, 218 males) baseline recordings with measurements of cerebral blood velocity in the middle cerebral artery (MCAv, transcranial Doppler), non-invasive arterial BP (Finometer) and end-tidal CO2(EtCO2, capnography). For each cardiac cycle CrCP was estimated from the instantaneous MCAv-BP relationship. Transfer function analysis of the MAP and MCAv (MAP-MCAv) and CrCP (MAP-CrCP) allowed estimation of the corresponding step responses (SR) to changes in MAP, with the output in MCAv (SRVMCAv) representing the autoregulation index (ARI), ranging from 0 to 9. Four main parameters were considered as potential determinants of the SRVCrCPtemporal pattern, including the coherence function, MAP spectral power and the reconstruction error for SRVMAP, from the other three separate SRs.Main results. The reconstruction error for SRVMAPwas the main determinant of SRVCrCPsignal quality, by removing the largest number of outliers (Grubbs test) compared to the other three parameters. SRVCrCPshowed highly significant (p< 0.001) changes with time, but its amplitude or temporal pattern was not influenced by sex or age. The main physiological determinants of SRVCrCPwere the ARI and the mean CrCP for the entire 5 min baseline period. The early phase (2-3 s) of SRVCrCPresponse was influenced by heart rate whereas the late phase (10-14 s) was influenced by diastolic BP.Significance. These results should allow better planning and quality of future research and clinical trials of novel metrics of CBF regulation.

Exploring the Feasibility of Estimating Intraocular Pressure Using Vibrational Response of the Eye: A Methodological Approach.

This study addresses the limitations of current tonometry techniques by exploring vibroacoustic properties for estimating intraocular pressure (IOP), a key diagnostic parameter for monitoring glaucoma-a significant risk factor for vision loss. Utilizing vivo porcine eyeballs, we investigated the relationship between IOP and the nonlinear vibration transfer function ratio (NVTFR). Through applying varying vibration levels and analyzing responses with transfer function analysis and univariate regression, we identified a strong negative correlation between NVTFR and IOP, evidenced by a Pearson correlation coefficient of -0.8111 and significant results from generalized linear model (GLM) regression (p-value < 0.001). These findings indicate the potential of NVTFR as a vital indicator of IOP changes. Our study highlights the feasibility of using vibroacoustic properties, specifically NVTFR, to measure IOP. While further refinement is necessary for in vivo application, this approach opens new possibilities for non-invasive and patient-friendly IOP monitoring, potentially enhancing ophthalmology diagnostic techniques and providing a foundation for future research and development in this critical area.

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.

Letter to the editor: Deriving transfer function analysis metrics from driven methods.

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.

Impaired Dynamic Cerebral Autoregulation in Patients With Cerebral Venous Sinus Thrombosis: Evaluation Using Transcranial Doppler and Silent Reading Stimulation.

OBJECTIVE: Cerebral venous sinus thrombosis (CVST) may impair dynamic cerebral autoregulation (dCA) of the middle cerebral artery (MCA). However, most studies have focused on dCA of the MCA; a few studies are based on the posterior cerebral artery (PCA) during silent reading and neurovascular coupling (NVC). This study explored the effects of CVST on dCA of the MCA and PCA during silent reading and NVC. METHODS: From January 2021 to August 2022, 60 CVST patients and 30 controls were enrolled in this study. Non-invasive continuous beat-to-beat blood pressure, cerebral blood flow velocity and other associated information on the MCA and PCA during silent reading were collected using a transcranial Doppler. NVC assessment was performed by opening and closing the eyes periodically based on voice prompts, and eye-opening visual stimulation was achieved by silently reading Chinese tourism materials. Visual stimulation signals can selectively activate Brodmann's areas 17, 18, and 19 of the occipital when reading silently with open eyes, prompting them to release neurotransmitters and dilate PCA. dCA was determined by transfer function analysis. RESULTS: In dCA of the PCA during silent reading, the CVST group's very low frequency phase was lower than that of the control group (p = 0.047). In NVC, the difference in the indexes of the cerebrovascular conductance and visually evoked flow response of the CVST group were lower than those of the control group (p = 0.017 and p = 0.019, respectively). CONCLUSION: Compared with the control group, dCA and NVC of the PCA during silent reading were impaired in CVST patients.

Point-Counterpoint: Transfer function analysis of dynamic cerebral autoregulation: To band or not to band?

Transfer function analysis (TFA) of dynamic cerebral autoregulation (dCA) is based on linear system theory to examine the relationship between changes in blood pressure and cerebral blood flow. With TFA, dCA is characterized as a frequency-dependent phenomenon quantified by gain, phase, and coherence in the distinctive frequency bands. These frequency bands likely reflect the underlying regulatory mechanisms of the cerebral vasculature. In addition, obtaining TFA metrics over a specific frequency band facilitates reliable spectral estimation and statistical data analysis to reduce random noise. This commentary discusses the benefits and cautions of banding TFA parameters in dCA studies.

Attenuated pulsatile transition to the cerebral vasculature during high-intensity interval exercise in young healthy men.

NEW FINDINGS: What is the central question of this study? High-intensity interval exercise (HIIE) is recommended for its favourable haemodynamic stimulation, but excessive haemodynamic fluctuations may stress the brain: is the cerebral vasculature protected against exaggerated systemic blood flow fluctuation during HIIE? What is the main finding and its importance? Time- and frequency-domain indices of aortic-cerebral pulsatile transition were lowered during HIIE. The findings suggest that the arterial system to the cerebral vasculature may attenuate pulsatile transition during HIIE as a defence mechanism against pulsatile fluctuation for the cerebral vasculature. ABSTRACT: High-intensity interval exercise (HIIE) is recommended because it provides favourable haemodynamic stimulation, but excessive haemodynamic fluctuations may be an adverse impact on the brain. We tested whether the cerebral vasculature is protected against systemic blood flow fluctuation during HIIE. Fourteen healthy men (age 24 ± 2 years) underwent four 4-min exercises at 80-90% of maximal workload (Wmax ) interspaced by 3-min active rest at 50-60% Wmax . Transcranial Doppler measured middle cerebral artery blood velocity (CBV). Systemic haemodynamics (Modelflow) and aortic pressure (AoP, general transfer function) were estimated from an invasively recorded brachial arterial pressure waveform. Using transfer function analysis, gain and phase between AoP and CBV (0.39-10.0 Hz) were calculated. Stroke volume, aortic pulse pressure and pulsatile CBV increased during exercise (time effect: P < 0.0001 for all), but a time-domain index of aortic-cerebral pulsatile transition (pulsatile CBV/pulsatile AoP) decreased throughout the exercise bouts (time effect: P < 0.0001). Furthermore, transfer function gain reduced, and phase increased throughout the exercise bouts (time effect: P < 0.0001 for both), suggesting the attenuation and delay of pulsatile transition. The cerebral vascular conductance index (mean CBV/mean arterial pressure; time effect: P = 0.296), an inverse index of cerebral vascular tone, did not change even though systemic vascular conductance increased during exercise (time effect: P < 0.0001). The arterial system to the cerebral vasculature may attenuate pulsatile transition during HIIE as a defence mechanism against pulsatile fluctuation for the cerebral vasculature.

Transfer function analysis assesses resting cerebral perfusion metrics using hypoxia-induced deoxyhemoglobin as a contrast agent.

Introduction: Use of contrast in determining hemodynamic measures requires the deconvolution of an arterial input function (AIF) selected over a voxel in the middle cerebral artery to calculate voxel wise perfusion metrics. Transfer function analysis (TFA) offers an alternative analytic approach that does not require identifying an AIF. We hypothesised that TFA metrics Gain, Lag, and their ratio, Gain/Lag, correspond to conventional AIF resting perfusion metrics relative cerebral blood volume (rCBV), mean transit time (MTT) and relative cerebral blood flow (rCBF), respectively. Methods: 24 healthy participants (17 M) and 1 patient with steno-occlusive disease were recruited. We used non-invasive transient hypoxia-induced deoxyhemoglobin as an MRI contrast. TFA and conventional AIF analyses were used to calculate averages of whole brain and smaller regions of interest. Results: Maps of these average metrics had colour scales adjusted to enhance contrast and identify areas of high congruence. Regional gray matter/white matter (GM/WM) ratios for MTT and Lag, rCBF and Gain/Lag, and rCBV and Gain were compared. The GM/WM ratios were greater for TFA metrics compared to those from AIF analysis indicating an improved regional discrimination. Discussion: Resting perfusion measures generated by The BOLD analysis resulting from a transient hypoxia induced variations in deoxyhemoglobin analyzed by TFA are congruent with those analyzed by conventional AIF analysis.

Effects of posture changes on dynamic cerebral autoregulation during early pregnancy in women with obesity and/or sleep apnea.

The incidence of syncope during orthostasis increases in early human pregnancy, which may be associated with cerebral blood flow (CBF) dysregulation in the upright posture. In addition, obesity and/or sleep apnea per se may influence CBF regulation due to their detrimental impacts on cerebrovascular function. However, it is unknown whether early pregnant women with obesity and/or sleep apnea could have impaired CBF regulation in the supine position and whether this impairment would be further exacerbated in the upright posture. Dynamic cerebral autoregulation (CA) was evaluated using transfer function analysis in 33 women during early pregnancy (13 with obesity, 8 with sleep apnea, 12 with normal weight) and 15 age-matched nonpregnant women during supine rest. Pregnant women also underwent a graded head-up tilt (30° and 60° for 6 min each). We found that pregnant women with obesity or sleep apnea had a higher transfer function low-frequency gain compared with nonpregnant women in the supine position (P = 0.026 and 0.009, respectively) but not normal-weight pregnant women (P = 0.945). Conversely, the transfer function low-frequency phase in all pregnancy groups decreased during head-up tilt (P = 0.001), but the phase was not different among pregnant groups (P = 0.180). These results suggest that both obesity and sleep apnea may have a detrimental effect on dynamic CA in the supine position during early pregnancy. CBF may be more vulnerable to spontaneous blood pressure fluctuations in early pregnant women during orthostatic stress compared with supine rest due to less efficient dynamic CA, regardless of obesity and/or sleep apnea.

Effect of dynamic cerebral autoregulation on the association between deep medullary vein changes and cerebral small vessel disease.

Changes in the deep medullary vein (DMV) are reported to be associated with cerebral small vessel disease (CSVD). While the mechanisms of this association are unclear, dynamic cerebral autoregulation (dCA) has been speculated to participate in this association. Thus, we aimed to verify the association between DMV changes and total CSVD burden and further investigate the effect of dCA function on this correlation. In this prospective study, 95 Asian patients aged ≥18 years were included in the final assessment. DMV scores and total CSVD burden were determined using magnetic resonance imaging sequences. Transfer function analysis was performed to analyze dCA function. Generalized linear regressions were used to assess the relationship between DMV changes and total CSVD burden as well as between DMV changes and dCA function. An interaction model was utilized to assess the effect of dCA function on the association between DMV changes and total CSVD burden. Generalized linear models showed a significant positive association between DMV changes and total CSVD burden (p = 0.039) and a significant negative association between DMV changes and dCA function (p = 0.018). The interaction model demonstrated a significant positive interaction of dCA impairment on the association between DMV changes and the total CSVD burden (p = 0.02). Thus, we came to the conclusion that changes in DMV were correlated independently with both CSVD and dCA impairment and furthermore, impaired dCA function play an interaction effect on the association between DMV changes and the total CSVD burden. Our results can help improve the understanding of the complex pathogenesis and progression of CSVD, thereby facilitating early intervention and treatment development.

Can Alterations in Cerebrovascular CO2 Reactivity Be Identified Using Transfer Function Analysis without the Requirement for Carbon Dioxide Inhalation?

The present study aimed to examine the validity of a novel method to assess cerebrovascular carbon dioxide (CO2) reactivity (CVR) that does not require a CO2 inhalation challenge, e.g., for use in patients with respiratory disease or the elderly, etc. In twenty-one healthy participants, CVR responses to orthostatic stress (50° head-up tilt, HUT) were assessed using two methods: (1) the traditional CO2 inhalation method, and (2) transfer function analysis (TFA) between middle cerebral artery blood velocity (MCA V) and predicted arterial partial pressure of CO2 (PaCO2) during spontaneous respiration. During HUT, MCA V steady-state (i.e., magnitude) and MCA V onset (i.e., time constant) responses to CO2 inhalation were decreased (p < 0.001) and increased (p = 0.001), respectively, indicative of attenuated CVR. In contrast, TFA gain in the very low-frequency range (VLF, 0.005-0.024 Hz) was unchanged, while the TFA phase in the VLF approached zero during HUT (-0.38 ± 0.59 vs. 0.31 ± 0.78 radians, supine vs. HUT; p = 0.003), indicative of a shorter time (i.e., improved) response of CVR. These findings indicate that CVR metrics determined by TFA without a CO2 inhalation do not track HUT-evoked reductions in CVR identified using CO2 inhalation, suggesting that enhanced cerebral blood flow response to a change in CO2 using CO2 inhalation is necessary to assess CVR adequately.

Respiratory training in older women: Unravelling central and peripheral hemodynamic slow oscillatory patterns.

We hypothesized that inspiratory muscle training (IMT) increases the respiratory-induced low-frequency oscillations of mean blood pressure (MBP) and middle cerebral artery blood velocity (MCAv), upregulating cerebrovascular function in older women. Firstly, participants were recorded with free-breathing (FB) and then breathed at a slow-paced frequency (0.1 Hz; DB test) supported by sonorous metronome feedback. Blood pressure was recorded using finger photoplethysmography method, ECG, and respiration using a thoracic belt. To obtain the MCAv a transcranial ultrasound Doppler device was used. Spectral analysis of MBP, R-R intervals, and mean MCAv time series was obtained by an autoregressive model. The transfer function analysis (TFA) was employed to calculate the coherence, gain, and phase. After that, older women were enrolled in a randomized controlled protocol, the IMT-group (n = 8; 64 ± 3 years-old) performed IMT at 50 % of maximal inspiratory pressure (MIP), and Sham-group, a placebo training at 5 % MIP (Sham-group; n = 6; 66 ± 3 years-old). Participants breathed against an inspiratory resistance twice a day for 4-weeks. DB test is repeated post IMT and Sham interventions. IMT-group, compared to Sham-group, augmented tidal volume responses to DB (Sham-group 1.03 ± 0.41 vs. IMT-group 1.61 ± 0.56 L; p = 0.04), increased respiratory-induced MBP (Sham-group 26.37 ± 4.46 vs. IMT-group 48.21 ± 3.15 mmHg2; p = 0.04) and MCAv (Sham-group 14.16 ± 31.26 vs. IMT-group 79.90 ± 21.76 cm2s-2; p = 0.03) slow oscillations, and reduced TFA gain (Sham-group 2.46 ± 1.32 vs. IMT-group 1.78 ± 1.30 cm·s-1.mmHg-1; p = 0.01). Our findings suggest that IMT increases the respiratory-induced oscillations in MBP and MCAv signals and reduces TFA gain. It seems compatible with an improved dynamic cerebrovascular regulation following IMT in older women.

Transfer function analysis of dynamic cerebral autoregulation: A CARNet white paper 2022 update.

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.

Point-Counterpoint: Transfer function analysis of dynamic cerebral autoregulation: To band or not to band?

Transfer function analysis (TFA) is the most frequently adopted method for assessing dynamic cerebral autoregulation (CA) with continuously recorded arterial blood pressure (ABP) and cerebral blood flow velocity (CBFV). Conventionally, values of autoregulatory metrics (e.g., gain and phase) derived from TFA are averaged within three frequency bands separated by cut-off frequencies at 0.07 Hz and 0.20 Hz, respectively, to represent the efficiency of dynamic CA. However, this is of increasing concerns, as there remains no solid evidence for choosing these specific cut-off frequencies, and the rigid adoption of these bands can stifle further developments in TFA of dynamic CA. In this 'Point-Counterpoint' mini-review, we provide evidence against the fixed banding, indicate possible alternatives, and call for awareness of the risk of the 'one-size-fits-all' banding becoming dogmatic. We conclude that we need to remain open to the multiple possibilities offered by TFA to realize its full potential in studies of human dynamic CA.