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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. [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. [ABSTRACT FROM AUTHOR]

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. [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]

This article discusses the challenge of assessing dynamic cerebral autoregulation (dCA), which refers to the ability of the cerebrovasculature to respond to changes in arterial blood pressure. The quantification of dCA is complex and lacks a gold-standard method. The article highlights the need for multi-method strategies and comparisons between analytical approaches when assessing dCA. It also explores the influence of different exercise training modalities on dCA and discusses the limitations of current analytical methods, such as transfer function analysis (TFA). The authors propose a directional sensitivity metric as a potentially more sensitive method to detect cerebral haemodynamic changes. However, further research is needed to validate this metric and explore its applicability in different conditions and populations. The article emphasizes the importance of finding the best metric or collection of metrics to accurately assess dCA and improve the understanding of the cerebral pressure-flow relationship. [Extracted from the article]

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. [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]

Transfer function analysis (TFA) is a commonly used method to measure dynamic cerebral autoregulation (dCA), which assesses the ability of the brain's blood vessels to regulate changes in arterial blood pressure (ABP). However, the reliability of TFA metrics calculated from spontaneous ABP oscillations is limited compared to forced oscillations. A study in Experimental Physiology found that a 5-minute recording of spontaneous ABP and cerebral blood velocity (CBv) oscillations is insufficient for stable and reliable TFA metrics, particularly in patients with subarachnoid hemorrhage and sepsis. The authors suggest using methods to induce ABP fluctuations, such as repeated squat-stands, to improve TFA interpretability. However, the study has limitations, such as the lack of continuous measurement of carbon dioxide levels and potential medication effects. Overall, researchers and clinicians may need to explore alternative analytical strategies, such as wavelet synchronization, for quantifying dCA using spontaneous ABP and CBv. [Extracted from the article]

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.

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

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. 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. 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). Compared with the control group, dCA and NVC of the PCA during silent reading were impaired in CVST patients. [ABSTRACT FROM AUTHOR]

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. 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. [ABSTRACT FROM AUTHOR]

Goal: This work investigates the presence of cerebral hemodynamics (namely Oxy (O) and Deoxy (D) hemoglobin concentrations) that are coherent with spontaneous oscillations in Arterial Blood Pressure (ABP) in 78 healthy subjects during a driving simulation task. Methods: Spatially resolved O and D were measured on the prefrontal cortex with multi-channel near-infrared spectroscopy (NIRS). Wavelet coherence and phasor analysis were performed between O and ABP, and between D and ABP to evaluate the amplitude ratio, phase difference, and duration of significant coherence. Results: In the low-frequency range, oscillations at 0.1 Hz featured significant coherence for the longest time fraction (∼10%–30%). At this frequency, the amplitude ratio and phase difference showed a greater variance across subjects than over cortical locations, and no significant difference between driving tasks and baseline. Conclusions: Measuring low-frequency cerebral hemodynamics that are coherent with systemic ABP holds promise for non-invasive assessment of cerebral perfusion and autoregulation at the cerebral microvascular level.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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.

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. [ABSTRACT FROM AUTHOR]

Background: Studies of the clinical application of dynamic cerebral autoregulation show considerable variations, and dierences in blood pressure devices may be one of the reasons for this variation. Few studies have examined the consistency of invasive and non-invasive arterial blood pressure for evaluating cerebral autoregulation. We attempted to investigate the agreement between invasive and non-invasive blood pressure methods in the assessment of dynamic cerebral autoregulation with transfer function analysis. Methods: Continuous cerebral blood flow velocity and continuous invasive and non-invasive arterial blood pressure were simultaneously recorded for 15 min. Transfer function analysis was applied to derive the phase shift, gain and coherence function at all frequency bands from the first 5, 10, and 15 min of the 15-min recordings. The consistency was assessed with Bland–Altman analysis and intraclass correlation coefficient. Results: The consistency of invasive and noninvasive blood pressure methods for the assessment of dynamic cerebral autoregulation was poor at 5 min, slightly improved at 10 min, and good at 15 min. The values of the phase shift at the low-frequency band measured by the non-invasive device were higher than those measured with invasive equipment. The coherence function values measured by the invasive technique were higher than the values derived from the non-invasive method. Conclusion: Both invasive and non-invasive arterial blood pressure methods have good agreement in evaluating dynamic cerebral autoregulation when the recording duration reaches 15 min. The phase shift values measured with non-invasive techniques are higher than those measured with invasive devices. We recommend selecting the most appropriate blood pressure device to measure cerebral autoregulation based on the disease, purpose, and design. [ABSTRACT FROM AUTHOR]

Transcranial Doppler ultrasonography (TCD) is used widely to evaluate dynamic cerebral autoregulation (dCA). However, the validity of TCD-determined dCA remains unknown because TCD is only capable of measuring blood velocity and thus only provides an index as opposed to true blood flow. To test the validity of TCD-determined dCA, in nine healthy subjects, dCA was evaluated by transfer function analysis (TFA) using cerebral blood flow (CBF) or TCD-measured cerebral blood velocity during a perturbation that induces reductions in TCD-determined dCA, lower body negative pressure (LBNP) at two different stages: LBNP − 15 mmHg and − 50 mmHg. Internal carotid artery blood flow (ICA Q) was assessed as an index of CBF using duplex Doppler ultrasound. The TFA low frequency (LF) normalized gain (ngain) calculated using ICA Q increased during LBNP at − 50 mmHg (LBNP50) from rest (P = 0.005) and LBNP at − 15 mmHg (LBNP15) (P = 0.015), indicating an impaired dCA. These responses were the same as those obtained using TCD-measured cerebral blood velocity (from rest and LBNP15; P = 0.001 and P = 0.015). In addition, the ICA Q-determined TFA LF ngain from rest to LBNP50 was significantly correlated with TCD-determined TFA LF ngain (r = 0.460, P = 0.016) despite a low intraclass correlation coefficient. Moreover, in the Bland–Altman analysis, the difference in the TFA LF ngains determined by blood flow and velocity was within the margin of error, indicating that the two measurement methods can be interpreted as equivalent. These findings suggest that TCD-determined dCA can be representative of actual dCA evaluated with CBF. [ABSTRACT FROM AUTHOR]

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.

Chronic Kidney Disease (CKD) patients experience an elevated risk for cerebrovascular disease. One factor that may contribute to this heightened risk is an impairment in dynamic cerebral autoregulation, the mechanism by which cerebral vessels modulate cerebral blood flow during fluctuations in arterial pressure. We hypothesized that dynamic cerebral autoregulation would be impaired in CKD. To test this hypothesis, we compared dynamic cerebral autoregulation between CKD patients stages III‐IV and matched controls (CON) without CKD. Fifteen patients with CKD and 20 CON participants performed 2, 5‐minute bouts of repeated sit‐to‐stand maneuvers at 0.05 Hz and 0.10 Hz while mean arterial pressure (MAP, via finger photoplethysmography) and middle cerebral artery blood velocity (MCAv, via transcranial Doppler ultrasound) were measured continuously. Cerebral autoregulation was characterized by performing a transfer function analysis (TFA) on the MAP‐MCAv relationship to derive coherence, phase, gain, and normalized gain (nGain). We observed no group differences in any of the TFA metrics during the repeated sit‐to‐stand maneuvers. During the 0.05 Hz maneuver, Coherence: CKD = 0.83 ± 0.13, CON = 0.85 ± 0.12, Phase (radians): CKD = 1.39 ± 0.41, CON = 1.25 ± 0.30, Gain (cm/s/mmHg): CKD = 0.69 ± 0.20, CON = 0.71 ± 0.22, nGain (%/mmHg): CKD = 1.26 ± 0.35, CON = 1.20 ± 0.28, p ≥ 0.24. During the 0.10 Hz maneuver (N = 6 CKD and N = 12 CON), Coherence: CKD = 0.61 ± 0.10, CON = 0.67 ± 0.11, Phase (radians): CKD = 1.43 ± 0.26, CON = 1.30 ± 0.23, Gain (cm/s/mmHg): CKD = 0.75 ± 0.15, CON = 0.84 ± 0.26, nGain (%/mmHg): CKD = 1.50 ± 0.28, CON = 1.29 ± 0.24, p ≥ 0.12. Contrary to our hypothesis, dynamic cerebral autoregulation remains intact in CKD stages III‐IV. These findings suggest that other mechanisms likely contribute to the increased cerebrovascular disease burden experienced by this population. Future work should determine if other cerebrovascular regulatory mechanisms are impaired and related to cerebrovascular disease risk in CKD. [ABSTRACT FROM AUTHOR]

Dynamic cerebral autoregulation is often assessed by continuously recorded arterial blood pressure (ABP) and transcranial Doppler-derived mean cerebral blood flow velocity followed by analysis in the time and frequency domain, respectively. Sequential correlation (in the time domain, yielding e.g., the measure mean flow index, Mxa) and transfer function analysis (TFA) (in the frequency domain, yielding, e.g., normalised and non-normalised gain as well as phase in the low frequency domain) are commonly used approaches. This study investigated the diagnostic and prognostic performance of these metrics. We included recordings from 48 healthy volunteers, 19 patients with sepsis, 36 with traumatic brain injury (TBI), and 14 patients admitted to a neurorehabilitation unit. The diagnostic (between healthy volunteers and patients) and prognostic performance (to predict death or poor functional outcome) of Mxa and the TFA measures were assessed by area under the receiver-operating characteristic (AUROC) curves. AUROC curves generally indicated that the measures were 'no better than chance' (AUROC ∼0.5) both for distinguishing between healthy volunteers and patient groups, and for predicting outcomes in our cohort. No metric emerged as superior for distinguishing between healthy volunteers and different patient groups, for assessing the effect of interventions, or for predicting mortality or functional outcome. [ABSTRACT FROM AUTHOR]

In patients with sickle cell disease (SCD), the delivery of oxygen to the brain is compromised by anemia, abnormal rheology, and steno‐occlusive vascular disease. Successful compensation depends on an increase in oxygen supply such as that provided by an increase in cerebral blood flow (CBF). We used magnetic resonance imaging to provide a high‐resolution assessment of the ability of SCD patients to respond to a vasoactive stimulus in middle, anterior, and posterior cerebral artery territories for both white and gray matter. Cerebrovascular reactivity (CVR) was measured as the blood oxygen level dependent signal (a surrogate for CBF) response to an increase in the end tidal partial pressure of CO2 (PETCO2). The dynamic aspect of the response was measured as the time constant of the first order response kinetics (tau). To confirm and support these findings we used an alternative examination of the response, transfer function analysis (TFA), to measure the responsiveness (gain), the speed of response (phase), and the consistency of the response over time (coherence). We tested 34 patients with SCD and compared the results to those of 24 healthy controls participants. The results from a three‐way ANOVA showed that patients with SCD have reduced CVR (p < 0.001) and lower coherence (p < 0.001) in gray matter and white matter and reduced gain in gray matter only (p < 0.001). In terms of the speed of the response to CO2, tau (p < 0.001) and TFA phase (p < 0.001) were increased in SCD patients compared to healthy control subjects. These findings show that the cerebrovascular responsiveness to CO2 in patients with SCD is both decreased and slowed compared to healthy controls. [ABSTRACT FROM AUTHOR]

Background: Dynamic cerebral autoregulation (CA) is known to be impaired in patients with acute ischemic stroke (AIS), but whether or not dynamic CA can predict long-term outcomes is unclear. Materials and Methods: This prospective study included 103 patients with AIS between September 2017 and April 2019. We measured the middle cerebral artery blood flow velocity and blood pressure within 7 days of AIS onset using a transcranial Doppler and Finometer, respectively. We conducted transfer function analysis to calculate dynamic CA indices (phase and gain), with lower phase and higher gain parameters reflecting less efficient CA. We followed up all patients after 3 and 12 months. Patients with 12-month modified Rankin Scale scores of <2 and ≥2 were defined as having favorable and unfavorable outcomes, respectively. We then analyzed the predictors of unfavorable outcomes after 3 and 12 months using logistic regression. Results: The ipsilesional phase parameter was significantly lower in patients with unfavorable outcomes than in those with favorable outcomes. Multiple logistic regression analysis revealed that the ipsilesional phase parameter and the National Institutes of Health Stroke Scale score were nonmodifiable predictors of short-term and long-term outcomes. Moreover, in receiver operating characteristic analysis, the area under the curve of the ipsilesional phase parameter was 0.646 (95% confidence interval: 0.513-0.779, P =0.044). Notably, the optimal cut-off value was 20.33 degrees (sensitivity: 63%, specificity: 70%). Conclusion: Dynamic CA is an independent predictor of outcomes at 3 and 12 months in patients with AIS. [ABSTRACT FROM AUTHOR]

Older adults have higher cerebrovascular impedance than young individuals which may contribute to chronic brain hypoperfusion. Besides, middle-aged athletes exhibit lower cerebrovascular impedance than their sedentary peers. We examined whether aerobic exercise training (AET) reduces cerebrovascular impedance in sedentary older adults. We conducted a proof-of-concept trial that randomized 73 older adults to 1 yr of AET (n = 36) or stretching and toning (SAT, n = 37) interventions. Cerebrovascular impedance was estimated from simultaneous recordings of carotid artery pressure (CAP) via applanation tonometry and cerebral blood flow velocity (CBFV) in the middle cerebral artery via transcranial Doppler using transfer function analysis. Fifty-six participants completed 1-yr interventions, and 41 of those completed cerebrovascular impedance measurements. AET group showed a significant increase in V̇o2peak after the intervention [estimated marginal mean (95% confidence interval); from 22.8 (21.6 to 24.1) to 24.9 (23.6 to 26.2) mL·kg−1·cm−1, P < 0.001], but not SAT [from 21.7 (20.5 to 22.9) to 22.3 (21.1 to 23.7) mL·kg−1·cm−1, P = 0.114]. Coherence between changes in CBFV and CAP was >0.90 in the frequency range of 0.78–3.12 Hz. The averaged cerebrovascular impedance modulus (Z) in this frequency range decreased after 1-yr AET [from 1.05 (0.96 to 1.14) to 0.95 (0.92 to 1.06) mmHg·s·cm−1, P = 0.023], but not SAT [from 0.96 (0.87 to 1.04) to 1.01 (0.92 to 1.10) mmHg·s·cm−1, P = 0.138]. Reductions in Z were correlated positively with reductions in carotid pulse pressure (r = 0.628, P = 0.004) and inversely with mean CBFV (r = −0.563, P = 0.012) in the AET group. One-year AET reduces cerebrovascular impedance in older adults, which may benefit brain perfusion. NEW & NOTEWORTHY Estimation of cerebrovascular impedance is essential for understanding dynamic cerebral blood flow regulation. This randomized controlled trial demonstrated that aerobic exercise training reduced cerebrovascular impedance in older adults, which may benefit brain perfusion. [ABSTRACT FROM AUTHOR]

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.

Abstract Chronic Kidney Disease (CKD) patients experience an elevated risk for cerebrovascular disease. One factor that may contribute to this heightened risk is an impairment in dynamic cerebral autoregulation, the mechanism by which cerebral vessels modulate cerebral blood flow during fluctuations in arterial pressure. We hypothesized that dynamic cerebral autoregulation would be impaired in CKD. To test this hypothesis, we compared dynamic cerebral autoregulation between CKD patients stages III‐IV and matched controls (CON) without CKD. Fifteen patients with CKD and 20 CON participants performed 2, 5‐minute bouts of repeated sit‐to‐stand maneuvers at 0.05 Hz and 0.10 Hz while mean arterial pressure (MAP, via finger photoplethysmography) and middle cerebral artery blood velocity (MCAv, via transcranial Doppler ultrasound) were measured continuously. Cerebral autoregulation was characterized by performing a transfer function analysis (TFA) on the MAP‐MCAv relationship to derive coherence, phase, gain, and normalized gain (nGain). We observed no group differences in any of the TFA metrics during the repeated sit‐to‐stand maneuvers. During the 0.05 Hz maneuver, Coherence: CKD = 0.83 ± 0.13, CON = 0.85 ± 0.12, Phase (radians): CKD = 1.39 ± 0.41, CON = 1.25 ± 0.30, Gain (cm/s/mmHg): CKD = 0.69 ± 0.20, CON = 0.71 ± 0.22, nGain (%/mmHg): CKD = 1.26 ± 0.35, CON = 1.20 ± 0.28, p ≥ 0.24. During the 0.10 Hz maneuver (N = 6 CKD and N = 12 CON), Coherence: CKD = 0.61 ± 0.10, CON = 0.67 ± 0.11, Phase (radians): CKD = 1.43 ± 0.26, CON = 1.30 ± 0.23, Gain (cm/s/mmHg): CKD = 0.75 ± 0.15, CON = 0.84 ± 0.26, nGain (%/mmHg): CKD = 1.50 ± 0.28, CON = 1.29 ± 0.24, p ≥ 0.12. Contrary to our hypothesis, dynamic cerebral autoregulation remains intact in CKD stages III‐IV. These findings suggest that other mechanisms likely contribute to the increased cerebrovascular disease burden experienced by this population. Future work should determine if other cerebrovascular regulatory mechanisms are impaired and related to cerebrovascular disease risk in CKD.

Abstract In patients with sickle cell disease (SCD), the delivery of oxygen to the brain is compromised by anemia, abnormal rheology, and steno‐occlusive vascular disease. Successful compensation depends on an increase in oxygen supply such as that provided by an increase in cerebral blood flow (CBF). We used magnetic resonance imaging to provide a high‐resolution assessment of the ability of SCD patients to respond to a vasoactive stimulus in middle, anterior, and posterior cerebral artery territories for both white and gray matter. Cerebrovascular reactivity (CVR) was measured as the blood oxygen level dependent signal (a surrogate for CBF) response to an increase in the end tidal partial pressure of CO2 (PETCO2). The dynamic aspect of the response was measured as the time constant of the first order response kinetics (tau). To confirm and support these findings we used an alternative examination of the response, transfer function analysis (TFA), to measure the responsiveness (gain), the speed of response (phase), and the consistency of the response over time (coherence). We tested 34 patients with SCD and compared the results to those of 24 healthy controls participants. The results from a three‐way ANOVA showed that patients with SCD have reduced CVR (p

Impairments in cerebral autoregulation (CA) are related to poor clinical outcome. Near infrared spectroscopy (NIRS) is a non-invasive technique applied to estimate CA. Our general purpose was to study the clinical feasibility of a previously published 'NIRS-only' CA methodology in a critically ill intensive care unit (ICU) population and determine its relationship with clinical outcome. Bilateral NIRS measurements were performed for 1–2 h. Data segments of ten-minutes were used to calculate transfer function analyses (TFA) CA estimates between high frequency oxyhemoglobin (oxyHb) and deoxyhemoglobin (deoxyHb) signals. The phase shift was corrected for serial time shifts. Criteria were defined to select TFA phase plot segments (segments) with 'high-pass filter' characteristics. In 54 patients, 490 out of 729 segments were automatically selected (67%). In 34 primary neurology patients the median (q1–q3) low frequency (LF) phase shift was higher in 19 survivors compared to 15 non-survivors (13° (6.3–35) versus 0.83° (−2.8–13), p = 0.0167). CA estimation using the NIRS-only methodology seems feasible in an ICU population using segment selection for more robust and consistent CA estimations. The 'NIRS-only' methodology needs further validation, but has the advantage of being non-invasive without the need for arterial blood pressure monitoring. [ABSTRACT FROM AUTHOR]

• A framework for evaluating the cascade effect of drought and flood events in different sub-regions and multiple levels is proposed. • The correlation degree of meteorological-hydrological drought and flood in the Yangtze River Basin is higher than that in the Yellow River Basin. • The flood-flood and drought-drought scenarios aggravated the disaster, but the probability of the same drought and flood scenarios in the two basins was higher. The flood-drought scenario is conducive to mitigating drought. Under the background of global change, the multivariate attributes, multi-temporal and multi-watershed regional characteristics of extreme drought and flood disasters are significant. It is very important to identify the drought and wetness encounter law and spatial cascade effect in the source region-upper-middle-lower reaches of the basin. In this paper, the Yangtze River and Yellow River basins are taken as the research objects. Based on the standardized precipitation index (SPI) characterizing meteorological drought and wetness and the standardized runoff index (SRI) characterizing hydrological drought and wetness, the evolution law of extreme drought and flood events in the source region-upper-middle-lower reaches of the two basins is analyzed. On this basis, the correlation analysis and transfer function analysis are used to explore the response relationship and lag effect between the two in different partitions. A two-dimensional joint distribution model is constructed by Copula function to quantitatively analyze the joint probability of drought and wetness encounters of 9 combined events, and to deeply analyze the impact of different drought and wetness encounter scenarios. The results show that: from 1957 to 2020, the two basins showed a trend from drought to wet. The SPI-12 in the Yellow River Basin ranged from-1.57 to 1.32, and that in the Yangtze River Basin ranged from-1.24 to 1.11. The severity of drought and wetness in the Yellow River Basin was higher than that in the Yangtze River Basin; The correlation coefficients between SPI and SRI in the source-upper-middle-lower reaches of the Yellow River (Yangtze River) were 0.78 (0.76), 0.23 (0.73), 0.44 (0.55) and 0.23 (0.63), respectively. The correlation degree of meteorological-hydrological drought and wetness in the Yangtze River Basin was significantly higher than that in the Yellow River Basin. The average probability of synchronous combination events of drought and wetness in the two basins is greater than 51.43 %. The probability of drought in the Yellow River Basin is greater than that of flood, while the Yangtze River Basin is the opposite. In the same drought and wetness scenario, an average of 54.1% of the event pairs were aggravated by disasters, and more than 52 % of the events in the wetness-drought scenario had obvious drought mitigation effects. The research results can provide important support for improving the early warning and risk management of river basin disasters. [ABSTRACT FROM AUTHOR]

Background and Purpose: Dynamic cerebral autoregulation is impaired after ischemic stroke. External counterpulsation (ECP) augments the cerebral blood flow of patients with ischemic stroke by elevation of blood pressure (BP). We aimed to investigate if cerebral augmentation effects during ECP were associated with impaired dynamic cerebral autoregulation in patients after acute ischemic stroke. Methods: Forty patients with unilateral ischemic stroke and large artery atherosclerosis in the anterior circulation territory within 7 days from symptom onset and eighteen healthy controls were recruited. We monitored changes in mean flow velocity over both middle cerebral arteries (MCA) by transcranial Doppler (TCD) before, during, and immediately after ECP. Cerebral augmentation index was MCA mean flow velocity increase in percentage during ECP compared with baseline to evaluate the augmentation effects of ECP. Spontaneous arterial BP and cerebral blood flow velocity in both bilateral MCAs were recorded using a servo-controlled plethysmograph and TCD, respectively. Transfer function analysis was used to derive the autoregulatory parameters, including phase difference (PD), and gain. Results: The cerebral augmentation index in patients with stroke was significantly higher on both the ipsilateral and contralateral sides than that in controls, while the PD in patients with stroke was significantly lower on both sides than those in controls (all P < 0.05). The cerebral augmentation index did not correlate with PD and gain on either the ipsilateral or contralateral side of patients with stroke or in controls (all P > 0.05). The cerebral augmentation index of patients with stroke was significantly related to mean BP change on the ipsilateral side (R 2 = 0.108, P = 0.038). Conclusion: The degree of ECP-induced cerebral augmentation effects as measured by the cerebral augmentation index did not correlate with the magnitude of impaired dynamic cerebral autoregulation. [ABSTRACT FROM AUTHOR]

Steady-state cerebral blood flow (CBF) and dynamic cerebral autoregulation are reportedly maintained during -10° head-down tilt (HDT) despite slight increases in intracranial pressure (ICP). However, the higher ICP during -30° HDT may alter steady-state CBF and dynamic cerebral autoregulation. The present study hypothesized that steady-state CBF and dynamic cerebral autoregulation would be altered by higher ICP during -30° HDT than during 0° and -10° HDT. Seventeen healthy participants were positioned horizontal (0°) and in -10° HDT and -30° HDT for 10 min in random order on separate days. The arterial blood pressure waveform was obtained using a finger blood pressure device and the cerebral blood velocity waveform in the middle cerebral artery was obtained using transcranial Doppler sonography (TCD) for the last 6 min in each position. ICP was estimated using noninvasive ICP (nICP) based on TCD. Dynamic cerebral autoregulation was evaluated by spectral and transfer function analysis. Although nICP was significantly higher during -30° HDT (12.4 mmHg) than during -10° HDT (8.9 mmHg), no significant differences in steady-state mean cerebral blood velocity or transfer function gain in any frequency ranges were seen among all angles of HDT. Counter to our hypothesis, the present results suggest that steady-state CBF and dynamic cerebral autoregulation may be preserved during short-term -30° HDT despite the higher ICP compared with that during -10° HDT. NEW & NOTEWORTHY This appears to be the first study to evaluate steady-state cerebral blood flow (CBF), dynamic cerebral autoregulation, and intracranial pressure (ICP) during -30° head-down tilt (HDT) compared with those during -10° HDT using noninvasive measurements. The results suggest that steady-state CBF and dynamic cerebral autoregulation are preserved despite the higher ICP during short-term -30° HDT compared with -10° HDT. [ABSTRACT FROM AUTHOR]

Dynamic cerebral autoregulation to spontaneous fluctuations in cerebral perfusion pressure (CPP) is often assessed by transcranial Doppler (TCD) in the time domain, yielding primarily the mean flow index (Mx), or in the frequency domain using transfer function analysis (TFA), yielding gain and phase. For both domains, the measurement of blood pressure is critical. This study assessed the inter‐method reliability of dynamic cerebral autoregulation using three different methods of pressure measurement. In 39 patients with aneurysmal subarachnoid hemorrhage, non‐invasive arterial blood pressure (ABP), invasive ABP (measured in the radial artery) and CPP were recorded simultaneously with TCD. Intraclass correlation coefficient (ICC) was used to quantify reliability. Mx was higher when calculated using invasive ABP (0.39; 95% confidence interval [95% CI]: 0.33; 0.44) compared to non‐invasive ABP, and CPP. The overall ICC showed poor to good reliability (0.65; 95% CI: 0.11; 0.84; n = 69). In the low frequency domain, the comparison between invasively measured ABP and CPP showed good to excellent (normalized gain, ICC: 0.87, 95CI: 0.81; 0.91; n = 96; non‐normalized gain: 0.89, 95% CI: 0.84; 0.92; n = 96) and moderate to good reliability (phase, ICC: 0.69, 95% CI: 0.55; 0.79; n = 96), respectively. Different methods for pressure measurement in the assessment of dynamic cerebral autoregulation yield different results and cannot be used interchangeably. [ABSTRACT FROM AUTHOR]

Background and PurposeDynamic cerebral autoregulation is impaired after ischemic stroke. External counterpulsation (ECP) augments the cerebral blood flow of patients with ischemic stroke by elevation of blood pressure (BP). We aimed to investigate if cerebral augmentation effects during ECP were associated with impaired dynamic cerebral autoregulation in patients after acute ischemic stroke.MethodsForty patients with unilateral ischemic stroke and large artery atherosclerosis in the anterior circulation territory within 7 days from symptom onset and eighteen healthy controls were recruited. We monitored changes in mean flow velocity over both middle cerebral arteries (MCA) by transcranial Doppler (TCD) before, during, and immediately after ECP. Cerebral augmentation index was MCA mean flow velocity increase in percentage during ECP compared with baseline to evaluate the augmentation effects of ECP. Spontaneous arterial BP and cerebral blood flow velocity in both bilateral MCAs were recorded using a servo-controlled plethysmograph and TCD, respectively. Transfer function analysis was used to derive the autoregulatory parameters, including phase difference (PD), and gain.ResultsThe cerebral augmentation index in patients with stroke was significantly higher on both the ipsilateral and contralateral sides than that in controls, while the PD in patients with stroke was significantly lower on both sides than those in controls (all P < 0.05). The cerebral augmentation index did not correlate with PD and gain on either the ipsilateral or contralateral side of patients with stroke or in controls (all P > 0.05). The cerebral augmentation index of patients with stroke was significantly related to mean BP change on the ipsilateral side (R2 = 0.108, P = 0.038).ConclusionThe degree of ECP-induced cerebral augmentation effects as measured by the cerebral augmentation index did not correlate with the magnitude of impaired dynamic cerebral autoregulation.

Abstract Dynamic cerebral autoregulation to spontaneous fluctuations in cerebral perfusion pressure (CPP) is often assessed by transcranial Doppler (TCD) in the time domain, yielding primarily the mean flow index (Mx), or in the frequency domain using transfer function analysis (TFA), yielding gain and phase. For both domains, the measurement of blood pressure is critical. This study assessed the inter‐method reliability of dynamic cerebral autoregulation using three different methods of pressure measurement. In 39 patients with aneurysmal subarachnoid hemorrhage, non‐invasive arterial blood pressure (ABP), invasive ABP (measured in the radial artery) and CPP were recorded simultaneously with TCD. Intraclass correlation coefficient (ICC) was used to quantify reliability. Mx was higher when calculated using invasive ABP (0.39; 95% confidence interval [95% CI]: 0.33; 0.44) compared to non‐invasive ABP, and CPP. The overall ICC showed poor to good reliability (0.65; 95% CI: 0.11; 0.84; n = 69). In the low frequency domain, the comparison between invasively measured ABP and CPP showed good to excellent (normalized gain, ICC: 0.87, 95CI: 0.81; 0.91; n = 96; non‐normalized gain: 0.89, 95% CI: 0.84; 0.92; n = 96) and moderate to good reliability (phase, ICC: 0.69, 95% CI: 0.55; 0.79; n = 96), respectively. Different methods for pressure measurement in the assessment of dynamic cerebral autoregulation yield different results and cannot be used interchangeably.

Objective: Recent studies have demonstrated the positive roles of remote ischemic conditioning (RIC) in patients with cerebrovascular diseases; however, the mechanisms remain unclear. This study aimed to explore the effect of serial RIC on dynamic cerebral autoregulation (dCA) and serum biomarkers associated with brain injury, both of which are related to the prognosis of cerebrovascular disease. Methods: This was a self-controlled interventional study in healthy adults. The RIC was conducted twice a day for 7 consecutive days (d1–d7) and comprised 4 × 5-min single arm cuff inflation/deflation cycles at 200 mmHg. All participants underwent assessments of dCA ten times, including baseline, d1, d2, d4, d7, d8, d10, d14, d21, and d35 of the study. Blood samples were collected four times (baseline, d1, d7, and d8) immediately after dCA measurements. The transfer function parameters [phase difference (PD) and gain] were used to quantify dCA. Four serum biomarkers associated with brain injury, ubiquitin C-terminal hydrolase-L1, neuron-specific enolase, glial fibrillary acidic protein, and S100β were tested. Results: Twenty-two healthy adult volunteers (mean age 25.73 ± 1.78 years, 3 men [13.6%], all Asian) were enrolled in this study. Bilateral PD values were significantly higher since four times of RIC were completed (d2) compared with PD values at baseline (left: 53.31 ± 10.53 vs. 45.87 ± 13.02 degree, p = 0.015; right: 54.90 ± 10.46 vs. 45.96 ± 10.77 degree, p = 0.005). After completing 7 days of RIC, the significant increase in dCA was sustained for at least 28 days (d35, left: 53.11 ± 14.51 degree, P = 0.038; right: 56.95 ± 14.57 degree, p < 0.001). No difference was found in terms of different serum biomarkers related to brain injury before and after RIC. Conclusion: The elevation in dCA was detected immediately after four repeated times of RIC, and 7-day consecutive RIC induced a sustained increase in dCA for at least 28 days and did not affect blood biomarkers of brain injury in healthy adults. These results will help us to formulate detailed strategies for the safe and effective application of RIC in patients with cerebrovascular disease. [ABSTRACT FROM AUTHOR]

Background: Cerebral autoregulation plays an important role in safeguarding adequate cerebral perfusion and reducing the risk of secondary brain injury, which is highly important for patients in the neurological intensive care unit (neuro-ICU). Although the consensus white paper suggests that a minimum of 5 min of data are needed for assessing dynamic cerebral autoregulation with transfer function analysis (TFA), it remains unknown if the length of these data is valid for patients in the neuro-ICU, of whom are notably different than the general populations. We aimed to investigate the effect of data length using transcranial Doppler ultrasound combined with invasive blood pressure measurement for the assessment of dynamic cerebral autoregulation in patients in the neuro-ICU. Methods: Twenty patients with various clinical conditions (severe acute encephalitis, ischemic stroke, subarachnoid hemorrhage, brain injury, cerebrovascular intervention operation, cerebral hemorrhage, intracranial space-occupying lesion, and toxic encephalopathy) were recruited for this study. Continuous invasive blood pressure, with a pressure catheter placed at the radial artery, and bilateral continuous cerebral blood flow velocity with transcranial Doppler ultrasound were simultaneously recorded for a length of 10 min for each patient. TFA was applied to derive phase shift, gain, and coherence function at all frequency bands from the first 2, 3, 4, 5, 6, 7, 8, 9, and 10 min of the 10-min recordings in each patient on both hemispheres. The variability in the autoregulatory parameters in each hemisphere was investigated by repeated measures analysis of variance. Results: Forty-one recordings (82 hemispheres) were included in the study. According to the critical values of coherence provided by the Cerebral Autoregulation Research Network white paper, acceptable rates for the data were 100% with a length ≥ 7 min. The final analysis included 68 hemispheres. The effects of data length on trends in phase shift in the very low frequency (VLF) band (F1.801,120.669 = 6.321, P = 0.003), in the LF band (F1.274,85.343 = 4.290, P = 0.032), and in the HF band (F1.391,93.189 = 3.868, P = 0.039) were significant for 3–7 min, for 4–7 min, and for 5–8 min, respectively. Effects were also significant on the gain in the VLF band (F1.927,129.134 = 3.215, P = 0.045) for 2–8 min and on the coherence function in all frequency bands (VLF F2.846,190.671 = 90.247, P < 0.001, LF F2.515,168.492 = 55.770, P < 0.001, HF F2.411, 161.542 = 33.833, P < 0.001) for 2–10 min. Conclusions: Considering the acceptable rates for the data and the variation in the TFA variables (phase shift and gain), we recommend recording data for a minimum length of 7 min for TFA in patients in the neuro-ICU. [ABSTRACT FROM AUTHOR]

Aims: Cerebral small vessel disease (CSVD) is characterized by functional and structural changes in small vessels. We aimed to elucidate the relationship between dynamic cerebral autoregulation (dCA) and neuroimaging characteristics of CSVD. Methods: A case‐control study was performed. Cerebral blood flow velocity (CBFV) of bilateral middle cerebral arteries and spontaneous arterial blood pressure were simultaneously recorded. Transfer function analysis was used to calculate dCA parameters (phase, gain, and the rate of recovery of CBFV [RoRc]). Neuroimaging characteristics of CSVD patients were evaluated, including lacunes, white matter hyperintensities (WMH), cerebral microbleeds (CMBs), perivascular spaces (PVS), and the total CSVD burden. Results: Overall, 113 patients and 83 controls were enrolled. Compared with the control group, the phase at low frequency and the RoRc in CSVD patients were lower, and the gain at very low and low frequencies were higher, indicating bilaterally impaired dCA. Total CSVD burden, WMH (total, periventricular and deep), severe PVS, and lobar CMBs were independently correlated with the phase at low frequency. Conclusions: Our findings suggested that dCA was compromised in CSVD patients, and some specific neuroimaging characteristics (the total CSVD burden, WMH, severe PVS and lobar CMBs) might indicate more severe dCA impairment in CSVD patients. [ABSTRACT FROM AUTHOR]

The incidence of depression is increasing, especially in the young adult population. Impaired cognitive function is one of the characteristics of depression, which may be related to impaired cerebral autoregulation (CA). We investigated the characteristics of CA in young adults with mild depression, as well as its validity for identifying patients with depression. Patients (aged 18–35 years) with Hamilton Depression Rating Scale (HAMD) scores ranging from 8 to 17 and a first episode of mild depression were enrolled in this study. Healthy volunteers were recruited as controls. Noninvasive continuous arterial blood pressure and bilateral middle cerebral artery blood flow velocity were simultaneously recorded from each subject. Transfer function analysis was applied to derive phase difference, gain, coherence and rate of recovery for the assessment of CA. Forty‐three patients and 43 healthy controls were enrolled. Phase difference values were significantly compromised in young adults with mild depression and were negatively correlated with HAMD scores. Rate of recovery values estimated from depressed patients was significantly lower. The validity in identifying patients with depression was favorable for the phase difference. The cutoff phase difference value was 29.66. Our findings suggest that dynamic CA was impaired in young patients with mild depression and negatively correlated with HAMD scores. CA represented by phase difference can be used as an objective auxiliary examination of depression, and has clinical diagnostic value for the early identification of patients with depression. Cognitive impairment is one of the most common features of depression, which may be related to impaired cerebral autoregulation (CA). The current study, for the first time, investigated the characteristics of CA in young adults with mild depression. The findings suggested that dynamic CA was compromised in young patients with mild depression. CA represented by phase difference has clinical diagnostic value for the early identification of patients with depression. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

ObjectiveRecent studies have demonstrated the positive roles of remote ischemic conditioning (RIC) in patients with cerebrovascular diseases; however, the mechanisms remain unclear. This study aimed to explore the effect of serial RIC on dynamic cerebral autoregulation (dCA) and serum biomarkers associated with brain injury, both of which are related to the prognosis of cerebrovascular disease.MethodsThis was a self-controlled interventional study in healthy adults. The RIC was conducted twice a day for 7 consecutive days (d1–d7) and comprised 4 × 5-min single arm cuff inflation/deflation cycles at 200 mmHg. All participants underwent assessments of dCA ten times, including baseline, d1, d2, d4, d7, d8, d10, d14, d21, and d35 of the study. Blood samples were collected four times (baseline, d1, d7, and d8) immediately after dCA measurements. The transfer function parameters [phase difference (PD) and gain] were used to quantify dCA. Four serum biomarkers associated with brain injury, ubiquitin C-terminal hydrolase-L1, neuron-specific enolase, glial fibrillary acidic protein, and S100β were tested.ResultsTwenty-two healthy adult volunteers (mean age 25.73 ± 1.78 years, 3 men [13.6%], all Asian) were enrolled in this study. Bilateral PD values were significantly higher since four times of RIC were completed (d2) compared with PD values at baseline (left: 53.31 ± 10.53 vs. 45.87 ± 13.02 degree, p = 0.015; right: 54.90 ± 10.46 vs. 45.96 ± 10.77 degree, p = 0.005). After completing 7 days of RIC, the significant increase in dCA was sustained for at least 28 days (d35, left: 53.11 ± 14.51 degree, P = 0.038; right: 56.95 ± 14.57 degree, p < 0.001). No difference was found in terms of different serum biomarkers related to brain injury before and after RIC.ConclusionThe elevation in dCA was detected immediately after four repeated times of RIC, and 7-day consecutive RIC induced a sustained increase in dCA for at least 28 days and did not affect blood biomarkers of brain injury in healthy adults. These results will help us to formulate detailed strategies for the safe and effective application of RIC in patients with cerebrovascular disease.