Sex modifies the relationship between age and neurovascular coupling in healthy adults.

Neurovascular coupling (NVC) is the matching between local neuronal activity and regional cerebral blood flow (CBF), but little is known about the effects of age and sex on NVC. This study aimed to investigate the relationships and interaction between age and sex on NVC. Sixty-four healthy adults (18-85 years, N = 34 female) completed a visual stimulus evoked NVC assessment to a flashing checkerboard. NVC responses were measured in the posterior cerebral artery (PCAv) using transcranial Doppler ultrasound. A hierarchical multiple regression was used to determine the relationships between age, sex, and the age by sex interaction on NVC. There was a significant age by sex interaction for baseline (P = 0.001) and peak PCAv (P = 0.01), with a negative relationship with age in females (P < 0.005), and no relationship in males (P ≥ 0.17). NVC responses as a percent increase from baseline showed a significant age by sex interaction (P = 0.014), with a positive relationship with age in females (P = 0.04) and no relationship in males (P = 0.17), even after adjusting for baseline PCAv. These data highlight important sex differences, with an association between age and NVC only apparent in females but not males, and thus a need to account for sex dependent effects of ageing when investigating cerebrovascular regulation.

Resistance, but not endurance exercise training, induces changes in cerebrovascular function in healthy young subjects.

It is generally considered that regular exercise maintains brain health and reduces the risk of cerebrovascular diseases such as stroke and dementia. Since the benefits of different "types" of exercise are unclear, we sought to compare the impacts of endurance and resistance training on cerebrovascular function. In a randomized and crossover design, 68 young healthy adults were recruited to participate in 3 mo of resistance and endurance training. Cerebral hemodynamics through the internal carotid, vertebral, middle and posterior cerebral arteries were measured using Duplex ultrasound and transcranial Doppler at rest and during acute exercise, dynamic autoregulation, and cerebrovascular reactivity (to hypercapnia). Following resistance, but not endurance training, middle cerebral artery velocity and pulsatility index significantly decreased (P < 0.01 and P = 0.02, respectively), whereas mean arterial pressure and indices of cerebrovascular resistance in the middle, posterior, and internal carotid arteries all increased (P < 0.05). Cerebrovascular resistance indices in response to acute exercise and hypercapnia also significantly increased following resistance (P = 0.02), but not endurance training. Our findings, which were consistent across multiple domains of cerebrovascular function, suggest that episodic increases in arterial pressure associated with resistance training may increase cerebrovascular resistance. The implications of long-term resistance training on brain health require future study, especially in populations with pre-existing cerebral hypoperfusion and/or hypotension.NEW & NOTEWORTHY Three months of endurance exercise did not elicit adaptation in any domain of cerebrovascular function in young healthy inactive volunteers. However, resistance training induced decreased pulsatility in the extracranial arteries and increased indices of cerebrovascular resistance in cerebral arteries. This increase in cerebrovascular resistance, apparent at baseline and in response to both hypercapnia and acute exercise, may reflect a protective response in the face of changes in arterial pressure during resistance exercise.

Global REACH 2018: Regional differences in cerebral blood velocity control during normoxic and hypoxic cold pressor tests.

The impact of oxygen on the cerebral response to the cold pressor test (CPT) remains unknown. In 13 participants, blood pressure, middle and posterior cerebral artery blood velocity (MCAv and PCAv, respectively) were measured during an isocapnic normoxic and hypoxic (SpO2 = 85%) CPT. The main findings were: 1) the MCAv response to the CPT was greater compared to the PCAv in both normoxic and hypoxic conditions (P = 0.003 and P = 0.002, respectively); and, 2) hypoxia did not alter the cerebral response to the CPT (P = 0.141 and P = 0.150, respectively). These data highlight that regional differences in cerebrovascular control exist during the CPT.

Comparable blood velocity changes in middle and posterior cerebral arteries during and following acute high-intensity exercise in young fit women.

The cerebral blood flow response to high-intensity interval training (HIIT) remains unclear. HIIT induces surges in mean arterial pressure (MAP), which could be transmitted to the brain, especially early after exercise onset. The aim of this study was to describe regional cerebral blood velocity changes during and following 30 s of high-intensity exercise. Ten women (age: 27 ± 6 years; VO2max : 48.6 ± 3.8 ml·kg·min-1 ) cycled for 30 s at the workload reached at V˙ O2max followed by 3min of passive recovery. Middle (MCAvmean ) and posterior cerebral artery mean blood velocities (PCAvmean ; transcranial Doppler ultrasound), MAP (finger photoplethysmography), and end-tidal carbon dioxide partial pressure (PET CO2 ; gaz analyzer) were measured. MCAvmean (+19 ± 10%) and PCAvmean (+21 ± 14%) increased early after exercise onset, returning toward baseline values afterward. MAP increased throughout exercise (p < .0001). PET CO2 initially decreased by 3 ± 2 mmHg (p < .0001) before returning to baseline values at end-exercise. During recovery, MCAvmean (+43 ± 15%), PCAvmean (+42 ± 15%), and PET CO2 (+11 ± 3 mmHg; p < .0001) increased. In young fit women, cerebral blood velocity quickly increases at the onset of a 30-s exercise performed at maximal workload, before returning to baseline values through the end of the exercise. During recovery, cerebral blood velocity augments in both arteries, along with PET CO2 .

Dynamic cerebral autoregulation across the cardiac cycle during 8 hr of recovery from acute exercise.

Current protocols examining cerebral autoregulation (CA) parameters require participants to refrain from exercise for 12-24 hr, however there is sparse objective evidence examining the recovery trajectory of these measures following exercise across the cardiac cycle (diastole, mean, and systole). Therefore, this study sought to determine the duration acute exercise impacts CA and the within-day reproducibility of these measures. Nine participants performed squat-stand maneuvers at 0.05 and 0.10 Hz at baseline before three interventions: 45-min moderate-continuous exercise (at 50% heart-rate reserve), 30-min high-intensity intervals (ten, 1-min at 85% heart-rate reserve), and a control day (30-min quiet rest). Squat-stands were repeated at hours zero, one, two, four, six, and eight after each condition. Transcranial doppler ultrasound of the middle cerebral artery (MCA) and the posterior cerebral artery (PCA) was used to characterize CA parameters across the cardiac cycle. At baseline, the systolic CA parameters were different than mean and diastolic components (ps < 0.015), however following both exercise protocols in both frequencies this disappeared until hour four within the MCA (ps > 0.079). In the PCA, phase values were affected only following high-intensity intervals until hour four (ps > 0.055). Normalized gain in all cardiac cycle domains remained different following both exercise protocols (ps < 0.005) and across the control day (p < .050). All systolic differences returned by hour six across all measures (ps < 0.034). Future CA studies may use squat-stand maneuvers to assess the cerebral pressure-flow relationship 6 hr after exercise. Finally, CA measures under this paradigm appear to have negligible within-day variation, allowing for reproducible interpretations to be drawn.

Evaluation of Cerebral Hemodynamics with Color-Coded Duplex Sonography: Normative Values with Correction of Insonation Angles.

BACKGROUND: Transcranial color-coded sonography (TCCS) allows direct observation of arteries and the possibility of correcting the insonation angle for reliable evaluation of hemodynamics. We obtained TCCS reference values of the cerebral hemodynamics after correction of insonation angles. METHODS: We studied 195 healthy adults equally allocated into 3 age groups: 18-40, 41-60, and greater than or equal to 61 years. The middle (MCA), anterior (ACA), and posterior cerebral arteries (PCA) were evaluated through the temporal acoustic window using conventional pulsed transcranial Doppler and TCCS. Peak systolic, end diastolic, and mean blood flow velocities were registered, as well as pulsatility and resistance indices at 0° and with correction by alignment of insonation angle parallel to the blood flow vector. We derived normative values assuming both the parametric and nonparametric distributions. RESULTS: We excluded 33 participants due to inadequate acoustic window (10.3%), carotid disease (2.1%), and embryonic variants (4.6%), leaving out 162 for final analysis (50% female, median age 48 years). The 2.5th-97.5th percentiles of the corrected angle for MCA was 0°-60°, ACA 0°-44°, and PCA 30°-60°. After angle correction, 2.5th-97.5th percentiles for flow velocity of MCA, ACA, and PCA were 37.7-112.5 cm/s, 25.6-71.2 cm/s, and 29.2-80.8 cm/s, respectively. There were wide discrepancies between hemodynamics values obtained with insonation angles at 0° and after angle correction. No differences were found between ultrasound methods at exactly 0° or between hemispheres, however, there were differences according to age and sex. CONCLUSIONS: Specific normative tables should be used in TCCS when the corrected angle is greater than 0° since the hemodynamics values greatly differ after correction of the insonation angle. Further studies are necessary to determine critical cutoffs indicating disease.

Neurovascular coupling and cerebral autoregulation in atrial fibrillation.

The risk of cognitive decline and stroke is increased by atrial fibrillation (AF). We sought to determine whether neurovascular coupling and cerebral autoregulation are blunted in people with AF in comparison with age-matched, patients with hypertension and healthy controls. Neurovascular coupling was assessed using five cycles of visual stimulation for 30 s followed by 30 s with both eyes-closed. Cerebral autoregulation was examined using a sit-stand test, and a repeated squat-to-stand (0.1 Hz) manoeuvre with transfer function analysis of mean arterial pressure (MAP; input) and middle cerebral artery mean blood flow velocity (MCA Vm; output) relationships at 0.1 Hz. Visual stimulation increased posterior cerebral artery conductance, but the magnitude of the response was blunted in patients with AF (18 [8] %; mean [SD]) and hypertension (17 [8] %), in comparison with healthy controls (26 [9] %) (P < 0.05). In contrast, transmission of MAP to MCA Vm was greater in AF patients compared to hypertension and healthy controls, indicating diminished cerebral autoregulation. We have shown for the first time that AF patients have impaired neurovascular coupling responses to visual stimulation and diminished cerebral autoregulation. Such deficits in cerebrovascular regulation may contribute to the increased risk of cerebral dysfunction in people with AF.

Selective posterior cerebral artery amobarbital test: a predictor of memory following subtemporal selective amygdalohippocampectomy.

BACKGROUND: The selective posterior cerebral artery (PCA) amobarbital test, or PCA Wada test, is used to predict memory impairment after epilepsy surgery in patients who have previously had a failed internal carotid artery (ICA) amobarbital test. METHODS: Medical records from 2012 to 2018 were retrospectively reviewed for all patients with seizures who underwent a selective PCA Wada test at our institution following a failed or inconclusive ICA Wada test. Standardized neuropsychological testing was performed before and during the Wada procedure and postoperatively in patients who underwent resection. RESULTS: Thirty-three patients underwent a selective PCA Wada test, with no complications. Twenty-six patients with medically refractory epilepsy had a seizure focus amenable to selective amygdalohippocampectomy (AHE). Six patients (23%, n=26) had a failed PCA Wada test and did not undergo selective AHE, seven (27%) declined surgical resection, leaving 13 patients who underwent subtemporal selective AHE. Hippocampal sclerosis was found in all 13 patients (100%). Twelve patients (92%) subsequently underwent formal neuropsychological testing and all were found to have stable memory. Ten patients (77%) were seizure-free (Engel Class I), with average follow-up of 13 months. CONCLUSION: The selective PCA Wada test is predictive of memory outcomes after subtemporal selective AHE in patients with a failed or inconclusive ICA Wada test. Furthermore, given the low risk of complications and potential benefit of seizure freedom, a selective PCA Wada test may be warranted in patients with medically intractable epilepsy who are candidates for a selective AHE and who have a prior failed or inconclusive ICA Wada test.

Effect of reading with direct or indirect light on the visually evoked flow response in the posterior cerebral artery.

PURPOSE: Reading with direct light from computer monitors or tablets may cause visual fatigue and hamper reading comprehension. Our aim was to compare the blood flow response in the supplying artery of the visual cortex when reading from tablet screen or from paper. The neurovascular coupling was tested also after 15-minute reading from either monitor or paper. METHODS: Flow velocity responses evoked by reading from paper and from monitor were measured by transcranial Doppler sonography in a random sequence in both posterior cerebral arteries (PCAs) of 20 young healthy adults. Afterward, PCA flow response evoked by reading from paper was also investigated after 15 minutes reading on the same tablet or paper, in a random order. RESULTS: Reading from monitor with its own source of light and reading from paper with indirect light caused very similar PCA flow response. Moreover, the flow velocity increase, evoked by reading form paper did not differ after 15-minute reading from monitor or from paper. CONCLUSIONS: Reading with direct or indirect light produces similar flow response in the occipital cortex.

Cerebral Blood Flow during Exercise in Heart Failure: Effect of Ventricular Assist Devices.

INTRODUCTION: In healthy individuals, cerebral blood flow (CBF) increases during exercise, but few studies have compared changes in CBF during exercise in patients with heart failure (HF) to healthy controls (CTRL) or assessed the effects of left ventricular assist devices (LVAD). We hypothesized that subjects implanted with LVAD would exhibit impaired cerebrovascular responses to cycle exercise when compared with age- and sex-matched healthy CTRL subjects but would have enhanced responses relative to subjects with HF. METHODS: Internal carotid artery (ICA) blood flow and intracranial middle (MCAv) and posterior cerebral (PCAv) artery velocities were measured continuously using Doppler ultrasound, alongside cardiorespiratory measures at rest and in response to an incremental submaximal cycle ergometer exercise protocol in nine LVAD participants (58 ± 15 yr, 87 ± 16 kg, 172 ± 8 cm, six females), nine age- and sex-matched subjects with HF (58 ± 8 yr, 84 ± 11 kg, 177 ± 6 cm), and nine CTRL (55 ± 14 yr, 74 ± 16 kg, 168 ± 10 cm). RESULTS: At rest, ICA hemodynamics (velocity, shear rate, and flow) were greater in CTRL and LVAD than that in HF (P < 0.05). Higher MCAv (+5.52 ± 1.59 cm·s, P = 0.003) and PCAv (+5.82 ± 1.41 cm·s, P = 0.001) were also observed in LVAD subjects than healthy CTRL. During exercise, ICA flow increased at all workloads in CTRL, but not in HF or LVAD groups. MCAv increased from baseline in both HF and CTRL participants (P = 0.0001), but not in LVAD subjects. Nonetheless, CTRL and LVAD showed higher MCAv (P = 0.006) and PCAv (P < 0.0001) values throughout exercise than HF. CONCLUSION: Our findings indicate that LVAD subjects exhibit higher CBF at rest and during exercise than matched HF participants but attenuated brain blood flows during exercise when compared with healthy subjects. CBF should be considered when designing exercise training interventions in patients with HF and LVAD.

Deployment of distal posterior cerebral artery flow diverter in tortuous anatomy.

Progressive deconstruction with flow diversion using a Pipeline embolization device (PED; Medtronic) can be utilized to promote thrombosis of broad-based fusiform aneurysms. Current flow diverters require a 0.027-inch microcatheter for deployment. The authors present a patient with a fusiform P2-3 junction posterior cerebral artery aneurysm in which they demonstrate the importance of haptics in microwire manipulation to recognize large-vessel anatomy versus perforator anatomy that may overlap, especially when access is needed in distal tortuous circulations. In addition, the authors demonstrate the need for appropriate visualization before PED deployment. Postembolization runs demonstrated optimal wall apposition with contrast stasis within the aneurysm dome.The video can be found here: https://youtu.be/8kfsSvN3XqM.

Reversible Dilation of Cerebral Macrovascular Changes in MELAS Episodes.

PURPOSE: To investigate the cerebral macrovascular changes as well as the relationship of large vessels and cerebral blood flow (CBF) in mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) using magnetic resonance angiography (MRA) and arterial spin labeling (ASL) perfusion MR imaging (MRI). METHODS: A total of 20 patients diagnosed with MELAS (12 males, 8 females; mean age, 23.3 years) underwent conventional MRI, time-of-flight (TOF) MRA and three dimensional ASL. Follow-up scans were performed in 10 patients. The changes of cerebral arteries and branches on MRA images from both acute and recovery patients were independently evaluated by two radiologists. Lesion distribution and CBF were observed on the integrated maps of MRA and ASL. RESULTS: In 14 patients with clinical onsets, increased CBF was observed in all stroke-like lesions. Dilations of a single artery (four middle cerebral arteries, two posterior cerebral arteries) were found in six patients. Dilations of multiple arteries (two anterior cerebral arteries, seven middle cerebral arteries, six posterior cerebral arteries) were found in seven patients. Normal angiography was shown in one acute patient. Cortical terminal branches feeding the lesion areas were more obviously dilated than the main trunks. The dilated vessels returned to normal on follow-up scans concurrently with decreased CBF in nine patients who were resuscitated from episode attacks. Vasodilation was even seen in one preclinical patient who suffered a recurrent episode 50 days later. CONCLUSION: Reversible dilation of cerebral macrovascular changes could be a new feature of MELAS and a presumed reason for fluctuant CBF. It would shed new light on the mitochondrial angiopathy.

Cerebral arterial time constant calculated from the middle and posterior cerebral arteries in healthy subjects.

The cerebral arterial blood volume changes (∆CaBV) during a single cardiac cycle can be estimated using transcranial Doppler ultrasonography (TCD) by assuming pulsatile blood inflow, constant, and pulsatile flow forward from large cerebral arteries to resistive arterioles [continuous flow forward (CFF) and pulsatile flow forward (PFF)]. In this way, two alternative methods of cerebral arterial compliance (Ca) estimation are possible. Recently, we proposed a TCD-derived index, named the time constant of the cerebral arterial bed (τ), which is a product of Ca and cerebrovascular resistance and is independent of the diameter of the insonated vessel. In this study, we aim to examine whether the τ estimated by either the CFF or the PFF model differs when calculated from the middle cerebral artery (MCA) and the posterior cerebral artery (PCA). The arterial blood pressure and TCD cerebral blood flow velocity (CBFVa) in the MCA and in the PCA were non-invasively measured in 32 young, healthy volunteers (median age: 24, minimum age: 18, maximum age: 31). The τ was calculated using both the PFF and CFF models from the MCA and the PCA and compared using a non-parametric Wilcoxon signed-rank test. Results are presented as medians (25th-75th percentiles). The cerebrovascular time constant estimated in both arteries using the PFF model was shorter than when using the CFF model (ms): [64.83 (41.22-104.93) vs. 178.60 (160.40-216.70), p < 0.001 in the MCA, and 44.04 (17.15-81.17) vs. 183.50 (153.65-204.10), p < 0.001 in the PCA, respectively]. The τ obtained using the PFF model was significantly longer from the MCA than from the PCA, p = 0.004. No difference was found in the τ when calculated using the CFF model. Longer τ from the MCA might be related to the higher Ca of the MCA than that of the PCA. Our results demonstrate MCA-PCA differences in the τ, but only when the PFF model was applied.

[Blood flow parameters of posterior cerebral artery in normal pregnancy during middle and late stage].

OBJECTIVE: To study the blood flow parameters for 2 anatomical segments of posterior cerebral artery (PCA) in normal singleton fetal.
 Methods: The blood flow velocity parameters peak systolic velocity (PSV), end diastolic velocity (EDV), time-average maximum velocity (TAMAXV), velocity time integral (VTI) and resistance parameters systolic peak velocity and end diastolic velocity ratio (S/D), pulsatility index (PI), resistance index (RI) for 2 anatomical segments in PCA were recorded. The first segment of the PCA (PCAS1) was recorded between the origin of PCA and the proximal part of the posterior communicating artery. The second segment of the PCA (PCAS2) was recorded at the distal part of the posterior communicating artery. The blood parameters in both PCAS1 and PCAS2 were analyzed by using Pearson correlation and multiple curves fitting with gestational age (GA). Paired student's t test was performed to compare the difference in blood parameter between PCAS1 and PCAS2.
 Results: The blood flow velocity parameters in both PCAS1 and PCAS2 were increased with the GA (P<0.0001), with the best fitted curves of Quadratic curve (P<0.0001). There were no correlations between resistance parameters in PCA and GA (P>0.05). Resistance parameters in PCAS1 were higher than those in PCAS2 (P<0.05).
 Conclusion: The blood flow velocity parameters in both PCAS1 and PCAS2 are increased with GA. The resistance parameters in both PCAS1 and PCAS2 do not change with GA. Study on the velocities and resistance in these 3 arterial branches provides a more comprehensive evaluation on the process of brain circulation.

Stimulus-evoked changes in cerebral vessel diameter: A study in healthy humans.

The high metabolic demand of neuronal tissue, coupled with its relatively low energy storage capacity, requires that increases in neuronal activation are quickly matched with increased blood flow to ensure efficient supply of oxygen and nutrients to the tissue. For this to occur, dilation of nearby arterioles must be coordinated with the dilation of larger upstream feeding arteries. As it stands, the exact spatial extent of such dilation in humans is unknown. Using non-invasive time-of-flight magnetic resonance angiography in healthy participants, we developed an automatic methodology for reconstructing cerebral arterial vessels and quantifying their diameter on a voxel-by-voxel basis. Specifically, we isolated the posterior cerebral artery (PCA) supplying each occipital lobe and quantified its vasodilation induced by visual stimulation. Stimulus-induced changes were strongest (∼30%) near primary visual cortex and progressively decreased in a non-linear fashion as a function of distance. Surprisingly, weak - albeit significant - changes (∼2%) were observed ∼70 mm from the visual cortex. This demonstrates that visual stimulation modulates vascular tone along the bulk of the PCA segment, and thus may have important implications for our understanding of functional hyperemia in healthy and diseased states.

Vascular territorial segmentation and volumetric blood flow measurement using dynamic contrast enhanced magnetic resonance angiography of the brain.

This study proposes a method for territorial segmentation and volumetric flow rate (VFR) distribution measurement of cerebral territories based on time-resolved contrast enhanced magnetic-resonance-angiography (MRA). The method uses an iterative region-growing algorithm based on bolus-arrival-time with increased temporal resolution. Eight territories were segmented: (1) right and (2) left internal carotid arteries, including the middle cerebral artery (ICA+MCA), excluding the anterior cerebral arteries (ACA); (3) right and left ACA (R+L-ACA); (4) right and (5) left external carotid arteries (ECA); (6) right and (7) left posterior cerebral arteries (PCA); and (8) vertebrobasilar territory. VFR percentage, relative to the entire brain (rVFR), was measured based on territorial volume as a function of time. Mean rVFR values of fifteen healthy subjects were: ICA+MCA = 23 ± 2%, R + L-ACA = 17 ± 3%, ECA = 4 ± 2%, PCA = 12 ± 2%, and vertebrobasilar territory = 31 ± 4%. Excluding the ECA-rVFR, which is underestimated, these values are comparable to previously reported values. Six subjects were scanned twice, demonstrating comparable and even higher reproducibility than previously reported using phase-contrast, yet with faster scan time (∼1 min). This method was implemented in one patient with MCA occlusion and one with Moyamoya syndrome scanned before and after bypass surgery, demonstrating its clinical potential for quantitative assessment of the degree of occlusion and the effect of surgery.

Transcranial Doppler-determined change in posterior cerebral artery blood flow velocity does not reflect vertebral artery blood flow during exercise.

We examined whether a change in posterior cerebral artery flow velocity (PCAv) reflected the posterior cerebral blood flow in healthy subjects during both static and dynamic exercise. PCAv and vertebral artery (VA) blood flow, as an index of posterior cerebral blood flow, were continuously measured during an exercise trial using transcranial Doppler (TCD) ultrasonography and Doppler ultrasound, respectively. Static handgrip exercise significantly increased both PCAv and VA blood flow. Increasing intensity of dynamic exercise further increased VA blood flow from moderate exercise, while PCAv decreased to almost resting level. During both static and dynamic exercise, the PCA cerebrovascular conductance (CVC) index significantly decreased from rest (static and high-intensity dynamic exercise, -11.5 ± 12.2% and -18.0 ± 16.8%, means ± SD, respectively) despite no change in the CVC of VA. These results indicate that vasoconstriction occurred at PCA but not VA during exercise-induced hypertension. This discrepancy in vascular response to exercise between PCA and VA may be due to different cerebral arterial characteristics. Therefore, to determine the effect of exercise on posterior cerebral circulation, at least, we need to carefully consider which cerebral artery to measure, regardless of exercise mode.NEW & NOTEWORTHY We examined whether transcranial Doppler-determined flow velocity in the posterior cerebral artery can be used as an index of cerebral blood flow during exercise. However, the changes in posterior cerebral artery flow velocity during exercise do not reflect vertebral artery blood flow.

Quantifying cerebrovascular reactivity in anterior and posterior cerebral circulations during voluntary breath holding.

NEW FINDINGS: What is the central question of this study? We developed and validated a 'stimulus index' (SI; ratio of end-tidal partial pressures of CO2 and O2 ) method to quantify cerebrovascular reactivity (CVR) in anterior and posterior cerebral circulations during breath holding. We aimed to determine whether the magnitude of CVR is correlated with breath-hold duration. What is the main finding and its importance? Using the SI method and transcranial Doppler ultrasound, we found that the magnitude of CVR of the anterior and posterior cerebral circulations is not positively correlated with physiological or psychological break-point during end-inspiratory breath holding. Our study expands the ability to quantify CVR during breath holding and elucidates factors that affect break-point. The central respiratory chemoreflex contributes to blood gas homeostasis, particularly in response to accumulation of brainstem CO2 . Cerebrovascular reactivity (CVR) affects chemoreceptor stimulation inversely through CO2 washout from brainstem tissue. Voluntary breath holding imposes alterations in blood gases, eliciting respiratory chemoreflexes, potentially contributing to breath-hold duration (i.e. break-point). However, the effects of cerebrovascular reactivity on break-point have yet to be determined. We tested the hypothesis that the magnitude of CVR contributes directly to breath-hold duration in 23 healthy human participants. We developed and validated a cerebrovascular stimulus index methodology [SI; ratio of end-tidal partial pressures of CO2 and O2 (P ET ,CO2/P ET ,O2)] to quantify CVR by correlating measured and interpolated values of P ET ,CO2 (r = 0.95, P < 0.0001), P ET ,O2 (r = 0.98, P < 0.0001) and SI (r = 0.94, P < 0.0001) during rebreathing. Using transcranial Doppler ultrasound, we then quantified the CVR of the middle (MCAv) and posterior (PCAv) cerebral arteries by plotting cerebral blood velocity against interpolated SI during a maximal end-inspiratory breath hold. The MCAv CVR magnitude was larger than PCAv (P = 0.001; +70%) during breath holding. We then correlated MCAv and PCAv CVR with the physiological (involuntary diaphragmatic contractions) and psychological (end-point) break-point, within individuals. There were significant inverse but modest relationships between both MCAv and PCAv CVR and both physiological and psychological break-points (r < -0.53, P < 0.03). However, these relationships were absent when MCAv and PCAv cerebrovascular conductance reactivity was correlated with both physiological and psychological break-points (r > -0.42; P > 0.06). Although central chemoreceptor activation is likely to be contributing to break-point, our data suggest that CVR-mediated CO2 washout from central chemoreceptors plays no role in determining break-point, probably because of a reduced arterial-to-tissue CO2 gradient during breath holding.

Influence of Vascular Variant of the Posterior Cerebral Artery (PCA) on Cerebral Blood Flow, Vascular Response to CO2 and Static Functional Connectivity.

INTRODUCTION: The fetal origin of the posterior cerebral artery (fPCA) is a frequent vascular variant in 11-29% of the population. For the fPCA, blood flow in the PCA originates from the anterior instead of the posterior circulation. We tested whether this blood supply variant impacts the cerebral blood flow assessed by arterial spin labeling (ASL), cerebrovascular reserve as well as resting-state static functional connectivity (sFC) in the sense of a systematic confound. METHODS: The study included 385 healthy, elderly subjects (mean age: 74.18 years [range: 68.9-90.4]; 243 female). Participants were classified into normal vascular supply (n = 296, 76.88%), right fetal origin (n = 23, 5.97%), left fetal origin (n = 16, 4.16%), bilateral fetal origin (n = 4, 1.04%), and intermediate (n = 46, 11.95%, excluded from further analysis) groups. ASL-derived relative cerebral blood flow (relCBF) maps and cerebrovascular reserve (CVR) maps derived from a CO2 challenge with blocks of 7% CO2 were compared. Additionally, sFC between 90 regions of interest (ROIs) was compared between the groups. RESULTS: CVR was significantly reduced in subjects with ipsilateral fPCA, most prominently in the temporal lobe. ASL yielded a non-significant trend towards reduced relCBF in bilateral posterior watershed areas. In contrast, conventional atlas-based sFC did not differ between groups. CONCLUSIONS: In conclusion, fPCA presence may bias the assessment of cerebrovascular reserve by reducing the response to CO2. In contrast, its effect on ASL-assessed baseline perfusion was marginal. Moreover, fPCA presence did not systematically impact resting-state sFC. Taken together, this data implies that perfusion variables should take into account the vascularization patterns.

Where's Waldo? The utility of a complicated visual search paradigm for transcranial Doppler-based assessments of neurovascular coupling.

BACKGROUND: The concept of neurovascular coupling has been postulated since the late 1800s and has been demonstrated most commonly in humans using visual stimuli (e.g. reading, checkerboards). These traditional paradigms evoke only a moderate cerebral blood flow response due to the relative simplicity of the visual stimuli. NEW METHOD: Forty subjects completed three visual paradigms each challenging the visual processing areas to a different extent: reading text, complicated visual searching (new method: Where's Waldo) and viewing coloured dots. Posterior and middle cerebral artery (PCA, MCA) velocities were recorded using transcranial Doppler ultrasound during each visual paradigm. RESULTS: Prior to the presentation of the visual stimuli there were no differences in mean arterial pressure, or PCA or MCA velocities for the three paradigms. All three paradigms led to an elevation in PCA and MCA velocities after a delay (∼1.1s). Whereas velocity elevation was consistent across the three paradigms in the MCA, it was markedly larger during the Where's Waldo task in the PCA. Thus, although the onset of the neurovascular coupling response was similar across the three visual paradigms, its overall magnitude was stimulus-dependent. COMPARISON WITH EXISTING METHODS: Given that PCA velocity can be affected by blood pressure or carbon dioxide alterations, traditional neurovascular coupling paradigms (e.g. reading, checkerboards) appear to have a lower signal-to-noise ratio than that observed in complicated visual search tasks such as Where's Waldo. CONCLUSIONS: We recommend complicated visual search paradigms such as Where's Waldo be considered for future transcranial Doppler-based neurovascular coupling studies.