Cerebral Blood Flow Velocity Response Research Articles

Neurovascular coupling in severe aortic valve stenosis.

Aortic stenosis (AS) is characterized by obstruction of blood outflow from the left ventricle, which can impair target organ perfusion such as the brain. We hypothesized that hemodynamic changes in AS may lead to dysfunction of cerebral blood flow regulatory mechanisms. The aim of our study was to evaluate neurovascular coupling in patients with AS by Transcranial Doppler ultrasonography. Neurovascular coupling was assessed using visually evoked cerebral blood flow velocity responses (VEFR) calculated as relative blood flow velocity changes in the posterior cerebral artery upon visual stimulation. We analyzed peak systolic, mean and end diastolic VEFR in 54 patients with severe AS and 43 controls in 10 consecutive cycles of visual stimulation. Repeated-measures ANOVA test was used to compare cerebral hemodynamic data by group. Patients with AS had significantly higher peak systolic (12.9%±5.6% and 10.5%±4.5%; p=.009) and mean VEFR (14.4%±5.8% and 12.2%±4.9%; p=.021) compared to controls, whereas only a tendency for higher end diastolic VEFR was observed (16.7%±6.9% and 14.4%±6.2%; p=.061). We have shown for the first time that patients with severe AS exhibit higher VEFR than controls indicating dysregulation of neurovascular coupling, which can be one of the factors contributing to development of cognitive decline.

Impairment of cerebral CO2 dynamic vasoreactivity in MCI & AD patients: a multi‐center study of cerebral flow regulation

AbstractBackgroundAlzheimer’s Disease Centers in Los Angeles (USC), Dallas (UT‐SWMC) and Kansas City (KUMC) have joined together to study the regulation of cerebral perfusion through analysis of spontaneous time‐series data using a modeling methodology that previously yielded indications of reduced CO2 dynamic vasomotor reactivity (DVR) in amnestic MCI patients. We report initial results from this ongoing multi‐center study that confirm those preliminary findings and, furthermore, elucidate the effects of slow‐paced breathing.MethodFive‐minute spontaneous changes in arterial blood pressure (ABP), end‐tidal CO2 (etCO2) and cerebral blood flow velocity (CBFV) in middle cerebral arteries were obtained before and after 5‐min session of slow‐paced breathing (8 breaths/minute). Using data from 25 MCI patients, 7 AD patients and 45 age‐matched cognitively normal controls (NC), we obtained predictive models of the dynamic effects of ABP and etCO2 (proxy for blood CO2) upon CBFV via our kernel‐based modeling methodology. These predictive models were used to compute indices (physio‐markers) that quantify the DVR in each participant, as time‐average of the model‐predicted CBFV response to unit‐step change of etCO2 over the first 30 seconds.ResultThe obtained DVR indices were significantly different for the 32 patients (MCI and AD lumped together due to small number of AD) vs. 45 age‐matched controls (p= 0.0099). Notably, the delineation between patients and controls improved (p= 0.0011) after a 5‐min session of slow‐paced breathing. Figure 1 shows the average model‐predicted CBFV response to unit‐step change of etCO2 for 32 MCI/AD patients (red line) and 45 controls (blue line) before and after the 5‐min paced‐breathing session. Note the negative average steady‐state CBFV response of the patients (red) that indicates polarity reversal of the normal CO2 vasomotor reactivity (blue). Better delineation between patients and controls is achieved (p= 2x10‐5) when the DVR indices from the two sessions, before and after slow‐paced breathing, were averaged (see histograms in Figure 2).ConclusionSignificantly lower DVR indices under resting spontaneous conditions were observed in 32 MCI/AD patients relative to 45 age‐matched controls. This reduction is detected more reliably after 5‐min of slow‐paced breathing. Averaging of the DVR indices obtained before and after slow‐paced breathing improved further this delineation (p= 2x10‐5).

Cerebrovascular regulation in patients with vasovagal syncope and autonomic failure due to familial amyloidotic polyneuropathy.

While there is strong evidence for autonomic involvement in cerebrovascular function acutely, long-term role of autonomic nervous system in cerebrovascular function has been controversial. We assessed autoregulation in 10 healthy individuals, nine patients with vasovagal syncope (VVS), and nine with Familial Amyloidotic Polyneuropathy (FAP), in response to head-up tilt test (HUTT). Arterial blood pressure heart rate, cardiac output, and bilateral cerebral blood flow velocity (CBFV) at the M1 segment of middle cerebral artery (transcranial Doppler ultrasound) were recorded during supine rest and 70° HUTT. Autoregulation was quantified using a validated nonlinear and nonparametric approach based on projection pursuit regression. Plasma adrenaline and noradrenaline were also measured at rest and during HUTT. During supine rest and HUTT, plasma noradrenaline content was lower in FAP patients. During HUTT, VVS patients had a hyperadrenergic status; CBFV decreased in all groups, which was greater in FAP patients (p<0.01). Healthy controls responded to HUTT with a reduction in CBFV responses to increases (p=0.01) and decreases (p<0.01) in arterial pressure without any change in the range or effectiveness of autoregulation. VVS patients responded to HUTT with a reduction in falling (p=0.02), but not rising slope (p=0.40). Autoregulatory range (p<0.01) and effectiveness increased (p=0.09), consistent with the rapid increase in levels of catecholamines. In FAP patients, the level of increase in range of autoregulation was significantly related to the magnitude of increase in plasma noradrenaline in response to HUTT (R2=0.26, p=0.05). Autonomic dysfunction affects the cerebral autoregulatory response orthostatic to challenge.

The scalability of common paradigms for assessment of cognitive function: A functional transcranial Doppler study.

Cognitive paradigms induce changes in cerebral blood flow (CBF) associated with increased metabolic demand, namely neurovascular coupling (NVC). We tested the hypothesis that the effect of complexity and duration of cognitive paradigms will either enhance or inhibit the NVC response. Bilateral CBF velocity (CBFV) in the middle cerebral arteries (MCAs) via transcranial Doppler ultrasound (TCD), blood pressure (BP), electrocardiogram (ECG) and end-tidal CO2 (EtCO2) of 16 healthy participants (aged 21–71 years) were simultaneously recorded at rest and during randomized paradigms of different complexities (naming words beginning with P-,R-,V- words and serial subtractions of 100–2,100–7,1000–17), and durations (5s, 30s and 60s). CBFV responses were population mean normalized from a 30-s baseline period prior to task initiation. A significant increase in bilateral CBFV response was observed at the start of all paradigms and provided a similar pattern in most responses, irrespective of complexity or duration. Although significant inter-hemispherical differences were found during performance of R-word and all serial subtraction paradigms, no lateralisation was observed in more complex naming word tasks. Also, the effect of duration was manifested at late stages of 100–7, but not for other paradigms. CBFV responses could not distinguish different levels of complexity or duration with a single presentation of the cognitive paradigm. Further studies of the ordinal scalability of the NVC response are needed with more advanced modelling techniques, or different types of neural stimulation.

Multi‐center study of regulation of cerebral perfusion using spontaneous time‐series data shows impairment of CO2 vasoreactivity in MCI &amp; AD patients

AbstractBackgroundThree AD Centers have joined together to study the regulation of cerebral perfusion at resting conditions using spontaneous time‐series data with a modeling methodology that previously yielded indications of reduced dynamic vasomotor CO2 reactivity in amnestic MCI patients [Marmarelis et al., J. Alzh. Dis. 56:89–105, 2017] and significant correlation of this reduction with functional impairment of the chemoreflex in these MCI patients [Marmarelis et al., J. Alzh. Dis. 75:1‐16, 2020]. The goal of this multi‐center study is to confirm these preliminary findings with larger cohorts of MCI patients, AD patients and age‐matched cognitively normal controls (NC), and to examine the time‐course of these impairments with longitudinal data over 5 years.MethodQuantitative results were obtained through dynamic modeling of the effects of spontaneous changes in arterial blood pressure (ABP) and end‐tidal CO2 (etCO2) upon cerebral blood flow velocity (CBFV) in the middle cerebral arteries measured via transcranial Doppler. The obtained subject‐specific input‐output predictive models were used to compute indices (physio‐markers) that quantify the Dynamic Vasomotor Reactivity (DVR) in each subject/patient and to compare differences between NC, and MCI/AD patients.ResultThe obtained DVR indices were significantly different for patients (9 MCI and 4 AD taken together due to small numbers) vs. 32 controls (p=0.026). Notably, the delineation between patients and controls improved (p=0.009) after a session of slow paced‐breathing (8 breaths/minute) that led to larger average DVR for controls and to reduction of inter‐subject variability of DVR indices. This is illustrated in Figure 1, where the average model‐predicted responses (representing the CBFV response to a unit‐step change of etCO2) are shown for 13 MCI/AD patients (red line) and 32 controls (blue line) before and after the paced‐breathing session. Further improvement in delineating patients from controls is achieved (p=9x10‐5) when the DVR indices from the two sessions were averaged for each subject/patient.ConclusionSignificantly lower DVR index under resting spontaneous conditions was observed in 13 MCI/AD patients relative to 32 NC before (p= 0.026) and after (p=0.009) slow paced‐breathing session. Averaging of the DVR indices obtained from data before and after paced‐breathing improved substantially this delineation (p=9x10‐5).

Cerebral blood flow response rate to task-activation using a novel method can discriminate cognitive impairment from healthy aging

Objective. A new method to classify individuals as ‘responders’ to task-activated cerebral blood flow velocity (CBFv) has recently been developed. This study investigated whether CBFv response rate to task-activation is affected by Alzheimer’s disease (AD) and mild cognitive impairment (MCI). Approach. The 95th thresholds for cross correlation function peak and variance ratio were derived from 270 unstimulated, healthy hemispheres, and were used to classify the presence of a response to task-activation. Thresholds were applied to five cognitive tasks (attention, verbal fluency, language, visuospatial, memory) in CBFv data from 30 healthy older adults (HC), 35 AD and 22 MCI participants. Cumulative response rate (CRR) was calculated from the sum of responses across five tasks, for both hemispheres. Area under the curve (AUC) was derived from receiver operating characteristic (ROC) curve analysis. Main results. The number of responders differed significantly between tasks (p < 0.005) and diagnostic groups (p = 0.011). On post hoc tests there were more responders in the visuospatial (79%–90%) compared to fluency (45%–80%), language (50%–77%), and memory (44%–70%) tasks bilaterally, and responders were greater in the HC (70%) compared to AD (41%) and MCI (23%) groups to at least eight out of ten tasks. At an optimal threshold of 7.5 out of 10 responses, the AUC-ROC distinguished HC from AD and MCI with a; sensitivity 66% and specificity 70% (AUC = 0.72). Significance. Using a novel method to classify responders to cognitive task-activation, HC demonstrated a higher CRR than those with MCI or AD, and a threshold of <8 responses distinguished healthy ageing from dementia.

The Cognition and Flow Study: A Feasibility Randomized Controlled Trial of the Effects of Cognitive Training on Cerebral Blood Flow.

Cognitive training (CT) has demonstrated benefits for healthy older adults (HG) and mild cognitive impairment (MCI), but the effects on vascular function are unknown. This is a feasibility trial investigating the effects of CT on cerebral blood flow velocity (CBFv). Twenty HG, 24 with Alzheimer's disease (AD), and 12 with MCI were randomized to 12 weeks of multi-domain CT or control. Outcomes included: cognition (Addenbrooke's Cognitive Examination III), mood, quality of life (QoL), physical, and neurovascular function (transcranial Doppler ultrasonography measured task activation of CBFv responses). Data are presented as mean difference (MD) and 95% confidence interval (CI). 47 participants completed the trial. There were three dropouts from the training arm in the AD group, and one in the HG group. The intervention was acceptable and feasible to the majority of participants with a high completion rate (89%). The dropout rate was higher among participants with dementia. Few changes were identified on secondary analyses, but QoL was significantly improved in HG post-training (MD: 4.83 [95% CI: 1.13, 8.54]). CBFv response rate was not significantly different in HG (MD: 1.84 [95% CI: -4.81, 1.12]), but a significant increase was seen in the patient group (MD: 1.79 [95% CI: 0.005, 3.58]), requiring sample sizes of 56 and 84 participants respectively for a fully-powered trial. A 12-week CT program was acceptable and feasible in HG, AD, and MCI. CT may be associated with alterations in vascular physiology which require further investigation in an appropriately powered randomized controlled trial.

Determinants of cerebral blood flow velocity change during squat-stand maneuvers.

The large changes in mean arterial blood pressure (MABP) and cerebral blood flow velocity (CBFV) induced by squat-stand maneuvers (SSM) make this approach particularly suited for studying dynamic cerebral autoregulation (CA). However, the role of other systemic determinants of CBFV has not been described and could provide alternative physiological interpretations of SSM results. In 32 healthy subjects (16 female), continuous recordings of MABP (Finometer), bilateral CBFV (transcranial Doppler, MCA), end-tidal CO2 (EtCO2; capnography), and heart rate (HR; electrocardiogram) were performed for 5 min standing at rest, and during 15 SSM at the frequency of 0.05 Hz. A time-domain, multivariate dynamic model estimated the CBFV variance explained by different inputs, corresponding to significant contributions from MABP (P < 0.00001), EtCO2 (P < 0.0001), and HR (P = 0.041). The autoregulation index (ARI; range 0-9) was estimated from the CBFV response to a step change in MABP. At rest, ARI values (typically 5.7) were independent of the number of model inputs, but during SSM, ARI was reduced compared with baseline (P < 0.0001), and the three input model yielded lower values for the right and left MCA (3.4 ± 1.2, 3.1 ± 1.3) when compared with the single-input MABP-CBFV model (4.1 ± 1.1, 3.9 ± 1.0; P < 0.0001). The high coherence of the MABP-CBFV transfer function at 0.05 Hz (typically 0.98) was considerably reduced (around 0.71-0.73; P < 0.0001) when the contribution of CBFV covariates was taken into account. Not taking into consideration other determinants of CBFV, in addition to MABP, could be misleading and introduce biases in physiological and clinical studies.

Comparisons of the Nonlinear Relationship of Cerebral Blood Flow Response and Cerebral Vasomotor Reactivity to Carbon Dioxide under Hyperventilation between Postural Orthostatic Tachycardia Syndrome Patients and Healthy Subjects.

Postural orthostatic tachycardia syndrome (POTS) typically occurs in youths, and early accurate POTS diagnosis is challenging. A recent hypothesis suggests that upright cognitive impairment in POTS occurs because reduced cerebral blood flow velocity (CBFV) and cerebrovascular response to carbon dioxide (CO2) are nonlinear during transient changes in end-tidal CO2 (PETCO2). This novel study aimed to reveal the interaction between cerebral autoregulation and ventilatory control in POTS patients by using tilt table and hyperventilation to alter the CO2 tension between 10 and 30 mmHg. The cerebral blood flow velocity (CBFV), partial pressure of end-tidal carbon dioxide (PETCO2), and other cardiopulmonary signals were recorded for POTS patients and two healthy groups including those aged >45 years (Healthy-Elder) and aged <45 years (Healthy-Youth) throughout the experiment. Two nonlinear regression functions, Models I and II, were applied to evaluate their CBFV-PETCO2 relationship and cerebral vasomotor reactivity (CVMR). Among the estimated parameters, the curve-fitting Model I for CBFV and CVMR responses to CO2 for POTS patients demonstrated an observable dissimilarity in CBFVmax (p = 0.011), mid-PETCO2 (p = 0.013), and PETCO2 range (p = 0.023) compared with those of Healthy-Youth and in CBFVmax (p = 0.015) and CVMRmax compared with those of Healthy-Elder. With curve-fitting Model II for POTS patients, the fit parameters of curvilinear (p = 0.036) and PETCO2 level (p = 0.033) displayed significant difference in comparison with Healthy-Youth parameters; range of change (p = 0.042), PETCO2 level, and CBFVmax also displayed a significant difference in comparison with Healthy-Elder parameters. The results of this study contribute toward developing an early accurate diagnosis of impaired CBFV responses to CO2 for POTS patients.

Beta‐amyloid deposition and Apolipoprotein E4 carrier status predict cerebral blood flow velocity response to exercise

AbstractBackgroundCerebral blood flow (CBF) provides crucial oxygen and nutrients and clears harmful metabolic waste products from the brain. The CBF decline observed in healthy aging is accelerated in Alzheimer’s disease (AD). We previously reported a lower CBF response during exercise in cognitively‐normal older adults with beta‐amyloid deposition. Recent studies suggest the Apolipoprotein E4 (ApoE4) gene may act mechanistically through vascular pathways to cause AD. Thus, we expanded our model to include ApoE4 carrier status. We hypothesized that beta‐amyloid deposition and positive ApoE4 carrier status would be associated with an attenuated CBF velocity response to exercise.MethodsWe conducted a secondary analysis on sedentary, cognitively‐normal adults (N = 39). For the parent study, individuals were recruited from the University of Kansas Alzheimer’s Disease Center. Genotyping was performed by LCG Genomics using KASP proprietary genotyping technology. Beta‐amyloid load was obtained from Positron Emission Tomography scans after [18F] Florbetapir administration. We recorded middle cerebral artery velocity (MCAv) using transcranial Doppler ultrasound at rest and during 8 minutes of moderate‐intensity exercise. We used these data to assess the CBF velocity response to exercise, defined as the percent change in MCAv from rest to exercise (%ΔMCAv = exercising MCAv – resting MCAv / resting MCAv). We ran a multiple regression to predict %ΔMCAv from age, gender, exercising carbon dioxide, exercising mean arterial pressure, beta‐amyloid load, and ApoE4 carrier status.ResultsOf the 39 participants (65‐86 years old), fourteen (36%) were ApoE4 carriers. The multiple regression model significantly predicted %ΔMCAv, F(6, 32) = 2.760, p = 0.028, adjusted R2 = 0.217. Regression coefficients and standard errors are found in Table 1. The standardized regression coefficients were β = ‐0.406 for beta‐amyloid load (p = 0.014) and β = 0.348 for ApoE4 carrier status (p = 0.025).ConclusionsHigher beta‐amyloid load was associated with a smaller %ΔMCAv, as hypothesized. However, contrary to our hypothesis, positive ApoE4 carrier status was associated with a larger %ΔMCAv from rest to exercise. This may reflect a compensatory CBF response in these adults who have maintained normal cognition despite having an elevated genetic risk of AD.

The critical closing pressure contribution to dynamic cerebral autoregulation in humans: influence of arterial partial pressure of CO2.

Dynamic cerebral autoregulation (CA) is often expressed by the mean arterial blood pressure (MAP)-cerebral blood flow (CBF) relationship, with little attention given to the dynamic relationship between MAP and cerebrovascular resistance (CVR). In CBF velocity (CBFV) recordings with transcranial Doppler, evidence demonstrates that CVR should be replaced by a combination of a resistance-area product (RAP) with a critical closing pressure (CrCP) parameter, the blood pressure value where CBFV reaches zero due to vessels collapsing. Transfer function analysis of the MAP-CBFV relationship can be extended to the MAP-RAP and MAP-CrCP relationships, to assess their contribution to the dynamic CA response. During normocapnia, both RAP and CrCP make a significant contribution to explaining the MAP-CBFV relationship. Hypercapnia, a surrogate state of depressed CA, leads to marked changes in dynamic CA, that are entirely explained by the CrCP response, without further contribution from RAP in comparison with normocapnia. Dynamic cerebral autoregulation (CA) is manifested by changes in the diameter of intra-cerebral vessels, which control cerebrovascular resistance (CVR). We investigated the contribution of critical closing pressure (CrCP), an important determinant of CVR, to explain the cerebral blood flow (CBF) response to a sudden change in mean arterial blood pressure (MAP). In 76 healthy subjects (age range 21-70years, 36 women), recordings of MAP (Finometer), CBF velocity (CBFV; transcranial Doppler ultrasound), end-tidal CO2 (capnography) and heart rate (ECG) were performed for 5min at rest (normocapnia) and during hypercapnia induced by breathing 5% CO2 in air. CrCP and the resistance-area product (RAP) were obtained for each cardiac cycle and their dynamic response to a step change in MAP was calculated by means of transfer function analysis. The recovery of the CBFV response, following a step change in MAP, was mainly due to the contribution of RAP during both breathing conditions. However, CrCP made a highly significant contribution during normocapnia (P<0.0001) and was the sole determinant of changes in the CBFV response, resulting from hypercapnia, which led to a reduction in the autoregulation index from 5.70±1.58 (normocapnia) to 4.14±2.05 (hypercapnia; P<0.0001). In conclusion, CrCP makes a very significant contribution to the dynamic CBFV response to changes in MAP and plays a major role in explaining the deterioration of dynamic CA induced by hypercapnia. Further studies are needed to assess the relevance of CrCP contribution in physiological and clinical studies.

Impact Of 6-month Exercise Training On Neurovascular Function In Persons With Spinal Cord Injury

Accumulating evidence shows an exacerbated incidence of cognitive impairment after spinal cord injury (SCI); however, the physiology that underlies this apparent post-SCI cognitive decline is unknown. PURPOSE: To investigate the impact of injury and 6-month full-body exercise training on neurovascular coupling in individuals with SCI. METHODS: In 24 participants with SCI and 16 controls, we investigated hemodynamic (heart rate, blood pressure, CO2) and middle cerebral artery blood flow velocity responses to a working memory task (neurovascular coupling) before and after training. Neurovascular coupling was compared across groups while accounting for injury parameters. Within individuals with SCI, 6-month changes in neurovascular coupling and its relation to changes in aerobic capacity were compared via linear mixed effect model. RESULTS: Reaction time tended to be higher in individuals with SCI, especially those with high-level (≥T4) injuries, possibly due to upper motor impairments. Neurovascular coupling was graded across task difficulty (p<0.01), while injury did not have a significant impact (group effect p=0.99, interaction p=0.70). Individuals with low-level injuries (<T4) had higher aerobic capacity than those with high-level injuries (p<0.01). Aerobic capacity increased significantly with training in both groups (p<0.01). While there was no overall significant improvement in neurovascular coupling with training at the group level, the degree of improvement was closely related to that in aerobic fitness in individuals with high-level (R2=0.19, p=0.03) but not low-level (R2=0.04, p=0.46) injuries, which translated to an increase in reaction time (R2=0.16, p=0.05). CONCLUSIONS: The apparent cognitive impairment after SCI is primarily due to physical deconditioning, rather than injury itself, and can be mitigated by aerobic exercise training. This has significant implications for long-term care and management for individuals with SCI. Supported by AHA Grant 15SDG2329000 (COT), Ellen R. and Melvin J. Gordon Center for the Cure and Treatment of Paralysis (COT). EDO was in part supported by the Harvard College Research Program.

Comparison of Autoregulation Index during Sit‐To‐Stand in Young Healthy Individuals across Races

Cerebral autoregulation is an important mechanism to protect the brain by maintaining the brain perfusion over varying blood pressures. The cerebral blood flow velocity response to Sit‐To‐ Stand maneuver has been widely used to assess dynamic cerebral autoregulation. Previous work has demonstrated sex differences in autoregulation; however, little is known about the impact of race. Potential racial differences in cerebral autoregulation may contribute to different incidences of cerebrovascular events between different races. Therefore, the purpose of this study was to compare the Autoregulatory index between four different racial groups. We enrolled 55 young healthy subjects (aged 18~35 years) with four racial groups, i.e. White/Caucasian (Age 27±5; n=11; 5 Males), Black/African American (Age 28±6; n=8; 4 Males), Latino (Age 28±6; n=6; 2 Males), and Asian (Age 27±3; n=30; 15 Males). The transcranial Doppler was used to continuously record the cerebral blood flow velocity at middle cerebral artery during 3 repeated sit‐to‐stand maneuvers, with simultaneous measurements of blood pressure, heart rate, and end‐tidal CO2 (ETCO2). There was no difference in demographic variables across groups except for BMI (24±4, 26±4, 27±5, and 23±3; kg/m2, P=0.043). Similarly, there were no differences in baseline cerebral blood flow velocity, blood pressure or heart rate with the exception of ETCO2 (35±3, 40±4, 35±3, and 38±3 mmHg, P=0.003). We found no differences between groups in the physiological response during sit‐to‐stand. Similarly, autoregulatory index was similar across all racial groups (3.6±2.4, 3.9±1.2, 3.3±2.6, and 3.6±1.5, P=0.948). These data suggest that cerebral autoregulation is similar in young healthy individuals across different races. However, these findings must be interpreted with caution due to the small number of participants in the various racial groups. Future studies are warranted to include larger sample size, older subjects and also to consider sex differences within each race.Support or Funding InformationSupported by the Funding from Rutgers University and U.S. Department of Defense.

Influence of Acute Fasting on Cerebrovascular Reactivity During Mental Stress

Acute fasting has been adopted in fitness communities, and has been practiced for religious purposes. Short‐term fasting does not affect cognitive function, and therefore may not affect cerebrovascular responsiveness. Cerebral blood flow velocity increases with mental stress, however the combined influences of an acute fast and mental stress on cerebrovascular responses are unknown. The purpose of this study was to describe the effects of a 24‐hour, water‐only fast on cerebral blood flow velocity responses to mental stress in a small cohort of research volunteers. Eight young healthy participants (7 males, average age of 25 yrs) completed the protocol in a fed state (4 hours post‐prandial) and in a fasted state (24–25 hours post‐prandial). Whole blood was collected and analyzed before experimentation for β‐Ketones, total cholesterol, HDL, LDL, triglycerides (TRG), and glucose. With participants in a supine position, we recorded the electrocardiogram, beat‐to‐beat arterial pressure (finger plethysmography), and cerebral artery blood flow velocity (transcranial Doppler). After a 5‐min baseline, participants performed 5‐min of mental stress via mental arithmetic (rapid continuous subtraction). Mental stress reactivity was calculated as the mean stress response for each minute of mental stress minus the corresponding 5‐min baseline. The minute‐by‐minute reactivity was analyzed with repeated measures ANOVA. Blood variables were analyzed with paired t‐tests. Data were expressed as mean ± SE. Baseline blood variables were different in the fasted compared with the fed state: TRG (112±14 fed vs. 68±13 mg/dL fasted; p&lt;.01) Glucose (101±5 fed vs. 79±6 mg/dL fasted; p&lt;.01) and β‐Ketone (.1±.01 fed vs. .5±.2 mmol/L fasted; p&lt;.05). Mean arterial pressures and heart rate reactivities to mental stress were not affected by fasting. Mean cerebral blood flow velocity reactivity to mental stress was reduced in the fasted compared with the fed condition (condition × time, p&lt;.01), with a particular divergent responsiveness during the third minute of mental stress. The results we present are new, but preliminary. We did not attempt to ascribe mechanisms to fasting and cerebral blood flow velocity reactivity during mental stress. The changes we observed with our preliminary data set suggest that fasting, and associated changes of plasma glucose, β‐Ketone and TRG may be associated with reductions of cerebral blood flow velocity during mental stress.Support or Funding InformationSupport was provided by the Michigan Space Grant Consortium and The Portage Health Foundation of Michigan.

21: Cerebral autoregulation in eclampsia

Eclampsia is the occurrence of tonic-clonic seizures in pregnant or recently postpartum women with preeclampsia. The etiology of these convulsions is unknown. Cerebral autoregulation (CA) is a physiological process that maintains blood flow constant despite changes in blood pressure (BP). Impaired CA may cause overperfusion injury, edema formation and neurological symptoms. We tested the hypothesis that eclampsia is associated with impaired cerebral autoregulation. In a prospective cohort study of recent postpartum patients, we included eclamptic patients studied at < 48 hour after the insult (n=7), and compared them with a normotensive control group (n=10), matched for gestational age (EGA). Eclamptic patients received MgSO4 and anti-hypertensive therapy according to local protocol. Preterm delivery in the control group was due to spontaneous preterm birth or fetal distress. Cerebral blood flow velocity (CBFV) in the middle cerebral artery (transcranial Doppler ultrasound), BP (noninvasive arterial volume clamping), and end-tidal carbon dioxide (EtCO2) were recorded during a 7-minute period of rest. Autoregulation Index (ARI) was determined from the CBFV responses to spontaneous fluctuations in BP. ARI values of 0 and 9 indicate absent and perfect autoregulation, respectively. Cerebral perfusion pressure (CPP) was calculated as previously described. Statistics: student t-test, with P< 0.05 considered significant. Data are presented as mean±SD The groups had similar EGA at delivery (33.6±5.3 vs 34.1±4.4 weeks) and no patients had neurological symptoms at time of recording. ARI was significantly reduced in eclampsia (ARI 4.3±0.7) when compared to controls (7.4±0.5, P< 0.01), while CPP was higher (108±13 vs 82±19 mmHg, P< 0.01). EtCO2 was similar (34.8±1.4 vs 33.8±1.8 mmHg). Women with a recent eclamptic insult have severely impaired CA and increased CPP compared with gestational age-matched normotensive women. Further research should focus on possible modifiable factors to improve CA and on the association between CA and long-term neurological outcome after eclampsia.

Intra-aortic balloon pump does not influence cerebral hemodynamics and neurological outcomes in high-risk cardiac patients undergoing cardiac surgery: an analysis of the IABCS trial

BackgroundThe intra-aortic balloon pump (IABP) is often used in high-risk patients undergoing cardiac surgery to improve coronary perfusion and decrease afterload. The effects of the IABP on cerebral hemodynamics are unknown. We therefore assessed the effect of the IABP on cerebral hemodynamics and on neurological complications in patients undergoing cardiac surgery who were randomized to receive or not receive preoperative IABP in the ‘Intra-aortic Balloon Counterpulsation in Patients Undergoing Cardiac Surgery’ (IABCS) trial.MethodsThis is a prospectively planned analysis of the previously published IABCS trial. Patients undergoing elective coronary artery bypass surgery with ventricular ejection fraction ≤ 40% or EuroSCORE ≥ 6 received preoperative IABP (n = 90) or no IABP (n = 91). Cerebral blood flow velocity (CBFV) of the middle cerebral artery through transcranial Doppler and blood pressure through Finometer or intra-arterial line were recorded preoperatively (T1) and 24 h (T2) and 7 days after surgery (T3) in patients with preoperative IABP (n = 34) and without IABP (n = 33). Cerebral autoregulation was assessed by the autoregulation index that was estimated from the CBFV response to a step change in blood pressure derived by transfer function analysis. Delirium, stroke and cognitive decline 6 months after surgery were recorded.ResultsThere were no differences between the IABP and control patients in the autoregulation index (T1: 5.5 ± 1.9 vs. 5.7 ± 1.7; T2: 4.0 ± 1.9 vs. 4.1 ± 1.6; T3: 5.7 ± 2.0 vs. 5.7 ± 1.6, p = 0.97) or CBFV (T1: 57.3 ± 19.4 vs. 59.3 ± 11.8; T2: 74.0 ± 21.6 vs. 74.7 ± 17.5; T3: 71.1 ± 21.3 vs. 68.1 ± 15.1 cm/s; p = 0.952) at all time points. Groups were not different regarding postoperative rates of delirium (26.5% vs. 24.2%, p = 0.83), stroke (3.0% vs. 2.9%, p = 1.00) or cognitive decline through analysis of the Mini-Mental State Examination (16.7% vs. 40.7%; p = 0.07) and Montreal Cognitive Assessment (79.16% vs. 81.5%; p = 1.00).ConclusionsThe preoperative use of the IABP in high-risk patients undergoing cardiac surgery did not affect cerebral hemodynamics and was not associated with a higher incidence of neurological complications.Trial registrationhttp://www.clinicaltrials.gov (NCT02143544).

Neuroergonomics and Vigilance: Probing the Event-Related Cerebral Hemodynamic Response

Vigilance is an operator’s ability to sustain attentional focus and remain alert for a prolonged period of time in order to monitor for and detect critical task-relevant stimuli (Davies & Parasuram...

The Effects of Hypoxia on Cerebral Blood Flow Velocity and Hemodynamics during Ergometer Bicycle Exercise

The cerebral blood flow velocity (CBFV) response to acute hypoxia during exercise has been known to increase. But, how hemodynamics might respond to exercise in hypoxic condition and be associated with the change of CBFV remains unclear. PURPOSE: To determine the effects of hypoxia on CBFV and hemodynamics during bicycle ergometer exercise. METHODS: In a randomized, double-blind, crossover study, Twelve healthy volunteers (22.1±0.6yrs) were asked to perform the bicycle ergometer exercise three times in two hypoxic (3150m and 1900m altitudes) and control (sea level) condition with a week interval, respectively. Exercise intensity was set initially at 50W and increased by 25W every 2 minutes to 125W. Acute normobaric hypoxic condition corresponding to the altitudes of 3150m and 1900m was maintained using low oxygen gas mixture for the whole procedure of 40 minutes. CBFV in middle cerebral artery (MCA) were measured at rest 15 minutes, 5 and 10 minutes during exercise, 10 minutes recovery using transcranial-Doppler sonography. Non-invasive electrical cardiometry was used to obtain cardiac output (CO), thoracic fluid content (TFC) and flow time corrected (FTC). All data were analyzed using two-way ANOVA with repeated measures and Pearson’s correlation. RESULTS: CBFV in MCA in 3150m and 1900m was significantly higher than in control condition at 10 minutes during exercise (110±28 and 99±25 vs. 75±18 cm/s, p<.05). Heart rate (HR) in 3150m was significantly higher than in 1900m and control condition at 10 minutes during exercise (163±10 vs. 154±6 and 152±8 bpm, p<05). TFC in 3150m and 1900m was significantly lower than in control condition at 10 minutes during exercise (27±1 and 26±1 vs. 30±2, p<.05). FTC in 3150m and 1900m was significantly lower than in control condition at 10 minutes during exercise (240±20 and 254±16 vs. 265±18 ms, p<.05). However, CO and stroke volume (SV) were not significant different between three conditions. CONCLUSIONS: These results suggest that exercise in normobaric hypoxic condition might increase CBFV, which might be independent of hemodynamic changes.

Primary involvement of neurovascular coupling in cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy.

Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most frequent monogenic cause of cerebral ischemia, but reliable biomarkers to monitor the disease are lacking. To evaluate cerebral autoregulation (CA), vasoreactivity (VR), and neurovascular coupling (NVC) in CADASIL patients through a battery of dynamic transcranial Doppler tests. We screened our database for all pre-dementia CADASIL cases. We monitored cerebral blood flow velocity (CBFV) with transcranial Doppler, blood pressure, and expiratory carbon dioxide (CO2) non-invasively. CA was assessed by transfer function from the spontaneous oscillations of blood pressure to CBFV, VR with inhalation of CO2 at 5%, and hyperventilation and NVC by the CBFV response to visual stimulation. We included 27 CADASIL patients and 20 healthy controls with similar age and sexes. CA and VR were similar between groups. However, NVC was significantly affected in CADASIL patients, with lower magnitudes of CBFV upsurge (overshoot 19 ± 5 vs 26 ± 6%, p = 0.013; gain 12 ± 7 vs 17 ± 5%, p = 0.003) and altered time behavior during visual stimulation (natural frequency 0.18 ± 0.06 vs 0.24 ± 0.06Hz, p = 0.005; rate time 0.7 ± 1.7 vs 2.7 ± 3.5s, p = 0.025). Our results express a primary and selective involvement of the neurovascular unit in CADASIL rather than a generalized cerebral vasomotor disturbance. Functional cerebrovascular testing could be useful in patient evaluation and monitoring.

No significant change of extracranial conduit vessel diameter during cerebral vasomotor reactivity test with moderately‐altered end‐tidal CO2

Cerebral vasomotor reactivity (CVMR) is often assessed using transcranial Doppler (TCD) to measure the cerebral blood flow velocity (CBFV) in the middle cerebral artery (MCA). Recently the validity of this technique has been questioned because of the assumption that MCA diameter does not change. The goal of this work was to test if the extracranial cerebral arteries, i.e. internal carotid and vertebral arteries (ICA and VA), have a significant diameter change during moderate alteration of end‐tidal carbon dioxide (ETCO2). Fifteen healthy subjects (6 males; age: 32±10 yrs) were enrolled. The CBFV at the MCA was continuously recorded with TCD during an 8‐min CVMR test, i.e. 2‐min resting ventilation, 2‐min inspiration of 5% CO2, 21% O2, balance nitrogen, 2‐min recovery, and 2‐min mild hyperventilation. 8 min protocol was repeated on the same subjects, to allow measurement of ICA diameter during one run and VA during the other using high‐frequency ultrasound. CVMR is expressed as the percent change in MCA's CBFV per mmHg change in ETCO2, as quantified by the slope of this relationship. The time‐averaged diameter during each static stage was measured offline with echo‐tracking software. All results presented as Mean ± SD. The experimental protocol resulted in a moderated change of ETCO2 (mmHg) during 5% CO2 inspiration (+6.9±2.0) and mild hyperventilation (−14.8±5.8) relative to the baseline values (34.6±2.7). Both hypercapnic and hypocapnic stages showed no significant changes (relative to the baseline) in blood pressure, heart rate, diameters of ICA (5.23±0.83 and 5.21±0.71, vs. baseline 5.22 ±0.83 mm; P = 0.88 and 0.86) and VA (3.91±0.69 and 3.91±0.72, vs. baseline 3.87±0.65 mm; P = 0.40 and 0.55), except for a slight increase (+7±8 bpm, P &lt; 0.001) of HR during hypocapnia. The individual variation of the diameter response showed no correlation with the concurrent blood pressure, heart rate, and CBFV responses. Based on these results, we concluded that the TCD appears to still be a reliable method to assess the CBF response during CVMR test with a moderate change of ETCO2, as no significant change of the conduit vessel diameter is likely to occur. However, future work is necessary to confirm that flow changes in the extracranial arteries are reflective of relative changes in TCD values.Support or Funding InformationSupported by the Funding from Rutgers University and U.S. Department of Defense.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.