Test-retest reliability of transfer function analysis metrics for assessing dynamic cerebral autoregulation to spontaneous blood pressure oscillations.

Transfer function analysis (TFA) is a widely used method for assessing dynamic cerebral autoregulation in humans. In the present study, we assessed the test-retest reliability of established TFA metrics derived from spontaneous blood pressure oscillations and based on 5 min recordings. The TFA-based gain, phase and coherence in the low-frequency range (0.07-0.20 Hz) from 19 healthy volunteers, 37 patients with subarachnoid haemorrhage and 19 patients with sepsis were included. Reliability assessments included the smallest real difference (SRD) and the coefficient of variance for comparing consecutive 5 min recordings, temporally separated 5 min recordings and consecutive recordings with a minimal length of 10 min. In healthy volunteers, temporally separating the 5 min recordings led to a 0.38 (0.01-0.79) cm s-1 mmHg-1 higher SRD for gain (P = 0.032), and extending the duration of recordings did not affect the reliability. In subarachnoid haemorrhage, temporal separation led to a 0.85 (-0.13 to 1.93) cm s-1 mmHg-1 higher SRD (P = 0.047) and a 20 (-2 to 41)% higher coefficient of variance (P = 0.038) for gain, but neither metric was affected by extending the recording duration. In sepsis, temporal separation increased the SRD for phase by 94 (23-160)° (P = 0.006) but was unaffected by extending the recording. A recording duration of 8 min was required to achieve stable gain and normalized gain measures in healthy individuals, and even longer recordings were required in patients. In conclusion, a recording duration of 5 min appears insufficient for obtaining stable and reliable TFA metrics when based on spontaneous blood pressure oscillations, particularly in critically ill patients with subarachnoid haemorrhage and sepsis.

Investigating the effects of tilting the postural drainage lithotripsy system on cerebral blood flow, intracranial pressure, heart rate, and blood pressure.

PURPOSE: To investigate the effect of the postural drainage lithotripsy system developed by our experimental team on the vital signs of patient with urinary stones during the stone removal process. METHODS: Four groups of 15 subjects (0°, 10°, 40°, and 70°) were subjected to different angles of head-down tilt to measure middle cerebral artery blood flow velocity (MCAv), cerebrovascular conductance coefficient (CVCi), intracranial pressure (nICP), heart rate (HR), and mean arterial blood pressure (MAP). RESULTS: As the angle of HDT changed, MCAv values, nICP values, CVCi values, HR values, and MAP values changed significantly (all P ≤ 0.001), and the difference was statistically significant. During 10°HDT, despite a slight increase in nICP, the other measurements remained stable. During 40°HDT, only the MCAv values did not change significantly, whereas the rest of the measures were significantly altered. During 70°HDT, all indicators changed significantly. CONCLUSIONS: The significant alterations in cerebral blood flow, intracranial pressure, and hemodynamics induced during the treatment of renal residual fragments with postural drainage should be used with caution in individuals with cerebrovascular accidents. CHINA CLINICAL TRIALS REGISTRY: ChiCTR2300070671; Registration date: 2023-04-18.

A single bout of aerobic exercise does not alter inhibitory control preparatory set cerebral hemodynamics: Evidence from the antisaccade task.

A single bout of exercise improves executive function (EF) and is a benefit - in part -attributed to an exercise-mediated increase in cerebral blood flow enhancing neural efficiency. Limited work has used an event-related protocol to examine postexercise changes in preparatory phase cerebral hemodynamics for an EF task. This is salient given the neural efficiency hypothesis' assertion that improved EF is related to decreased brain activity. Here, event-related transcranial Doppler ultrasound was used to measure pro- (saccade to target) and antisaccades (saccade mirror-symmetrical target) preparatory phase middle cerebral artery velocity (MCAv) prior to and immediately after 15-min of aerobic exercise. Antisaccades produced longer reaction times (RT) and an increased preparatory phase MCAv than prosaccades - a result attributed to greater EF neural activity for antisaccades. Antisaccades selectively produced a postexercise RT reduction (ps < 0.01); however, antisaccade preparatory phase MCAv did not vary from pre- to postexercise (p=0.53) and did not correlate with the antisaccade RT benefit (p = 0.31). Accordingly, results provide no evidence that improved neural efficiency indexed via functional hyperemia is linked to a postexercise EF behavioural benefit. Instead, results support an evolving view that an EF benefit represents the additive interplay between interdependent exercise-mediated neurophysiological changes.

Neurophysiologic Features Reflecting Brain Injury During Pediatric ECMO Support.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) provides lifesaving support to critically ill patients who experience refractory cardiopulmonary failure but carries a high risk for acute brain injury. We aimed to identify characteristics reflecting acute brain injury in children requiring ECMO support. METHODS: This is a prospective observational study from 2019 to 2022 of pediatric ECMO patients undergoing neuromonitoring, including continuous electroencephalography, cerebral oximetry, and transcranial Doppler ultrasound (TCD). The primary outcome was acute brain injury. Clinical and neuromonitoring characteristics were collected. Multivariate logistic regression was implemented to model odds ratios (ORs) and identify the combined characteristics that best discriminate risk of acute brain injury using the area under the receiver operating characteristic curve. RESULTS: Seventy-five pediatric patients requiring ECMO support were enrolled in this study, and 62 underwent neuroimaging or autopsy evaluations. Of these 62 patients, 19 experienced acute brain injury (30.6%), including seven (36.8%) with arterial ischemic stroke, four (21.1%) with hemorrhagic stroke, seven with hypoxic-ischemic brain injury (36.8%), and one (5.3%) with both arterial ischemic stroke and hypoxic-ischemic brain injury. A univariate analysis demonstrated acute brain injury to be associated with maximum hourly seizure burden (p = 0.021), electroencephalographic suppression percentage (p = 0.022), increased interhemispheric differences in electroencephalographic total power (p = 0.023) and amplitude (p = 0.017), and increased differences in TCD Thrombolysis in Brain Ischemia (TIBI) scores between bilateral middle cerebral arteries (p = 0.023). Best subset model selection identified increased seizure burden (OR = 2.07, partial R2 = 0.48, p = 0.013), increased quantitative electroencephalographic interhemispheric amplitude differences (OR = 2.41, partial R2 = 0.48, p = 0.013), and increased interhemispheric TCD TIBI score differences (OR = 4.66, partial R2 = 0.49, p = 0.006) to be independently associated with acute brain injury (area under the receiver operating characteristic curve = 0.92). CONCLUSIONS: Increased seizure burden and increased interhemispheric differences in both quantitative electroencephalographic amplitude and TCD MCA TIBI scores are independently associated with acute brain injury in children undergoing ECMO support.

Exploring cerebral laterality of writing and the relationship to handedness: a functional transcranial Doppler ultrasound investigation.

Cerebral lateralization of oral language has been investigated in a plethora of studies and it is well established that the left hemisphere is dominant for production tasks in the majority of individuals. However, few studies have focused on written language and even fewer have sampled left-handers. Writing comprises language and motor components, both of which contribute to cerebral activation, yet previous research has not disentangled. The aim of this study was to disentangle the language and motor components of writing lateralization. This was achieved through the comparison of cerebral activation during (i) written word generation and (ii) letter copying, as assessed by functional Transcranial Doppler (fTCD) ultrasound. We further assessed cerebral laterality of oral language. The sample was balanced for handedness. We preregistered the hypotheses that (i) cerebral lateralization of the linguistic component of writing would be weaker in left-handers compared to right-handers and (ii) oral language and the linguistic component of written language would not be correlated in terms of cerebral lateralization. No compelling evidence for either of our hypotheses was found. Findings highlight the complexity of the processes subserving written and oral language as well as the methodological challenges to isolate the linguistic component of writing.

Changes in cerebral autoregulation and vasoreactivity after surgical aortic valve replacement: a prospective study.

NEW FINDINGS: What is the central question of this study? How are dynamic cerebral autoregulation and brain vasoreactivity influenced by severe aortic stenosis and its surgical treatment? What are the main findings and their importance? Dynamic cerebral autoregulation is preserved in the long term in patients with severe aortic stenosis and does not change after surgical aortic valve replacement. However, carbon dioxide vasoreactivity is impaired in these patients. ABSTRACT: Surgical aortic valve replacement (SAVR) alters the natural course of severe aortic stenosis (AS). In this study, we aimed to determine the effects of the disease on dynamic cerebral autoregulation and vasoreactivity (VR) and to assess their changes after SAVR. We recruited 23 patients diagnosed with severe AS eligible for SAVR and 15 healthy matched controls. AS patients had lower mean VR to CO2 (P = 0.005) than controls, but dynamic cerebral autoregulation was preserved. Cerebral haemodynamics showed no significant change after SAVR. Patients with smaller baseline aortic valve areas presented with smaller low frequency phase changes after surgery (P = 0.016). Severe AS does not seem to impact dynamic cerebral autoregulation but does reduce VR to CO2 . SAVR does not alter cerebral autoregulation nor vasoreactivity.

Increased cerebral vascular resistance underlies preserved cerebral blood flow in response to orthostasis in humans on a high-salt diet.

Cerebral blood flow autoregulation protects brain tissue from blood pressure variations and maintains cerebral perfusion pressure by changes in vascular resistance. High salt (HS) diet impairs endothelium-dependent vasodilation in many vascular beds, including cerebral microcirculation, and may affect vascular resistance. The aim of present study was to determine if 7-day HS diet affected the reactivity of middle cerebral artery (MCA) to orthostatic challenge in healthy human individuals, and if autoregulatory mechanisms and sympathetic neural regulation were involved in this phenomenon.Twenty-seven persons participated in study (F:21, M:6, age range 19-24). Participants consumed 7-day low-salt (LS) diet (< 2.3 g kitchen salt/day) and afterwards 7-day HS diet (> 11.2 g kitchen salt/day). Blood and urine analysis and anthropometric measurements were performed after each diet. Arterial blood pressure, heart rate and heart rate variability, and cerebral and systemic hemodynamic parameters were recorded simultaneously with transcranial Doppler ultrasound and The Task Force® Monitor in response to orthostatic test.Participants remained normotensive during HS diet. Following both, the LS and HS dietary protocols, mean cerebral blood flow (CBF), as well as the velocity time integral and diastolic blood pressure decreased, and cerebral pulsatility index increased after rising up. Importantly, cerebrovascular resistance significantly increased in response to orthostasis only after HS diet. Urine concentration of noradrenaline and vanillylmandelic acid, baroreflex sensitivity (BRS), and sympathetic neural control was significantly decreased in HS diet.Results suggest that CBF in response to orthostatic test was preserved in HS condition due to altered vascular reactivity of MCA, with increased cerebrovascular resistance and blunted BRS and sympathetic activity.

Distinct cortical haemodynamics during squat-stand and continuous aerobic exercise do not influence the magnitude of a postexercise executive function benefit.

A single bout of aerobic exercise benefits executive function (EF). A potential mechanism for this benefit is an exercise-mediated increase in cerebral blood flow (CBF) that elicits vascular endothelial shear-stress improving EF efficiency. Moderate intensity continuous aerobic exercise (MCE) asymptotically increases CBF, whereas continuous body weight squat-stand exercise (SSE) provides a large amplitude oscillatory response. Some work has proposed that an increase in CBF oscillation amplitude provides the optimal shear-stress for improving EF and brain health. We examined whether a large amplitude oscillatory CBF response associated with a single bout of SSE imparts a larger postexercise EF benefit than an MCE cycle ergometer protocol. Exercise changes in middle cerebral artery velocity (MCAv) were measured via transcranial Doppler ultrasound to estimate CBF, and pre- and postexercise EF was assessed via the antisaccade task. MCE produced a steady state increase in MCAv, whereas SSE produced a large amplitude MCAv oscillation. Both conditions produced a postexercise EF benefit that null hypothesis and equivalence tests showed to be comparable in magnitude. Accordingly, we provide a first demonstration that a single bout of SSE benefits EF; however, the condition's oscillatory CBF response does not impart a larger benefit than a time- and intensity-matched MCE protocol.

Evaluation of Cerebral Vasomotor Reactivity by Transcranial Doppler Ultrasound in Patients with Diabetic Retinopathy.

The aim of this study was to assess the correlation between cerebral vasomotor reactivity (CVR) and the grade of diabetic retinopathy. A total of 43 diabetic patients with matched severity of diabetic retinopathy between their right and left eyes were included in this study. Diabetic retinopathy was graded in three groups. Right and left middle cerebral artery CVR was assessed by the breath-holding index (BHI) using transcranial Doppler ultrasound (TCD). The mean age of the patients was 56.51 ± 9.34 years with a mean duration of having diabetes mellitus of 14.49 ± 8.06 years. Diabetic retinopathy was graded as mild, moderately severe, and severe in 27.9%, 34.9%, and 37.2% of the patients, respectively. The grade of diabetic retinopathy was associated with the HbA1c level (p < .049), microalbuminuria (p < .024), and BHI (p = .001). In patients with severe diabetic retinopathy, the right-sided BHI was significantly lower as compared to those with mild or moderately severe retinopathy (p = .001 and p = .008, respectively). The left-sided BHI value in patients with severe diabetic retinopathy was significantly lower as compared to those with mild or moderately severe retinopathy (p = .001 and p = .012, respectively). In subjects with moderately severe diabetic retinopathy, both-sided BHI was significantly reduced compared to those with mild retinopathy (p = .001). Our results indicate that the grade of diabetic retinopathy was associated with impaired CVR.

Cerebral laterality of writing in right- and left-handers: A functional transcranial Doppler ultrasound study.

The cerebral lateralization of written language has received very limited research attention in comparison to the wealth of studies on the cerebral lateralization of oral language. The purpose of the present study was to further our understanding of written language lateralization, by elucidating the relative contribution of language and motor functions. We compared written word generation with a task that has equivalent visuomotor demands but does not include language: the repeated drawing of symbols. We assessed cerebral laterality using functional transcranial Doppler ultrasound (fTCD), a non-invasive, perfusion-sensitive neuroimaging technique in 23 left- and 31 right-handed participants. Findings suggest that the linguistic aspect of written word generation recruited more left-hemispheric areas during writing, in right-handers compared to left-handers. This difference could be explained by greater variability in cerebral laterality patterns within left-handers or the possibility that the areas subserving language in left-handers are broader than in right-handers. Another explanation is that the attentional demands of the more novel symbol copying task (compared to writing) contributed more right-hemispheric activation in right-handers, but this could not be captured in left-handers due to ceiling effects. Future work could investigate such attentional demands using both simple and complex stimuli in the copying condition.

On the use and misuse of cerebral hemodynamics terminology using transcranial Doppler ultrasound: a call for standardization.

Cerebral hemodynamics, e.g., cerebral blood flow, can be measured and quantified using many different methods, with transcranial Doppler ultrasound (TCD) being one of the most commonly used approaches. In human physiology, the terminology used to describe metrics of cerebral hemodynamics are inconsistent and in some instances technically inaccurate; this is especially true when evaluating, reporting, and interpreting measures from TCD. Therefore, this perspective article presents recommended terminology when reporting cerebral hemodynamic data. We discuss the current use and misuse of the terminology in the context of using TCD to measure and quantify cerebral hemodynamics and present our rationale and consensus on the terminology that we recommend moving forward. For example, one recommendation is to discontinue the use of the term "cerebral blood flow velocity" in favor of "cerebral blood velocity" with precise indication of the vessel of interest. We also recommend clarity when differentiating between discrete cerebrovascular regulatory mechanisms, namely, cerebral autoregulation, neurovascular coupling, and cerebrovascular reactivity. This will be a useful guide for investigators in the field of cerebral hemodynamics research.

Intracranial Blood Flow Quantification by Accelerated Dual-venc 4D Flow MRI: Comparison With Transcranial Doppler Ultrasound.

BACKGROUND: Dual-venc 4D flow MRI, recently introduced for the assessment of intracranial hemodynamics, may provide a promising complementary approach to well-established tools such as transcranial Doppler ultrasound (TCD) and overcome some of their disadvantages. However, data comparing intracranial flow measures from dual-venc 4D flow MRI and TCD are lacking. PURPOSE: To compare cerebral blood flow velocity measures derived from dual-venc 4D flow MRI and TCD. STUDY TYPE: Prospective cohort. SUBJECTS: A total of 25 healthy participants (56 ± 4 years old, 44% female). FIELD STRENGTH/SEQUENCE: A 3 T/dual-venc 4D flow MRI using a time-resolved three-dimensional phase-contrast sequence with three-dimensional velocity encoding. ASSESSMENT: Peak velocity measurements in bilateral middle cerebral arteries (MCA) were quantified from dual-venc 4D flow MRI and TCD. The MRI data were quantified by two independent observers (S.M and Y.M.) and TCD was performed by a trained technician (A.L.M.). We assessed the agreement between 4D flow MRI and TCD measures, and the interobserver agreement of 4D flow MRI measurements. STATISTICAL TESTS: Peak velocity from MRI and TCD was compared using Bland-Altman analysis and coefficient of variance. Intraclass correlation coefficient (ICC) was used to assess MRI interobserver agreement. A P value < 0.05 was considered statistically significant. RESULTS: There was excellent interobserver agreement in dual-venc 4D flow MRI-based measurements of peak velocity in bilateral MCA (ICC = 0.97 and 0.96 for the left and right MCA, respectively). Dual-venc 4D flow MRI significantly underestimated peak velocity in the left and right MCA compared to TCD (bias = 0.13 [0.59, -0.33] m/sec and 0.15 [0.47, -0.17] m/sec, respectively). The coefficient of variance between dual-venc 4D flow MRI and TCD measurements was 26% for the left MCA and 22% for the right MCA. DATA CONCLUSION: There was excellent interobserver agreement for the assessment of MCA peak velocity using dual-venc 4D flow MRI, and ≤20% under-estimation compared with TCD. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

Mechanisms of Transcranial Doppler Ultrasound phenotypes in paediatric cerebral malaria remain elusive.

BACKGROUND: Cerebral malaria (CM) results in significant paediatric death and neurodisability in sub-Saharan Africa. Several different alterations to typical Transcranial Doppler Ultrasound (TCD) flow velocities and waveforms in CM have been described, but mechanistic contributors to these abnormalities are unknown. If identified, targeted, TCD-guided adjunctive therapy in CM may improve outcomes. METHODS: This was a prospective, observational study of children 6 months to 12 years with CM in Blantyre, Malawi recruited between January 2018 and June 2021. Medical history, physical examination, laboratory analysis, electroencephalogram, and magnetic resonance imaging were undertaken on presentation. Admission TCD results determined phenotypic grouping following a priori definitions. Evaluation of the relationship between haemodynamic, metabolic, or intracranial perturbations that lead to these observed phenotypes in other diseases was undertaken. Neurological outcomes at hospital discharge were evaluated using the Paediatric Cerebral Performance Categorization (PCPC) score. RESULTS: One hundred seventy-four patients were enrolled. Seven (4%) had a normal TCD examination, 57 (33%) met criteria for hyperaemia, 50 (29%) for low flow, 14 (8%) for microvascular obstruction, 11 (6%) for vasospasm, and 35 (20%) for isolated posterior circulation high flow. A lower cardiac index (CI) and higher systemic vascular resistive index (SVRI) were present in those with low flow than other groups (p < 0.003), though these values are normal for age (CI 4.4 [3.7,5] l/min/m2, SVRI 1552 [1197,1961] dscm-5m2). Other parameters were largely not significantly different between phenotypes. Overall, 118 children (68%) had a good neurological outcome. Twenty-three (13%) died, and 33 (19%) had neurological deficits. Outcomes were best for participants with hyperaemia and isolated posterior high flow (PCPC 1-2 in 77 and 89% respectively). Participants with low flow had the least likelihood of a good outcome (PCPC 1-2 in 42%) (p < 0.001). Cerebral autoregulation was significantly better in children with good outcome (transient hyperemic response ratio (THRR) 1.12 [1.04,1.2]) compared to a poor outcome (THRR 1.05 [0.98,1.02], p = 0.05). CONCLUSIONS: Common pathophysiological mechanisms leading to TCD phenotypes in non-malarial illness are not causative in children with CM. Alternative mechanistic contributors, including mechanical factors of the cerebrovasculature and biologically active regulators of vascular tone should be explored.

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OBJECTIVES: To study the value of bedside transcranial doppler (TCD) in evaluating the level of intracranial pressure (ICP) in critically ill pediatric patients with nervous system disease in the pediatric intensive care unit (PICU). METHODS: A prospective analysis was performed on the critically ill pediatric patients with nervous system disease who were admitted to the PICU of Shengjing Hospital, China Medical University, from November 2020 to November 2021. Bedside TCD was performed on all patients, and pulsatility index (PI) was calculated. Bedside lumbar puncture was performed to measure ICP. A Pearson correlation analysis was used to assess the correlation between PI and ICP. The receiver operating characteristic (ROC) curve was used to assess the value of PI in the diagnosis of elevated ICP (≥20 mm Hg). RESULTS: A total of 56 children were included in the study. The top three primary diseases were intracranial infection (24 children, 43%), traumatic brain injury (TBI) (11 children, 20%), and cerebrovascular disease (5 children, 9%). The Pearson correlation analysis showed that PI was positively correlated with ICP (r=0.536, P<0.001). The subgroup analysis based on primary disease showed that in the TBI group, PI was positively correlated with ICP (r=0.655, P=0.029), while no significant correlation between PI and ICP was observed in the intracranial infection group (r=0.324, P=0.122). The ROC curve analysis showed that PI had an area under the curve of 0.828 (95%CI: 0.677-0.979) in predicting ICP≥20 mm Hg, with a sensitivity of 83.3% and a specificity of 79.5% at the optimal cut-off value of 1.255. CONCLUSIONS: TCD technology for ICP monitoring can predict the change in ICP in critically ill pediatric patients with nervous system disease, suggesting it is useful for treatment options and prognosis evaluation.

Central command-related increases in blood velocity of anterior cerebral artery and prefrontal oxygenation at the onset of voluntary tapping.

The anterior cerebral artery (ACA) supplies blood predominantly to the frontal lobe including the prefrontal cortex. Our laboratory reported that prefrontal oxygenated-hemoglobin concentration (Oxy-Hb) increased before and at exercise onset, as long as exercise is arbitrarily started. Moreover, the increased prefrontal oxygenation seems independent of both exercise intensity and muscle mass. If so, mean blood velocity of the ACA (ACABV) should increase with "very light motor effort," concomitantly with the preexercise and initial increase in prefrontal Oxy-Hb. This study aimed to examine the responses in ACABV and vascular conductance index (ACAVCI) of the ACA as well as prefrontal Oxy-Hb during arbitrary or cued finger tapping in 12 subjects, an activity with a Borg scale perceived exertion rating of 7 (median). With arbitrary start, ACABV increased at tapping onset (14 ± 9%) via an elevation in ACAVCI. Likewise, prefrontal Oxy-Hb increased at the onset of tapping with a time course resembling that of ACABV. A positive cross correlation between the initial changes in ACABV and prefrontal Oxy-Hb was found significant in 67% of subjects, having a time lag of 2 s, whereas a positive linear regression between them was significant in 75% of subjects. When tapping was forced to start by cue, the initial increases in ACABV, ACAVCI, and prefrontal Oxy-Hb were delayed and blunted as compared with an arbitrary start. Thus, active vasodilatation of the ACA vascular bed occurs at tapping onset, as long as tapping is arbitrarily started, and contributes to immediate increases in blood flow and prefrontal oxygenation.NEW & NOTEWORTHY Anterior cerebral artery blood velocity and vascular conductance index along with prefrontal oxygenated-hemoglobin concentration all increased at the onset of finger tapping, peaking immediately after tapping onset, as long as tapping was arbitrarily started. Positive cross correlation and linear regression between the increases in ACABV and prefrontal Oxy-Hb were significant in 67%-75% of subjects. Active vasodilatation of the ACA vascular bed occurs with arbitrary tapping onset and contributes to increased ACABV and prefrontal oxygenation.

Long-term heart transplant recipients: heart rate-related effects on augmented transfer function coherence during repeated squat-stand maneuvers in males.

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.

Vasodilatation by carbon dioxide and sodium nitroglycerin reduces compliance of the cerebral arteries in humans.

NEW FINDINGS: What is the central question of this study? Vascular compliance importantly contributes to the regulation of cerebral perfusion and complex mechanisms are known to influence compliance of a vascular bed: while vasodilatation mediates changes in vascular resistance, does it also affect compliance, particularly in the cerebral vasculature? What is the main finding and its importance? Cerebral vasodilatation, elicited by hypercapnia and sodium nitroglycerin administration, reduced cerebrovascular compliance by approximately 26% from baseline. This study provides new insight into mechanisms mediating cerebrovascular compliance. ABSTRACT: Changes in vascular resistance and vascular compliance contribute to the regulation of cerebral perfusion. While changes in vascular resistance are known to be mediated by vasodilatation, the mechanisms contributing to changes in vascular compliance are complex. In particular, whether vasodilatation affects compliance of the vasculature within the cranium remains unknown. Therefore, the present study examined the impact of two vasodilatation pathways on cerebrovascular compliance in humans. Fifteen young, healthy adults (26 ± 5 years, seven females) completed two protocols: (i) sublingual sodium nitroglycerin (SNG; 0.4 mg) and (ii) hypercapnia (5-6% carbon dioxide gas mixture for 4 min). Blood pressure waveforms (finger photoplethysmography) and middle cerebral artery blood velocity waveforms (transcranial Doppler ultrasound) were input into a modified Windkessel model and an index of cerebrovascular compliance (Ci) was calculated. During the SNG protocol, Ci decreased 24 ± 17% from baseline ((5.0 ± 2.3) × 10-4  cm s-1  mmHg-1 ) to minute 10 ((3.6 ± 1.2) × 10-4  cm s-1  mmHg-1 ; P = 0.009). During the hypercapnia protocol, Ci decreased 28 ± 9% from baseline ((4.4 ± 1.9) × 10-4  cm s-1  mmHg-1 ) to minute 4 ((3.1 ± 1.4) × 10-4  cm s-1  mmHg-1 ; P < 0.001). Cerebral vasodilatory stimuli induced by nitric oxide and carbon dioxide mechanisms reduced compliance of the cerebral vascular bed by approximately 26% from supine baseline values.

'Delaying' a saccade: Preparatory phase cortical hemodynamics evince the neural cost of response inhibition.

Minimally delayed (MD) saccades require inhibition of a prepotent response until a target is extinguished, and unlike the more extensively studied antisaccade task, do not require the additional cognitive component of vector inversion (i.e., 180° target spatial transposition). Here, participants completed separate blocks of MD and prepotent stimulus-driven saccades (i.e., respond at target onset) while cortical hemodynamics were measured via functional transcranial Doppler ultrasound. MD saccades produced longer and more variable reaction times (RT). In turn, MD and stimulus-driven saccade preparatory phase cortical hemodynamics increased and decreased, respectively, relative to baseline and the two conditions differed from one another throughout the preparatory phase. The longer RTs and increased cortical hemodynamics of MD saccades is taken to evince response complexity and the increased neural activity to accommodate response inhibition. To our knowledge, such findings provide the first work to examine the neural foundations of MD saccades.

Critical Closing Pressure by Diffuse Correlation Spectroscopy in a Neonatal Piglet Model.

The critical closing pressure (CrCP) of the cerebral vasculature is the arterial blood pressure (ABP) at which cerebral blood flow (CBF) ceases. Because the ABP of preterm infants is low and close to the CrCP, there is often no CBF during diastole. Thus, estimation of CrCP may become clinically relevant in preterm neonates. Transcranial Doppler (TCD) ultrasound has been used to estimate CrCP in preterm infants. Diffuse correlation spectroscopy (DCS) is a continuous, noninvasive optical technique that measures microvascular CBF. Our objective was to compare and validate CrCP measured by DCS versus TCD ultrasound. Hemorrhagic shock was induced in 13 neonatal piglets, and CBF was measured continuously by both modalities. CrCP was calculated using a model of cerebrovascular impedance, and CrCP determined by the two modalities showed good correlation by linear regression, median r 2 = 0.8 (interquartile range (IQR) 0.71-0.87), and Bland-Altman analysis showed a median bias of -3.5 (IQR -4.6 to -0.28). This is the first comparison of CrCP determined by DCS versus TCD ultrasound in a neonatal piglet model of hemorrhagic shock. The difference in CrCP between the two modalities may be due to differences in vasomotor tone within the microvasculature of the cerebral arterioles versus the macrovasculature of a major cerebral artery.

Assesment of Cerebral Blood Flow Velocities with Transcranial Doppler Ultrasonography in Heart Failure Patients with Reduced Ejection Fraction.

BACKGROUND: Heart and brain interaction is a well-known entity in heart failure (HF) and left ventricular systolic dysfunction poses an increased risk for stroke and cognitive impairment. Transcranial Doppler (TCD) provides valuable information on cerebral blood flow velocities (CBFV). However, less is known about CBFV in HF patients with reduced EF. So, we aimed to evaluate CBFV by means of TCD in patients with HF and reduced ejection fraction (HFrEF). METHODS: This study included 46 HFrEF patients (mean age 65.2±11 years, mean EF 20.1±3.8%) who underwent to TCD examination. In addition, 26 healthy individuals with sinus rhythm and EF >50% were included in the study as a control group. Peak systolic, mean and end diastolic flow velocities of the both right and left middle cerebral artery (RMCA and LMCA) were analyzed. In subgroup analysis, HFrEF patients compared according to rhythm. Correlation analyses was performed in HFrEF group between EF and TCD velocities. RESULTS: The average of RMCA and LMCA peak systolic and mean flow velocities were significantly lower in HF patients than those in control group (76,06±23,7 cm/s and 48,49±16,4 cm/s in HF group vs 87,84±14,5 cm/s and 56,41±10,7 cm/s in control group, p=0,025 and p=0,016, respectively, for RMCA and 75,1±22,3 cm/s and 47,57±14.8 cm/s in HF group vs 88,73±17,7 cm/s and 57,15±12,4 cm/s in control group, p=0,009 and p=0,007, respectively, for LMCA). The average mean flow velocity of RMCA and LMCA was significantly lower in HFrEF patients with AF than HFrEF patients with sinus rhythm. (P=0.04 and P= 0.03, respectively) In correlation analysis, EF was significantly positively correlated with both LMCA and RMCA flow velocities in HFrEF group. CONCLUSION: This study showed that HFrEF patients have lower CBFV as compared to healthy controls and HFrEF patients with AF rhythm have lower CBFV compared to HFrEF with sinus rhythm which might be one of the explanations of the adverse interaction between heart and brain in HFrEF.