Neurovascular coupling is altered in women who have a history of brain injury from intimate partner violence: a preliminary study.

Introduction: Intimate partner violence (IPV) is a global health crisis with 30% of women over the age of 15 experiencing at least one event in their lifetime. Brain injury (BI) due to head impacts and/or strangulation is a common but understudied part of this experience. Previous research has shown BI from other injury mechanisms can disrupt neurovascular coupling (NVC). To gain further insight into whether similar changes occur in this population, we assessed NVC responses in women with a history of IPV-BI. Methods: NVC responses were measured for the middle and posterior cerebral arteries (MCA, PCA) using transcranial Doppler ultrasound while participants performed a complex visual search task. The lifetime history of previous exposure to IPV-BI was captured using the Brain Injury Severity Assessment (BISA) along with measures of post-traumatic stress disorder (PTSD), anxiety, depression, substance use, and demographic information. Initial analyses of NVC metrics were completed comparing participants who scored low vs. high on the BISA or did or did not experience non-fatal strangulation followed by a stepwise multiple regression to examine the impact of PTSD, anxiety, and depression on the relationship between the NVC metrics and IPV-BI. Results: Baseline and peak cerebral blood velocity were higher and the percentage increase was lower in the PCA in the low compared to the high BISA group whereas no differences between the groups were apparent in the MCA. In addition, those participants who had been strangled had a lower initial slope and area under the curve in the PCA than those who had not experienced strangulation. Finally, the stepwise multiple regression demonstrated the percentage increase in the PCA was significantly related to the BISA score and both depression and anxiety significantly contributed to different components of the NVC response. Conclusions: This preliminary study demonstrated that a lifetime history of IPV-BI leads to subtle but significant disruptions to NVC responses which are modulated by comorbid depression and anxiety. Future studies should examine cerebrovascular function at the acute and subacute stages after IPV episodes to shed additional light on this experience and its outcomes.

Metabolism changes during direct revascularization in moyamoya disease: illustrative case.

BACKGROUND: Cerebral revascularization is recommended for patients with moyamoya disease (MMD) with reduced cerebral perfusion reserve and recurrent or progressive ischemic events. The standard surgical treatment for these patients is a low-flow bypass with or without indirect revascularization. The use of intraoperative monitoring of the metabolic profile using analytes such as glucose, lactate, pyruvate, and glycerol has not yet been described during cerebral artery bypass surgery for MMD-induced chronic cerebral ischemia. The authors aimed to describe an illustrative case using intraoperative microdialysis and brain tissue oxygen partial pressure (PbtO2) probes in a patient with MMD during direct revascularization. OBSERVATIONS: The patient's severe tissue hypoxia situation was confirmed by a PbtO2:partial pressure of oxygen (PaO2) ratio below 0.1 and anaerobic metabolism by a lactate:pyruvate ratio greater than 40. Following bypass, a rapid and sustained increase in PbtO2 up to normal values (PbtO2:PaO2 ratio between 0.1 and 0.35) and the normalization of cerebral energetic metabolism with a lactate/pyruvate ratio less than 20 was observed. LESSONS: The results show a quick improvement of regional cerebral hemodynamics due to the direct anastomosis procedure, reducing the incidence of subsequent ischemic stroke in pediatric and adult patients immediately.

The effect of burst suppression on cerebral blood flow and autoregulation: a scoping review of the human and animal literature.

Background: Burst suppression (BS) is an electroencephalography (EEG) pattern in which there are isoelectric periods interspersed with bursts of cortical activity. Targeting BS through anaesthetic administration is used as a tool in the neuro-intensive care unit but its relationship with cerebral blood flow (CBF) and cerebral autoregulation (CA) is unclear. We performed a systematic scoping review investigating the effect of BS on CBF and CA in animals and humans. Methods: We searched MEDLINE, BIOSIS, EMBASE, SCOPUS and Cochrane library from inception to August 2022. The data that were collected included study population, methods to induce and measure BS, and the effect on CBF and CA. Results: Overall, there were 66 studies that were included in the final results, 41 of which examined animals, 24 of which examined humans, and 1 of which examined both. In almost all the studies, BS was induced using an anaesthetic. In most of the animal and human studies, BS was associated with a decrease in CBF and cerebral metabolism, even if the mean arterial pressure remained constant. The effect on CA during periods of stress (hypercapnia, hypothermia, etc.) was variable. Discussion: BS is associated with a reduction in cerebral metabolic demand and CBF, which may explain its usefulness in patients with brain injury. More evidence is needed to elucidate the connection between BS and CA.

Cerebrovascular pressure reactivity and brain tissue oxygen monitoring provide complementary information regarding the lower and upper limits of cerebral blood flow control in traumatic brain injury: a CAnadian High Resolution-TBI (CAHR-TBI) cohort study.

BACKGROUND: Brain tissue oxygen tension (PbtO2) and cerebrovascular pressure reactivity monitoring have emerged as potential modalities to individualize care in moderate and severe traumatic brain injury (TBI). The relationship between these modalities has had limited exploration. The aim of this study was to examine the relationship between PbtO2 and cerebral perfusion pressure (CPP) and how this relationship is modified by the state of cerebrovascular pressure reactivity. METHODS: A retrospective multi-institution cohort study utilizing prospectively collected high-resolution physiologic data from the CAnadian High Resolution-TBI (CAHR-TBI) Research Collaborative database collected between 2011 and 2021 was performed. Included in the study were critically ill TBI patients with intracranial pressure (ICP), arterial blood pressure (ABP), and PbtO2 monitoring treated in any one of three CAHR-TBI affiliated adult intensive care units (ICU). The outcome of interest was how PbtO2 and CPP are related over a cohort of TBI patients and how this relationship is modified by the state of cerebrovascular reactivity, as determined using the pressure reactivity index (PRx). RESULTS: A total of 77 patients met the study inclusion criteria with a total of 377,744 min of physiologic data available for the analysis. PbtO2 produced a triphasic curve when plotted against CPP like previous population-based plots of cerebral blood flow (CBF) versus CPP. The triphasic curve included a plateau region flanked by regions of relative ischemia (hypoxia) and hyperemia (hyperoxia). The plateau region shortened when cerebrovascular pressure reactivity was disrupted compared to when it was intact. CONCLUSIONS: In this exploratory analysis of a multi-institution high-resolution physiology TBI database, PbtO2 seems to have a triphasic relationship with CPP, over the entire cohort. The CPP range over which the plateau exists is modified by the state of cerebrovascular reactivity. This indicates that in critically ill TBI patients admitted to ICU, PbtO2 may be reflective of CBF.

The Quantitative Associations Between Near Infrared Spectroscopic Cerebrovascular Metrics and Cerebral Blood Flow: A Scoping Review of the Human and Animal Literature.

Cerebral blood flow (CBF) is an important physiologic parameter that is vital for proper cerebral function and recovery. Current widely accepted methods of measuring CBF are cumbersome, invasive, or have poor spatial or temporal resolution. Near infrared spectroscopy (NIRS) based measures of cerebrovascular physiology may provide a means of non-invasively, topographically, and continuously measuring CBF. We performed a systematically conducted scoping review of the available literature examining the quantitative relationship between NIRS-based cerebrovascular metrics and CBF. We found that continuous-wave NIRS (CW-NIRS) was the most examined modality with dynamic contrast enhanced NIRS (DCE-NIRS) being the next most common. Fewer studies assessed diffuse correlation spectroscopy (DCS) and frequency resolved NIRS (FR-NIRS). We did not find studies examining the relationship between time-resolved NIRS (TR-NIRS) based metrics and CBF. Studies were most frequently conducted in humans and animal studies mostly utilized large animal models. The identified studies almost exclusively used a Pearson correlation analysis. Much of the literature supported a positive linear relationship between changes in CW-NIRS based metrics, particularly regional cerebral oxygen saturation (rSO2), and changes in CBF. Linear relationships were also identified between other NIRS based modalities and CBF, however, further validation is needed.

Behavioral and physiological monitoring for awake neurovascular coupling experiments: a how-to guide.

Significance: Functional brain imaging in awake animal models is a popular and powerful technique that allows the investigation of neurovascular coupling (NVC) under physiological conditions. However, ubiquitous facial and body motions (fidgeting) are prime drivers of spontaneous fluctuations in neural and hemodynamic signals. During periods without movement, animals can rapidly transition into sleep, and the hemodynamic signals tied to arousal state changes can be several times larger than sensory-evoked responses. Given the outsized influence of facial and body motions and arousal signals in neural and hemodynamic signals, it is imperative to detect and monitor these events in experiments with un-anesthetized animals. Aim: To cover the importance of monitoring behavioral state in imaging experiments using un-anesthetized rodents, and describe how to incorporate detailed behavioral and physiological measurements in imaging experiments. Approach: We review the effects of movements and sleep-related signals (heart rate, respiration rate, electromyography, intracranial pressure, whisking, and other body movements) on brain hemodynamics and electrophysiological signals, with a focus on head-fixed experimental setup. We summarize the measurement methods currently used in animal models for detection of those behaviors and arousal changes. We then provide a guide on how to incorporate this measurements with functional brain imaging and electrophysiology measurements. Results: We provide a how-to guide on monitoring and interpreting a variety of physiological signals and their applications to NVC experiments in awake behaving mice. Conclusion: This guide facilitates the application of neuroimaging in awake animal models and provides neuroscientists with a standard approach for monitoring behavior and other associated physiological parameters in head-fixed animals.

Compromised resting cerebral metabolism after sport-related concussion: A calibrated MRI study.

Altered resting cerebral blood flow (CBF0) in the acute phase post-concussion may contribute to neurobehavioral deficiencies, often reported weeks after the injury. However, in addition to changes in CBF0, little is known about other physiological mechanisms that may be disturbed within the cerebrovasculature. The aim of this study was to assess whether changes in baseline perfusion following sport-related concussion (SRC) were co-localized with changes in cerebral metabolic demand. Forty-two subjects (15 SRC patients 8.0 ± 4.6 days post-injury and 27 age-matched healthy control athletes) were studied cross-sectionally. CBF0, cerebrovascular reactivity (CVR), resting oxygen extraction (OEF0) and cerebral metabolic rate of oxygen consumption (CMRO2|0) were measured using a combination of hypercapnic and hyperoxic breathing protocols, and the biophysical model developed in calibrated MRI. Blood oxygenation level dependent and perfusion data were acquired simultaneously using a dual-echo arterial spin labelling sequence. SRC patients showed significant decreases in CBF0 spread across the grey-matter (P < 0.05, corrected), and these differences were also confounded by the effects of baseline end-tidal CO2 (P < 0.0001). Lower perfusion was co-localized with reductions in regional CMRO2|0 (P = 0.006) post-SRC, despite finding no group-differences in OEF0 (P = 0.800). Higher CVR within voxels showing differences in CBF was also observed in the SRC group (P = 0.001), compared to controls. Reductions in metabolic demand despite no significant changes in OEF0 suggests that hypoperfusion post-SRC may reflect compromised metabolic function after the injury. These results provide novel insight about the possible pathophysiological mechanisms underlying concussion that may affect the clinical recovery of athletes after sport-related head injuries.

Neurovascular physiology and neurocritical care.

The neurological intensive care unit plays an integral role in the management of cerebrovascular disease in the acute and perioperative period. Understanding the use of intracranial pressure (ICP) monitoring and how to apply the appropriate intervention for ICP elevation to ensure adequate cerebral perfusion is the foundation of neurocritical care. Careful management of the interplay between cerebral and systemic physiology, particularly in disorders of cerebral autoregulation, is critical in preventing secondary brain injury. Finally, understanding the cerebral pathophysiology of the underlying injured brain in acute stroke, subarachnoid hemorrhage, and arterial stenosis can help to guide the optimal use of interventional endovascular procedures in these disease states.

Rude mechanicals in brain haemodynamics: non-neural actors that influence blood flow.

Fluctuations in blood oxygenation and flow are widely used to infer brain activity during resting-state functional magnetic resonance imaging (fMRI). However, there are strong systemic and vascular contributions to resting-state signals that are unrelated to ongoing neural activity. Importantly, these non-neural contributions to haemodynamic signals (or 'rude mechanicals') can be as large as or larger than the neurally evoked components. Here, we review the two broad classes of drivers of these signals. One is systemic and is tied to fluctuations in external drivers such as heart rate and breathing, and the robust autoregulatory mechanisms that try to maintain a constant milieu in the brain. The other class comprises local, active fluctuations that appear to be intrinsic to vascular tissue and are likely similar to active local fluctuations seen in vasculature all over the body. In this review, we describe these non-neural fluctuations and some of the tools developed to correct for them when interpreting fMRI recordings. However, we also emphasize the links between these vascular fluctuations and brain physiology and point to ways in which fMRI measurements can be used to exploit such links to gain valuable information about neurovascular health and about internal brain states. This article is part of the theme issue 'Key relationships between non-invasive functional neuroimaging and the underlying neuronal activity'.

Resting CMRO2 fluctuations show persistent network hyper-connectivity following exposure to sub-concussive collisions.

Exposure to head impacts may alter brain connectivity within cortical hubs such as the default-mode network (DMN). However, studies have yet to consider the confounding effects of altered resting cerebral blood flow (CBF0) and cerebrovascular reactivity (CVR) on changes in connectivity following sub-concussive impacts. Here, 23 Canadian collegiate football players were followed during a season using calibrated resting-state MRI and helmet accelerometers to examine the interplay between the neural and vascular factors that determine functional connectivity (FC). Connectivity-based analyses using blood oxygen level dependent (BOLD) and cerebral metabolic rate of oxygen consumption (CMRO2) mapping were used to study the DMN longitudinally. Network-specific decreases in CBF0 were observed one month following the season, while impaired CVR was documented at both mid-season and one month following the season, compared to pre-season baseline. Alterations in CBF0 and BOLD-based CVR throughout the season suggest that neurophysiological markers may show different susceptibility timelines following head impacts. DMN connectivity was increased throughout the season, independent of changes in cerebrovascular physiology, suggesting that alterations in FC following sub-concussive impacts are robust and independent of changes in brain hemodynamics. No significant correlations between impact kinematics and DMN connectivity changes were documented in this study. Altogether, these findings create a strong paradigm for future studies to examine the underlying neural and vascular mechanisms associated with increases in network connectivity following repeated exposure to sub-concussive collisions, in an effort to improve management of head impacts in contact sports.

Awake craniotomy in a patient with ejection fraction of 10%: considerations of cerebrovascular and cardiovascular physiology.

A 37-year-old man with nonischemic 4-chamber dilated cardiomyopathy and low-output cardiac failure (estimated ejection fraction of 10%) underwent awake craniotomy for a low-grade oligodendroglioma resection under monitored anesthesia care. The cerebrovascular and cardiovascular physiologic challenges and our management of this patient are discussed.

A comparison of dynamic cerebral autoregulation across changes in cerebral blood flow velocity for 200 s.

OBJECTIVES: The dynamic interaction between blood pressure (BP) and cerebral blood flow velocity (CBFV) is not fully understood, especially for CBFV changes lasting longer than 50 s. The interaction between BP and CBFV is relatively well characterized for periods <50 s using transfer function (TF) estimations of phase, gain, and coherence. We used TF estimations to compare the phase and gain for periods >50 s with those for periods <50 s. MATERIALS AND METHODS: BP and CBFV (of the middle cerebral artery) were simultaneously recorded in 23 healthy subjects (10 men, 13 women, mean age 35 ± 10 years) under normo- and hypocapnia (induced by hyperventilation). TF and coherence estimations were based on Welch's periodogram method with a windowing of 200 s (frequency resolution, 0.005 Hz, corresponding to a period of 200 s). Means of the phase, gain, and coherence were calculated over frequency periods of 0.005-0.02 Hz (sVLF), 0.02-0.07 Hz (VLF), 0.07-0.15 Hz (LF), and 0.15-0.40 Hz (HF) and analyzed using the t-test and Pearson correlation. RESULTS: Compared with the VLF range, normo- and hypocapnia phases were slightly but significantly lower in sVLF, while gain and coherence were not different. Hypocapnia induced significant (mostly p < 0.01) phase increases and gain decreases as well as coherence decreases in all frequency ranges. The phase and gain correlated significantly (-0.87 < r > -0.99) (p < 0.001) and inversely in all frequency ranges <0.15 Hz under both respiratory conditions. In some instances, the phase indicated disturbed autoregulation. CONCLUSION: In the frequency range <0.15 Hz, the phase and gain correlate highly and linearly with high consistency. The phase, gain, and coherence were similar in sVLF and VLF ranges. The phase was slightly lower in the sVLF range than in the VLF range. Notably, the data suggest that autoregulatory failure may occur in healthy persons.