Noninvasive Ventilation for Preoxygenation during Emergency Intubation.

BACKGROUND: Among critically ill adults undergoing tracheal intubation, hypoxemia increases the risk of cardiac arrest and death. The effect of preoxygenation with noninvasive ventilation, as compared with preoxygenation with an oxygen mask, on the incidence of hypoxemia during tracheal intubation is uncertain. METHODS: In a multicenter, randomized trial conducted at 24 emergency departments and intensive care units in the United States, we randomly assigned critically ill adults (age, ≥18 years) undergoing tracheal intubation to receive preoxygenation with either noninvasive ventilation or an oxygen mask. The primary outcome was hypoxemia during intubation, defined by an oxygen saturation of less than 85% during the interval between induction of anesthesia and 2 minutes after tracheal intubation. RESULTS: Among the 1301 patients enrolled, hypoxemia occurred in 57 of 624 patients (9.1%) in the noninvasive-ventilation group and in 118 of 637 patients (18.5%) in the oxygen-mask group (difference, -9.4 percentage points; 95% confidence interval [CI], -13.2 to -5.6; P<0.001). Cardiac arrest occurred in 1 patient (0.2%) in the noninvasive-ventilation group and in 7 patients (1.1%) in the oxygen-mask group (difference, -0.9 percentage points; 95% CI, -1.8 to -0.1). Aspiration occurred in 6 patients (0.9%) in the noninvasive-ventilation group and in 9 patients (1.4%) in the oxygen-mask group (difference, -0.4 percentage points; 95% CI, -1.6 to 0.7). CONCLUSIONS: Among critically ill adults undergoing tracheal intubation, preoxygenation with noninvasive ventilation resulted in a lower incidence of hypoxemia during intubation than preoxygenation with an oxygen mask. (Funded by the U.S. Department of Defense; PREOXI ClinicalTrials.gov number, NCT05267652.).

Characteristic BOLD signals are detectable in white matter of the spinal cord at rest and after a stimulus.

We report the reliable detection of reproducible patterns of blood-oxygenation-level-dependent (BOLD) MRI signals within the white matter (WM) of the spinal cord during a task and in a resting state. Previous functional MRI studies have shown that BOLD signals are robustly detectable not only in gray matter (GM) in the brain but also in cerebral WM as well as the GM within the spinal cord, but similar signals in WM of the spinal cord have been overlooked. In this study, we detected BOLD signals in the WM of the spinal cord in squirrel monkeys and studied their relationships with the locations and functions of ascending and descending WM tracts. Tactile sensory stimulus -evoked BOLD signal changes were detected in the ascending tracts of the spinal cord using a general-linear model. Power spectral analysis confirmed that the amplitude at the fundamental frequency of the response to a periodic stimulus was significantly higher in the ascending tracts than the descending ones. Independent component analysis of resting-state signals identified coherent fluctuations from eight WM hubs which correspond closely to the known anatomical locations of the major WM tracts. Resting-state analyses showed that the WM hubs exhibited correlated signal fluctuations across spinal cord segments in reproducible patterns that correspond well with the known neurobiological functions of WM tracts in the spinal cord. Overall, these findings provide evidence of a functional organization of intraspinal WM tracts and confirm that they produce hemodynamic responses similar to GM both at baseline and under stimulus conditions.

The influence of voxelotor on cerebral blood flow and oxygen extraction in pediatric sickle cell disease.

ABSTRACT: Voxelotor is an inhibitor of sickle hemoglobin polymerization that is used to treat sickle cell disease. Although voxelotor has been shown to improve anemia, the clinical benefit on the brain remains to be determined. This study quantified the cerebral hemodynamic effects of voxelotor in children with sickle cell anemia (SCA) using noninvasive diffuse optical spectroscopies. Specifically, frequency-domain near-infrared spectroscopy combined with diffuse correlation spectroscopy were used to noninvasively assess regional oxygen extraction fraction (OEF), cerebral blood volume, and an index of cerebral blood flow (CBFi). Estimates of CBFi were first validated against arterial spin-labeled magnetic resonance imaging (ASL-MRI) in 8 children with SCA aged 8 to 18 years. CBFi was significantly positively correlated with ASL-MRI-measured blood flow (R2 = 0.651; P = .015). Next, a single-center, open-label pilot study was completed in 8 children with SCA aged 4 to 17 years on voxelotor, monitored before treatment initiation and at 4, 8, and 12 weeks (NCT05018728). By 4 weeks, both OEF and CBFi significantly decreased, and these decreases persisted to 12 weeks (both P < .05). Decreases in CBFi were significantly correlated with increases in blood hemoglobin (Hb) concentration (P = .025), whereas the correlation between decreases in OEF and increases in Hb trended toward significance (P = .12). Given that previous work has shown that oxygen extraction and blood flow are elevated in pediatric SCA compared with controls, these results suggest that voxelotor may reduce cerebral hemodynamic impairments. This trial was registered at www.ClinicalTrials.gov as #NCT05018728.

Oxygen-Saturation Targets for Critically Ill Adults Receiving Mechanical Ventilation.

BACKGROUND: Invasive mechanical ventilation in critically ill adults involves adjusting the fraction of inspired oxygen to maintain arterial oxygen saturation. The oxygen-saturation target that will optimize clinical outcomes in this patient population remains unknown. METHODS: In a pragmatic, cluster-randomized, cluster-crossover trial conducted in the emergency department and medical intensive care unit at an academic center, we assigned adults who were receiving mechanical ventilation to a lower target for oxygen saturation as measured by pulse oximetry (Spo2) (90%; goal range, 88 to 92%), an intermediate target (94%; goal range, 92 to 96%), or a higher target (98%; goal range, 96 to 100%). The primary outcome was the number of days alive and free of mechanical ventilation (ventilator-free days) through day 28. The secondary outcome was death by day 28, with data censored at hospital discharge. RESULTS: A total of 2541 patients were included in the primary analysis. The median number of ventilator-free days was 20 (interquartile range, 0 to 25) in the lower-target group, 21 (interquartile range, 0 to 25) in the intermediate-target group, and 21 (interquartile range, 0 to 26) in the higher-target group (P = 0.81). In-hospital death by day 28 occurred in 281 of the 808 patients (34.8%) in the lower-target group, 292 of the 859 patients (34.0%) in the intermediate-target group, and 290 of the 874 patients (33.2%) in the higher-target group. The incidences of cardiac arrest, arrhythmia, myocardial infarction, stroke, and pneumothorax were similar in the three groups. CONCLUSIONS: Among critically ill adults receiving invasive mechanical ventilation, the number of ventilator-free days did not differ among groups in which a lower, intermediate, or higher Spo2 target was used. (Supported by the National Heart, Lung, and Blood Institute and others; PILOT ClinicalTrials.gov number, NCT03537937.).

Neuroplasticity of visual brain network induced by hypoxia.

The effects of hypoxia on brain function remain largely unknown. This study aimed to clarify this issue by visual-stimulated functional magnetic resonance imaging design. Twenty-three college students with a 30-d high-altitude exposure were tested before, 1 week and 3 months after returning to sea level. Brain functional magnetic resonance imaging and retinal electroretinogram were acquired. One week after returning to sea level, decreased blood oxygenation level dependent in the right lingual gyrus accompanied with increased blood oxygenation level dependent in the frontal cortex and insular cortex, and decreased amplitude of electroretinogram a-wave in right eye; moreover, the bilateral lingual gyri showed increased functional connectivity within the dorsal visual stream pathway, and the blood oxygenation level dependent signals in the right lingual gyrus showed positive correlation with right retinal electroretinogram a-wave. Three months after returning to sea level, the blood oxygenation level dependent signals recovered to normal level, while intensively increased blood oxygenation level dependent signals in a broad of brain regions and decreased retinal electroretinogram were also existed. In conclusion, hypoxic exposure has long-term effects on visual cortex, and the impaired retinal electroretinogram may contribute to it. The increased functional connectivity of dorsal stream may compensate for the decreased function of retinal photoreceptor cells to maintain normal visual function.

fMRI spectral signatures of sleep.

Sleep can be distinguished from wake by changes in brain electrical activity, typically assessed using electroencephalography (EEG). The hallmark of nonrapid-eye-movement (NREM) sleep is the shift from high-frequency, low-amplitude wake EEG to low-frequency, high-amplitude sleep EEG dominated by spindles and slow waves. Here we identified signatures of sleep in brain hemodynamic activity, using simultaneous functional MRI (fMRI) and EEG. We found that, at the transition from wake to sleep, fMRI blood oxygen level-dependent (BOLD) activity evolved from a mixed-frequency pattern to one dominated by two distinct oscillations: a low-frequency (<0.1 Hz) oscillation prominent in light sleep and correlated with the occurrence of spindles, and a high-frequency oscillation (>0.1 Hz) prominent in deep sleep and correlated with the occurrence of slow waves. The two oscillations were both detectable across the brain but exhibited distinct spatiotemporal patterns. During the falling-asleep process, the low-frequency oscillation first appeared in the thalamus, then the posterior cortex, and lastly the frontal cortex, while the high-frequency oscillation first appeared in the midbrain, then the frontal cortex, and lastly the posterior cortex. During the waking-up process, both oscillations disappeared first from the thalamus, then the frontal cortex, and lastly the posterior cortex. The BOLD oscillations provide local signatures of spindle and slow wave activity. They may be employed to monitor the regional occurrence of sleep or wakefulness, track which regions are the first to fall asleep or wake up at the wake-sleep transitions, and investigate local homeostatic sleep processes.

In adults with COVID-19 and severe hypoxemia, lower vs. higher oxygenation targets increased days alive without life support.

SOURCE CITATION: Nielsen FM, Klitgaard TL, Siegemund M, et al; HOT-COVID Trial Group. Lower vs higher oxygenation target and days alive without life support in COVID-19: the HOT-COVID randomized clinical trial. JAMA. 2024;331:1185-1194. 38501214.

Behavioral Bias for Exploration Is Associated with Enhanced Signaling in the Lateral and Medial Frontopolar Cortex.

Should we keep doing what we know works for us, or should we risk trying something new as it could work even better? The exploration-exploitation dilemma is ubiquitous in daily life decision-making, and balancing between the two is crucial for adaptive behavior. Yet, we only have started to unravel the neurocognitive mechanisms that help us to find this balance in practice. Analyzing BOLD signals of healthy young adults during virtual foraging, we could show that a behavioral tendency for prolonged exploitation was associated with weakened signaling during exploration in central node points of the frontoparietal attention network, plus the frontopolar cortex. These results provide an important link between behavioral heuristics that we use to balance between exploitation and exploration and the brain function that supports shifts from one tendency to the other. Importantly, they stress that interindividual differences in behavioral strategies are reflected in differences in brain activity during exploration and should thus be more in the focus of basic research that aims at delineating general laws governing visual attention.

Cortical and Subcortical Mechanisms of Orthographic Word-form Learning.

We examined the initial stages of orthographic learning in real time as literate adults learned spellings for spoken pseudowords during fMRI scanning. Participants were required to learn and store orthographic word forms because the pseudoword spellings were not uniquely predictable from sound to letter mappings. With eight learning trials per word form, we observed changes in the brain's response as learning was taking place. Accuracy was evaluated during learning, immediately after scanning, and 1 week later. We found evidence of two distinct learning systems-hippocampal and neocortical-operating during orthographic learning, consistent with the predictions of dual systems theories of learning/memory such as the complementary learning systems framework [McClelland, J. L., McNaughton, B. L., & O'Reilly, R. C. Why there are complementary learning systems in the hippocampus and neocortex: Insights from the successes and failures of connectionist models of learning and memory. Psychological Review, 102, 419-457, 1995]. The bilateral hippocampus and the visual word form area (VWFA) showed significant BOLD response changes over learning, with the former exhibiting a rising pattern and the latter exhibiting a falling pattern. Moreover, greater BOLD signal increase in the hippocampus was associated with better postscan recall. In addition, we identified two distinct bilateral brain networks that mirrored the rising and falling patterns of the hippocampus and VWFA. Functional connectivity analysis revealed that regions within each network were internally synchronized. These novel findings highlight, for the first time, the relevance of multiple learning systems in orthographic learning and provide a paradigm that can be used to address critical gaps in our understanding of the neural bases of orthographic learning in general and orthographic word-form learning specifically.

Instantaneous effects of prefrontal transcranial magnetic stimulation on brain oxygenation: A systematic review.

This systematic review investigates how prefrontal transcranial magnetic stimulation (TMS) immediately influences neuronal excitability based on oxygenation changes measured by functional magnetic resonance imaging (fMRI) or functional near-infrared spectroscopy (fNIRS). A thorough understanding of TMS-induced excitability changes may enable clinicians to adjust TMS parameters and optimize treatment plans proactively. Five databases were searched for human studies evaluating brain excitability using concurrent TMS/fMRI or TMS/fNIRS. Thirty-seven studies (13 concurrent TMS/fNIRS studies, 24 concurrent TMS/fMRI studies) were included in a qualitative synthesis. Despite methodological inconsistencies, a distinct pattern of activated nodes in the frontoparietal central executive network, the cingulo-opercular salience network, and the default-mode network emerged. The activated nodes included the prefrontal cortex (particularly dorsolateral prefrontal cortex), insula cortex, striatal regions (especially caudate, putamen), anterior cingulate cortex, and thalamus. High-frequency repetitive TMS most consistently induced expected facilitatory effects in these brain regions. However, varied stimulation parameters (e.g., intensity, coil orientation, target sites) and the inter- and intra-individual variability of brain state contribute to the observed heterogeneity of target excitability and co-activated regions. Given the considerable methodological and individual variability across the limited evidence, conclusions should be drawn with caution.

Impaired muscle oxygenation despite normal pulmonary function in type 2 diabetes without complications.

Long-term hyperglycemia in individuals with type 2 diabetes (T2D) can detrimentally impact pulmonary function and muscle oxygenation. As a result, these factors can impede the body's adaptation to physical exertion. We aimed to evaluate the oxygen pathway during maximal exercise among overweight/obese individuals with type 2 diabetes free from complications, in comparison with a group of matched overweight/obese individuals without diabetes, specifically concentrating on the effects on pulmonary function and muscle oxygenation. Fifteen overweight/obese adults with type 2 diabetes [glycated hemoglobin (HbA1c) = 8.3 ± 1.2%] and 15 matched overweight/obese adults without diabetes underwent pre- and post exercise lung function assessment. A maximal incremental exercise test was conducted, monitoring muscle oxygenation using near-infrared spectroscopy and collecting arterial blood gas samples. Both groups exhibited normal lung volumes at rest and after exercise. Spirometric lung function did not significantly differ pre- and post exercise in either group. During maximal exercise, the type 2 diabetes group showed significantly lower augmentation in total hemoglobin and deoxygenated hemoglobin compared with the control group. Despite comparable usual physical activity levels and comparable heart rates at exhaustion, the type 2 diabetes group had a lower peak oxygen consumption than controls. No significant differences were found in arterial blood gas analyses ([Formula: see text], [Formula: see text], [Formula: see text], and [Formula: see text]) between the groups. Individuals with type 2 diabetes free from complications displayed normal pulmonary function at rest and post exercise. However, impaired skeletal muscle oxygenation during exercise, resulting from reduced limb blood volume and altered muscle deoxygenation, may contribute to the lower V̇o2peak observed in this population.NEW & NOTEWORTHY Individuals with type 2 diabetes free from micro- and macrovascular complications have normal resting pulmonary function, but their V̇o2peak is impaired due to poor skeletal muscle oxygenation during exercise. Tailoring exercise regimes for this population should prioritize interventions aimed at enhancing muscle oxygenation and blood flow improvement.

Lower or Higher Oxygenation Targets for Acute Hypoxemic Respiratory Failure.

BACKGROUND: Patients with acute hypoxemic respiratory failure in the intensive care unit (ICU) are treated with supplemental oxygen, but the benefits and harms of different oxygenation targets are unclear. We hypothesized that using a lower target for partial pressure of arterial oxygen (Pao2) would result in lower mortality than using a higher target. METHODS: In this multicenter trial, we randomly assigned 2928 adult patients who had recently been admitted to the ICU (≤12 hours before randomization) and who were receiving at least 10 liters of oxygen per minute in an open system or had a fraction of inspired oxygen of at least 0.50 in a closed system to receive oxygen therapy targeting a Pao2 of either 60 mm Hg (lower-oxygenation group) or 90 mm Hg (higher-oxygenation group) for a maximum of 90 days. The primary outcome was death within 90 days. RESULTS: At 90 days, 618 of 1441 patients (42.9%) in the lower-oxygenation group and 613 of 1447 patients (42.4%) in the higher-oxygenation group had died (adjusted risk ratio, 1.02; 95% confidence interval, 0.94 to 1.11; P = 0.64). At 90 days, there was no significant between-group difference in the percentage of days that patients were alive without life support or in the percentage of days they were alive after hospital discharge. The percentages of patients who had new episodes of shock, myocardial ischemia, ischemic stroke, or intestinal ischemia were similar in the two groups (P = 0.24). CONCLUSIONS: Among adult patients with acute hypoxemic respiratory failure in the ICU, a lower oxygenation target did not result in lower mortality than a higher target at 90 days. (Funded by the Innovation Fund Denmark and others; HOT-ICU ClinicalTrials.gov number, NCT03174002.).

Reliability of variability and complexity measures for task and task-free BOLD fMRI.

Brain activity continuously fluctuates over time, even if the brain is in controlled (e.g., experimentally induced) states. Recent years have seen an increasing interest in understanding the complexity of these temporal variations, for example with respect to developmental changes in brain function or between-person differences in healthy and clinical populations. However, the psychometric reliability of brain signal variability and complexity measures-which is an important precondition for robust individual differences as well as longitudinal research-is not yet sufficiently studied. We examined reliability (split-half correlations) and test-retest correlations for task-free (resting-state) BOLD fMRI as well as split-half correlations for seven functional task data sets from the Human Connectome Project to evaluate their reliability. We observed good to excellent split-half reliability for temporal variability measures derived from rest and task fMRI activation time series (standard deviation, mean absolute successive difference, mean squared successive difference), and moderate test-retest correlations for the same variability measures under rest conditions. Brain signal complexity estimates (several entropy and dimensionality measures) showed moderate to good reliabilities under both, rest and task activation conditions. We calculated the same measures also for time-resolved (dynamic) functional connectivity time series and observed moderate to good reliabilities for variability measures, but poor reliabilities for complexity measures derived from functional connectivity time series. Global (i.e., mean across cortical regions) measures tended to show higher reliability than region-specific variability or complexity estimates. Larger subcortical regions showed similar reliability as cortical regions, but small regions showed lower reliability, especially for complexity measures. Lastly, we also show that reliability scores are only minorly dependent on differences in scan length and replicate our results across different parcellation and denoising strategies. These results suggest that the variability and complexity of BOLD activation time series are robust measures well-suited for individual differences research. Temporal variability of global functional connectivity over time provides an important novel approach to robustly quantifying the dynamics of brain function. PRACTITIONER POINTS: Variability and complexity measures of BOLD activation show good split-half reliability and moderate test-retest reliability. Measures of variability of global functional connectivity over time can robustly quantify neural dynamics. Length of fMRI data has only a minor effect on reliability.

Vessel-specific quantification of cerebral venous oxygenation with velocity-encoding preparation and rapid acquisition.

PURPOSE: Non-invasive measurement of cerebral venous oxygenation (Yv) is of critical importance in brain diseases. The present work proposed a fast method to quantify regional Yv map for both large and small veins. METHODS: A new sequence was developed, referred to as TRU-VERA (T2 relaxation under velocity encoding and rapid acquisition, which isolates blood spins from static tissue with velocity-encoding preparation, modulates the T2 weighting of venous signal with T2-preparation and utilizes a bSSFP readout to achieve fast acquisition with high resolution. The sequence was first optimized to achieve best sensitivity for both large and small veins, and then validated with TRUST (T2 relaxation under spin tagging), TRUPC (T2 relaxation under phase contrast), and accelerated TRUPC MRI. Regional difference of Yv was evaluated, and test-retest reproducibility was examined. RESULTS: Optimal Venc was determined to be 3 cm/s, while recovery time and balanced SSFP flip angle within reasonable range had minimal effect on SNR efficiency. Venous T2 measured with TRU-VERA was highly correlated with T2 from TRUST (R2 = 0.90), and a conversion equation was established for further calibration to Yv. TRU-VERA sequences showed consistent Yv estimation with TRUPC (R2 = 0.64) and accelerated TRUPC (R2 = 0.79). Coefficient of variation was 0.84% for large veins and 2.49% for small veins, suggesting an excellent test-retest reproducibility. CONCLUSION: The proposed TRU-VERA sequence is a promising method for vessel-specific oxygenation assessment.

Selected and shared hematological responses to apnea in elite human free divers and northern elephant seals (Mirounga angustirostris).

Despite elite human free divers achieving incredible feats in competitive free diving, there has yet to be a study that compares consummate divers, (i.e. northern elephant seals) to highly conditioned free divers (i.e., elite competitive free-diving humans). Herein, we compare these two diving models and suggest that hematological traits detected in seals reflect species-specific specializations, while hematological traits shared between the two species are fundamental mammalian characteristics. Arterial blood samples were analyzed in elite human free divers (n = 14) during a single, maximal volitional apnea and in juvenile northern elephant seals (n = 3) during rest-associated apnea. Humans and elephant seals had comparable apnea durations (∼6.5 min) and end-apneic arterial Po2 [humans: 40.4 ± 3.0 mmHg (means ± SE); seals: 27.1 ± 5.9 mmHg; P = 0.2]. Despite similar increases in arterial Pco2 (humans: 33 ± 5%; seals: 16.3 ± 5%; P = 0.2), only humans experienced reductions in pH from baseline (humans: 7.45 ± 0.01; seals: 7.39 ± 0.02) to end apnea (humans: 7.37 ± 0.01; seals: 7.38 ± 0.02; P < 0.0001). Hemoglobin P50 was greater in humans compared to elephant seals (29.9 ± 1.5 and 28.7 ± 0.6 mmHg, respectively; P = 0.046). Elephant seals overall had higher carboxyhemoglobin (COHb) levels (5.9 ± 2.6%) compared to humans (0.8 ± 1.2%; P < 0.0001); however, following apnea, COHb was reduced in seals (baseline: 6.1 ± 0.3%; end apnea: 5.6 ± 0.3%) and was slightly elevated in humans (baseline: 0.7 ± 0.1%; end apnea: 0.9 ± 0.1%; P < 0.0002, both comparisons). Our data indicate that during static apnea, seals have reduced hemoglobin P50, greater pH buffering, and increased COHb levels. The differences in hemoglobin P50 are likely due to the differences in the physiological environment between the two species during apnea, whereas enhanced pH buffering and higher COHb may represent traits selected for in elephant seals.NEW & NOTEWORTHY This study uses similar methods and protocols in elite human free divers and northern elephant seals. Using highly conditioned divers (elite free-diving humans) and highly adapted divers (northern elephant seals), we explored which hematological traits are fundamentally mammalian and which may have been selected for. We found differences in P50, which may be due to different physiological environments between species, while elevated pH buffering and carbon monoxide levels might have been selected for in seals.

Validation of retinal oximetry vessel selection using fluorescein angiography in patients with optic disc drusen.

Retinal oximetry could provide insights into the pathophysiology of optic nerve disease, including optic disc drusen (ODD). Vessel selection for oximetry analysis is based on morphological characteristics of arterioles and venules and supported by an overlay of estimated blood oxygen saturations. The purpose of this cross-sectional study was to determine the validity of this vessel selection procedure by comparing it with vessel selection supported by video fluorescein angiography (FA). The study included 36 eyes of 36 patients with ODD who underwent retinal oximetry (Oxymap retinal oximeter T1) followed by FA (Heidelberg Spectralis). Two trained graders selected vessel segments in a pre-defined measurement area around the optic disc. One of these graders additionally performed the vessel segment selection with the support of FA images. When performed by the same grader, FA-supported and non-FA-supported vessel selection did not lead to significant differences in total vessel segment length, estimated oxygen saturations or vessel diameters (all p > 0.05). Inter-grader differences were found for arterial and venous segment lengths and arterial saturation (p < 0.05). A similar tendency was found for the arteriovenous saturation difference (p = 0.10). In conclusion, identifying vessel segments for retinal oximetry analysis based on vessel morphology and supported by a color-coded saturation overlay appears to be a valid method without the need for invasive angiography. A numerically small inter-grader variation may influence oximetry results. Further studies of retinal oximetry in ODD are warranted.

Maternal tadalafil treatment does not increase uterine artery blood flow or oxygen delivery in the pregnant ewe.

Increasing placental perfusion (PP) could improve outcomes of growth-restricted fetuses. One way of increasing PP may be by using phosphodiesterase (PDE)-5 inhibitors, which induce vasodilatation of vascular beds. We used a combination of clinically relevant magnetic resonance imaging (MRI) techniques to characterize the impact that tadalafil infusion has on maternal, placental and fetal circulations. At 116-117 days' gestational age (dGA; term, 150 days), pregnant ewes (n = 6) underwent fetal catheterization surgery. At 120-123 dGA ewes were anaesthetized and MRI scans were performed during three acquisition windows: a basal state and then ∼15-75 min (TAD 1) and ∼75-135 min (TAD 2) post maternal administration (24 mg; intravenous bolus) of tadalafil. Phase contrast MRI and T2 oximetry were used to measure blood flow and oxygen delivery. Placental diffusion and PP were assessed using the Diffusion-Relaxation Combined Imaging for Detailed Placental Evaluation-'DECIDE' technique. Uterine artery (UtA) blood flow when normalized to maternal left ventricular cardiac output (LVCO) was reduced in both TAD periods. DECIDE imaging found no impact of tadalafil on placental diffusivity or fetoplacental blood volume fraction. Maternal-placental blood volume fraction was increased in the TAD 2 period. Fetal D O 2 ${D_{{{\mathrm{O}}_2}}}$ and V ̇ O 2 ${\dot V_{{{\mathrm{O}}_2}}}$ were not affected by maternal tadalafil administration. Maternal tadalafil administration did not increase UtA blood flow and thus may not be an effective vasodilator at the level of the UtAs. The increased maternal-placental blood volume fraction may indicate local vasodilatation of the maternal intervillous space, which may have compensated for the reduced proportion of UtA D O 2 ${D_{{{\mathrm{O}}_2}}}$ .

Assessment of single-vessel cerebral blood velocity by phase contrast fMRI.

Current approaches to high-field functional MRI (fMRI) provide 2 means to map hemodynamics at the level of single vessels in the brain. One is through changes in deoxyhemoglobin in venules, i.e., blood oxygenation level-dependent (BOLD) fMRI, while the second is through changes in arteriole diameter, i.e., cerebral blood volume (CBV) fMRI. Here, we introduce cerebral blood flow-related velocity-based fMRI, denoted CBFv-fMRI, which uses high-resolution phase contrast (PC) MRI to form velocity measurements of flow. We use CBFv-fMRI in measure changes in blood velocity in single penetrating microvessels across rat parietal cortex. In contrast to the venule-dominated BOLD and arteriole-dominated CBV fMRI signals, CBFv-fMRI is comparable from both arterioles and venules. A single fMRI platform is used to map changes in blood pO2 (BOLD), volume (CBV), and velocity (CBFv). This combined high-resolution single-vessel fMRI mapping scheme enables vessel-specific hemodynamic mapping in animal models of normal and diseased states and further has translational potential to map vascular dementia in diseased or injured human brains with ultra-high-field fMRI.

Attention controls multisensory perception via two distinct mechanisms at different levels of the cortical hierarchy.

To form a percept of the multisensory world, the brain needs to integrate signals from common sources weighted by their reliabilities and segregate those from independent sources. Previously, we have shown that anterior parietal cortices combine sensory signals into representations that take into account the signals' causal structure (i.e., common versus independent sources) and their sensory reliabilities as predicted by Bayesian causal inference. The current study asks to what extent and how attentional mechanisms can actively control how sensory signals are combined for perceptual inference. In a pre- and postcueing paradigm, we presented observers with audiovisual signals at variable spatial disparities. Observers were precued to attend to auditory or visual modalities prior to stimulus presentation and postcued to report their perceived auditory or visual location. Combining psychophysics, functional magnetic resonance imaging (fMRI), and Bayesian modelling, we demonstrate that the brain moulds multisensory inference via two distinct mechanisms. Prestimulus attention to vision enhances the reliability and influence of visual inputs on spatial representations in visual and posterior parietal cortices. Poststimulus report determines how parietal cortices flexibly combine sensory estimates into spatial representations consistent with Bayesian causal inference. Our results show that distinct neural mechanisms control how signals are combined for perceptual inference at different levels of the cortical hierarchy.