Neurovascular Responses Research Articles

Improving dynamic vessel analysis: A new pipeline for localized retinal vessel response evaluation

Aims/Purpose: Dynamic Vessel Analysis (DVA) is a non‐invasive imaging modality that evaluates the reactivity of retinal arteriolar and venular vessels in response to flicker light stimulation. This study aims to introduce a novel data‐processing pipeline that involves noise reduction techniques localized to different locations along the vessel wall. Additionally, it employs standardized parameter extraction, allowing for a more precise assessment of retinal vessel responses across these locations.Methods: Previous studies used robust principal component analysis (RPCA) on averaged time series data for arteries and veins, combining one averaged time series per patient into arterial and venous matrices. Our method retains individual location time series for each arteriole and venule, preserving local responses. We combine these individual time series into arteriolar and venular matrices and apply RPCA, resulting in sparse matrices containing noise and low‐rank matrices capturing common features. The low‐rank matrices, containing the noise‐reduced information, are then used for further analysis. This approach maintains the granularity of local vascular responses.Results: We identified and integrated key parameters from existing literature to delineate vasodilation and vasoconstriction profiles. By applying analysis of covariance (ANCOVA) for age, sex, baseline vessel dilation, and mean arterial pressure, we identified significantly lower Baseline‐Corrected Flicker Response of the proximal retinal venules in normal tension glaucoma patients (2.46%, n = 23) compared to healthy controls (4.23%, n = 21, p = 0.049).Conclusions: Our novel pipeline adds to all previously published methods and effectively identified altered neurovascular responses in glaucoma patients after the necessary adjustments. This standardized and automated approach is a promising catalysator for DVA research, offering a more localized and precise understanding of retinal vascular dynamics.

Functional ultrasound and brain connectivity reveal central nervous system compromise in Trembler-J mice model of Charcot-Marie-Tooth disease

The Charcot-Marie-Tooth-1E (CMT1E) disease is typically described as a peripheral neuropathy in humans, causing decreased nerve conduction, spastic paralysis, and tremor. The Trembler-J (TrJ) mice serve as a high fidelity model of this disease. Here, we use functional ultrasound (fUS) and functional connectivity (FC) to analyze TrJ mice’s brain activity during sensory stimulation and resting state experiments against wild type (WT) mice - the healthy counterpart. fUS is an imaging technique that measures cerebral blood volume (CBV) temporal changes. We study these changes in the primary somatosensory cortex barrel field (S1BF) of both mice populations during periodic vibrissae stimulation, measuring the number of pixels that correlate to the stimulation (i.e., the size of the activation area), the average correlation of these pixels (i.e., the response strength), and the CBV’s rate of change for each stimulation (i.e., the hemodynamic response). Then, we construct a FC matrix for each genotype and experiment by correlating the CBV signals from the eight cortical regions defined by the Paxinos and Franklin atlas. Our results show that TrJ mice have significantly diminished neurovascular responses and altered brain connectivity with respect to WT mice, pointing to central nervous system effects that could shift our understanding of the CMT1E disease.

Abnormal visual cortex activity using functional magnetic resonance imaging in treatment resistant photophobia in Friedreich Ataxia

PurposeFriedreich ataxia (FDRA) is a debilitating neurodegenerative disease that can have ophthalmological manifestations including visual dysfunction, nystagmus, and optic atrophy. However, severe photophobia has not been reported nor evaluated with functional magnetic resonance imaging (fMRI). MethodsA 64-year-old white female with a 37-year history of FDRA presented to the eye clinic with worsening photophobia of 3 years. To measure her visual cortex activation and subjective responses during episodes of photophobia, she underwent event-related fMRI with light stimuli. In comparison, the same protocol was conducted in an individual with photophobia but without FDRA. After the fMRI, both patients were treated with 35 units of BoNT-A applied to the forehead. ResultsAnalysis of visual cortex activity in response to light stimulus in the FDRA patient showed no correlation between blood oxygen level dependent (BOLD) activation and light stimuli in the first (r = −0.100, p = 0.235), and a weak negative correlation in the second half of the fMRI scan (r = −0.236 p = 0.004). In notable contrast, significant positive correlations were noted between visual cortex activity and the light stimulus (1st half: r = 0.742, p < 0.001, vs. 2nd half: r = 0.614, p < 0.001) in the comparator. Six weeks later, no improvement in photophobia was noted in either patient. ConclusionOur study highlights photophobia as one potential ocular manifestation of FDRA and suggests that one underlying contributor may be a decoupled cortical neurovascular response to light. Our study provides novel information that may guide physiologic understanding and future treatments in this disease.

The Influence of Tobacco Smoking Intensity on Hemodynamic Parameters: A Functional Transcranial Doppler Study on Vascular Reserve in Chronic Smokers.

Tobacco smoking is an independent risk factor for stroke. In acute and chronic settings, it affects cerebral blood flow, mean systolic velocities, changes of velocities in response to metabolic challenges, pulsatility, and resistance indices in otherwise healthy smokers. The objective of the study was to determine the influence of smoking intensity on hemodynamic parameters in nonsmokers and smokers. This prospective study enrolled 34 healthy volunteers, 19 smokers and 15 nonsmokers. Epidemiological data were taken from all patients, and exhaled carbon monoxide concentration was measured in smokers. To obtain hemodynamic parameters, we performed functional transcranial Doppler (fTCD) recordings on the posterior cerebral artery for six minutes, consisting of three cycles with closed and opened eyes. We investigated mean systolic velocities, neurovascular responses, and pulsatility indices. Smokers had significantly lower blood flow velocities than nonsmokers (28.36±5.87 and 30.19±6.41, respectively). Neurovascular response as a marker of vasodilatory potential was significantly lower in smokers (14.27%±0.08%) than in the nonsmoker group (17.33%±0.06%). Smokers with higher exhaled carbon monoxide concentrations had lower blood flow velocities than those with lower CO concentrations. Smokers had higher levels of pulsatility indices compared to nonsmokers. The vasodilatory mechanism of cerebral blood vessels is impaired in chronic, otherwise healthy smokers.

VEGF-B prevents chronic hyperglycemia-induced retinal vascular leakage by regulating the CDC42-ZO1/VE-cadherin pathway.

Non-proliferative diabetic retinopathy (NPDR) is the early stage of diabetic retinopathy (DR) and is a chronic oxidative stress-related ocular disease. Few treatments are approved for early DR. This study aimed to investigate the pathogenic mechanisms underlying the retinal micro-vasculopathy induced by diabetes and to explore an early potential for treating early DR in a mouse model. The mouse model of type 1 diabetes was established by intraperitoneal injection of streptozotocin (STZ, 180 mg/kg), which was used as the early DR model. The body weight and blood glucose mice were measured regularly; The retinal vascular leakage in the early DR mice was determined by whole-mount staining; Label-free quantitative proteomic analysis and bioinformatics were used to explore the target proteins and signaling pathways associated with the retinal tissues of early DR mice; To detect the effects of target protein on endothelial cell proliferation, migration, and tube formation, knockdown and overexpression of VEGF-B were performed in human retinal vascular endothelial cells (HRECs); Western blotting was used to detect the expression of target proteins invitro and invivo; Meanwhile, the therapeutic effect of VEGF-B on vascular leakage has also been evaluated invitro and invivo. The protein expressions of vascular endothelial growth factor (VEGF)-B and the Rho GTPases family member CDC42 were reduced in the retinal tissues of early DR. VEGF-B upregulated the expression of CDC42/ZO1/VE-cadherin and prevented hyperglycemia-induced vascular leakage in HRECs. Standard intravitreal VEGF-B injections improved the retinal vascular leakage and neurovascular response in early DR mice. Our findings demonstrated, for the first time, that in diabetes, the retinal vessels are damaged due to decreased VEGF-B expression through downregulation of CDC42/ZO1/VE-cadherin expression. Therefore, VEGF-B could be used as a novel therapy for early DR.

Investigating cerebral neurovascular responses to hyperglycemia in a rat model of type 2 diabetes using multimodal assessment techniques

To study neurovascular function in type 2 diabetes mellitus (T2DM), we established a high-fat diet/streptozotocin (HFD/STZ) rat model. Electrocorticography-laser speckle contrast imaging (ECoG-LSCI) revealed that the somatosensory-evoked potential (SSEP) amplitude and blood perfusion volume were significantly lower in the HFD/STZ group. Cortical spreading depression (CSD) velocity was used as a measure of neurovascular function, and the results showed that the blood flow velocity and the number of CSD events were significantly lower in the HFD/STZ group. In addition, to compare changes during acute hyperglycemia and hyperglycemia, we used intraperitoneal injection (IPI) of glucose to induce transient hyperglycemia. The results showed that CSD velocity and blood flow were significantly reduced in the IPI group. The significant neurovascular changes observed in the brains of rats in the HFD/STZ group suggest that changes in neuronal apoptosis may play a role in altered glucose homeostasis in T2DM.

Long-duration bed rest augments sympathetic neurovascular responses to simulated orthostatic stress among females

Our understanding of the impact of long-duration head-down bed rest (HDBR) on sympathetic neurovascular regulation during orthostatic stress remains incomplete. Through retrospective analysis of the WISE-2005 long-duration bed rest trial, this study aimed to investigate the impact of 60 days of -6° HDBR on the transduction of integrated muscle sympathetic nerve activity (MSNA; peroneal microneurography) into total peripheral resistance (TPR; Finometer Modelflow) responses during rest and graded lower body negative pressure (LBNP; -20, -30, and -45 mmHg). Signal averaging quantified sympathetic transduction for 12 cardiac cycles (ECG) following integrated MSNA bursts in healthy females ( n = 12; 25-40 years). Mixed-effects modeling and post-hoct-tests assessed the impact of HDBR on sympathetic transduction during rest (5-min) and graded LBNP (3-min per level). Data are presented as mean ± SD. Long-duration HDBR did not affect resting total MSNA (pre-HDBR: 909 ± 368 AU/min, post-HDBR: 910 ± 254 AU/min; p = 0.999). HDBR did not affect total MSNA responses to -20 mmHg LBNP (pre-HDBR: 1430 ± 599 AU/min, post-HDBR: 1823 ± 433 AU/min), -30 mmHg LBNP (pre-HDBR: 1574 ± 549 AU/min, post-HDBR: 1924 ± 587 AU/min), or -45 mmHg LBNP (pre-HDBR: 1950 ± 819 AU/min, post-HDBR: 2328 ± 880 AU/min; p = 0.191). HDBR did not affect resting sympathetic transduction to TPR (pre-HDBR: 0.002 ± 0.16 mmHg/L/min, post-HDBR: -0.091 ± 0.12 mmHg/L/min; p = 0.296). However, HDBR augmented TPR transduction responses to graded LBNP (HDBR-by-LBNP interaction: p = 0.050). Pre-HDBR, TPR transduction responses were unchanged with graded LBNP (all p &gt; 0.05). In contrast, post-HDBR, TPR transduction responses increased progressively with graded LBNP (rest: -0.09 ± 0.12 mmHg/L/min, -20 mmHg: 0.22 ± 0.31 mmHg/L/min, -30 mmHg: 0.30 ± 0.34 mmHg/L/min, -45 mmHg: 0.44 ± 0.12 mmHg/L/min; all p &lt; 0.005). The same effect of HDBR was observed when sympathetic transduction of mean arterial pressure was analyzed (data not shown). These data suggest that long-duration HDBR augments sympathetic neurovascular responses to integrated MSNA bursts during orthostatic stress among females. This work was supported by the Canadian Space Agency, the French “Centre National d’Etudes Spatiales”, the European Space Agency, and the National Aeronautics and Space Administration of the USA. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Comparison of LED- and LASER-based fNIRS technologies to record the human peri‑spinal cord neurovascular response

Recently, functional Near-Infrared Spectroscopy (fNIRS) was applied to obtain, non-invasively, the human peri‑spinal Neuro-Vascular Response (NVR) under a non-noxious electrical stimulation of a peripheral nerve. This method allowed the measurements of changes in the concentration of oxyhemoglobin (O2Hb) and deoxyhemoglobin (HHb) from the peri‑spinal vascular network. However, there is a lack of clarity about the potential differences in perispinal NVR recorded by the different fNIRS technologies currently available. In this work, the two main noninvasive fNIRS technologies were compared, i.e., LED and LASER-based. The recording of the human peri‑spinal NVR induced by non-noxious electrical stimulation of a peripheral nerve was recorded simultaneously at C7 and T10 vertebral levels. The amplitude, rise time, and full width at half maximum duration of the perispinal NVRs were characterized in healthy volunteers and compared between both systems. The main difference was that the LED-based system shows about one order of magnitude higher values of amplitude than the LASER-based system. No statistical differences were found for rise time and for duration parameters (at thoracic level). The comparison of point-to-point wave patterns did not show significant differences between both systems. In conclusion, the peri‑spinal NRV response obtained by different fNIRS technologies was reproducible, and only the amplitude showed differences, probably due to the power of the system which should be considered when assessing the human peri‑spinal vascular network.

IDF23-0508 Abnormal peri-spinal neurovascular responses in nonneuropathic type II diabetes patients: a novel diagnostic method

IDF23-0508 Abnormal peri-spinal neurovascular responses in nonneuropathic type II diabetes patients: a novel diagnostic method

Integrated Feedforward and Feedback Mechanisms in Neurovascular Coupling.

Neurovascular coupling (NVC) is the mechanism that drives the neurovascular response to neural activation, and NVC dysfunction has been implicated in various neurologic diseases. NVC is driven by (1) nonmetabolic feedforward mechanisms that are mediated by various signaling pathways and (2) metabolic feedback mechanisms that involve metabolic factors. However, the interplay between these feedback and feedforward mechanisms remains unresolved. We propose that feedforward mechanisms normally drive a swift, neural activation-induced regional cerebral blood flow (rCBF) overshoot, which floods the tissue beds, leading to local hypocapnia and hyperoxia. The feedback mechanisms are triggered by the resultant hypocapnia (not hyperoxia), which causes cerebral vasoconstriction in the neurovascular unit that counterbalances the rCBF overshoot and returns rCBF to a level that matches the metabolic activity. If feedforward mechanisms function improperly (eg, in a disease state), the rCBF overshoot, tissue-bed flooding, and local hypocapnia fail to occur or occur on a smaller scale. Consequently, the neural activation-related increase in metabolic activity results in local hypercapnia and hypoxia, both of which drive cerebral vasodilation and increase rCBF. Thus, feedback mechanisms ensure the brain milieu's stability when feedforward mechanisms are impaired. Our proposal integrates the feedforward and feedback mechanisms underlying NVC and suggests that these 2 mechanisms work like a fail-safe system, to a certain degree. We also discussed the difference between NVC and cerebral metabolic rate-CBF coupling and the clinical implications of our proposed framework.

The significance and limited influence of cerebrovascular reactivity on age and sex effects in task- and resting-state brain activity.

Functional MRI measures the blood-oxygen-level dependent signals, which provide an indirect measure of neural activity mediated by neurovascular responses. Cerebrovascular reactivity affects both task-induced and resting-state blood-oxygen-level dependent activity and may confound inter-individual effects, such as those related to aging and biological sex. We examined a large dataset containing breath-holding, checkerboard, and resting-state tasks. We used the breath-holding task to measure cerebrovascular reactivity, used the checkerboard task to obtain task-based activations, and quantified resting-state activity with amplitude of low-frequency fluctuations and regional homogeneity. We hypothesized that cerebrovascular reactivity would be correlated with blood-oxygen-level dependent measures and that accounting for these correlations would result in better estimates of age and sex effects. We found that cerebrovascular reactivity was correlated with checkerboard task activations in the visual cortex and with amplitude of low-frequency fluctuations and regional homogeneity in widespread fronto-parietal regions, as well as regions with large vessels. We also found significant age and sex effects in cerebrovascular reactivity, some of which overlapped with those observed in amplitude of low-frequency fluctuations and regional homogeneity. However, correcting for the effects of cerebrovascular reactivity had very limited influence on the estimates of age and sex. Our results highlight the limitations of accounting for cerebrovascular reactivity with the current breath-holding task.

Vasodilatory Peripheral Response and Pain Levels following Radiofrequency Stressor Application in Women with Fibromyalgia.

Fibromyalgia (FM) is a syndrome of unknown pathogenesis that presents, among other symptoms, chronic widespread musculoskeletal pain. This study aims to analyze the effects of radiofrequency on core body temperature and the peripheral temperature of the dorsal surfaces and palms of the hands and its association with pain levels in patients with FM. A case-control observational study was conducted with a total of twenty-nine women diagnosed with FM and seventeen healthy women. Capacitive monopolar radiofrequency was applied to the palms of the hands using the Biotronic Advance Develops device. Peripheral hand temperature was analyzed using a thermographic camera, and core body temperature was analyzed with an infrared scanner. Pressure pain thresholds (PPTs) and electrical pain were recorded with an algometer and a Pain Matcher device, respectively. A significant decrease was observed in women with FM in pain electrical threshold (95% CI [0.01-3.56], p = 0.049), electrical pain (95% CI [2.87-10.43], p = 0.002), dominant supraspinatus PPT (95% CI [0.04-0.52], p = 0.023), non-dominant supraspinatus PPT (95% CI [0.03-0.60], p = 0.029), and non-dominant tibial PPT (95% CI [0.05-0.89], p = 0.031). Women with FM have increased hypersensitivity to pain as well as increased peripheral temperature after exposure to a thermal stimulus, such as radiofrequency, which could indicate disorders of their neurovascular response.

Neurovascular coupling of striatal dopamine D2/3 receptor availability and perfusion using simultaneous PET/MR in humans

The midbrain dopamine system contributes to important neural functions in the basal ganglia, and is involved in aspects of pathological processes in schizophrenia. In preclinical and clinical studies, pharmacological blockade or stimulation of brain dopamine receptors alters cerebral perfusion, which is a surrogate marker of metabolic activity. However, there is scant documentation of this neurofunctional coupling in relation to individual differences in the dopamine system of healthy humans. We therefore tested the hypothesis that baseline dopamine D2/3 receptor availability predicts individual blood flow responses to challenge with a dopamine agonist.We used [18F]fallypride positron emission tomography (PET) imaging to quantify dopamine D2/3 receptor availability as binding potential (BPND) in nine healthy subjects. Using simultaneous perfusion-weighted functional magnetic resonance imaging (fMRI), we measured perfusion at baseline and after challenge with the dopamine agonist apomorphine.Results of this multimodal imaging study revealed a strong negative association between baseline D2/3 dopamine receptor availability and apomorphine-induced perfusion changes in the human basal ganglia. There was considerable intra-individual variation in the neurovascular response to the apomorphine challenge, which may call for further investigation of the dopaminergic regulation of cerebral perfusion in patients with schizophrenia.This study describes a novel paradigm for assessing dopamine sensitivity, facilitating an exploration of the dopamine supersensitivity hypothesis.

TrkA-mediated sensory innervation of injured mouse tendon supports tendon sheath progenitor cell expansion and tendon repair.

Peripheral neurons terminate at the surface of tendons partly to relay nociceptive pain signals; however, the role of peripheral nerves in tendon injury and repair remains unclear. Here, we show that after Achilles tendon injury in mice, there is new nerve growth near tendon cells that express nerve growth factor (NGF). Conditional deletion of the Ngf gene in either myeloid or mesenchymal mouse cells limited both innervation and tendon repair. Similarly, inhibition of the NGF receptor tropomyosin receptor kinase A (TrkA) abrogated tendon healing in mouse tendon injury. Sural nerve transection blocked the postinjury increase in tendon sensory innervation and the expansion of tendon sheath progenitor cells (TSPCs) expressing tubulin polymerization promoting protein family member 3. Single cell and spatial transcriptomics revealed that disruption of sensory innervation resulted in dysregulated inflammatory signaling and transforming growth factor-β (TGFβ) signaling in injured mouse tendon. Culture of mouse TSPCs with conditioned medium from dorsal root ganglia neuron further supported a role for neuronal mediators and TGFβ signaling in TSPC proliferation. Transcriptomic and histologic analyses of injured human tendon biopsy samples supported a role for innervation and TGFβ signaling in human tendon regeneration. Last, treating mice after tendon injury systemically with a small-molecule partial agonist of TrkA increased neurovascular response, TGFβ signaling, TSPC expansion, and tendon tissue repair. Although further studies should investigate the potential effects of denervation on mechanical loading of tendon, our results suggest that peripheral innervation is critical for the regenerative response after acute tendon injury.

Dual-color miniscope imaging of microvessels and neuronal activity in the hippocampus CA1 region of freely moving mice following alcohol administration.

Moderate-to-heavy episodic ("binge") drinking is the most common form of alcohol consumption in the United States. Alcohol at binge drinking concentrations reduces brain artery diameter in vivo and in vitro in many species including rats, mice, and humans. Despite the critical role played by brain vessels in maintaining neuronal function, there is a shortage of methodologies to simultaneously assess neuron and blood vessel function in deep brain regions. Here, we investigate cerebrovascular responses to ethanol by choosing a deep brain region that is implicated in alcohol disruption of brain function, the hippocampal CA1, and describe the process for obtaining simultaneous imaging of pyramidal neuron activity and diameter of nearby microvessels in freely moving mice via a dual-color miniscope. Recordings of neurovascular events were performed upon intraperitoneal injection of saline versus 3 g/kg ethanol in the same mouse. In male mice, ethanol mildly increased the amplitude of calcium signals while robustly decreasing their frequency. Simultaneously, ethanol decreased microvessel diameter. In females, ethanol did not change the amplitude or frequency of calcium signals from CA1 neurons but decreased microvessel diameter. A linear regression of ethanol-induced reduction in number of active neurons and microvessel constriction revealed a positive correlation (R = 0.981) in females. Together, these data demonstrate the feasibility of simultaneously evaluating neuronal and vascular components of alcohol actions in a deep brain area in freely moving mice, as well as the sexual dimorphism of hippocampal neurovascular responses to alcohol.

Secondary neurodegeneration following Stroke: what can blood biomarkers tell us?

Stroke is one of the leading causes of death and the primary source of disability in adults, resulting in neuronal necrosis of ischemic areas, and in possible secondary degeneration of regions surrounding or distant to the initial damaged area. Secondary neurodegeneration (SNDG) following stroke has been shown to have different pathogenetic origins including inflammation, neurovascular response and cytotoxicity, but can be associated also to regenerative processes. Aside from focal neuronal loss, ipsilateral and contralateral effects distal to the lesion site, disruptions of global functional connectivity and a transcallosal diaschisis have been reported in the chronic stages after stroke. Furthermore, SNDG can be observed in different areas not directly connected to the primary lesion, such as thalamus, hippocampus, amygdala, substantia nigra, corpus callosum, bilateral inferior fronto-occipital fasciculus and superior longitudinal fasciculus, which can be highlighted by neuroimaging techniques. Although the clinical relevance of SNDG following stroke has not been well understood, the identification of specific biomarkers that reflect the brain response to the damage, is of paramount importance to investigate in vivo the different phases of stroke. Actually, brain-derived markers, particularly neurofilament light chain, tau protein, S100b, in post-stroke patients have yielded promising results. This review focuses on cerebral morphological modifications occurring after a stroke, on associated cellular and molecular changes and on state-of-the-art of biomarkers in acute and chronic phase. Finally, we discuss new perspectives regarding the implementation of blood-based biomarkers in clinical practice to improve the rehabilitation approaches and post stroke recovery.

Neurovascular and hemodynamic responses to mental stress and exercise in severe COVID-19 survivors.

Previous studies show that COVID-19 survivors have elevated muscle sympathetic nerve activity (MSNA), endothelial dysfunction, and aortic stiffening. However, the neurovascular responses to mental stress and exercise are still unexplored. We hypothesized that COVID-19 survivors, compared with age- and body mass index (BMI)-matched control subjects, exhibit abnormal neurovascular responses to mental stress and physical exercise. Fifteen severe COVID-19 survivors (aged: 49 ± 2 yr, BMI: 30 ± 1 kg/m2) and 15 well-matched control subjects (aged: 46 ± 3 yr, BMI: 29 ± 1 kg/m2) were studied. MSNA (microneurography), forearm blood flow (FBF), and forearm vascular conductance (FVC, venous occlusion plethysmography), mean arterial pressure (MAP, Finometer), and heart rate (HR, ECG) were measured during a 3-min mental stress (Stroop Color-Word Test) and during a 3-min isometric handgrip exercise (30% of maximal voluntary contraction). During mental stress, MSNA (frequency and incidence) responses were higher in COVID-19 survivors than in controls (P < 0.001), and FBF and FVC responses were attenuated (P < 0.05). MAP was similar between the groups (P > 0.05). In contrast, the MSNA (frequency and incidence) and FBF and FVC responses to handgrip exercise were similar between the groups (P > 0.05). MAP was lower in COVID-19 survivors (P < 0.05). COVID-19 survivors exhibit an exaggerated MSNA and blunted vasodilatory response to mental challenge compared with healthy adults. However, the neurovascular response to handgrip exercise is preserved in COVID-19 survivors. Overall, the abnormal neurovascular control in response to mental stress suggests that COVID-19 survivors may have an increased risk to cardiovascular events during mental challenge.

Peri-spinal Neurovascular Response Triggered by a Painless Electrical Nerve Stimulation in Patients with Chronic Arterial Hypertension

Peri-spinal Neurovascular Response Triggered by a Painless Electrical Nerve Stimulation in Patients with Chronic Arterial Hypertension

Calcium transients in nNOS neurons underlie distinct phases of the neurovascular response to barrel cortex activation in awake mice

Neuronal nitric oxide (NO) synthase (nNOS), a Ca2+ dependent enzyme, is expressed by distinct populations of neocortical neurons. Although neuronal NO is well known to contribute to the blood flow increase evoked by neural activity, the relationships between nNOS neurons activity and vascular responses in the awake state remain unclear. We imaged the barrel cortex in awake, head-fixed mice through a chronically implanted cranial window. The Ca2+ indicator GCaMP7f was expressed selectively in nNOS neurons using adenoviral gene transfer in nNOScre mice. Air-puffs directed at the contralateral whiskers or spontaneous motion induced Ca2+ transients in 30.2 ± 2.2% or 51.6 ± 3.3% of nNOS neurons, respectively, and evoked local arteriolar dilation. The greatest dilatation (14.8 ± 1.1%) occurred when whisking and motion occurred simultaneously. Ca2+ transients in individual nNOS neurons and local arteriolar dilation showed various degrees of correlation, which was strongest when the activity of whole nNOS neuron ensemble was examined. We also found that some nNOS neurons became active immediately prior to arteriolar dilation, while others were activated gradually after arteriolar dilatation. Discrete nNOS neuron subsets may contribute either to the initiation or to the maintenance of the vascular response, suggesting a previously unappreciated temporal specificity to the role of NO in neurovascular coupling.

Implicit IAT Measures and Neurophysiological fNIRS Markers in Response to High-Engagement Advertising.

Self-report measures partially explain consumers' purchasing choices, which are inextricably linked to cognitive, affective processes and implicit drives. These aspects, which occur outside of awareness and tacitly affect the way consumers make decisions, could be explored by exploiting neuroscientific technology. The study investigates implicit behavioural and neurovascular responses to emotionally arousing and high-engagement advertisements (COVID-19 content). High-engagement advertisements and control stimuli were shown in two experimental sessions that were counterbalanced across participants. During each session, hemodynamic variations were recorded with functional Near-Infrared Spectroscopy (fNIRS) of the prefrontal cortex (PFC), a neurophysiological marker for emotional processing. The implicit association task (IAT) was administered to investigate the implicit attitude. An increase in the concentration of oxygenated haemoglobin (O2Hb) was found for the high-engagement advertising when this category of stimuli was seen first. Specular results were found for deoxygenated haemoglobin (HHb) data. The IAT reported higher values for highly engaging stimuli. Increased activity within the PFC suggests that highly engaging content may be effective in generating emotional arousal and increasing attention when presented before other stimuli, which is consistent with the higher IAT scores, indicating more favourable implicit attitudes. This evidence suggests that the effectiveness of highly engaging advertising-related messages may be constrained by the order of advertisement administration.