Journal of Cerebral Blood Flow and Metabolism最新文献

{"title":"Correcting <i>SUVR</i> bias by accounting for radiotracer clearance in tissue: A validation study with [¹⁸F]FE-PE2I PET in cross-sectional, test-retest and longitudinal cohorts.","authors":"Minyoung Oh, Praveen Honhar, Richard E Carson, Ansel T Hillmer, Andrea Varrone","doi":"10.1177/0271678X251322407","DOIUrl":"10.1177/0271678X251322407","url":null,"abstract":"<p><p>Quantification of dopamine transporter (DAT) with [¹⁸F]FE-PE2I PET is an important progression marker for Parkinson's disease (PD). This study aimed to validate a novel correction (<i>SUVR</i>c) for a less-biased estimate of <i>SUVR</i> by accounting for [¹⁸F]FE-PE2I clearance-rate, in independent cross-sectional (38 PD, 38 controls), test-retest (9 PD) and longitudinal cohorts (21 PD). <i>SUVR</i>c was calculated as <math><mfrac><mrow><mi>SUVR</mi></mrow><mrow><mn>1</mn><mi> </mi><mo>-</mo><mi> </mi><mfrac><mrow><msub><mrow><mi>β</mi></mrow><mrow><mi>ref</mi></mrow></msub></mrow><mrow><msub><mrow><mi>k</mi></mrow><mrow><mn>2</mn><mo>,</mo><mi>ref</mi></mrow></msub></mrow></mfrac><mi> </mi><mo>+</mo><msub><mrow><mi>β</mi></mrow><mrow><mi>tar</mi></mrow></msub><mfrac><mrow><mi>SUVR</mi></mrow><mrow><msub><mrow><mi>k</mi></mrow><mrow><mn>2</mn><mo>,</mo><mi>ref</mi></mrow></msub><msub><mrow><mi>R</mi></mrow><mrow><mn>1</mn></mrow></msub></mrow></mfrac></mrow></mfrac></math>. <i>β</i>_tar and <i>β</i>_ref are the clearance rates from the target and reference tissues. Bias relative to <i>DVR</i>, discriminative power, test-retest variability (TRV) and annual longitudinal change (ALC) were used to compare <i>SUVR</i>_50-80 min, <i>SUVR</i>c_50-80 min, <i>SUVR</i>_15-45 min and <i>DVR. SUVR</i>_50-80 min showed high bias across all regions (HC: mean: 48.31 ± 20.49% [range: 28.32-53.80%]; PD: 29.91 ± 13.95% [20.45-39.80%]) that was corrected by <i>SUVR</i>c_50-80 min (HC: -0.80 ± 12.72% [-9.69-11.64%]; PD: -0.13 ± 7.41% [-5.04-2.97%]), <i>p < </i>0.001 for both groups compared to mean bias of <i>SUVR</i>_50-80 min, similar to <i>SUVR</i>_15-45 min. For the striatum, Cohen's <i>d</i> was similar for all measures. TRV were 3.2 ± 2.5% (<i>DVR</i>), 6.4 ± 5.7% (<i>SUVR</i>_50-80 min), 6.8 ± 5.9% (<i>SUVR</i>c_50-80 min) and 3.9 ± 3.2% (<i>SUVR</i>_15-45 min). Higher TRV of <i>SUVR</i>c_50-80 min was due to TRV of 9.2 ± 5.1% [1.1-19.4] for β_tar. ALC was 4.5 ± 4.2% (<i>DVR</i>), 5.2 ± 6.5% (<i>SUVR</i>_50-80 min), 4.4 ± 4.1% (<i>SUVR</i>c_50-80 min) and 4.2 ± 4.1% (<i>SUVR</i>_15-45 min). <i>SUVR</i>c_50-80 min reduced bias compared to <i>SUVR</i>_50-80 min, as previously reported. <i>SUVR</i>c_50-80 min was sensitive to small changes of β_tar, with higher TRV compared to <i>DVR</i>, but with similar ALC, suggesting that it can reliably assess longitudinal DAT changes.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X251322407"},"PeriodicalIF":4.9,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11846093/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aging alters calcium signaling in vascular mural cells and drives remodeling of neurovascular coupling in the awake brain.","authors":"Xiao Zhang, Lechan Tao, Amalie H Nygaard, Yiqiu Dong, Teddy Groves, Xiaoqi Hong, Carolyn M Goddard, Chen He, Dmitry Postnov, Ilary Allodi, Martin J Lauritzen, Changsi Cai","doi":"10.1177/0271678X251320455","DOIUrl":"10.1177/0271678X251320455","url":null,"abstract":"<p><p>Brain aging leads to reduced cerebral blood flow and cognitive decline, but how normal aging affects neurovascular coupling (NVC) in the awake brain is unclear. Here, we investigated NVC in relation to calcium changes in vascular mural cells (VMCs) in awake adult and aged mice. We show that NVC responses are reduced and prolonged in the aged brain and that this is more pronounced at the capillary level than in arterioles. However, the overall NVC response, measured as the time integral of vasodilation, is the same in the two age groups. In adult, but not in aged mice, the NVC response correlated with Ca2+ signaling in VMCs, while the overall Ca2+ kinetics were slower in aged than in adult mice. In particular, the rate of Ca2+ transport, and the Ca2+ sensitivity of VMCs were reduced in aged mice, explaining the reduced and prolonged vasodilation. Spontaneous locomotion was less frequent and reduced in aged mice as compared to young adult mice, and this was reflected in the 'slow but prolonged' NVC and vascular Ca2+ responses. Taken together, our data characterize the NVC in the aged, awake brain as slow but prolonged, highlighting the remodeling processes associated with aging.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X251320455"},"PeriodicalIF":4.9,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11826828/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel model to quantify blood transit time in cerebral arteries using ASL-based 4D magnetic resonance angiography with example clinical application in moyamoya disease.","authors":"Alex A Bhogal, Simone M Uniken Venema, Pieter T Deckers, Kim van de Ven, Maarten Versluis, Kees P Braun, Albert van der Zwan, Jeroen Cw Siero","doi":"10.1177/0271678X251321640","DOIUrl":"10.1177/0271678X251321640","url":null,"abstract":"<p><p>Angiography is critical for visualizing cerebral blood flow in intracranial steno-occlusive diseases. Current 4D magnetic resonance angiography (MRA) techniques primarily focus on macrovascular structures, yet few have quantified hemodynamic timing. This study introduces a novel model to estimate macrovascular arterial transit time (mATT) derived from arterial spin labeling (ASL)-based 4D-MRA. We provide examples of our method that visualize mATT differences throughout the brain of patients with intracranial steno-occlusive disease (moyamoya), as well as changes in mATT resulting from the cerebrovascular reactivity response to an acetazolamide (ACZ) injection. Furthermore, we present a method that projects sparse arterial signals into a 3D native brain-region atlas space and correlates regional mATT with other hemodynamic parameters of interest, such as tissue transit time and cerebrovascular reactivity. This approach offers a non-invasive, quantitative assessment of macrovascular dynamics, with potential to enhance understanding of large-vessel and tissue-level hemodynamics and augment monitoring of treatment outcomes in steno-occlusive disease patients. Furthermore, it sets the stage for more in-depth investigations of the macrovascular contribution to brain hemodynamics.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X251321640"},"PeriodicalIF":4.9,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11826826/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in sporadic brain arteriovenous malformations: Novel genetic insights, innovative animal models, and emerging therapeutic approaches.","authors":"Yasuhito Ueki, Ryan M Naylor, Sherief A Ghozy, Kasthuri Thirupathi, Lorenzo Rinaldo, David F Kallmes, Ramanathan Kadirvel","doi":"10.1177/0271678X251319913","DOIUrl":"10.1177/0271678X251319913","url":null,"abstract":"<p><p>Brain arteriovenous malformations (bAVMs) are a notable cause of intracranial hemorrhage, strongly associated with severe morbidity and mortality. Contemporary treatment options include surgery, stereotactic radiosurgery, and endovascular embolization, each of which has limitations. Hence, development of pharmacological interventions is urgently needed. The recent discovery of the presence of activating Kirsten rat sarcoma (<i>KRAS</i>) viral oncogene homologue mutations in most sporadic bAVMs has opened the door for a more comprehensive understanding of the pathogenesis of bAVMs and has pointed to entirely novel possible therapeutic targets. Herein, we review the status quo of genetics, animal models, and therapeutic approaches in bAVMs.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X251319913"},"PeriodicalIF":4.9,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11826813/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynamic diffusion-weighted imaging of intracranial cardiac impulse propagation along arteries to arterioles in the aging brain.","authors":"Qiuting Wen, Joseph Muskat, Charles F Babbs, Adam M Wright, Yi Zhao, Xiaopeng Zhou, Chengcheng Zhu, Yunjie Tong, Yu-Chien Wu, Shannon L Risacher, Andrew J Saykin","doi":"10.1177/0271678X251320902","DOIUrl":"10.1177/0271678X251320902","url":null,"abstract":"<p><p>Intracranial cardiac impulse propagation along penetrating arterioles is vital for both nutrient supply via blood circulation and waste clearance via CSF circulation. However, current neuroimaging methods are limited to simultaneously detecting impulse propagation at pial arteries, arterioles, and between them. We hypothesized that this propagation could be detected via paravascular CSF dynamics and that it may change with aging. Using dynamic diffusion-weighted imaging (dynDWI), we detected oscillatory CSF motion synchronized with the finger photoplethysmography in the subarachnoid space (SAS) and cerebral cortex, with a delay revealing an impulse propagation pathway from the SAS to the cortex, averaging 84 milliseconds. Data from 70 subjects aged 18 to 85 years showed a bimodal age-related change in the SAS-Cortex travel time: it initially increases with age, peaks around 45 years, then decreases. Computational biomechanical modeling of the cardiovascular system was performed and replicated this 84-millisecond delay. Sensitivity analysis suggests that age-related variations in travel time are primarily driven by changes in arteriolar compliance. These findings support the use of dynDWI for measuring intracranial impulse propagation and highlight its potential in assessing related vascular and waste clearance functions.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X251320902"},"PeriodicalIF":4.9,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11826823/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early metabolic changes in the brain of Alzheimer's disease rats are driven by GLAST+ cells.","authors":"William J Morrey, Kelly Ceyzériat, Quentin Amossé, Aurélien M Badina, Ben Dickie, Ingo Schiessl, Stergios Tsartsalis, Philippe Millet, Hervé Boutin, Benjamin B Tournier","doi":"10.1177/0271678X251318923","DOIUrl":"10.1177/0271678X251318923","url":null,"abstract":"<p><p>Glucose metabolic dysfunction is a hallmark of Alzheimer's disease (AD) pathology and is used to diagnose the disease or predict imminent cognitive decline. The main method to measure brain metabolism <i>in vivo</i> is positron emission tomography with 2-Deoxy-2-[¹⁸F]fluoroglucose ([¹⁸F]FDG-PET). The cellular origin of changes in the [¹⁸F]FDG-PET signal in AD is controversial. We addressed this by combining [¹⁸F]FDG-PET with subsequent cell-sorting and γ-counting of [¹⁸F]FDG-accumulation in sorted cell populations. 7-month-old male TgF344-AD rats and wild-type controls (n = 24/group) received sham or ceftriaxone (200 mg/kg) injection prior to [¹⁸F]FDG-PET imaging to increase glutamate uptake and glucose utilisation. The same animals were injected again one week later, and radiolabelled brains were dissected, with hippocampi taken for magnetically-activated cell sorting of radioligand-treated tissues (MACS-RTT). Radioactivity in sorted cell populations was measured to quantify cell-specific [¹⁸F]FDG uptake. Transcriptional analyses of metabolic enzymes/transporters were also performed. <i>Hypo</i>metabolism in the frontal association cortex of TgF344-AD rats was identified using [¹⁸F]FDG-PET, whereas <i>hyper</i>metabolism was identified in the hippocampus using MACS-RTT. Hypermetabolism was primarily driven by GLAST+ cells. This was supported by transcriptional analyses which showed alteration to metabolic apparatus, including upregulation of hexokinase 2 and altered expression of glucose/lactate transporters. See Figure 1 for summary.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X251318923"},"PeriodicalIF":4.9,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11806453/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fecal microbiota transplantation fails to impart the benefits of circadian-dependent intermittent fasting following ischemic stroke.","authors":"Soomin Jeong, Charles K Davis, Anil K Chokkalla, Bori Kim, Sena Park, Raghu Vemuganti","doi":"10.1177/0271678X251319636","DOIUrl":"10.1177/0271678X251319636","url":null,"abstract":"<p><p>Intermittent fasting (IF) is known to induce significant ischemic tolerance. Diet is a major proponent of gut microbiota, and gut microbial dysbiosis plays a role in post-stroke brain damage. Hence, we currently evaluated whether IF-mediated ischemic tolerance is mediated by gut microbiota. Additionally, circadian cycle is known to modulate post-ischemic outcomes, and thus we further evaluated if gut microbiota would be influenced by prophylactic IF during the inactive phase (fasting during daytime; IIF) or active phase (fasting during nighttime; AIF). The AIF, but not IIF, cohort showed a significantly decreased fecal Firmicutes/Bacteroidetes ratio compared with the ad libitum (AL) cohort. Moreover, the levels of gut microbiota-derived metabolites butyrate and propionate decreased in AL cohort following focal ischemia, whereas they increased in AIF cohort. However, fecal microbiota transplantation (FMT) from IIF or AIF cohort had no significant effects on post-ischemic motor and cognitive function recovery, anxiety-, and depression-like behaviors compared with FMT from AL cohort. Furthermore, FMT from IIF or AIF cohort did not influence the post-ischemic infarct volume, atrophy volume or white matter damage. Overall, the current findings indicate that the beneficial effects of IF after focal ischemia are not mediated by the gut microbiota.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X251319636"},"PeriodicalIF":4.9,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11806450/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Progression of experimental autoimmune encephalomyelitis in mice and neutrophil-mediated blood-brain barrier dysfunction requires non-muscle myosin light chain kinase.","authors":"Richard S Beard, Brian A Hoettels, Jessica M McAllister, Jamie E Meegan, Travis S Wertz, Desiree A Self, Dylan E Hrkach, Daniel Greiner, Kristina Chapman, Nuria Villalba, Xiaoyuan Yang, Byeong J Cha, Cheryl L Jorcyk, Julia T Oxford, Mack H Wu, Sarah Y Yuan","doi":"10.1177/0271678X251318620","DOIUrl":"10.1177/0271678X251318620","url":null,"abstract":"<p><p>Blood-brain barrier (BBB) dysfunction occurs in numerous central nervous system disorders. Unfortunately, a limited understanding of the mechanisms governing barrier function hinders the identification and assessment of BBB-targeted therapies. Previously, we found that non-muscle myosin light chain kinase (nmMLCK) negatively regulates the tight junction protein claudin-5 in brain microvascular endothelial cells (BMVECs) under inflammatory conditions. Here, we used complementary animal and primary cell co-culture models to further investigate nmMLCK and claudin-5 during neuroinflammation. We found that <i>nmMLCK</i>-knockout mice resisted experimental autoimmune encephalomyelitis (EAE), including paralysis, demyelination, neutrophil infiltration, and BBB dysfunction. However, transiently silencing claudin-5 culminated in a fulminant disease course. In parallel, we found that neutrophil-secreted factors triggered a biphasic loss in the barrier quality of wild-type BMVEC monolayers, plus pronounced neutrophil migration during the second phase. Conversely, <i>nmMLCK</i>-knockout monolayers resisted barrier dysfunction and neutrophil migration. Lastly, we found an inverse relationship between claudin-5 expression in BMVECs and neutrophil migration. Overall, our findings support a pathogenic role for nmMLCK in BMVECs during EAE that includes BBB dysfunction and neutrophil infiltration, reveal that claudin-5 contributes to the immune barrier properties of BMVECs, and underscore the harmful effects of claudin-5 loss during neuroinflammation.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X251318620"},"PeriodicalIF":4.9,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11806455/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic determinants of insufficiency of the collateral circulation.","authors":"James E Faber","doi":"10.1177/0271678X251317880","DOIUrl":"10.1177/0271678X251317880","url":null,"abstract":"<p><p>It has been estimated that approximately two million neurons, sixteen billion synapses and twelve kilometers of axons are lost each minute following anterior large-vessel stroke. The level of collateral blood flow has become recognized as a primary determinant of the pace of this loss and an important factor in clinical decision-making. Many of the topics in this review cover recent developments that have not been reviewed elsewhere. These include that: the number and diameter of collaterals and collateral blood flow vary greatly in the brain and other tissues of healthy individuals; a large percentage of individuals are deficient in collaterals; the underlying mechanism arises primarily from naturally occurring polymorphisms in genes/genetic loci within the pathway that drives collateral formation during development; evidence indicates collateral abundance does not exhibit sexual dimorphism; and that collaterals-besides their function as endogenous bypass vessels-may have a physiological role in optimizing oxygen delivery. Animal and human studies in brain and other tissues, where available, are reviewed. Details of many of the studies are provided so that the strength of the findings and conclusions can be assessed without consulting the original literature. Key questions that remain unanswered and strategies to address them are also discussed.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X251317880"},"PeriodicalIF":4.9,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypocapnia, eucapnia, and hypercapnia during \"Where's Waldo\" search paradigms: Neurovascular coupling across the cardiac cycle and biological sexes.","authors":"Nathan E Johnson, Joel S Burma, Matthew G Neill, Joshua J Burkart, Elizabeth Ks Fletcher, Jonathan D Smirl","doi":"10.1177/0271678X251318922","DOIUrl":"10.1177/0271678X251318922","url":null,"abstract":"<p><p>This investigation explored the impact of partial pressure of end-tidal carbon dioxide (P_ETCO₂) alterations on temporal neurovascular coupling (NVC) responses across the cardiac cycle and the influence of biological sex via a complex visual scene-search task (\"<i>Where's Waldo?</i>\"). 10 females and 10 males completed five puzzles, each with 40 seconds of eyes open and 20 seconds of eyes closed, under P_ETCO₂ clamped at ∼40 mmHg (eucapnia), ∼55 mmHg (hypercapnia), and ∼25 mmHg (hypocapnia). Cerebral blood velocity (CBv) in the middle and posterior cerebral arteries (MCAv, PCAv) were measured via Transcranial Doppler ultrasound. Linear mixed-effects models with participants as a random effect analyzed NVC metrics, including baseline and peak CBv, relative increase, and area-under-the-curve (AUC30). During hypercapnic trials, reductions in PCAv and MCAv AUC30 were noted across the cardiac cycle (all <i>p < 0.001</i>). Hypocapnic PCAv AUC30 was reduced (all <i>p < 0.012</i>), as was systolic MCAv AUC30 (<i>p = 0.003</i>). Females displayed greater baseline PCA diastole (<i>p = 0.048</i>). No other biological sex differences were observed across conditions in baseline (all <i>p > 0.050</i>), peak (all <i>p</i> > <i>0.054</i>), relative increase (all <i>p > 0.511</i>), and AUC30 metrics (all <i>p > 0.514</i>). Despite differences in responses to hypercapnic and hypocapnic stimuli, NVC responses to complex visual tasks remain robust, across the physiological CO₂ range.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X251318922"},"PeriodicalIF":4.9,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11795569/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}