Frontiers in Neuroscience最新文献

{"title":"Optimizing staging of Meniere's disease: integrating electrocochleography with vestibular tests.","authors":"Muchen Huang, Xianren Wang, Minqi Chen","doi":"10.3389/fnins.2025.1600665","DOIUrl":"10.3389/fnins.2025.1600665","url":null,"abstract":"<p><strong>Objectives: </strong>This study aimed to evaluate the diagnostic and staging efficacy of integrating electrocochleography (ECochG) with vestibular function tests-specifically cervical and ocular vestibular evoked myogenic potentials (cVEMP and oVEMP), caloric test (CT), and video head impulse test (vHIT)-for Ménière's disease (MD).</p><p><strong>Design: </strong>Data were collected from 54 MD patients (66 affected ears) admitted to a hospital between January 2023 and January 2024. Each participant underwent pure tone audiometry, ECochG, cVEMP, oVEMP, CT, and vHIT. The results were compared against both established clinical criteria and a newly proposed staging system. Inclusion criteria followed the 2015 diagnostic guidelines for MD. Statistical analyses, including ANOVA, Chi-square, and Kruskal-Wallis H tests, were conducted, and a random forest model was employed to validate the robustness of the proposed staging system.</p><p><strong>Results: </strong>The novel staging system, incorporating vestibular function tests, demonstrated superior sensitivity and diagnostic accuracy compared to traditional audiometry-based staging. Early-stage MD detection improved significantly, with vestibular test abnormalities strongly correlating with disease progression. The overall positive rate for any test was 98.5%. ECochG abnormalities were detected in 54.5% of cases, while cVEMP and oVEMP abnormalities were observed in 75.8% and 69.7% of cases, respectively. The new staging system exhibited a stronger correlation with vestibular dysfunction, effectively identifying functional impairment prior to significant hearing loss.</p><p><strong>Conclusion: </strong>The integration of ECochG with vestibular function tests provides a more comprehensive diagnostic framework for MD. This multimodal approach enhances early detection, improves staging accuracy, and offers deeper insights into disease progression, thereby facilitating more personalized treatment strategies.</p>","PeriodicalId":12639,"journal":{"name":"Frontiers in Neuroscience","volume":"19 ","pages":"1600665"},"PeriodicalIF":3.2,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12279762/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144690006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Listening effort and stress in tinnitus: a multidimensional approach.","authors":"Giovanna Giliberto, Maria Itati Palacio, Giulia Cartocci, Emiliano Fernandez-Villalba, Dario Rossi, Nieves Minguez, Maria Botia, Jose Domingo Cubillana, Jose Joaquin Ceron, Fabio Babiloni, Maria Trinidad Herrero","doi":"10.3389/fnins.2025.1591622","DOIUrl":"10.3389/fnins.2025.1591622","url":null,"abstract":"<p><strong>Introduction: </strong>This study investigated the impact of chronic tinnitus on auditory perception, text comprehension, and physiological stress responses, with a focus on sex-related differences. The main objectives were to assess the influence of sex and stress on tinnitus severity, examine neurophysiological indicators of listening effort, and evaluate the effects of background noise on perceived difficulty and listening pleasantness.</p><p><strong>Materials and methods: </strong>Forty-seven participants (24 with tinnitus, 23 controls) performed a listening task involving audiobook excerpts presented at different signal-to-noise ratios. Subjective ratings, comprehension scores, and physiological data were collected, including salivary alpha-amylase, electrodermal activity, heart rate, and EEG-based measures of listening pleasantness.</p><p><strong>Results: </strong>Control participants outperformed tinnitus participants during the initial quiet condition (<i>p</i> = 0.020), with male controls scoring significantly higher than males with tinnitus (<i>p</i> = 0.008). Tinnitus participants rated listening as less pleasant in both quiet (<i>p</i> = 0.036) and high-noise conditions (<i>p</i> = 0.012). Female participants reported greater difficulty under moderate noise (<i>p</i> = 0.030), while EEG data showed higher enjoyment in males (<i>p</i> = 0.005). Salivary amylase increased post-task (<i>p</i> = 0.016), electrodermal activity differed between the initial and final quiet phases (<i>p</i> < 0.001), and heart rate varied according to noise levels (<i>p</i> = 0.008). Negative correlation emerged between subjective and EEG-based pleasantness in the quiet condition.</p><p><strong>Discussion: </strong>These findings suggest that tinnitus imposes a measurable cognitive and emotional burden, influenced by both sex and stress responses. They emphasize the need for multimodal, personalized, and gender-sensitive approaches in the assessment and management of tinnitus.</p>","PeriodicalId":12639,"journal":{"name":"Frontiers in Neuroscience","volume":"19 ","pages":"1591622"},"PeriodicalIF":3.2,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12277253/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A theory of intervention model to define the essential characteristics of music to support emotion regulation development in early childhood.","authors":"Kimberly Sena Moore, Kailah Burbach, Deanna Hanson-Abromeit","doi":"10.3389/fnins.2025.1568789","DOIUrl":"10.3389/fnins.2025.1568789","url":null,"abstract":"<p><p>Recent work in the area of health intervention development has emphasized the need to articulate a theory of intervention. This begins with the development of a working theoretical model, which includes three elements: (1) theory of the health problem, (2) theory of change, and (3) theory of implementation. The purpose of this project was to expand and refine the intervention theory underlying the music-based intervention, Musical Contour Regulation Facilitation (MCRF). MCRF is a multi-component music intervention designed to promote emotion regulation (ER) development in early childhood. Preschooler ER is characterized by greater self-regulation of emotions, increased understanding and use of socially- and culturally-appropriate emotion display rules, and decreased reliance on caregivers for ER needs. Further, it is informed by determinants, factors such as temperament and attachment style, that serve as a protective or risk function for the development of adaptive ER skills. We propose that the determinants associated with ER development that can be modified by a music intervention include physiological arousal (i.e., parasympathetic reactivity as measured by vagal tone), cognitive skills (specifically effortful control), and coregulation (both peer-peer and adult-peer). This can occur through both bottom-up and top-down neural mechanisms, specifically music's influence on physiologic arousal and attentional processes. As such, this intervention theory informs the design and delivery of the MCRF intervention components, including the specific and non-specific components of the intervention. The specific components define the active ingredients needed to produce the intended outcomes for preschooler ER development through the Therapeutic Function of Music (TFM) Plan, with an emphasis on the role of tempo in the intervention. Non-specific intervention components include the specific types of music experiences and interventionist facilitation techniques.</p>","PeriodicalId":12639,"journal":{"name":"Frontiers in Neuroscience","volume":"19 ","pages":"1568789"},"PeriodicalIF":3.2,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12277271/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Self-supervised learning analysis of multi-FISH labeled cell-type map in thick brain slices.","authors":"Weijie Zheng, Yiping An, Kang Li, Jinyue Wang, Jianqing Gao, Huawei Mu, Jin Tang, Hao Wang","doi":"10.3389/fnins.2025.1622950","DOIUrl":"10.3389/fnins.2025.1622950","url":null,"abstract":"<p><strong>Introduction: </strong>Accurate mapping of the spatial distribution of diverse cell types is essential for understanding the cellular organization of brain. However, the cellular heterogeneity and the substantial cost of manual annotation of cells in volumetric images hinder existing neural networks from achieving high-precision segmentation of multiple cell-types within a unified framework.</p><p><strong>Methods: </strong>To address this challenge, we introduce a self-supervised learning framework, Voxelwise U-shaped Swin-Mamba network (VUSMamba), for automatic segmentation of multiple neuronal populations in 300 μm thick brain slices. VUSMamba employs contrastive learning and pretext tasks for self-supervised learning on unlabeled data, followed by fine-tuning with minimal annotations. As a proof of concept, we applied the framework to a multi-cell-type dataset obtained using multiplexed fluorescence in situ hybridization (multi-FISH) combined with high-speed volumetric microscopy VISoR.</p><p><strong>Results: </strong>Compared to state-of-the-art baseline models, VUSMamba achieves higher segmentation accuracy with reduced computational cost. The framework enables simultaneous high-precision segmentation of glutamatergic neurons, GABAergic neurons, and nuclei.</p><p><strong>Discussion: </strong>This work presents a unified self-supervised neural network framework that offers a standardized pipeline for constructing and analyzing whole-brain cell-type atlases.</p>","PeriodicalId":12639,"journal":{"name":"Frontiers in Neuroscience","volume":"19 ","pages":"1622950"},"PeriodicalIF":3.2,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12277362/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vagal nerve signals are modulated by spontaneous seizures in Genetic Absence Epilepsy Rats from Strasbourg.","authors":"Elise Collard, Enrique Germany Morrison, Elena Acedo Reina, Ayse S Dereli, Auriane Apaire, Antoine Nonclercq, Riem El Tahry","doi":"10.3389/fnins.2025.1568261","DOIUrl":"10.3389/fnins.2025.1568261","url":null,"abstract":"<p><strong>Introduction: </strong>One-third of epileptic patients are resistant to conventional treatments. Vagus nerve stimulation is a promising therapy, especially when applied early during seizure onset. This study explores vagus nerve activity (VNA) during seizures in Genetic Absence Epilepsy Rat from Strasbourg (GAERS) model and explores how VNA changes with epilepsy duration.</p><p><strong>Methods: </strong>Eleven rats (4, 6, and 10 months old, <i>n = 4</i>, 4, 3, respectively) were continuously recorded with electroencephalography, VNA recordings, and video for 24 h. Ictal VNA root mean square (RMS) values preceded by NREM sleep extracted from 11 rats were studied in a total of 620 seizures.</p><p><strong>Results: </strong>Overall, VNA RMS increased during seizures, with a median rise of 60%. However, this modulation decreased with age, despite stable seizure severity. Significant differences in VNA activity and inter-quartile range were observed between age groups.</p><p><strong>Discussion: </strong>These results support seizure severity-dependent changes in ictal VNA modulation and point toward the potential of VNA as a biomarker for seizure detection and autonomic dysfunction.</p>","PeriodicalId":12639,"journal":{"name":"Frontiers in Neuroscience","volume":"19 ","pages":"1568261"},"PeriodicalIF":3.2,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12277265/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sensory-spinal neuron co-culture platform enables analysis of sensory-driven spinal activation.","authors":"Yuki Miyahara, Kenta Shimba, Kiyoshi Kotani, Yasuhiko Jimbo","doi":"10.3389/fnins.2025.1619340","DOIUrl":"10.3389/fnins.2025.1619340","url":null,"abstract":"<p><strong>Background: </strong>Pain plays a crucial role in selecting behaviors essential for survival. Nociceptive stimuli are converted into neuronal signals by dorsal root ganglion (DRG) neurons and transmitted via the spinal cord to the brain, where pain is perceived. Chronic pain, characterized by prolonged nociceptive signaling, significantly reduces the quality of life. Specifically, nociplastic pain arises due to heightened spinal neuronal activity. However, the mechanisms underlying this persistent increase remain unclear, impeding the development of effective treatments. Therefore, the present study aimed to develop an experimental platform to investigate how sensory neuron signals increase spinal neuronal activity.</p><p><strong>Methods: </strong>We developed a specialized microstructure enabling a separate culture of DRG and spinal neurons connected functionally by axons extending through microtunnels.</p><p><strong>Results: </strong>Immunofluorescence staining confirmed precise spatial separation and robust neuronal network formation. Microstructures were integrated with high-density microelectrode arrays to facilitate electrophysiological recordings during co-culture. Optogenetic stimulation of DRG neurons significantly activate the spinal neurons, which are not active spontaneously, and increase synchronous activity by 11.8-fold in the spinal neuronal network. Notably, elevated spinal neuron activity persisted for at least 20 min after stimulation ceased, indicating a prolonged neuronal response.</p><p><strong>Conclusion: </strong>This novel co-culture system provides a powerful tool for elucidating the pathogenic mechanisms underlying chronic pain, potentially guiding future therapeutic strategies.</p>","PeriodicalId":12639,"journal":{"name":"Frontiers in Neuroscience","volume":"19 ","pages":"1619340"},"PeriodicalIF":3.2,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12277374/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel potential neuroprotective targets for DengZhanXiXin injection in middle cerebral artery occlusion rats recommended by quantitative proteomics and simulated docking.","authors":"Min Li, Linshuang Wang, Haiting An, Xin Li, Yaojing Chen, Dongfeng Wei, Zhanjun Zhang","doi":"10.3389/fnins.2025.1499214","DOIUrl":"10.3389/fnins.2025.1499214","url":null,"abstract":"<p><p>Stroke, which leads to death and disability in high proportions globally, is one of the most deleterious neurological diseases. Ischemic stroke (IS) is the major cause of disease attack and accounts for ~70% of all incident stroke cases in China. Up to now, only two therapies for IS were officially approved, which are intravenous administration of recombinant tissue-plasminogen activator (rt-PA) and endovascular mechanical thrombectomy to rapidly recanalize the occluded artery, which both recanalize the occluded artery rapidly to reduce disability, but are limited in a fixed time window. In this study, the therapeutic effect of a traditional Chinese medicine, DengZhanXiXin injection (DZXI), was evaluated on middle cerebral artery occlusion (MCAO) rats at the neurobehavioral and pathophysiological levels through neurological tests, neurohistological staining, proteomic assay, and biological information analysis. We found that DZXI significantly ameliorated the neurological deficit, prevented infarct volume evolution, and protected cortical neural cells from death in ischemia penumbra on MCAO rats. Furthermore, corresponding therapeutic molecular targets were investigated through proteomic analysis of ischemic hemispheres of MCAO rats. One hundred ninety-one differentially expressed proteins involved in response to metal ions, neurofilament bundle assembly, and modulation of chemical synaptic transmission were identified between the MCAO model and DZXI groups after 7 days. DZXI influenced the expression levels of proteins in 13 specific biological functions, with cell signaling and chemical synaptic transmission-associated proteins being most affected. Subsequent molecular docking analysis predicted binding potential between key target proteins and DZXI compounds. The results suggested that DZXI ameliorates neurological deficits by potentially affecting cellular signaling and chemical synaptic transmission physiological processes.</p>","PeriodicalId":12639,"journal":{"name":"Frontiers in Neuroscience","volume":"19 ","pages":"1499214"},"PeriodicalIF":3.2,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12277316/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intraperitoneal administration of NMDA-Subunit NR1-receptor antibodies does not improve long-term outcome in a murine MCAo-stroke model.","authors":"Carolin Albrecht, Christoph Harms, Jakob Kreye, Matthias Endres, Susanne Mueller, Philipp Boehm-Sturm, Stefan Paul Koch, Dorette Freyer, Harald Prüss, Samuel Knauss","doi":"10.3389/fnins.2025.1614924","DOIUrl":"10.3389/fnins.2025.1614924","url":null,"abstract":"<p><p>Ischemic stroke is a major cause of disability worldwide, and current treatment is largely limited to thrombolytics. Therefore, additional therapeutic strategies are warranted. Previous evidence suggests that NMDA receptor antibodies targeting specific subunits may reduce excitotoxicity and lesion size. This study evaluates the effects of a specific NMDAR-NR1 antibody in both <i>in vitro</i> and <i>in vivo</i> models of ischemic stroke. Neuronal cultures were treated with NMDAR-NR1-AB, a control antibody (mGO-AB) or phosphate-buffered saline followed by NMDA exposure or oxygen-glucose deprivation (OGD). Cell death was measured by lactate dehydrogenase assay. NMDA and OGD significantly increased cell death, but NMDAR-NR1-AB did not exert neuroprotective effects <i>in vitro</i>. <i>In vivo</i>, C57BL/6J mice were subjected to middle cerebral artery occlusion (MCAo) for 45 min and treated intraperitoneally with NMDAR-NR1-AB or mGO-AB. Lesion size and neurobehavioral outcomes were assessed at 24 and 72 h and 28 days after MCAo. No differences in lesion sizes or long-term neuroprotective effects were evident at 24 h and 28 days post-MCAo. These findings underscore both the potential and limitations of targeting NMDAR-mediated excitotoxicity in ischemic stroke therapy and highlight the need for further research into the long-term efficacy of NMDAR-NR1-AB.</p>","PeriodicalId":12639,"journal":{"name":"Frontiers in Neuroscience","volume":"19 ","pages":"1614924"},"PeriodicalIF":3.2,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12277321/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An international questionnaire highlights and supports the case for including girls in Creatine Transporter Deficiency research.","authors":"Carole Chehowah, Audrey Mittelman, Vincent des Portes","doi":"10.3389/fnins.2025.1620586","DOIUrl":"10.3389/fnins.2025.1620586","url":null,"abstract":"<p><p>Over the last 15 years, significant progress has been made for Creatine Transporter Deficiency (CTD) patients, with increased awareness and visibility, better diagnosis, and improved care. Research projects have paved the way for clinical trials on the horizon. However, girls with CTD have been overlooked. Because they are considered a negligible cohort with less serious symptoms compared to males, girls with rare X-linked disorders have never been a priority for diagnosis and research. This results in underdiagnosis, systematic exclusion from clinical studies, and a considerable impact on the development of female patients. As a patient association, Xtraordinaire aims to counter these beliefs and to show that females deserve as much attention as males. Our first initiative identified girls with CTD within our community and led to the development of an international questionnaire to collect more specific data in this population. Of the 22 families who completed the questionnaire, the delay between symptom onset (mean age 1.8 years) and diagnosis (mean age 11.8 years) highlighted the difficulty of diagnosis for girls, often given several wavering diagnoses before reaching a CTD diagnosis. Almost half of families (47%) had difficulties securing a specialist appointment. Our questionnaire emphasized that girls with CTD have identical symptoms to males and similar delays in development milestones. These data have generated interest, and researchers have started to include girls in their studies. We strongly believe that upcoming studies on females will enrich our knowledge, further our understanding of CTD, help better diagnose girls, and develop adapted treatments.</p>","PeriodicalId":12639,"journal":{"name":"Frontiers in Neuroscience","volume":"19 ","pages":"1620586"},"PeriodicalIF":3.2,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12277310/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phase contrast-derived cerebral blood flow is associated with neurodegeneration and cerebrovascular injury in older adults.","authors":"Jeffrey D Pyne, Clarissa D Morales, A Zarina Kraal, Mohamad J Alshikho, Patrick J Lao, Indira C Turney, Erica Amarante, Rafael V Lippert, Julia F Chang, Jose Gutierrez, Jennifer J Manly, Richard Mayeux, Adam M Brickman","doi":"10.3389/fnins.2025.1538956","DOIUrl":"10.3389/fnins.2025.1538956","url":null,"abstract":"<p><p>Global cerebral blood flow and the local delivery of blood through the vascular network are essential to maintain brain and cognitive health throughout the lifespan. In this cross-sectional study, we examined the association of extracranial blood flow into the brain, measured with phase contrast magnetic resonance imaging, with regional brain volumes, cortical thickness, white matter tract integrity, white matter hyperintensity volume, and cerebral microbleeds. Our study included 311 older adults (mean age: 77 years, standard deviation: 5.6) from the Washington Heights Inwood Columbia Aging Project (WHICAP), a community-based study in northern Manhattan. We found that lower extracranial cerebral blood flow is associated with lower cortical regional volumes, lower white matter tract integrity, and higher white matter hyperintensity volume. We observed that lower extracranial cerebral blood flow, quantified by total, anterior, and posterior circulations, is associated with lower white matter tract integrity in the forceps minor, cingulum cingulate gyrus, and inferior fronto-occipital fasciculus. Additionally, lower total extracranial cerebral blood flow is associated with higher white matter hyperintensity volume, a marker of small vessel cerebrovascular disease. These findings support our hypothesis that lower extracranial cerebral blood flow is associated with a greater degree of vascular brain injury and indicators of neurodegeneration and are consistent with the guiding conceptual framework that diminished extracranial blood flow could be a factor that promotes or exacerbates neurodegeneration and cerebrovascular injury in older adults. Future longitudinal studies are needed to establish causality and temporality.</p>","PeriodicalId":12639,"journal":{"name":"Frontiers in Neuroscience","volume":"19 ","pages":"1538956"},"PeriodicalIF":3.2,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12271140/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144674529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}