Brain and Behavior最新文献

{"title":"Brain Microstructural Alteration and Its Implications for Postoperative Delirium in Elderly Surgical Patients: A Narrative Review","authors":"Yali Chen,&nbsp;Huanyu Luo,&nbsp;Jing Dong,&nbsp;Jun Zhang","doi":"10.1002/brb3.70872","DOIUrl":"10.1002/brb3.70872","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose</h3>\u0000 \u0000 <p>Postoperative delirium (POD) remains poorly understood in terms of predictors and underlying mechanisms. This review summarized emerging evidence on the association between brain microstructural alterations and POD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>This is a narrative review, describing the microstructural changes in aging brain, microstructural MRI findings, relationship among microstructural alterations, cognitive reserve and POD, and potential interventions targeting microstructure.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Finding</h3>\u0000 \u0000 <p>Brain microstructural alterations may predispose elderly patients to POD, with variability in microstructural alterations in gray/white matter organization potentially determining the fate of brain aging and performance of cognitive reserve. Advanced neuroimaging techniques could play a critical role in understanding the microstructural changes, enabling better prediction of POD and elucidation of its pathogenesis. Enhancing brain resilience to mitigate the adverse effects of surgical trauma may prove vital in preventing POD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Pre-existing brain microstructural alterations may be associated with subsequent development of POD, interventions targeting brain microstructure may decrease POD risk.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9081,"journal":{"name":"Brain and Behavior","volume":"15 9","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/brb3.70872","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cortical Structure Abnormalities in Patients With Noise-Induced Hearing Loss: A Surface-Based Morphometry Study","authors":"Yunxin Li,&nbsp;Ranran Huang,&nbsp;Aijie Wang,&nbsp;Liping Wang,&nbsp;Minghui Lv,&nbsp;Xianghua Bao,&nbsp;Guowei Zhang","doi":"10.1002/brb3.70813","DOIUrl":"https://doi.org/10.1002/brb3.70813","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To investigate the characteristics of brain structures in patients with noise-induced hearing loss (NIHL) using source-based morphometry (SBM) and to evaluate the correlation between abnormal brain regions and clinical data.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>High-resolution 3D T1 structural images were acquired from 81 patients with NIHL and 74 age- and education level-matched healthy controls (HCs). The clinical data of all subjects were collected, including noise exposure time, monaural hearing threshold weighted values (MTWVs), Mini-Mental State Examination (MMSE), and Hamilton Anxiety Scale (HAMA) scores. The FreeSurfer software was used to perform whole-brain SBM analysis based on T1 images. The cortical morphological parameters included cortical thickness, surface area, and cortical volume. The correlations between abnormal cortical morphological changes in brain regions and noise exposure time, MTWV (superiority), and HAMA scores were further analyzed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>SBM results: NIHL patients had a greater cortical thickness in the left inferior parietal gyrus (IPG) and right superior parietal gyrus (SPG) compared with HCs (<i>t</i> = 2.916, <i>p</i> = 0.0474; <i>t </i>= 2.916, <i>p</i> = 0.0046); increased surface area and cortical volume were observed both in the left lateral occipital gyrus (LOG) in NIHL patients (<i>t</i> = 3.468, <i>p </i>= 0.0377; <i>t</i> = 3.091, <i>p</i> = 0.0002). Correlation analysis revealed that MTWV (superiority) was positively correlated with noise exposure time (<i>r</i> = 0.260, <i>p = </i>0.019), and HAMA scores were negatively correlated with noise exposure time (<i>r</i> = −0.297, <i>p </i>= 0.007). Further, thicker cortical thickness in the left IPG and right SPG and increased cortical volume in the left LOG were negatively correlated with MTWV (superiority) (<i>r</i> = −0.238, <i>p</i> <i>=</i> 0.032; <i>r</i> = −0.255, <i>p</i> <i>=</i> 0.022; <i>r</i> = −0.272, <i>p</i> <i>=</i> 0.014). Increased cortical volume in the left LOG had a positive correlation with HAMA scores (<i>r</i> = 0.172, <i>p</i> <i>=</i> 0.032).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>On the basis of the SBM method, we have discovered alterations in cortical morphology within the auditory–visual network regions such as the parietal and occipital lobes in NIHL patients. These findings suggest that auditory deprivation may initiate the restructuring of the auditory–visual cortex, providing new insights into the underlying mechanisms of brain ","PeriodicalId":9081,"journal":{"name":"Brain and Behavior","volume":"15 9","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/brb3.70813","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145022181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dissecting the Causal Association Between Bulimia Nervosa and Structural Brain Abnormalities: A Two-Sample Bidirectional Mendelian Randomization Study","authors":"Weihua Li,&nbsp;Xinghao Wang,&nbsp;Yiling Wang,&nbsp;Jiani Wang,&nbsp;Xinyu Huang,&nbsp;Marcin Grzegorzek,&nbsp;Qian Chen,&nbsp;Zhenchang Wang,&nbsp;Peng Zhang,&nbsp;Lirong Tang","doi":"10.1002/brb3.70859","DOIUrl":"10.1002/brb3.70859","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Diverse correlations between structural brain abnormalities and the clinical feature of bulimia nervosa (BN) have been identified in previous observational studies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To explore the bidirectional causality between BN and brain structural magnetic resonance imaging (MRI) phenotypes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Genome-wide association studies (GWAS) of 2441 participants identified genetic variants associated with disordered eating and predicted BN, whereas UK Biobank 3D-T1 MRI data were used to analyze brain structural phenotypes. A bidirectional two-sample Mendelian randomization (MR) approach was used to investigate the causal relationships between BN and brain structural traits.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The forward MR analysis showed that BN exerted a significant causal effect on decreased volume of left nucleus accumbens area (NAc), decreased surface area (SA) of left inferior temporal gyrus, and increased cortical thickness (CT) of left planum temporale and right inferior temporal gyrus. In the reverse MR analysis, we found that right putamen volume, left hippocampus volume, and right planum temporale gyrus CT were positively associated with BN risk. Besides, SA of right inferior temporal gyrus and left lateral orbital gyrus and CT of left superior occipital gyrus were inversely correlated with BN risk.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings confirmed the potential causal effects of BN on brain structure changes involving multiple functional regions and identified that genetically determined variation in specific brain structural regions could be causal for BN to some extent.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9081,"journal":{"name":"Brain and Behavior","volume":"15 9","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/brb3.70859","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiple Demographic, Lifestyle, and Biological Factors Associated With Brain Iron Deposition in the Basal Ganglia: A Comprehensive Analysis of 25,980 UK Biobank Participants","authors":"Pengcheng Liang,&nbsp;Linfeng Yang,&nbsp;Yiwen Chen,&nbsp;Zhenyu Cheng,&nbsp;Yian Gao,&nbsp;Chaofan Sui,&nbsp;Xinyue Zhang,&nbsp;Na Wang,&nbsp;Yuanyuan Wang,&nbsp;Changhu Liang,&nbsp;Lingfei Guo","doi":"10.1002/brb3.70862","DOIUrl":"10.1002/brb3.70862","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The susceptibility values of the basal ganglia reflect the health status of these nuclei. We aimed to explore the associations between various demographic characteristics, lifestyle factors, and biological factors that have the potential to contribute to magnetic susceptibility and investigate the comprehensive impact of these multiple factors on basal ganglia susceptibility values.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;We included 25,980 participants from the UK Biobank. Linear regression analysis was employed to assess the relationship between basal ganglia susceptibility values and demographic characteristics (age, sex, ethnicity), lifestyle factors (tea consumption, coffee intake, smoking status, alcohol consumption, physical activity, insomnia status), and biological factors (C-reactive protein, blood cell counts, anthropometric measures, blood pressure parameters).&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Multiple factors demonstrated significant associations with basal ganglia iron deposition. Among biological factors, C-reactive protein showed significant positive correlations with susceptibility values in the caudate nucleus (&lt;i&gt;β&lt;/i&gt; = 0.028, &lt;i&gt;p&lt;/i&gt; &lt; 0.001), globus pallidus (&lt;i&gt;β&lt;/i&gt; = 0.046, &lt;i&gt;p&lt;/i&gt; &lt; 0.001), and substantia nigra (&lt;i&gt;β&lt;/i&gt; = 0.031, &lt;i&gt;p&lt;/i&gt; &lt; 0.001). Waist circumference, another biological measure, had substantial positive effects on most basal ganglia regions (&lt;i&gt;β&lt;/i&gt; = 0.115 in caudate, &lt;i&gt;β&lt;/i&gt; = 0.122 in putamen, &lt;i&gt;β&lt;/i&gt; = 0.058 in globus pallidus). Among lifestyle factors, current smoking status was significantly associated with increased susceptibility values across all four basal ganglia nuclei (&lt;i&gt;β&lt;/i&gt; = 0.053–0.061, all &lt;i&gt;p&lt;/i&gt; &lt; 0.001). Tea consumption demonstrated dose-dependent protective effects, with daily consumption of ≥ 4 cups showing significant negative associations with all basal ganglia regions (−0.032 to −0.093 standard deviations). Age demonstrated significant positive associations with most basal ganglia regions. Gender differences were observed in tea consumption effects, with females showing stronger protective benefits (5.59 vs. 1.50 years of equivalent “rejuvenation” effect for 0–3 cups daily).&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusions&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;We provide evidence for multiple demographic, lifestyle, and biological factors influencing brain iron deposition in healthy middle-aged and elderly individuals. Systemic inflammation, smoking, and increased adiposity were associated with greater iron deposition, while tea consumpti","PeriodicalId":9081,"journal":{"name":"Brain and Behavior","volume":"15 9","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/brb3.70862","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Hypometabolic State of the Migraine Brain: Is a Ketogenic Diet the Answer?","authors":"Lakshini Gunasekera,&nbsp;Jason C. Ray,&nbsp;Helmut Butzkueven,&nbsp;Terence J. O'Brien,&nbsp;Elspeth Hutton,&nbsp;Neha Kaul","doi":"10.1002/brb3.70860","DOIUrl":"10.1002/brb3.70860","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Migraine pathophysiology involves a constellation of metabolic abnormalities. These interlinked contributory factors include mitochondrial dysfunction, an altered gut microbiome, neuroinflammation, oxidative stress, weight imbalance, and altered glucose metabolism. The ketogenic diet is an emerging therapy which may restore hypometabolism seen in chronic migraine. We describe contributions of metabolic dysfunction to chronic migraine pathophysiology and discuss the role of ketogenic diet therapy to improve cerebral metabolism.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A literature search of articles from OVID Medline, Embase, and Cochrane Library were reviewed until May 6, 2024. A total of 50 articles were included comprising case reports, case series, observational clinical trials, and narrative review articles.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Migraine pathophysiology involves significant hypometabolism, seen on functional imaging studies, so therapeutics which target these underlying deficiencies may ameliorate chronic migraine symptoms. The ketogenic diet reduces migraine days, pain intensity, and acute analgesic use. Current studies are limited by small sample sizes, inconsistent methodology precluding direct comparison between studies or pooling of results, and limited longitudinal follow-up.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>While there is biological plausibility to reason that a ketogenic diet could correct metabolic mismatch in people with migraine, further randomized clinical trials with larger sample sizes are required to confirm the positive results of preliminary, uncontrolled studies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9081,"journal":{"name":"Brain and Behavior","volume":"15 9","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/brb3.70860","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Causal Effects of Immune Cell Populations on Cognitive Performance: A Mendelian Randomization Study","authors":"Jingfeng Fu,&nbsp;Minmin Yang,&nbsp;Qingteng Zheng","doi":"10.1002/brb3.70861","DOIUrl":"10.1002/brb3.70861","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Recent research has started to uncover an important connection between immune system activity and cognitive abilities. Although correlative associations have been documented, the causal mechanisms connecting specific immune cell subpopulations to cognitive capabilities remain insufficiently characterized. Our research aimed to determine directional relationships between distinct immune cell subtypes and cognitive function, potentially identifying targets for immunomodulatory interventions.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;We performed a two-sample Mendelian randomization (MR) analysis using genome-wide association study data from 3757 Sardinian individuals, paired with detailed immunophenotyping. We also incorporated cognitive performance summary statistics from the cohort described by Lee et al. (&lt;i&gt;n&lt;/i&gt; = 257,841). Our analytical strategy utilized various MR techniques, with inverse variance weighted analysis serving as the primary method. To confirm result reliability, we conducted sensitivity analyses, including weighted median estimation, mode-based approaches, MR-Egger regression for evaluating pleiotropic effects, MR-PRESSO for outlier identification, and Cochran's &lt;i&gt;Q&lt;/i&gt;-statistic to examine heterogeneity. Additionally, to explore possible reverse causation mechanisms, we conducted bidirectional MR analyses.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Post false discovery rate (FDR) correction (&lt;i&gt;P&lt;/i&gt;&lt;sub&gt;FDR&lt;/sub&gt; &lt; 0.05), we identified two immune cell phenotypes significantly linked to cognitive performance. &lt;i&gt;IgD&lt;sup&gt;−&lt;/sup&gt; CD27&lt;sup&gt;−&lt;/sup&gt; B cells %lymphocyte&lt;/i&gt; showed a positive correlation with cognitive outcomes (&lt;i&gt;β&lt;/i&gt; = 0.04, 95% confidence interval [CI]: 0.02–0.06, &lt;i&gt;P&lt;/i&gt;&lt;sub&gt;FDR&lt;/sub&gt; = 3.02 × 10^&lt;sup&gt;−2&lt;/sup&gt;), whereas &lt;i&gt;unswitched memory B cells %lymphocyte&lt;/i&gt; demonstrated negative association (&lt;i&gt;β&lt;/i&gt; = −0.06, 95% CI: −0.09 to −0.03, &lt;i&gt;P&lt;/i&gt;&lt;sub&gt;FDR&lt;/sub&gt; = 3.02 × 10^&lt;sup&gt;−2&lt;/sup&gt;). When applying stricter statistical thresholds (&lt;i&gt;p&lt;/i&gt; &lt; 0.005), five distinct immune subpopulations demonstrated significant relationships: among B-lymphocytes (&lt;i&gt;IgD&lt;/i&gt;&lt;sup&gt;−&lt;/sup&gt; &lt;i&gt;CD27&lt;/i&gt;&lt;sup&gt;−&lt;/sup&gt; &lt;i&gt;B cells&lt;/i&gt;, &lt;i&gt;CD27&lt;sup&gt;+&lt;/sup&gt; memory B cells&lt;/i&gt;, and &lt;i&gt;CD38&lt;sup&gt;+&lt;/sup&gt; transitional B cells&lt;/i&gt;), T-lymphocytes (&lt;i&gt;CCR7&lt;sup&gt;+&lt;/sup&gt; naive CD4&lt;sup&gt;+&lt;/sup&gt; T cells&lt;/i&gt;), and mononuclear phagocytes (&lt;i&gt;HLA-DR&lt;sup&gt;+&lt;/sup&gt; CD14&lt;sup&gt;−&lt;/sup&gt; CD16&lt;sup&gt;−&lt;/sup&gt; cells&lt;/i&gt;). These findings reveal distinct immunophenotypic signatures potentially influencing cognitive function through various cellular pathways. Importantly, bidirectional MR analyses revealed no significa","PeriodicalId":9081,"journal":{"name":"Brain and Behavior","volume":"15 9","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/brb3.70861","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cognitive Compensation Depends on Frontoparietal Network Structure–Function Coupling in Patients With White Matter Hyperintensity","authors":"Xiao Zhu,&nbsp;Yifei Li,&nbsp;Ying Zhou,&nbsp;Yaode He,&nbsp;Haiwei Huang,&nbsp;Huihong Ke,&nbsp;Jianzhong Sun,&nbsp;Min Lou","doi":"10.1002/brb3.70871","DOIUrl":"10.1002/brb3.70871","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Purpose:</h3>\u0000 \u0000 <p>White matter hyperintensity (WMH) impairs cognitive function but is not evident in the early stage, raising the need to explore the underlying mechanism. We aimed to investigate the potential role of network structure–function coupling (SC–FC coupling) in cognitive performance of WMH patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods:</h3>\u0000 \u0000 <p>A total of 617 participants with WMH (mean age = 61 [SD = 8]; 287 females [46.5%]) were retrospectively included from the Cognitive Impairment, Retinopathy, and Cerebrovascular Lesions in the Elderly (CIRCLE) study who underwent multimodal MRI and comprehensive cognitive assessments. Severe WMH was defined as periventricular WMH with a Fazekas score of 3 and/or deep WMH with Fazekas score ≥ 2; otherwise it was defined as mild WMH. The network SC-FC coupling was derived from diffusion tensor imaging and functional MRI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results:</h3>\u0000 \u0000 <p>Across networks, the frontoparietal network exhibited the lowest SC–FC coupling, while the somatomotor network was the highest. Within the mild WMH subgroup, only frontoparietal network SC–FC coupling was positively correlated with WMH volume (<i>β</i> = 0.136, <i>p</i> = 0.014), a pattern not observed in the whole cohort and the severe WMH subgroup (all <i>p</i> &gt; 0.05). Furthermore, in the mild WMH subgroup, frontoparietal network SC–FC coupling was also positively correlated with cognitive performance on the digit span forward task, both in cross-sectional (<i>β</i> = 0.110, <i>p</i> = 0.023) and longitudinal analyses (<i>β</i> = 0.245, <i>p</i> = 0.038).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions:</h3>\u0000 \u0000 <p>Overall, the frontoparietal network SC–FC coupling may contribute to cognitive compensation during the mild stage of WMH and could be a target for interventions aimed at preserving cognitive abilities.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9081,"journal":{"name":"Brain and Behavior","volume":"15 9","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/brb3.70871","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Relationship Between Human Cerebrospinal Fluid Proteins and the Risk of Delirium: A Study Based on Genetic Data","authors":"Zhihui Xu,&nbsp;Fei Ye,&nbsp;Zhantang Yuan,&nbsp;Chiyi Liu,&nbsp;Simin Zhu,&nbsp;Binfei Li,&nbsp;Qibiao Wu","doi":"10.1002/brb3.70836","DOIUrl":"https://doi.org/10.1002/brb3.70836","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Delirium is an acute cognitive disturbance that is linked to increased healthcare costs, extended hospitalization, and a greater incidence of adverse outcomes, including cognitive decline. Despite its clinical importance, existing strategies for predicting and managing delirium remain inadequate. This study, therefore, sought to investigate the potential relationship between cerebrospinal fluid proteins and delirium via Mendelian randomization (MR) and to identify potential therapeutic targets.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Genetic data related to delirium were obtained from the 11th iteration of the FinnGen Biobank, which includes a total of 431,880 individuals of Finnish ancestry consisting of 3827 cases and 428,053 controls. Data on 910 cerebrospinal fluid proteins from 970 samples were collected via the ONTIME platform (https://ontime.wustl.edu/hg38/). MR analysis was used to evaluate genetic associations between cerebrospinal fluid proteins and delirium. Additionally, enrichment analysis was performed on cerebrospinal fluid proteins with genetic associations to identify potential cellular pathways and therapeutic targets.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;We identified 46 cerebrospinal fluid proteins associated with the occurrence of delirium. Among these, insulin (odds ratio [OR]: 1.35, 95% confidence interval [CI]: 1.07–1.70, &lt;i&gt;p&lt;/i&gt; = 0.01), interleukin-7 (OR: 0.56, 95% CI: 0.37–0.85, &lt;i&gt;p&lt;/i&gt; = 0.01), and B-cell lymphoma/leukemia 2-like protein 1 (OR: 0.63, 95% CI: 0.45–0.88, &lt;i&gt;p&lt;/i&gt; = 0.01) were identified as key proteins. Horizontal pleiotropy had a minimal impact on establishing causal relationships, with &lt;i&gt;p&lt;/i&gt; values of 0.08, 0.26, and 0.32, respectively. Additionally, no evidence of heterogeneity in genetic variation was found between these three cerebrospinal fluid proteins and delirium, with &lt;i&gt;p&lt;/i&gt; values of 0.07, 0.45, and 0.96, respectively. Leave-one-out analysis further confirmed the stability and robustness of these associations. The enrichment analysis indicated that the cytokine-mediated signaling pathway plays a significant role in the pathogenesis of delirium.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusion&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Our study identified a genetic causal relationship between specific cerebrospinal fluid proteins and delirium, with insulin being a key factor. We also found that cytokine-mediated signaling pathways may contribute to the pathophysiology of delirium. Future research should focus on the roles of peripheral and central glucose metabolism, as well a","PeriodicalId":9081,"journal":{"name":"Brain and Behavior","volume":"15 9","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/brb3.70836","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145021803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential Causal Relationships Between Circulating Micronutrient Levels and Multiple Neuroimmune Diseases: A Genetic Association Analysis","authors":"Longhao Chen,&nbsp;Xuzhou Wu,&nbsp;Kaizheng Wang,&nbsp;Xingchen Zhou,&nbsp;Yika Mou,&nbsp;Zhen Liu,&nbsp;Zhifang Shen,&nbsp;Zhizhen Lv,&nbsp;Lijiang Lv","doi":"10.1002/brb3.70848","DOIUrl":"https://doi.org/10.1002/brb3.70848","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Growing evidence suggests a close association between circulating micronutrient levels and neuroimmune diseases. Nevertheless, the causal relationship between them remains unclear. Furthermore, due to confounding factors, many micronutrients implicated in these diseases remain unidentified. This study aimed to determine the causal relationship between circulating micronutrients and neuroimmune diseases through genetic association analysis, and to analyze the regulatory role of circulating micronutrients in neuroimmune diseases.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>In this study, we used a two-sample mendelian randomization (MR) analysis to explore the causal relationship between micronutrients levels and neuroimmune disease. Fourteen micronutrients were screened from a published genome-wide association study (GWAS). Neuroimmune diseases include multiple sclerosis (MS), Guillain–Barre syndrome (GBS), acute disseminated encephalomyelitis (ADEM), acute poliomyelitis (AP), sequelae of poliomyelitis (SP), optic neuritis (ON), and myasthenia gravis (MG). Data on these seven neuroimmune diseases came from the FinnGen database and included 5523 cases and 2,860,006 controls. The inverse variance weighting (IVW) method was used as the main MR analysis method, and sensitivity analysis was performed to determine MR hypotheses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Through MR analysis and sensitivity testing, we identified significant causal relationships between four neuroimmune diseases and micronutrient levels. Specifically, MS was causally associated with magnesium levels (OR: 0.467, 95% CI: 0.269–0.809, <i>p</i> = 0.007), ADEM with folate levels (OR: 0.022, 95% CI: 0.001–0.957, <i>p</i> = 0.047), ON with vitamin B6 levels (OR: 0.382, 95% CI: 0.187–0.778, <i>p</i> = 0.008), and MG with iron levels (OR: 0.194, 95% CI: 0.043–0.867, <i>p</i> = 0.032). Sensitivity analysis showed that there was no level pleiotropic or heterogeneity in our study results.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study established the causal relationship between micronutrients and neuroimmune diseases. These findings provide new insights into the etiology of neuroimmune diseases and provide a theoretical basis for micronutrient regulation, prevention, and treatment of neuroimmune diseases.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9081,"journal":{"name":"Brain and Behavior","volume":"15 9","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/brb3.70848","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145022277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systematic Exploration of Potential Druggable Genes for Ischemic Stroke Employing Genome-Wide Mendelian Randomization Analysis","authors":"Peng Zhang,&nbsp;Yulu He,&nbsp;Qing Zhen,&nbsp;Yan Zhang","doi":"10.1002/brb3.70857","DOIUrl":"https://doi.org/10.1002/brb3.70857","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Ischemic stroke (IS) treatment remains a significant challenge. This study aimed to identify potential druggable genes for IS using a systematic druggable genome-wide Mendelian Randomization (MR) analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Two-sample MR analysis was conducted to identify the causal association between potential druggable genes and IS. This involved integrating data from the druggable genome, expression quantitative trait loci (eQTL), protein quantitative trait loci (pQTL), and genome-wide association study summary data of IS. Sensitivity and Bayesian colocalization analyses were used to validate the causal relationships. In addition, phenome-wide MR analysis was used to evaluate the side effects or other indications of the identified druggable genes, and their functions were explored using the Metascape database.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our MR analysis identified 16 potential druggable genes significantly associated with IS, three of which were significant in the two QTL datasets. Colocalization analysis revealed six druggable genes (two in the blood eQTL [<i>CALCRL, KCNJ11</i>], two in the brain eQTL [<i>NEK3, THSD1</i>], one in the blood pQTL [<i>MMP12</i>], and one in the brain pQTL [<i>HSD17B12</i>]) had a PP.H4 greater than 0.75. Phenome-wide MR analysis indicated that <i>CALCRL</i> is correlated with benign breast neoplasms, and <i>HSD17B12</i> is associated with essential hypertension and hypertension.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study identified six potential druggable genes (<i>CALCRL</i>, <i>KCNJ11</i>, <i>NEK3</i>, <i>THSD1</i>, <i>MMP12</i>, and <i>HSD17B12</i>) associated with IS risk. Further research is required to explore the specific roles of these druggable genes in the onset and progression of IS.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9081,"journal":{"name":"Brain and Behavior","volume":"15 9","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/brb3.70857","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145021877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}