Brain communications最新文献

{"title":"The metabolic debt model: cumulative bioenergetic burden and network vulnerability in brain disorders-a hypothesis article.","authors":"Effiong N Effiong, Daniel M Gimbason, Yakubu B Ngwai, Julius B Gajere","doi":"10.1093/braincomms/fcag359","DOIUrl":"10.1093/braincomms/fcag359","url":null,"abstract":"<p><p>Effiong <i>et al</i>. propose the Metabolic Debt Model, a hypothesis-generating framework that links four metabolic constraints, phosphocreatine buffering, astrocyte-neuron coupling, mitochondrial flexibility and nicotinamide adenine dinucleotide⁺-dependent recovery to network-level dysfunction and clinical symptoms in myalgic encephalomyelitis and long coronavirus diseases.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"8 5","pages":"fcag359"},"PeriodicalIF":4.5,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13673110/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149217373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic connectivity and memory in mesial temporal lobe epilepsy.","authors":"Ondřej Strýček, Pavel Říha, Martin Kojan, Eva Brichtová, Zuzana Hummelová, Zdeněk Řehák, Milan Brázdil","doi":"10.1093/braincomms/fcag365","DOIUrl":"https://doi.org/10.1093/braincomms/fcag365","url":null,"abstract":"<p><p>Memory decline after anterior mesial temporal resection in mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) remains incompletely explained by structural and clinical factors, suggesting that networks may contribute to cognitive vulnerability. We investigated whether presurgical metabolic connectivity (MC), derived from fluorodeoxyglucose positron emission tomography (FDG-PET) and reflecting metabolic network organization, is associated with memory performance and postsurgical cognitive outcome in MTLE-HS. We studied 83 patients with MTLE-HS who underwent anterior mesial temporal resection. All had interictal FDG-PET and pre- and postsurgical neuropsychological testing. MC was computed using a normative connectivity framework and examined in relation to memory performance, analysed separately for left and right TLE. The effect of resection extent on cognitive outcome was also assessed. Presurgical analyses revealed distinct lateralized patterns. In right temporal lobe epilepsy (RTLE), immediate visual memory correlated positively with MC across widespread fronto-cingulate-temporal networks, frequently including the lesional hippocampus. In left temporal lobe epilepsy (LTLE), immediate verbal memory showed only negative correlations with extratemporal MC. In RTLE, presurgical MC also correlated with postsurgical change in immediate visual memory. Predominantly negative associations involved ipsilateral hippocampal-cingulate and fronto-temporal pathways, whereas positive correlations were confined to contralateral posterior cingulate connections with frontal and temporal regions. In LTLE, no significant correlations with postsurgical memory change were identified. Extent of resection did not correlate with cognitive outcome. MC was significantly associated with memory performance in MTLE-HS, showing clear lateralized differences. In RTLE, presurgical MC was associated with postsurgical outcome: ipsilateral hippocampal-cingulate connectivity was linked to decline, whereas contralateral posterior cingulate pathways supported preservation. No such associations were found in LTLE, consistent with more constrained network reorganization within left-lateralized verbal memory systems. These effects were independent of resection extent, indicating that memory prognosis after AMTR in RTLE may depend on network-level mechanisms and that FDG-PET-derived MC could serve as a biomarker for cognitive risk assessment.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"8 5","pages":"fcag365"},"PeriodicalIF":4.5,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13663807/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149198472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Longitudinal associations between physical activity and cognition post-stroke: the Nor-COAST study.","authors":"Geske Luzum, Stina Aam, Heather G Allore, Ingvild Saltvedt, Asta K Håberg, Torunn Askim","doi":"10.1093/braincomms/fcag367","DOIUrl":"10.1093/braincomms/fcag367","url":null,"abstract":"<p><p>Previous research has been inconsistent regarding the longitudinal relationship between physical activity and cognition after a stroke. In this study, we hypothesized that (i) higher levels of objectively measured daily step counts would be associated with better cognitive function at a group level (between-person level), and (ii) at an individual level, changes from expected step counts would be bi-directionally associated with changes from expected cognitive performance (within-person level) at the same and subsequent time points. We used data from 468 participants of the Norwegian Cognitive Impairment after Stroke study (Nor-COAST), a large multicentre cohort study with follow-up at 3, 18 and 36 months post-stroke. At each follow-up, average step count over 7 days was recorded using accelerometers, and cognitive performance was assessed with the Montreal Cognitive Assessment (MoCA), the Trail Making Test A and B (TMT-A, TMT-B), and the Word List Memory and Recall Test (delayed recall). Adjusted random intercept cross-lagged panel models (RI-CLPMs) were implemented. One RI-CLPM was built for each cognitive outcome, separating between- from within-person associations. To balance baseline characteristics of included and excluded participants in Nor-COAST and to account for selection bias, inverse probability weighting was performed using age, sex, and baseline functional independence. Between-persons, we found a time-invariant association between step count and TMT-A (<i>β</i> = 0.24, 95% CI: 0.09 to 0.40) and TMT-B (<i>β</i> = 0.22, 95% CI: 0.09 to 0.34); after correcting for multiple comparison the association with MoCA was not significant (<i>β</i> = 0.14, 95% CI: 0.01 to 0.28), and there was no association with the Word List Memory and Recall Test (<i>β</i> = 0.09, 95% CI: -0.04 to 0.22). At the within-person level, we observed neither cross-sectional nor cross-lagged associations between step count and any of the cognitive tests. The RI-CLPM fitted the data appropriately and had robust testing models with and without inverse probability weighting. After a stroke, people who, on average, took more steps tended to also perform better on TMT-A and TMT-B scores. However, at an individual level, a person who walked more (or had better cognitive scores) than expected did not have a higher likelihood of also performing better on cognitive tests (or walking more) than their expected average, respectively. Therefore, the observed association between step count and cognitive function after stroke might be explained by consistent individual differences over time, rather than by temporary changes within an individual's typical level of physical activity or cognition.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"8 5","pages":"fcag367"},"PeriodicalIF":4.5,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13655615/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149170567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Arachidonic and docosahexaenoic acid supplementation affects white matter microstructure in preterm infants.","authors":"Gunnthorunn Gunnarsdottir, Ivan I Maximov, Oliver Marcel Geier, Tone Nordvik, Anette Ramm-Pettersen, Tom Stiris, Sissel J Moltu, Helle Cecilie Viekilde Pfeiffer","doi":"10.1093/braincomms/fcag362","DOIUrl":"https://doi.org/10.1093/braincomms/fcag362","url":null,"abstract":"<p><p>Arachidonic acid and docosahexaenoic acid are long-chain polyunsaturated fatty acids that serve as key structural components of neuronal cell membranes and exhibit anti-inflammatory properties. They accumulate most rapidly during the third trimester of pregnancy, leaving very preterm infants deprived at birth. We conducted a double-blind randomized controlled trial comparing arachidonic and docosahexaenoic acid supplementation to medium chain triglycerides oil and assessed effects on white matter maturation using advanced diffusion imaging techniques. We used tract-based spatial statistics to localize significant changes across major tracts. Diffusion kurtosis imaging and Bayesian rotation invariant approach were applied to describe white matter microstructure within the intra- and extra-axonal water compartments enabling a more detailed characterization of tissue changes. These advanced diffusion MRI data were acquired at term-equivalent age for 64 infants born before 29 weeks of gestation, including 33 in the supplemented group and 31 in the control group. We identified significantly higher fractional anisotropy and lower radial diffusivity in several white matter regions in the supplemented group, mostly pronounced in areas that myelinate early. There were no significant differences in diffusion kurtosis imaging metrics between the two groups, but the Bayesian rotational invariant approach revealed several significant differences. This might illustrate a different developmental trajectory in the supplemented group compared to the control group. Applying advanced diffusion models can potentially provide a deeper understanding of early brain development and facilitate opportunities for early detection and intervention for preterm children.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"8 5","pages":"fcag362"},"PeriodicalIF":4.5,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13663797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149198439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correlation of blood biomarkers with microstructural brain injury in survivors of out-of-hospital cardiac arrest.","authors":"Mikael V Laaksonen, Jussi P Posti, Carita C Hollmén, Kaj Blennow, Henrik Zetterberg, Jaakko K Rinne, Sami M Virtanen, Jani P Saunavaara, Riitta K Parkkola, Ruut M Laitio, Olli J Arola, Marja S Hynninen, Emmi K Ylikoski, Juha A Martola, Marjaana S Tiainen, Risto O Roine, Harry Scheinin, Mervyn Maze, Timo Roine, Tero Vahlberg, Timo T Laitio","doi":"10.1093/braincomms/fcag378","DOIUrl":"10.1093/braincomms/fcag378","url":null,"abstract":"<p><p>In-hospital mortality among resuscitated out-of-hospital cardiac arrest (OHCA) patients remains high. Identifying patients who will benefit from intensive care while avoiding prolonged, potentially unnecessary treatments is essential. Blood-based biomarkers provide a novel method for evaluating brain injury. The ability of glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), neuron-specific enolase (NSE) and total-tau (t-tau) to measure white and grey matter injury is unestablished in comatose OHCA survivors treated with targeted temperature management (TTM) or xenon combined with TTM. We examined correlations between the biomarkers and white and grey matter injury assessed with diffusion tensor imaging (DTI). This was a randomized, single-blind, phase 2 clinical drug trial involving two multipurpose intensive care units in Finland. It was conducted between August 2009 and March 2015. One hundred and ten comatose OHCA patients aged 24 to 76 years were randomly assigned to either inhaled xenon treatment combined with 24-h TTM (33°C) (<i>n</i> = 55, xenon group) or TTM alone (<i>n</i> = 55, control group). MRI data were available from 96 patients, with a median imaging time of 53 h (interquartile range, 47-64 h) after OHCA. Biomarker data were obtained from 105 patients. In the control group of 48 patients, after adjusting for age, sex and site, a disruption of white matter microintegrity as measured by decreased fractional anisotropy (FA) of DTI, the primary endpoint of the trial, showed a significant negative correlation with NfL at 24, 48 and 72 h (ρ = -0.28 to -0.37; <i>P</i> < 0.05), NSE at 48 and 72 h (ρ = -0.30 to -0.35; <i>P</i> < 0.05) and t-tau only at 72 h (ρ = -0.30; <i>P</i> < 0.05). In the xenon group (<i>n</i> = 48), these correlations were absent at all timepoints. The NfL-FA partial correlations showed progressive divergence between the xenon and control groups, with a statistically significant between-group difference observed at 72 h (ρ = -0.37 versus ρ = 0.14; <i>P</i> = 0.016). Cortical or basal ganglia grey matter mean diffusivity did not have a consistent correlation with biomarker levels at different time points. No statistically significant differences were found between the xenon and control groups in the adjusted geometric mean levels of GFAP, NfL, NSE or t-tau at various time points following OHCA. In conclusion, NfL correlated with FA in controls but not in the xenon group. This between-group difference reached significance at 72 h, suggesting that xenon may modify the relationship between axonal injury and white matter microstructure after OHCA.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"8 5","pages":"fcag378"},"PeriodicalIF":4.5,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13673109/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149217442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of brain-derived versus conventional pTau biomarkers in CSF and plasma for detecting Alzheimer's disease.","authors":"Lydia Trudel, Joseph Therriault, Valentina Ghisays, Arthur C Macedo, Serge Gauthier, Paolo Vitali, Andrea L Benedet, Henrik Zetterberg, Yi Su, Alpana Singh, Tainá Marques, Marisa N Denkinger, Nicholas T Seyfried, Allan I Levey, Michael W Weiner, Kendall Van Keuren-Jensen, Eric M Reiman, Nicholas J Ashton, Pedro Rosa-Neto","doi":"10.1093/braincomms/fcag376","DOIUrl":"10.1093/braincomms/fcag376","url":null,"abstract":"<p><p>Brain-derived phosphorylated tau species are postulated to improve the detection of Alzheimer's disease pathology by mitigating non-specific increases. However, their true diagnostic performance, relative to conventional CSF and plasma phosphorylated tau assays, remains uncharacterized. The objective was to compare the diagnostic performance of brain-derived and conventional phosphorylated tau assays across multiple analytes (phosphorylated tau 181, phosphorylated tau 217, phosphorylated tau 231) in CSF and plasma, and to examine biomarker differences across amyloid-β status and cognitive groups. This study included 1098 participants with amyloid-PET imaging and CSF samples from the Alzheimer's Disease Neuroimaging Initiative, and a subset of 925 individuals with plasma samples. Diagnostic performance of brain-derived and conventional phosphorylated tau assays was assessed by receiver operating characteristic curves, with calculation of area under the curve, sensitivity, specificity and optimal cutpoints. Associations with amyloid-β burden were evaluated using Spearman correlations, and fold-changes between amyloid-PET-positive and amyloid-PET-negative participants were computed in cognitively unimpaired and cognitively impaired subgroups with 95% confidence intervals from 2000 bootstrap resamples. Brain-derived phosphorylated tau assays showed significantly higher diagnostic performance than conventional phosphorylated tau assays at the same phosphorylation site in both CSF and plasma in the overall sample and in cognitively impaired individuals, except for CSF phosphorylated tau 217. While CSF brain-derived phosphorylated tau correlations with amyloid-PET were similar to conventional CSF assays, pairwise comparisons using DeLong's test revealed significantly higher diagnostic accuracy for brain-derived assays. Receiver operating characteristic performance was generally better in cognitively impaired participants than in cognitively unimpaired participants. Additionally, using a three-range method with cutpoints corresponding to 90% sensitivity and 90% specificity, plasma brain-derived phosphorylated tau 181, phosphorylated tau 217 and brain-derived phosphorylated tau 217 had <20% of participants in the intermediate range overall and in cognitively impaired individuals. In summary, brain-derived phosphorylated tau assays improve detection of amyloid-β positivity relative to conventional assays, especially in plasma, and provide robust differentiation of amyloid-PET-positive and amyloid-PET-negative participants. If these findings are confirmed using fully automated diagnostic platforms that are intended for use in clinical settings, brain-derived phosphorylated tau assays may support future blood-based biomarker triage workflows for identifying Alzheimer's disease.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"8 5","pages":"fcag376"},"PeriodicalIF":4.5,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13669629/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149217390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of neurofilament light chain and other fluid biomarkers in cerebellar ataxias.","authors":"Charlotte Mouraux, Magda M Santana, Liana S Rosenthal, Andrea Cortese, Filippo M Santorelli, Puneet Opal, Giulia Coarelli","doi":"10.1093/braincomms/fcag313","DOIUrl":"10.1093/braincomms/fcag313","url":null,"abstract":"&lt;p&gt;&lt;p&gt;The genetic and phenotypic heterogeneity of hereditary ataxias complicates the design of clinical trials since each ataxia progresses at different rates. Consequently, robust biomarkers are urgently needed to monitor therapeutic efficacy and safety of potential therapeutic interventions. Neurofilament light chain has emerged as a leading candidate, serving as a sensitive pharmacodynamic biomarker of neuronal injury and treatment response in neurodegenerative disorders. This review explores the utility of neurofilament light chain across various ataxias, including polyglutamine spinocerebellar ataxias, Friedreich's ataxia, multiple system atrophy, and other genetic ataxias, such as ataxias associated with &lt;i&gt;RCF1&lt;/i&gt; and &lt;i&gt;SPG7&lt;/i&gt; genes. We synthesize evidence from recent studies that have used ultra-sensitive assays. These studies consistently demonstrate elevated neurofilament light chain levels in cerebrospinal fluid and blood, correlating with disease severity, progression and neuroimaging findings. Notably, neurofilament light chain levels rise during the presymptomatic stage in spinocerebellar ataxias, highlighting its potential for stratifying individuals for trial enrolment and tracking therapeutic effects. A treatment-induced reduction in neurofilament light chain could function as a surrogate endpoint for target engagement, analogous to its validated use in amyotrophic lateral sclerosis. Finally, we discuss the results of other studies conducted on other biomarkers, including glial fibrillary acidic protein, total tau and phosphorylated tau, which may reflect complementary aspects of neurodegeneration and glial activation. Glial fibrillary acidic protein may provide insights into astroglial reactivity and neuroinflammation. Similarly, alteration in total tau and phosphorylated tau levels may suggest dysfunction in neuronal cytoskeleton and axonal integrity. The review also focuses on target-engagement biomarkers, including polyglutamine-expanded ataxin proteins in spinocerebellar ataxias and frataxin in Friedreich's ataxia, as critical tools to complement the ataxia biomarker toolkit. The quantification of mutant ataxin proteins provides a mechanistic readout for emerging gene-silencing or protein-lowering therapies. In parallel, the measurement of frataxin levels serves as a pharmacodynamic marker in therapeutic strategies aiming to restore frataxin expression. These target-engagement biomarkers are valuable in early phases of clinical trials, which mainly aim to demonstrate the biological activity of a treatment before later-phase trials assessing clinical efficacy. Finally, we report on somatic instability in polyglutamine spinocerebellar ataxias as an emerging and highly relevant therapeutic target. CAG repeat mosaicism is gene specific and correlates with disease progression. Integrating measures of repeat instability with neurodegenerative biomarkers could provide a comprehensive monitoring approach in clinical studies. Thi","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"8 5","pages":"fcag313"},"PeriodicalIF":4.5,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13639701/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149120151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ubiquitin C-hydrolase L1 as a cerebrospinal fluid and blood biomarker for prion diseases.","authors":"Sezgi Canaslan, Matthias Schmitz, Anna-Lisa Fischer, Susana Da Silva Correia, Angela Da Silva Correia, Tayyaba Saleem, Peter Hermann, Inga Zerr","doi":"10.1093/braincomms/fcag363","DOIUrl":"https://doi.org/10.1093/braincomms/fcag363","url":null,"abstract":"<p><p>Digital enzyme-linked immunosorbent assays are based on single-molecule array technology. In this study, ubiquitin C-terminal hydrolase L1 (UCH-L1) levels were measured in cerebrospinal fluid (CSF) and blood samples (serum or plasma) obtained from patients with sporadic Creutzfeldt-Jakob disease and fatal familial insomnia using a commercially available UCH-L1 assay. We determined the inter- and intra-assay variability as well as the stability of UCH-L1 detection to ensure a reliable assay performance. Cut-off values were calculated to differentiate prion disease patients from neurodegenerative and non-neurodegenerative control groups. Patients with Creutzfeldt-Jakob disease exhibited significantly higher levels of UCH-L1 in both CSF and serum than controls. Receiver operating characteristic (ROC) analysis yielded area under the curve (AUC) values ranging from 0.91 to 0.97 for CSF and from 0.58 to 0.86 for serum. These values allow an excellent discrimination between Creutzfeldt-Jakob disease patients and controls. Similar findings were observed in the fatal familial insomnia cohort. Here, ROC analysis indicated AUC values between 0.79 and 0.91 for CSF and up to 0.95 for plasma when distinguishing fatal familial insomnia patients from neurodegenerative, non-neurodegenerative and healthy controls. Altogether, our study suggests that detection of UCH-L1 levels in CSF and blood is suitable for the diagnosis of prion diseases.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"8 5","pages":"fcag363"},"PeriodicalIF":4.5,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13663794/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149198386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"COVID-19 pleiotropy with brain imaging-derived phenotypes highlights novel insights into the biology shared between immune function and brain variation.","authors":"Qianyu Chen, Jun He, Brenda Cabrera-Mendoza, Ziang Xu, Dan Qiu, Renato Polimanti","doi":"10.1093/braincomms/fcag372","DOIUrl":"10.1093/braincomms/fcag372","url":null,"abstract":"<p><p>This study investigated the pleiotropy and the underlying biology linking COVID-19 outcomes to brain variation, leveraging genome-wide data from the COVID-19 Host Genetics Initiative and multimodal brain-wide magnetic resonance imaging from the UK Biobank. In our analyses, COVID-19 outcomes showed evidence of polygenic overlap with respect to 11 imaging-derived phenotypes (IDPs) related to brain structure (e.g. parahippocampal and entorhinal cortical thickness) and connectivity (e.g. Broca's area and dorsolateral prefrontal cortex). Among these, the genetic liability to COVID-19 hospitalization and SARS-CoV-2 infection was inversely related to the area of pars opercularis. We also identified local genetic correlations between COVID-19 outcomes and brain IDPs within five loci mapping genes involved in inflammatory response, immune regulation, brain development, and neuropsychiatric disorders (e.g. <i>LAMP3</i>, <i>SOX2</i>, and <i>TSHZ2</i>). Additionally, we uncovered colocalized variants linking COVID-19 outcomes to brain structural variation (rs13107325 with entorhinal mean thickness) and brain transcriptomic regulation of immune-related genes (e.g. <i>IL6R</i> in brain cortex and <i>HLA-C</i> in caudate basal ganglia). Our drug-repurposing analysis based on gene ontologies shared between COVID-19 outcomes and brain IDPs uncovered 41 compounds, including psychiatric medications that appear to also have antiviral and immunomodulatory activity. Overall, the present findings contributed to dissecting the biological mechanisms shared between COVID-19 and brain variation, highlighting the systemic nature of their relationship.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"8 5","pages":"fcag372"},"PeriodicalIF":4.5,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13669621/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149217383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reappraising the claims of evolutionary continuity between thanatosis and near-death experiences.","authors":"Jorge A Delgado-Ron","doi":"10.1093/braincomms/fcag368","DOIUrl":"10.1093/braincomms/fcag368","url":null,"abstract":"","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"8 5","pages":"fcag368"},"PeriodicalIF":4.5,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13655614/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149170850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}