Brain最新文献

{"title":"MRI R2* captures inflammation in disconnected brain structures after stroke: a translational study.","authors":"Ismail Koubiyr, Takayuki Yamamoto, Laurent Petit, Nadège Dubourdieu, Elena Avignone, Elise Cozensa, Chloé Galmiche, Hikaru Fukutomi, Igor Sibon, Vincent Dousset, Michel Thiebaut de Schotten, Aude Panatier, Marion Tible, Thomas Tourdias","doi":"10.1093/brain/awaf082","DOIUrl":"10.1093/brain/awaf082","url":null,"abstract":"<p><p>Ischaemic strokes disrupt brain networks, leading to remote effects in key regions like the thalamus, a critical hub for brain functions. However, non-invasive methods to quantify these remote consequences still need to be explored. This study aimed to demonstrate that MRI-derived R2* changes can capture iron accumulation linked with inflammation secondary to stroke-induced disconnection. To link remote R2* changes to stroke-induced disconnection, we first conducted a secondary analysis of 156 prospectively included stroke patients who underwent MRI at baseline and 1-year follow-up. We mapped fibres disconnected by baseline infarcts to compare the R2* changes over 1 year according to the disconnectivity status in specific thalamic nuclei groups. We also identified the variables associated with elevated R2* at 1 year in a multivariate context through linear regressions. In parallel, to understand the biological underpinning of the remote R2* changes, we set up a translational mouse model through photothrombotic induction of focal cortical infarcts or sham procedures in 110 C57BL/6J mice. We explored the mice through combinations of in vivo MRI at 72 h, 2-, 4- and 8-weeks, histology, qPCR for gene expression, mass spectrometry for iron concentration quantification and additional ex vivo high-resolution diffusion tensor imaging. In stroke patients, we found a significant increase of R2* within severely disconnected medial and lateral thalamic nuclei groups from baseline to 1 year. At the same time, no change occurred if these structures were not disconnected. We also showed that the disconnectivity status at baseline was significantly associated with R2* at follow-up, independently from confounders, establishing a direct and independent relationship between baseline disconnection and the subsequent R2* increase within the associated locations. In mice, we recapitulated the patients' conditions by observing increased R2* in the stroke groups, specifically within the disconnected thalamic nuclei. Such remote and focal R2* changes peaked at 2 weeks, preceding and correlating with longer-term atrophy at 8 weeks. We established that the remote R2* increase was spatially and temporally correlated with a significant increase of chemically determined iron load bound to ferritin within activated microglial cells. This study provides critical evidence that R2* is a sensitive marker of inflammation secondary to network disconnection, potentially informing future neuroprotective strategies targeting remote brain regions after stroke.</p>","PeriodicalId":9063,"journal":{"name":"Brain","volume":" ","pages":"3551-3562"},"PeriodicalIF":11.7,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extreme exercise in males is linked to mTOR signalling and onset of amyotrophic lateral sclerosis.","authors":"David O'Brien, Elham Alhathli, Ceryl Harwood, Debarati Bhattacharya, Kriti Gupta, Thomas Julian, Marcel Weinreich, Ryan J H West, Dennis Wang, Ross P Byrne, Russell L McLaughlin, Joanne Wuu, Michael Benatar, Johnathan Cooper-Knock, Pamela J Shaw","doi":"10.1093/brain/awaf235","DOIUrl":"10.1093/brain/awaf235","url":null,"abstract":"<p><p>Amyotrophic lateral sclerosis (ALS) is thought to be caused by interaction between genetic and environmental factors leading to motor neuron (MN) degeneration. Physical exercise has been linked to ALS but controversy remains. A key question is to determine which individuals might be at risk of exercise-associated ALS, because unnecessary avoidance of exercise could be harmful. We implemented complementary strategies including Mendelian randomization (MR) and multiple questionnaire-based measures of physical exercise in different cohorts. We include a prospective study involving UK Biobank participants where we could test for a relationship between exercise and the timing of future ALS symptom onset. To interrogate the molecular basis of our observations we performed a genetic association study of 'extreme' exercise, equivalent to >6 h of strenuous exercise or >12 h of any leisure-time exercise per week. Our data suggest that the link between increased physical exercise and ALS is particularly important for males who perform the most activity; with no evidence of a link in females. We determined that extreme exercise in males is associated with loss-of-function genetic variants within a number of mammalian target of rapamycin (mTOR) signalling genes that are also differentially expressed in ALS spinal cord. Activity-induced mTOR signalling has been shown to selectively benefit MN. Therefore, our findings could imply that moderate exercise is neuroprotective via enhanced mTOR signalling, but extreme exercise in men is associated with neurotoxicity and ALS via a failure of this mechanism. There was no significant overlap between genes associated with extreme exercise and those associated with ALS risk, consistent with a true gene-environment interaction rather than a shared genetic basis. We are not yet able to make individual-level recommendations regarding exercise and risk of ALS, but our conclusions should provide focus for future investigation.</p>","PeriodicalId":9063,"journal":{"name":"Brain","volume":" ","pages":"3652-3664"},"PeriodicalIF":11.7,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12493055/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144511517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"If patients only knew how bureaucracy obstructs their involvement in research and clinical trials.","authors":"Masud Husain","doi":"10.1093/brain/awaf309","DOIUrl":"https://doi.org/10.1093/brain/awaf309","url":null,"abstract":"","PeriodicalId":9063,"journal":{"name":"Brain","volume":"37 1","pages":"3423-3424"},"PeriodicalIF":14.5,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145209302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply: Brainstem cavernous malformations: observation, microsurgical resection or stereotactic radiosurgery.","authors":"Da Li, Jian-Cong Weng, Liang Wang","doi":"10.1093/brain/awaf206","DOIUrl":"10.1093/brain/awaf206","url":null,"abstract":"","PeriodicalId":9063,"journal":{"name":"Brain","volume":" ","pages":"3785-3786"},"PeriodicalIF":11.7,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144214874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transforming tissue transcriptomes, delivering on the promise of machine learning.","authors":"Eric B Dammer","doi":"10.1093/brain/awaf323","DOIUrl":"10.1093/brain/awaf323","url":null,"abstract":"","PeriodicalId":9063,"journal":{"name":"Brain","volume":" ","pages":"3433-3434"},"PeriodicalIF":11.7,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12493043/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144942066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brainstem cavernous malformations: observation, microsurgical resection or stereotactic radiosurgery.","authors":"Constantin Tuleasca, Jean Régis","doi":"10.1093/brain/awaf205","DOIUrl":"10.1093/brain/awaf205","url":null,"abstract":"","PeriodicalId":9063,"journal":{"name":"Brain","volume":" ","pages":"e90-e91"},"PeriodicalIF":11.7,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144214873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynamic reorganization of task-related network interactions in post-stroke aphasia recovery.","authors":"Zhizhao Jiang, Philipp Kuhnke, Anika Stockert, Max Wawrzyniak, Ajay Halai, Dorothee Saur, Gesa Hartwigsen","doi":"10.1093/brain/awaf036","DOIUrl":"10.1093/brain/awaf036","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Post-stroke aphasia is a network disorder characterized by language impairments and aberrant network activation. While patients with post-stroke aphasia recover over time, the dynamics of the underlying changes in the brain remain elusive. Neuroimaging work demonstrated that language recovery is a heterogeneous process, characterized by varying activation levels in several regions of the left-hemispheric language network and the domain-general bilateral multiple-demand network. Crucially, this activation seems to depend on the time elapsed since stroke and the lesion location. Yet, beyond task-related brain activation, the degree and nature of interactions between regions of the language and the multiple-demand network are not well understood. In this longitudinal functional neuroimaging study, we characterized task-related functional interactions between regions of the language and the multiple-demand network during language processing. We hypothesized that interactions between language regions and between language and multiple-demand regions should change over time and depend on lesion location. We compared changes in effective connectivity in patients with left-hemispheric frontal or temporo-parietal stroke (n = 17 per group) and healthy controls (n = 17) with Dynamic Causal Modelling. All patients repeatedly underwent an auditory sentence comprehension paradigm during functional neuroimaging in the acute (≤1 week), subacute (1-2 weeks) and chronic (&gt;6 months) phases after stroke. We found overall increased task-related connectivity from regions of the multiple-demand to the language network across patients, resembling the principal pattern of task-related interactions in controls. Early facilitation from multiple-demand to language regions correlated with later language improvement across both groups. Crucially, recruitment of specific connections from regions of the multiple-demand to language network depended on lesion location and changed over time. In the chronic phase, patients with frontal stroke showed facilitatory modulation from the right dorsolateral prefrontal cortex, while patients with temporo-parietal stroke integrated the supplementary motor area/dorsal anterior cingulate cortex. Besides this across-network reorganization, facilitatory connectivity between regions of the language network emerged in all patients in the subacute phase. Additionally, patients with frontal stroke showed facilitatory influences from the right lesion homologue to the remaining undamaged left inferior frontal cortex in the acute phase. Collectively, we provide first evidence that functional interactions of regions within and across the language and the multiple-demand network facilitate aphasia recovery. The identified dynamic reorganization principles over the time course of recovery may inform the future use of personalized treatment protocols with neurostimulation in aphasia rehabilitation. These protocols should be tailored to the individual","PeriodicalId":9063,"journal":{"name":"Brain","volume":" ","pages":"3563-3575"},"PeriodicalIF":11.7,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12493039/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stem cell-derived dopamine cell therapies for Parkinson's disease: what have the first trials shown?","authors":"Roger A Barker, Malin Parmar","doi":"10.1093/brain/awaf322","DOIUrl":"10.1093/brain/awaf322","url":null,"abstract":"","PeriodicalId":9063,"journal":{"name":"Brain","volume":" ","pages":"3428-3430"},"PeriodicalIF":11.7,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144942052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selective vulnerability and resilience to Alzheimer's disease tauopathy as a function of genes and the connectome.","authors":"Chaitali Anand, Farras Abdelnour, Benjamin Sipes, Daren Ma, Pedro D Maia, Justin Torok, Ashish Raj","doi":"10.1093/brain/awaf179","DOIUrl":"10.1093/brain/awaf179","url":null,"abstract":"<p><p>Brain regions in Alzheimer's disease exhibit distinct vulnerability to its hallmark pathology with the entorhinal cortex and hippocampus succumbing early to tau tangles while others like the primary sensory cortices remain resilient. The quest to understand how local/regional genetic factors, pathogenesis and network-mediated pathology spread, together govern this selective vulnerability (SV) or resilience (SR) is ongoing. Although many Alzheimer's risk genes are known from gene association and transgenic studies, it is still unclear whether and how their baseline expression confers SV/SR to pathology. Prior analyses have yielded conflicting results, pointing to a disconnect between the location of genetic risk factors and downstream tau pathology. The spatial distribution of vulnerability doesn't always align with genetic factors, suggesting a role for non-cell-autonomous mechanisms like transneuronal tau transmission. We hypothesize that a full accounting of the role of genes in mediating SV/SR would require modelling of network-based vulnerability, whereby tau misfolds, aggregates and propagates along fibre projections. We employed an extended network diffusion model (eNDM) and fitted it on tau PET data from 196 patients from the Alzheimer's Disease Neuroimaging Initiative. The fitted eNDM then becomes a reference from which to assess the role of innate genetic factors. Using the residual (observed - model-predicted) tau as a novel target outcome, we obtained its association with 100 Alzheimer's risk genes, whose baseline spatial transcriptional profiles were obtained from the Allen Human Brain Atlas. Our eNDM was successful in capturing tau pathology distribution in patients. After regressing out the model, we found that while many risk genes have spatial expression patterns that correlate with regional tau, many others showed a stronger association with residual tau. This suggests that direct vulnerability aligned with the network, as well as network-independent vulnerability, are conferred by risk genes. We report four classes of risk genes: network-aligned SV (SV-NA), network-independent SV (SV-NI), network-aligned SR (SR-NA) and network-independent SR (SR-NI), each with a distinct spatial signature and associated vulnerability to tau. Remarkably, using gene ontology analysis, we found that the identified gene classes have distinct and sometimes surprising functional enrichment patterns. Network-aligned genes broadly participate in cell death, stress response and metabolic processing; network-independent genes in amyloid-β processing and immune response. These previously unreported segregated roles point to multiple distinct pathways by which risk genes confer vulnerability or resilience in Alzheimer's disease. Our findings offer new insights into vulnerability signatures in Alzheimer's disease and may prove helpful in identifying potential intervention targets.</p>","PeriodicalId":9063,"journal":{"name":"Brain","volume":" ","pages":"3679-3693"},"PeriodicalIF":11.7,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12493037/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144590484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Vogt Collection: reactivating a treasure facilitating brain research, neurology and psychiatry","authors":"Katrin Amunts","doi":"10.1093/brain/awaf365","DOIUrl":"https://doi.org/10.1093/brain/awaf365","url":null,"abstract":"Over 125 years ago, Cécile and Oskar Vogt began assembling an extensive collection of brain histological sections and related documents. Katrin Amunts explains how digitising these materials will connect them with modern neuroscience, creating resources for research spanning basic science, medicine, history and ethics.","PeriodicalId":9063,"journal":{"name":"Brain","volume":"39 1","pages":""},"PeriodicalIF":14.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145203176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}