Brain最新文献

{"title":"Correction to: Inhibition of YAP/TAZ-driven TEAD activity prevents growth of NF2-null schwannoma and meningioma.","authors":"","doi":"10.1093/brain/awae353","DOIUrl":"10.1093/brain/awae353","url":null,"abstract":"","PeriodicalId":9063,"journal":{"name":"Brain","volume":" ","pages":"e16-e20"},"PeriodicalIF":10.6,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11884762/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142692349","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":"Stereo-EEG propagating source reconstruction identifies new surgical targets for epilepsy patients","authors":"Brandon J Thio, Nishant Sinha, Kathryn A Davis, Saurabh R Sinha, Warren M Grill","doi":"10.1093/brain/awae297","DOIUrl":"https://doi.org/10.1093/brain/awae297","url":null,"abstract":"Epilepsy surgery can eliminate seizures in patients with drug-resistant focal epilepsy. Surgical intervention requires proper identification of the epileptic network and often involves implanting stereo-EEG electrodes in patients where non-invasive methods are insufficient. However, only ∼60% of patients achieve seizure-freedom following surgery. Quantitative methods have been developed to help improve surgical outcomes. However, previous quantitative methods that localized interictal spike and seizure activity using stereo-EEG recordings did not account for the propagation path encoded by the temporal dynamics of stereo-EEG recordings. Reconstructing the seizure propagation path can aid in determining whether a signal originated from the seizure onset or propagation zone, which directly informs treatment decisions. We developed a novel source reconstruction algorithm, Temporally Dependent Iterative Expansion (TEDIE), that accurately reconstructs propagating and expanding neural sources over time. TEDIE iteratively optimizes the number, location and size of neural sources to minimize the differences between the reconstructed and recorded stereo-EEG signals using temporal information to refine the reconstructions. The TEDIE output comprises a movie of seizure activity projected onto patient-specific brain anatomy. We analysed data from 46 epilepsy patients implanted with stereo-EEG electrodes at Duke Hospital (12 patients) and the Hospital of the University of Pennsylvania (34 patients). We reconstructed seizure recordings and found that TEDIE’s seizure onset zone reconstructions were closer to the resected brain region for Engel 1 compared to Engel 2–4 patients, retrospectively validating the clinical utility of TEDIE. We also demonstrated that TEDIE has prospective clinical value, whereby metrics that can be determined presurgically accurately predict whether a patient would achieve seizure-freedom following surgery. Furthermore, we used TEDIE to delineate new potential surgical targets in 12/23 patients who are currently Engel 2–4. We validated TEDIE by accurately reconstructing various dynamic synthetic neural sources with known locations and sizes. TEDIE generated more accurate, focal and interpretable dynamic reconstructions of seizures compared to other algorithms (sLORETA and IRES). Our findings demonstrate that TEDIE is a promising clinical tool that can greatly improve epileptogenic zone localization and epilepsy surgery outcomes.","PeriodicalId":9063,"journal":{"name":"Brain","volume":"87 1 1","pages":""},"PeriodicalIF":14.5,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143570462","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":"On the responsibilities of intellectuals and the rise of bullshit jobs in universities.","authors":"Masud Husain","doi":"10.1093/brain/awaf045","DOIUrl":"https://doi.org/10.1093/brain/awaf045","url":null,"abstract":"","PeriodicalId":9063,"journal":{"name":"Brain","volume":"148 3","pages":"687-688"},"PeriodicalIF":10.6,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143571998","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":"Correction to: GDF5 as a rejuvenating treatment for age-related neuromuscular failure.","authors":"","doi":"10.1093/brain/awae375","DOIUrl":"10.1093/brain/awae375","url":null,"abstract":"","PeriodicalId":9063,"journal":{"name":"Brain","volume":" ","pages":"e21"},"PeriodicalIF":10.6,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142680776","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":"Metformin may reduce Alzheimer's disease risk by increasing soluble amyloid-β42 levels.","authors":"Timothy Daly, Bruno P Imbimbo","doi":"10.1093/brain/awae367","DOIUrl":"10.1093/brain/awae367","url":null,"abstract":"","PeriodicalId":9063,"journal":{"name":"Brain","volume":" ","pages":"e14-e15"},"PeriodicalIF":10.6,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602695","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":"p75NTR modulation prevents cellular, cortical activity and cognitive dysfunctions caused by perinatal hypoxia","authors":"Bidisha Chattopadhyaya, Karen K Y Lee, Maria Isabel Carreño-Muñoz, Andrea Paris-Rubianes, Marisol Lavertu-Jolin, Martin Berryer, Frank M Longo, Graziella Di Cristo","doi":"10.1093/brain/awaf084","DOIUrl":"https://doi.org/10.1093/brain/awaf084","url":null,"abstract":"Children who experienced moderate perinatal hypoxia are at risk of developing long-lasting subtle cognitive and behavioural deficits, including learning disabilities and emotional problems. Understanding the underlying mechanisms is an essential step for designing targeted therapy. Fast-spiking, parvalbumin-positive (PV) GABAergic interneurons modulate the generation of gamma oscillations, which in turn regulate many cognitive functions including goal-directed attentional processing and cognitive flexibility. Due to their fast-firing rate, PV cell function requires high levels of energy, which may render them highly vulnerable to conditions of metabolic and oxidative stress caused by perinatal hypoxia. Here, we show that adult mice that experienced moderate perinatal hypoxia (MPH) have decreased cortical PV expression levels in addition to specific impairments in social behaviour, recognition memory and cognitive flexibility. We further found that the expression level of the neurotrophin receptor p75NTR, which limits PV cell maturation during the first postnatal weeks, is increased in MPH mice. Genetic deletion of p75NTR in GABAergic neurons expressing the transcription factor Nkx2.1, which include PV cells, protects mice from PV expression loss and the long-term cognitive effects of MPH. Finally, treatment with a p75NTR inhibitor starting after MPH and lasting for a week, prevented PV expression loss and the occurrence of cognitive and cortical activity deficits in adult mice. Altogether our data reveals p75NTR-mediated signaling, as a potential molecular target, for the treatment of the cognitive alterations caused by MPH.","PeriodicalId":9063,"journal":{"name":"Brain","volume":"85 1","pages":""},"PeriodicalIF":14.5,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143546601","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":"CD21lo B cell subsets are recruited to the central nervous system in acute neuromyelitis optica.","authors":"Ryusei Nishigori, Mio Hamatani, Hiroyuki Yoshitomi, Kimitoshi Kimura, Masaki Takata, Shinji Ashida, Chihiro Fujii, Hirofumi Ochi, Ryosuke Takahashi, Takayuki Kondo, Hideki Ueno","doi":"10.1093/brain/awaf086","DOIUrl":"https://doi.org/10.1093/brain/awaf086","url":null,"abstract":"<p><p>Neuromyelitis optica (NMO) is an acute inflammatory demyelinating disease of the CNS. The presence of astrocyte-targeted AQP4-immunoglobulin G (IgG) in peripheral blood is a major factor in its diagnosis. Previous studies show that AQP4-IgG directly contributes to CNS inflammation, and B cells play a central pathogenic role in NMO. However, where and how B cell response is altered remains controversial. In this study, we comprehensively analyzed with high-parameter flow cytometry the immune cell populations in the CSF samples obtained from first-episode acute-phase NMO patients, and compared to those from patients with acute-phase Multiple Sclerosis (MS) and other neurological diseases (OND). Among ten immune cell populations defined in the analysis, only the frequency of B cells and antibody-secreting cells (ASC) were higher in the CSF of acute-phase NMO compared to OND. Detailed assessments of B cell and ASC subsets in the CSF revealed differences in the dominant subsets between NMO and MS. In NMO, a series of CD21lo B cell subsets ranging from \"activated\" naïve B, double negative, and switched memory, thus subsets considered as ASC-precursors, were dominant. A majority of these CD21lo B cell subsets expressed CD69 and CXCR3, suggesting their CNS residency. An increase of CD21lo B cell subsets was also observed in the CSF of treatment-refractory NMO patients. Furthermore, two B helper T cell subsets, T peripheral helper type1 and T follicular helper type1 cells, both highly expressing CD69 and CXCR3, were enriched in the CSF of NMO patients, suggesting their interactions with ASC-precursors in the CNS. In vitro culture experiments using blood samples from patients with NMO showed that CD21lo B cells contained AQP4-IgG-producing cells and displayed a high propensity to differentiate into ASCs. We further found that CD21lo B cell subsets in NMO upregulated the expression of C5a receptors, and C5a signals promoted their differentiation into ASCs. ASCs derived from CD21lo B cells expressed high levels of CXCR3 and CD138. The increase in CD21lo B cell subsets significantly correlated with the annual relapse rate. Collectively, our study highly suggests that the mechanism to promote the generation of CD21lo B cells, likely via the extrafollicular pathway, becomes activated during the acute phase of NMO, and the generated CD21lo B cell subsets contribute to the pathogenesis. Targeting CD21lo B cell subsets might be useful for the development of novel therapeutic approaches.</p>","PeriodicalId":9063,"journal":{"name":"Brain","volume":" ","pages":""},"PeriodicalIF":10.6,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555861","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":"Harnessing psychedelics for stroke recovery: therapeutic potential and mechanisms.","authors":"Yuefeng Yang, Yibo Wang, Xiaohui Wang","doi":"10.1093/brain/awaf093","DOIUrl":"https://doi.org/10.1093/brain/awaf093","url":null,"abstract":"","PeriodicalId":9063,"journal":{"name":"Brain","volume":" ","pages":""},"PeriodicalIF":10.6,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143565933","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":"Towards precision MRI biomarkers in epilepsy with normative modelling.","authors":"Remika Mito, James Cole, Sila Genc, Graeme Jackson, Andrew Zalesky","doi":"10.1093/brain/awaf090","DOIUrl":"https://doi.org/10.1093/brain/awaf090","url":null,"abstract":"<p><p>Epilepsy is recognised as one of the leading targets for precision medicine, following on from the successes in cancer therapy, due to its substantial clinical heterogeneity and divergent therapeutic options. To bring personalised care to the epilepsies, there is a need for appropriate precision biomarkers that can identify disease processes or predict treatment outcomes at the individual patient level. Neuroimaging techniques, including magnetic resonance imaging (MRI), have been transformative for clinical practice, particularly in medically refractory focal epilepsies. Advanced MRI techniques have the potential to bring precision medicine clearly into view for epileptology; however, there are challenges that must be overcome before cutting-edge neuroimaging tools can be used in clinical practice. In this Review article, we communicate our view that implementation of normative modelling frameworks will help to deliver robust quantitative MRI biomarkers for individualized prediction. Here, we provide recommendations for researchers and clinicians alike, from careful research design to clinical applications, that will help to identify diagnostic and predictive imaging biomarkers. Such precision markers will be key to delivering personalised medicine for the epilepsies.</p>","PeriodicalId":9063,"journal":{"name":"Brain","volume":" ","pages":""},"PeriodicalIF":10.6,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143565936","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":"The presence and prognosis of nerve pathology following whiplash injury: a prospective cohort study.","authors":"Joel Fundaun, Colette Ridehalgh, Soraya Koushesh, Alex Novak, Macarena Tejos-Bravo, Stephen Bremner, Georgios Baskozos, Andrew Dilley, Annina B Schmid","doi":"10.1093/brain/awaf088","DOIUrl":"https://doi.org/10.1093/brain/awaf088","url":null,"abstract":"<p><p>Whiplash Associated Disorders (WAD) affect 20-50 million individuals globally each year, with up to 50% developing persistent pain. WAD grade II (WADII) is the most common type and is characterised by neck symptoms and musculoskeletal signs without apparent nerve injury on routine diagnostic testing. However, emerging evidence suggests nerve pathology may be present in some people with WADII. This longitudinal cohort study aimed to comprehensively investigate the presence, temporal patterns, and prognostic value of nerve pathology and neuropathic pain in acute WADII. A prospective longitudinal cohort study was conducted with 129 acute participants with WADII (median age 36.0 years, 58% female) and 36 healthy controls (median age 39.0 years, 61% female). Participants with WADII were recruited within four weeks of injury from local emergency departments. Data collection included bedside neurological assessments, quantitative sensory testing (QST), intraepidermal nerve fibre density, and serum neurofilament light chain (NfL) concentrations. Follow-up assessments were conducted 6-months after injury. Signs of neuropathic pain were present in 65% (84/129) acutely and persisted in 32% (21/66) 6-months post-injury. Bedside neurological assessment revealed somatosensory loss of function was present in 54% (70/129) acutely reducing to 25% (17/67) 6-months post-injury. QST demonstrated significantly reduced cold, warm, thermal sensory limen, mechanical, and vibration detection thresholds in acute WADII compared to controls (d>0.47). Acute loss of function in at least one QST parameter was present in 67.6% (85/126) of WADII. At 6-months, participants with WADII showed persistent hypoaesthesia to warm, thermal sensory limen, and mechanical detection thresholds, and decreased mechanical pain and pressure pain sensitivity compared to controls (d>0.44). These functional neurological changes were accompanied by elevated serum neurofilament light chain levels in acute WADII compared to controls (d=-0.52 (95% confidence interval -0.94, -0.10). Intraepidermal nerve fibre densities at the index finger were not significantly different between groups. However, dermal MBP+/PGP+ myelinated nerve bundles at the index finger were reduced 6-months post-injury in WADII compared to controls (d=0.69 (0.26, 1.11). Multivariable linear regression suggested bedside tests for hypoaesthesia at the index finger were prognostic for whiplash-related upper quadrant pain 6-months post-injury (r2=0.13, p=0.02). In conclusion, two-thirds of participants with acute WADII initially exhibited signs of neuropathic pain and nerve pathology. At the 6-month follow-up, neuropathic pain persisted in one-third of participants with WADII, while nerve pathology persisted in two-thirds. These findings challenge the traditional musculoskeletal classification of WADII and underscore the need for targeted neurological assessments and treatment.</p>","PeriodicalId":9063,"journal":{"name":"Brain","volume":" ","pages":""},"PeriodicalIF":10.6,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555865","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}