Brain最新文献

{"title":"Neural substrates of the link between dual-task gait and dementia: an intermediary step in which direction?","authors":"A Charlotte Menart,M Arfan Ikram,Frank J Wolters","doi":"10.1093/brain/awaf187","DOIUrl":"https://doi.org/10.1093/brain/awaf187","url":null,"abstract":"","PeriodicalId":9063,"journal":{"name":"Brain","volume":"136 1","pages":""},"PeriodicalIF":14.5,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144114085","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: Sex-specific modulation of amyloid-β on tau phosphorylation underlies faster tangle accumulation in females.","authors":"","doi":"10.1093/brain/awaf174","DOIUrl":"https://doi.org/10.1093/brain/awaf174","url":null,"abstract":"","PeriodicalId":9063,"journal":{"name":"Brain","volume":"25 1","pages":""},"PeriodicalIF":14.5,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144103698","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: Neural substrates of the link between dual-task gait and dementia: an intermediary step in which direction?","authors":"Pauline Ali,Frederico Pieruccini-Faria,Cédric Annweiler,Mickaël Dinomais,Surim Son,Scott K Wilson,Richard Camicioli,Susan Muir-Hunter,Robert Bartha,Manuel Montero-Odasso","doi":"10.1093/brain/awaf192","DOIUrl":"https://doi.org/10.1093/brain/awaf192","url":null,"abstract":"","PeriodicalId":9063,"journal":{"name":"Brain","volume":"51 1","pages":""},"PeriodicalIF":14.5,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144114117","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":"Pure autonomic failure: a natural history study of the Queen Square cohort","authors":"Giacomo Chiaro, Ekawat Vichayanrat, Shiwen Koay, Antoine Rogeau, Gordon T Ingle, Patricia McNamara, Laura Watson, Jamshed Bomanji, Christopher J Mathias, Valeria Iodice","doi":"10.1093/brain/awaf191","DOIUrl":"https://doi.org/10.1093/brain/awaf191","url":null,"abstract":"The current research challenge in pure autonomic failure (PAF) lies in identifying specific biomarkers that can differentiate it from the other Lewy body disorders (Parkinson’s disease, Parkinson’s disease dementia, dementia with Lewy bodies) and multiple system atrophy in the early stages and predict phenoconversion trajectories to more widespread impairment. In this study, we described the natural history of our cohort of PAF patients over five decades and validated a cluster of clinical, autonomic, and neuroimaging biomarkers that help identify clinical profiles susceptible to further neurodegeneration, working towards a biological definition of PAF. Consecutive patients with an initial diagnosis of PAF were recruited and monitored through key milestones (disease onset, first and repeat autonomic assessment, phenoconversion, and death/final contact). A subset underwent brain magnetic resonance imaging and DaTSCAN. Uni- and multivariate regression analyses explored the associations among different factors, survival times, and phenoconversion, and were used to predict the probability of phenoconversion. 281 PAF patients were followed for a median of 10 years. Of these, 33% (91) converted to a more widespread synucleinopathy, and 41% (115) died during follow-up, of whom 53% (61) retained a PAF phenotype. Baseline cardiovascular autonomic biomarkers were key in differentiating disease trajectories and repeat testing indicated worsening of autonomic failure during the disease course. Median survival of PAF patients was 15 years from orthostatic symptoms onset and was mostly influenced by age and the severity of orthostatic hypotension. 39% of patients had abnormal DaTSCAN results up to 7 years before phenoconversion, with 84% of these patients progressing to more widespread synucleinopathy. Male sex, older age, dream enactment behaviour, and supine noradrenaline levels >200 pg/mL were correlated with the risk of phenoconversion to Lewy body disorders, whereas younger age, bladder dysfunction, catheter use, and dream enactment behaviour were associated with phenoconversion to multiple system atrophy. Our natural history study involves the largest single-centre longitudinal cohort of patients with an initial diagnosis of PAF and identifies robust clinical, autonomic, and neuroimaging biomarkers that, when used together, could serve as a novel and sensitive screening tool for early identification and stratification of patients at risk of phenoconversion to more widespread synucleinopathy.","PeriodicalId":9063,"journal":{"name":"Brain","volume":"32 1","pages":""},"PeriodicalIF":14.5,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144113831","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":"Neurotransmitter-informed connectivity maps and their application for outcome inference after stroke.","authors":"Philipp J Koch,Benedikt M Frey,Winifried Backhaus,Nora Petersen,Gabriel Girard,Pawel P Wróbel,Hanna Braaß,Marlene Bönstrup,Lisa Kunkel Genannt Bode,Bastian Cheng,Götz Thomalla,Christian Gerloff,Hannes Schacht,Peter Schramm,Georg Royl,Fanny Quandt,Robert Schulz","doi":"10.1093/brain/awaf185","DOIUrl":"https://doi.org/10.1093/brain/awaf185","url":null,"abstract":"Neuroscience has evolved by framing numerous neuropsychiatric conditions as network diseases. Alterations within neurotransmitter (NT) systems are central to the development of these diseases. Recently, normative data on whole-brain NT fingerprints derived from PET tracer data has become accessible; limited data related such information to sequelae after stroke. This work aims to explore (1) the integration of NT data into whole-brain structural connectivity analyses and (2) its potential contribution to understanding outcome variability following stroke. Normative maps of NT receptor and transporter densities were integrated with a normative structural connectome to generate NT-specific connectivity maps for serotonin, dopamine, GABA, glutamate, and acetylcholine receptors and transporters. Stroke lesion data from two independent, matched cohorts comprising a total of 126 severely impaired acute stroke patients were used to assess NT-related network damage on a patient-specific basis across each receptor and transporter distribution. Multivariable logistic regression models were applied to evaluate the relationship between NT-informed network disconnections and functional outcomes three to six months post-stroke, operationalised by the modified Rankin scale (mRS). Analyses were adjusted for lesion-induced global network damage, age, sex, lesion volume, and baseline neurological symptom burden. We present an innovative method to incorporate PET tracer data of various NT systems into normative structural connectome data. The resulting NT-informed connectivity maps revealed distinct spatial distributions consistent with the established literature. In both cohorts of severely impaired stroke patients, incorporating lesion-induced disruptions within specific NT systems provided more insights into variability in stroke outcomes than structural disconnection alone. Notably, greater damage to networks with high dopamine transporter (DAT) density was associated with poorer functional recovery. Based on NT-informed structural connectivity maps with distinct topographical features for individual receptors and transporters, we show that lesion-induced disruptions in large-scale dopaminergic brain networks, beyond global structural network damage, may play a key role in stroke recovery. These insights hold significant translational potential for advancing personalised medicine in stroke care, such as those achieved by targeted pharmacologic interventions.","PeriodicalId":9063,"journal":{"name":"Brain","volume":"63 1","pages":""},"PeriodicalIF":14.5,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144103701","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":"Are brain arteriovenous malformations congenital or developmental? Evidence from paediatric age data.","authors":"Sivaram S Emani,Ari D Kappel,Shivani D Rangwala,Paulina Piwowarczyk,Nikita Singh,Joon Hyeok Choi,Alfred P See,Darren B Orbach","doi":"10.1093/brain/awaf190","DOIUrl":"https://doi.org/10.1093/brain/awaf190","url":null,"abstract":"The natural history of pediatric brain arteriovenous malformations (AVMs) remains uncertain, particularly regarding their origin (congenital versus postnatal) and risk of rupture. This study analyzes age-related patterns in AVM presentation from a single quaternary referral center. A retrospective review of 275 pediatric AVM cases from 2009-2022, was conducted using radiological, surgical, and hospital records to identify age at first hemorrhage and associated AVM characteristics. Two mathematical models were developed: (i) a congenital model with a variable age-dependent rupture risk, and (ii) a postnatal model of AVM development, assuming age-dependent variable incidence and a constant rupture rate. Data were normalized to institutional age-based presentation rates. Hemorrhagic presentation peaked between ages 7 and 14, before declining sharply, a trend which remained after normalization. A congenital model with age-dependent rupture rate accounted well for the empirical distribution, while the postnatal model overpredicted adolescent hemorrhage and could not account for the observed decline. However, the rising distribution of asymptomatic AVMs with age suggests that a purely congenital model is implausible. The study supports a model where pediatric brain AVMs are largely postnatally acquired, though likely very early, with age-dependent varying annual risk of rupture peaking at age 13, before declining to an adult risk rate.","PeriodicalId":9063,"journal":{"name":"Brain","volume":"37 1","pages":""},"PeriodicalIF":14.5,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144103742","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":"Ventriculitis characteristics and outcomes (VELCRO): an international retrospective cohort study.","authors":"David Luque Paz, Beatriz Díaz-Pollán, Marielle Boyer-Besseyre, Flora Djanikian, Anne-Lise Munier, Flávia Cunha, Lélia Escaut, Guillaume Martin-Blondel, Benjamine Sarton, Pierre Jaquet, François Arrivé, Rémi Wolf, Vincent Legros, Mathieu Willig, Oguz Resat Sipahi, Laure Flurin, Antoine Bianchi, Baptiste Balança, Alejandro Díez-Vidal, Joshua Puel, Benjamin Soyer, Rita Lino, Thibaut Leveque, Alexis Salomon, Alexandra Serris, Romaric Larcher, Fabrice Bruneel, Nicolas Mongardon, Martin Martinot, Aurélien Mazeraud, Michel Wolff, Romain Sonneville, Florent Valour, Pierre Tattevin","doi":"10.1093/brain/awaf178","DOIUrl":"https://doi.org/10.1093/brain/awaf178","url":null,"abstract":"<p><p>Ventriculitis is a dreaded complication of central nervous system infections, which has been scarcely described in the literature. We aimed to present a contemporary picture of ventriculitis, describing its characteristics and outcomes across the spectrum of aetiologies that may lead to ventriculitis. VELCRO is an international retrospective multicentre cohort study conducted at 34 hospitals in six countries. Adult patients fulfilling clinical, microbiological and imaging criteria of ventriculitis between 2010 and 2021 were included. Survival analyses were performed using a multivariable Cox proportional hazards regression model to identify risk factors for 1-year all-cause mortality. Overall, 436 patients with ventriculitis were included: 274 (62.8%) males, median age 58 years [interquartile range 48-68], 68 (15.6%) had diabetes mellitus and 62 (14.2%) were immunocompromised. The most common neuroimaging features of ventriculitis were ependymal enhancement (n=310/436, 71.1%), intraventricular pus (n=286/436, 65.6%) and intraventricular septations (n=85/436, 19.5%). To describe the cohort, patients were divided into three groups: ventriculitis with brain abscess(es) (V-BA, n=181), community-acquired ventriculitis without brain abscess (CA-V, n=88), and healthcare-associated ventriculitis without brain abscess (HCA-V, n=167). Intensive care unit admission was required for 351 patients (80.5%) and the median hospital length of stay was 45 days [26-74]. One-year mortality rate was 33.7% (n=147/436), with a lower rate in patients with V-BA (n=50/181, 27.6%) than in patients with CA-V (n=30/88, 34.1%) and HCA-V (n=67/167, 40.1%). On multivariable analysis, the predictive factors for 1-year mortality were: age > 60 years, immunosuppression, diabetes mellitus, Glasgow Coma Scale score < 13 at presentation, infection involving Enterobacterales or fungi, acute hydrocephalus, cerebral ischemia and intraventricular septations. Staphylococcal ventriculitis was associated with a lower 1-year mortality. Long-term unfavourable outcome (modified Rankin score (mRS) > 2 after 6 months of follow-up) occurred in 43.3% (n=91/210), considering that 26.7% (n=56) had a mRS > 2 before the onset of ventriculitis. Ventriculitis is associated with high mortality and neurological morbidity. Further large prospective studies are needed in this area of research.</p>","PeriodicalId":9063,"journal":{"name":"Brain","volume":" ","pages":""},"PeriodicalIF":10.6,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144207636","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":"Direct electrical stimulation maps white matter anatomy to function.","authors":"Davide Giampiccolo,Guillaume Herbet,Hugues Duffau","doi":"10.1093/brain/awaf188","DOIUrl":"https://doi.org/10.1093/brain/awaf188","url":null,"abstract":"","PeriodicalId":9063,"journal":{"name":"Brain","volume":"9 1","pages":""},"PeriodicalIF":14.5,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144087647","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":"FGF14 repeat length and mosaic interruptions: modifiers of spinocerebellar ataxia 27B?","authors":"Joshua Laß, Mirja Thomsen, Max Borsche, Theresa Lüth, Julia C Prietzsche, Susen Schaake, Andona Milovanović, Hannah Macpherson, Emil K Gustavsson, Paula Saffie Awad, Nataša Dragašević-Mišković, Björn-Hergen Laabs, Inke R König, Ana Westenberger, Christopher E Pearson, Norbert Brüggemann, Christine Klein, Joanne Trinh","doi":"10.1093/brain/awaf183","DOIUrl":"https://doi.org/10.1093/brain/awaf183","url":null,"abstract":"Deep intronic FGF14 repeat expansions have been identified as a frequent genetic cause of late-onset cerebellar ataxias, explaining up to 30% of patients. Interruptions between repeats have previously been identified to impact the penetrance in other repeat expansion disorders. Repeat interruptions within FGF14 have yet to be characterized in detail. We utilized long-range PCR, Sanger sequencing, repeat-primed PCR, Nanopore, and PacBio sequencing to distinguish the repeat motifs, mosaicism, and number of repeat interruptions present in FGF14-related ataxia patients and unaffected individuals. A total of 304 patients with late-onset ataxia and 190 unaffected individuals were previously screened for repeat expansions in the FGF14 gene by long-range PCR, identifying 37 individuals with expanded repeat lengths (≥250 repeats). These, along with three newly identified expansion carriers were included in the present study, and advanced genetic methods were applied to investigate the repeat composition in 27 patients and 13 unaffected individuals. The expansions, based on Nanopore data, ranged from 236 to 486 repeats (SD = 60), with 20 individuals showing repeat interruptions, including complex motifs such as GAG, GAAGGA, GAAGAAAGAA, GAAAAGAAGAAGGAAGAAGGAA, GAAAAGAAGAAGGAA, and GCAGAAGAAGAAGAA. We calculated the longest pure GAA length from the long-read data for all 40 individuals. When comparing the pure GAA tract between patients and unaffected individuals, clusters were apparent based on greater or less than 200 repeats. Five ataxia patients with interruptions still had a remaining pure GAA expansion &amp;lt;200. We observed an association of the pure GAA length with age at onset (p=0.016, R2=0.256). Somatically-incurred mosaic divergent repeat interruptions were discovered that affect motif length and sequence (mDRILS), which varied in number and mosaicism (frequency: 0.37-0.93). The mDRILS correlated with pure GAA length (p=0.022, R2=0.334), with a higher mosaic frequency of interruptions in unaffected individuals compared to patients (unaffected: 0.90; patients: 0.67; p=0.009). We demonstrate that i) long-read sequencing is required to detect complex repeat interruptions accurately; ii) repeat interruptions in FGF14 are mosaic, have various lengths and start positions in the repeat tract, and can thereby be annotated as mDRILS, which iii) enabled us to establish a categorization based on remaining pure GAA repeats quantifying the impact of mDRILS on pathogenicity or age at onset, dependent on the interruption length and position, with high accuracy. Finally, we iv) provide evidence that mosaicism stabilizes pure GAA repeats in interrupted FGF14 repeat expansions.","PeriodicalId":9063,"journal":{"name":"Brain","volume":"18 1","pages":""},"PeriodicalIF":14.5,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144066910","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":"Astrocytic mGluR5-dependent calcium hyperactivity promotes amyloid-β pathology and cognitive impairment.","authors":"Tianqi Yang,Dianjun Zhang,Haiwei Huang,Fangyue Liu,Juanli Wu,Xiaolin Ma,Shuangshuang Liu,Man Huang,Yu-Dong Zhou,Yi Shen","doi":"10.1093/brain/awaf186","DOIUrl":"https://doi.org/10.1093/brain/awaf186","url":null,"abstract":"Astrocytic dysfunction is a crucial factor for the pathogenesis of Alzheimer's disease. Metabotropic glutamate receptor 5 (mGluR5) is ubiquitously expressed in the brain and is a key molecule that regulates synaptic transmission and plasticity. It has been shown that mGluR5 is elevated in astrocytes in Alzheimer's disease. However, it remains elusive how astrocytic mGluR5 contributes to the pathogenesis of Alzheimer's disease. Here, we first quantified a high expression level of astrocytic mGluR5 in the hippocampus of Alzheimer's disease brains and demonstrated that the expression of astrocytic mGluR5 was positively correlated with Alzheimer's disease progression in both humans and mice. Upregulating astrocytic mGluR5 in the CA1 area at an early stage accelerated, whereas downregulating these receptors rescued, Aβ pathology and cognitive impairment in Alzheimer's disease mice. Moreover, the activation of mGluR5 led to calcium hyperactivity in astrocytes, causing Aβ pathology progression due to dysregulated Aβ uptake and degradation in astrocytes. Importantly, attenuating astrocytic calcium hyperactivity in the hippocampal CA1 area in the prodromal phase ameliorated Aβ pathology and cognitive defects in Alzheimer's disease mice. Our findings thus reveal a fundamental contribution of astrocytic mGluR5 in presymptomatic Alzheimer's disease that may serve as a potential diagnostic and therapeutic target for early Alzheimer's disease pathogenesis.","PeriodicalId":9063,"journal":{"name":"Brain","volume":"4 1","pages":""},"PeriodicalIF":14.5,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144065808","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}