Brain最新文献

{"title":"Overcoming the dopamine-centric model of impulse control disorders in Parkinson’s disease: the role of 5-HT","authors":"Roberto Cilia, Valtteri Kaasinen","doi":"10.1093/brain/awaf145","DOIUrl":"https://doi.org/10.1093/brain/awaf145","url":null,"abstract":"This scientific commentary refers to ‘Serotonergic dysfunction in patients with impulse control disorders in Parkinson’s disease’ by Prange et al. (https://doi.org/10.1093/brain/awaf087).","PeriodicalId":9063,"journal":{"name":"Brain","volume":"57 1","pages":""},"PeriodicalIF":14.5,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143940147","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":"Against the moral hemiplegia of the intellectual class.","authors":"José Alberto González Cáceres","doi":"10.1093/brain/awaf138","DOIUrl":"https://doi.org/10.1093/brain/awaf138","url":null,"abstract":"","PeriodicalId":9063,"journal":{"name":"Brain","volume":"29 1","pages":"e41-e42"},"PeriodicalIF":14.5,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143945557","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":"Yes, the human brain has around 86 billion neurons.","authors":"Roberto Lent","doi":"10.1093/brain/awaf048","DOIUrl":"10.1093/brain/awaf048","url":null,"abstract":"","PeriodicalId":9063,"journal":{"name":"Brain","volume":" ","pages":"e37-e38"},"PeriodicalIF":10.6,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143363626","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":"Mental health disorders before, during and after the COVID-19 pandemic: a nationwide study.","authors":"Clara S Grønkjær, Rune H B Christensen, Daniel Kondziella, Michael E Benros","doi":"10.1093/brain/awae360","DOIUrl":"10.1093/brain/awae360","url":null,"abstract":"<p><p>The coronavirus disease 2019 (COVID-19) pandemic and lockdowns prompted a major concern for mental health effects. Comprehensive nationwide studies are lacking on the indirect effect of the COVID-19 pandemic on the mental health of the population. We aimed to determine whether the COVID-19 pandemic and lockdowns affected mental health service usage, suicide attempts and suicides. This comprehensive nationwide register-linked study followed all individuals in Denmark from 1990. The main outcomes were rates of psychiatric admissions, use of psychotropic medication, suicide attempts, suicides, patients in community-based private psychiatry or psychology practices and referrals to psychiatric hospitals. The impact of the pandemic (11 March 2020-30 June 2023) and lockdowns was assessed with log-normal models adjusted for pre-pandemic trends (1 January 2017-10 March 2020). We reported rate ratios (RR) of the observed and counterfactual rates. We identified the 5 807 714 (50.3% female) individuals living in Denmark on 1 March 2020. The rates of psychiatric admissions [RR: 0.95, 95% confidence interval (CI): 0.91 to 0.99, P-value: 0.017] and suicide attempts (RR: 0.85, 95% CI: 0.76 to 0.95, P-value: 0.007) were lower during the pandemic compared with the pre-pandemic trend. The rates of suicides (RR: 0.89, 95% CI: 0.75-1.05, P-value: 0.173), patients in private practices (RR: 1.00, 95% CI: 0.96-1.04, P-value: 0.986) and referrals (RR: 1.06, 95% CI: 0.95-1.18, P-value: 0.307) were not significantly different during the pandemic compared with the pre-pandemic trend. During the first lockdown, rates were lower for psychiatric admissions (RR: 0.85, 95% CI: 0.80 to 0.90, P-value <0.001), suicide attempts (RR: 0.80, 95% CI: 0.69 to 0.94, P-value: 0.007), suicides (RR: 0.67, 95% CI: 0.52 to 0.86, P-value: 0.002), patients in private practices (RR: 0.88, 95% CI: 0.82 to 0.93, P-value <0.001) and referrals (RR: 0.69, 95% CI: 0.60 to 0.81, P-value <0.001) compared with the pre-pandemic trend. However, during the pandemic, the rate of psychotropic medication users increased by 6% compared with the pre-pandemic trend (RR: 1.06, 95% CI: 1.05 to 1.06, P-value < 0.001). The COVID-19 pandemic and lockdowns did not severely influence pre-pandemic trends of the mental health burden in the population of Denmark on a nationwide level.</p>","PeriodicalId":9063,"journal":{"name":"Brain","volume":" ","pages":"1829-1840"},"PeriodicalIF":10.6,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590009","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":"Three-dimensional tissue engineered skeletal muscle modelling facioscapulohumeral muscular dystrophy.","authors":"Marnix Franken, Erik van der Wal, Dongxu Zheng, Bianca den Hamer, Patrick J van der Vliet, Richard J L F Lemmers, Anita van den Heuvel, Alexandra L Dorn, Cas G A Duivenvoorden, Stijn L M In 't Groen, Christian Freund, Bert Eussen, Rabi Tawil, Baziel G M van Engelen, W W M Pim Pijnappel, Silvère M van der Maarel, Jessica C de Greef","doi":"10.1093/brain/awae379","DOIUrl":"10.1093/brain/awae379","url":null,"abstract":"<p><p>Facioscapulohumeral muscular dystrophy (FSHD) is caused by sporadic misexpression of the transcription factor double homeobox 4 (DUX4) in skeletal muscles. So far, monolayer cultures and animal models have been used to study the disease mechanism of FSHD and for development of FSHD therapy, but these models do not fully recapitulate the disease and there is a lack of knowledge on how DUX4 misexpression leads to skeletal muscle dysfunction. To overcome these barriers, we have developed a 3D tissue engineered skeletal muscle (3D-TESM) model by generating genetically matched myogenic progenitors from human induced pluripotent stem cells of three mosaic FSHD patients. 3D-TESMs derived from genetically affected myogenic progenitors recapitulated pathological features including DUX4 and DUX4 target gene expression, smaller myofibre diameters and reduced absolute forces upon electrical stimulation. RNA-sequencing data illustrated increased expression of DUX4 target genes in 3D-TESMs compared with 2D myotubes, and cellular differentiation was improved by 3D culture conditions. Treatment of 3D-TESMs with three different small molecules identified in drug development screens in 2D muscle cultures showed no improvements, and sometimes even declines, in contractile force and sarcomere organization. These results suggest that these compounds either have a detrimental effect on the formation of 3D-TESMs, an effect that might have been overlooked or was challenging to detect in 2D cultures and in vivo models, and/or that further development of the 3D-TESM model is needed. In conclusion, we have developed a 3D skeletal muscle model for FSHD that can be used for preclinical research focusing on DUX4 expression and downstream pathways of FSHD in relationship to contractile properties. In the future, we expect that this model can also be used for preclinical drug screening.</p>","PeriodicalId":9063,"journal":{"name":"Brain","volume":" ","pages":"1723-1739"},"PeriodicalIF":10.6,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12074006/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667128","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":"Reshaping computational neuropsychiatry beyond synaptopathy.","authors":"Hugo Bottemanne, Stephane Mouchabac, Christophe Gauld","doi":"10.1093/brain/awaf031","DOIUrl":"10.1093/brain/awaf031","url":null,"abstract":"<p><p>Computational neuropsychiatry is a leading discipline in explaining psychopathology in terms of neuronal message passing, distributed processing and belief propagation in neuronal networks. Active Inference (AI) is a way of representing this dysfunctional signal processing. According to the AI approach, all neuronal processing and action selection can be explained by maximizing Bayesian model evidence or minimizing variational free energy. Following these principles, it has been suggested that dysconnection in neuronal networks results in aberrant belief updating and erroneous inference, leading to psychiatric and neurologic symptoms. However, there is a classic distinction between disorders of inference (or synaptopathy-including the majority of psychiatric disorders) and disorders of brain function (including vascular neurological pathologies and severe forms of tauopathy and synucleinopathies). This distinction is generally based on the idea that synaptopathies impair neuromodulatory precision weighting, leading to rigid inferences or heightened sensitivity to noise, while disorders of brain function are linked to damage in the nervous system (disconnection). This makes it challenging to apply the logic of the free energy principle. We suggest that this distinction will enable future models of neuropsychiatric symptoms to be improved by considering more than neuronal message passing.</p>","PeriodicalId":9063,"journal":{"name":"Brain","volume":" ","pages":"1526-1530"},"PeriodicalIF":10.6,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051544","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":"We're all in this together: a rejoinder to Masud Husain's (rant) editorial.","authors":"Fritz Sager,Hugues Abriel,Markus Brönnimann,Andrew Chan,Heike Mayer,Virginia Richter","doi":"10.1093/brain/awaf139","DOIUrl":"https://doi.org/10.1093/brain/awaf139","url":null,"abstract":"","PeriodicalId":9063,"journal":{"name":"Brain","volume":"4 1","pages":"e43-e44"},"PeriodicalIF":14.5,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143945556","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":"Inferring the 'functions' of tracts: a cautionary note.","authors":"Emiel van den Hoven, Cornelius Weiller, Marco Reisert, Michel Rijntjes","doi":"10.1093/brain/awaf114","DOIUrl":"10.1093/brain/awaf114","url":null,"abstract":"","PeriodicalId":9063,"journal":{"name":"Brain","volume":" ","pages":"1447-1450"},"PeriodicalIF":10.6,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699588","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":"Smaller cingulate grey matter mediates the association between dual-task gait and incident dementia.","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/awae356","DOIUrl":"10.1093/brain/awae356","url":null,"abstract":"<p><p>Individuals with mild cognitive impairment who have high dual-task gait cost (≥20% slowing in gait speed while performing a cognitive brain-demanding task) are 3-fold more likely to progress to dementia. However, the cortical regions that might explain this association are unknown, which might identify potentially treatable areas. The aim of the present study was to investigate whether brain grey matter volume loss and motor cortex metabolite levels explain the association between dual-task cost and incident dementia in individuals with mild cognitive impairment. We included participants with mild cognitive impairment from the Gait and Brain Study Cohort, who had a baseline MRI and were followed up for 9 years with cognitive and gait assessments every 6 months. Gait performance was investigated in four conditions: usual gait, counting backwards by ones, naming animals and subtracting serial sevens. Dual-task cost was calculated as the percentage change in gait speed in dual-task conditions relative to usual gait speed. Data were collected from July 2007 to June 2023. From the 139 individuals with mild cognitive impairment included at baseline [mean (standard deviation) age, 73 (6) years; 62 (44%) female], 33 (24%) progressed to dementia. Baseline high dual-task cost (≥20%) during counting backwards by ones and naming animals conditions were associated with smaller grey matter volume in several brain structures. A higher ratio of choline to creatine in the primary motor cortex was associated with higher serial sevens dual-task cost. High dual-task cost while counting backwards by ones and naming animals was associated with a 3-fold risk of incident dementia (P = 0.02). Mediation analyses revealed that grey matter volume clusters localized in the right anterior and middle cingulate cortices mediated the association between counting backwards by ones dual-task cost and incident dementia (effect: 48%; P = 0.045) with no mediation observed in grey matter loss in other brain regions or through motor cortex metabolite levels. Smaller grey matter volume of the right anterior and middle cingulate cortices explained the association between high dual-task cost and incident dementia in mild cognitive impairment. This result sheds light on the neural mechanisms of cognitive-motor interaction linked with cognitive decline and dementia in mild cognitive impairment and supports the use of gait under dual-tasking as a motor biomarker of dementia.</p>","PeriodicalId":9063,"journal":{"name":"Brain","volume":" ","pages":"1551-1561"},"PeriodicalIF":10.6,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12073990/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581242","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":"Parvalbumin neurons mediate neurological phenotypes of anti-NMDAR encephalitis.","authors":"Yi-Fan Feng, Zi-Ke Zeng, You Ni, Yue Hu, Ke-Xin Yang, Fang Cai, Qin-Ming Zhou, Ming Chen, Xiao-Na Zhu, Sheng Chen, Ji Hu","doi":"10.1093/brain/awae374","DOIUrl":"10.1093/brain/awae374","url":null,"abstract":"<p><p>Patients with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis, often present with severe psychiatric symptoms, yet the neuropathological mechanisms underlying their cognitive deficits remain insufficiently understood. In this study, we constructed an animal model using anti-NMDAR IgG purified from the serum of patients with anti-NMDAR encephalitis, and we used IgG obtained from healthy individuals as a control. Daily administration of anti-NMDAR IgG into the medial prefrontal cortex (mPFC) of mice for 7 days resulted in cognitive impairments resembling clinical symptoms, which spontaneously resolved 30 days after discontinuing the injections. Immunohistochemical staining and electrophysiological testing of parvalbumin neurons in the mPFC treated with anti-NMDAR IgG revealed significant cellular morphological damage, reduced excitability, synaptic dysfunction and a loss of NMDAR antagonist-induced gamma oscillations. Application of optogenetic and pharmacogenetic techniques to activate parvalbumin neurons in the mPFC successfully reversed the cognitive impairments observed in the anti-NMDAR-IgG-treated mice. Single-cell sequencing of anti-NMDAR-IgG-treated parvalbumin neurons identified differentially expressed genes and pathways related to synapses and neuronal development, offering potential targets for therapeutic intervention. Additionally, we showed that these alterations in parvalbumin neurons were not confined to the mPFC, as similar changes were detected in the hippocampus after anti-NMDAR IgG injections. In summary, our findings elucidate distinct alterations in parvalbumin neurons during the pathogenesis of anti-NMDAR encephalitis, providing preclinical rationale for exploring approaches to modulate parvalbumin neuronal function to treat anti-NMDAR encephalitis.</p>","PeriodicalId":9063,"journal":{"name":"Brain","volume":" ","pages":"1652-1664"},"PeriodicalIF":10.6,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12073974/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603773","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}