Brain最新文献

{"title":"Effects of atidarsagene autotemcel gene therapy on peripheral nerves in late-infantile metachromatic leukodystrophy","authors":"Alberto A Zambon, Paola M V Rancoita, Angelo Quattrini, Calogera Butera, Francesco Gentile, Marcella Facchini, Sara Mazza, Salvatore Recupero, Vera Gallo, Andrew Shenker, Nicholas D Gollop, Ubaldo Del Carro, Valeria Calbi, Clelia Di Serio, Maria Grazia Natali Sora, Massimo Filippi, Alessandro Aiuti, Francesca Fumagalli","doi":"10.1093/brain/awaf157","DOIUrl":"https://doi.org/10.1093/brain/awaf157","url":null,"abstract":"This study evaluates the efficacy of arsa-cel gene therapy (GT) in mitigating the severity and progression of peripheral neuropathy as assessed by nerve conduction velocity (NCV) in individuals affected by late-infantile metachromatic leukodystrophy (LI-MLD). This is a post-hoc analysis conducted on pre-symptomatic patients affected by LI-MLD treated with ex vivo autologous hematopoietic stem cell GT (atidarsagene autotemcel, “arsa-cel”) in the context of prospective open-label, single-arm, interventional trials and expanded access programs. All patients were followed longitudinally with nerve conduction studies (NCSs) of peripheral motor (ulnar - UN, deep peroneal - DPN) and sensory (median - MN, sural - SN) nerves. These results were compared with those from a control group of untreated patients (NHx) studied with the same standardized protocol. We then analyzed the effects of baseline characteristics (age at treatment, severity of neuropathy pre-treatment expressed as age-matched NCV Z-scores) and arylsulfatase A (ARSA) enzyme activity (measured in peripheral blood myeloid CD15+ cells post treatment) on NCVs of treated patients. The primary endpoint of this post-hoc analysis was NCV, reflecting severity of demyelinating neuropathy. Changes in dermal nerve histopathology in skin biopsies were used as an exploratory outcome. Fifteen treated and 16 NHx patients were included in the analyses, with a median age (IQR) at treatment of 13 (9.1;14.5) months. At 36 months of age, treated patients showed higher estimated NCVs in all nerves compared to age-matched controls (∼15 m/s difference in motor nerves). Peripheral neuropathy was observed in the majority of treated patients at their pre-treatment examination (age range 7.3-17.4 months). Severity of pre-treatment neuropathy in treated patients did not have an effect on NCV values at 2 years post-GT, or on the rate of NCV slowing afterwards. A younger age at treatment was associated with higher NCVs of motor UN and sensory MN 2 years post-GT. Overall, ARSA levels in CD15+ cells correlated with NCVs of motor DPN at 2 years post-GT, and ARSA levels were associated with a slower decrease or a slight increase in NCVs of the DPN, UN and MN nerves afterwards. In summary, peripheral neuropathy assessed by NCV is significantly ameliorated in LI patients treated with arsa-cel compared to untreated patients of similar age. In addition to the potential role of early age at treatment in the preservation of myelin, supraphysiological ARSA levels may slow demyelination of the DPN and other peripheral nerves. Arsa-cel may exert a stronger effect on NCV than allogeneic hematopoietic stem cell transplantation due to its greater ARSA expression.","PeriodicalId":9063,"journal":{"name":"Brain","volume":"17 1","pages":""},"PeriodicalIF":14.5,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143878126","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":"Markers of axonal injury in blood and tissue triggered by acute and chronic demyelination","authors":"Ahmed Abdelhak, Christian Cordano, Greg J Duncan, Katie Emberley, Sonia Nocera, Wendy Xin, Kirtana Ananth, Nour Jabassini, Kiarra Ning, Henriette Reinsberg, Frederike Cosima Oertel, Alexandra Beaudry-Richard, Jens Kuhle, Axel Petzold, Praveen J Patel, Ana P Ribeiro Reis, Paul Foster, Trent Watkins, Jonah Chan, Ben Emery, Ari J Green","doi":"10.1093/brain/awaf144","DOIUrl":"https://doi.org/10.1093/brain/awaf144","url":null,"abstract":"Neuroaxonal injury is a major driver of irreversible disability in demyelinating conditions. Accurate assessment of the association between demyelination and axonal pathology is critical for evaluating and developing effective therapeutic approaches. Measuring neurofilament light chain (NfL) in blood could putatively allow longitudinal monitoring of neuroaxonal injury at “single protein resolution” with high pathological specificity. Here, we demonstrate a robust association between blood and tissue NfL-based assessment of neuroaxonal injury and severity of inflammatory demyelination in experimental autoimmune encephalitis (EAE). In EAE, high levels of NfL were evident at peak of demyelination and correlated with tissue evidence of NfL loss when using antibodies that target the same NfL epitopes. In addition, we validate the longitudinal NfL dynamics in relation to de- and remyelination in an inducible genetic model of inflammatory-independent myelin loss. Through inducible knockout of myelin regulatory protein (Myrf) in proteolipid protein (PLP) expressing cells in Myrffl/fl PLP1-CreERT (MyrfΔiPLP) mice, serum NfL peaked at time of demyelination and were reduced following effective remyelination. In people with multiple sclerosis, the most common demyelinating condition, we confirmed the association between NfL and myelin breakdown proteins in two independent cohorts using Olink proximity extension assays, the ReBUILD clinical trial, and the MS participants in the UK-Biobank. Our study provides a translational framework to understand the biology behind NfL changes in the context of de- and remyelination and reveals novel aspects related to monitoring potentially reversible neuroaxonal pathology in humans and rodents.","PeriodicalId":9063,"journal":{"name":"Brain","volume":"254 1","pages":""},"PeriodicalIF":14.5,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143875944","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":"Interferon-γ causes myogenic cell dysfunction and senescence in immune myopathies","authors":"Cyrielle Hou, Baptiste Periou, Marianne Gervais, Ludovic Martin, Juliette Berthier, Yasmine Baba-Amer, Sarah Souvannanorath, Emmanuele Lechapt-Zalcman, Edoardo Malfatti, Romain K Gherardi, Fréderic Relaix, Maximilien Bencze, François Jérôme Authier","doi":"10.1093/brain/awaf153","DOIUrl":"https://doi.org/10.1093/brain/awaf153","url":null,"abstract":"Idiopathic immune myopathies (IIM) represent a heterogeneous group of diseases, in which muscle lesions result from deregulated immune reactions. Typical histological features include myofibre necrosis, leukocyte infiltration, and aberrant myofibre Major Histocompatibility Complex (MHC) expression. To investigate the link between MHC expression, inflammation, and muscle lesions, muscle biopsies from IIM patients were analysed by transcriptomics. Both, anti-synthetase syndrome (ASS) and inclusion body myositis (IBM) displayed the upregulation of IFNγ and senescence signalling pathways. Notably, IFNγ expression significantly correlated with myofibre atrophy in ASS and IBM muscle biopsies. In addition to MHC-II expression at the myofibre sarcolemma in IBM, we observed a marked overexpression in the muscle stem cells (MuSC) population, suggesting that resident satellite cells respond to IFNγ in this condition. To examine the link between IFNγ and muscle atrophy via MuSCs, we implanted an osmotic pump chronically releasing recombinant mouse IFNγ in wild-type mice subjected to acute muscle injury. Under IFNγ exposure, post-injury muscle repair was associated with significantly reduced muscle weight and myofibre diameter, while promoting interstitial fibrosis and fat deposition. The mechanism of action of the IFNγ-induced myofibre atrophy was further investigated in vitro using cultured human MuSCs. IFNγ stimulation dramatically impaired MuSCs proliferation, fusion, and promoted cell senescence. Isolated myofibres from IFNγ-treated wild-type mice displayed a significant decrease of MyoD expression and cell cycling, suggesting that IFNγ also prevents MuSC activation. In vitro, ruxolitinib, a commercially available JAK1/2 antagonist, blocked IFNγ-induced expression of MHC-II, restored normal MuSC proliferation, and reduced β-Galactosidase activity, a marker of cell senescence. In vivo, oral delivery of ruxolitinib improved myofibre size and biomarkers of muscle atrophy. Our study provides multiple lines of evidence that IFNγ may mediate muscle atrophy in IBM patients. The identified mechanism of action involves JAK1/2 pathways, which impair MuSC function by preventing post-lesion myogenesis and promoting cell senescence. Our data suggest that repurposing JAK1/2 inhibitors may offer a new therapeutic option for treating IBM, a condition known for its resistance to classical immunosuppressant drugs, despite their effectiveness in other IIM.","PeriodicalId":9063,"journal":{"name":"Brain","volume":"66 1","pages":""},"PeriodicalIF":14.5,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143884834","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":"Neuropsychiatric symptoms and progression to pathologically confirmed Alzheimer’s disease","authors":"Sergio F Sharif, Dylan X Guan, Tamara Bodnar, Jeffery T Joseph, Henrik Zetterberg, Eric E Smith, Zahinoor Ismail","doi":"10.1093/brain/awaf156","DOIUrl":"https://doi.org/10.1093/brain/awaf156","url":null,"abstract":"Whether or not neuropsychiatric symptoms (NPS) in advance of dementia are associated with Alzheimer disease (AD) and/or other neurodegenerative dementias remains to be determined. The mild behavioural impairment (MBI) construct selects persons with NPS that are later-life emergent and persistent to identify a high-risk group for cognitive decline and incident dementia. Here, in older adults without dementia at baseline, we examined whether postmortem AD and other neurodegenerative pathologies were associated with MBI in the five years before death. National Alzheimer’s Coordinating Center study autopsy participants (n=1016, 82.6 years, 48.7% female, 60% normal cognition) were included in the analyses. Using the Neuropsychiatric Inventory–Questionnaire, MBI+ status was operationalized as NPS persistence at >2/3 of pre-dementia study visits; otherwise, status was non-MBI NPS. The presence of AD, Lewy body disease (LBD), and TDP-43 neuropathological changes were determined using published guidelines. Adjusted multinomial logistic regressions modeled pathology-NPS status associations. Adjusted Cox proportional hazards regressions modeled hazard for AD-dementia at each NPS status level, including interaction terms with cognitive status and each co-pathology. AD+ individuals (51.4%) were 88.4% more likely to be MBI+ ∼5 years prior than AD- individuals (odds ratio (OR):1.88, 95% confidence interval (CI):1.29-2.75, p<0.01); however, the likelihood of having non-MBI NPS was not different (OR:1.22, CI:0.90-1.66, p=0.20). No significant associations were seen for LBD pathology, even among AD+ participants. There were no significant differences in the levels of LBD or TDP-43 in those with MBI compared to no MBI. Among MBI progressors to dementia (n=106), 33.0% were solely AD+, 18.9% were mixed AD+/LBD+, and 11.3% had all three pathologies. For all those with MBI (including dementia non-progressors), of persons with LBD, 83.4% were comorbid with AD. In the survival analysis, MBI+ individuals had a 2.03-fold greater progression rate to AD-dementia than noNPS (CI: 1.60-2.57, p<0.01). Progression rate was higher in MCI, but the effect of MBI on progression was greater in NC (HR:3.05, CI:1.37-6.80, p<0.01) vs. MCI (HR:1.93, CI:1.51-2.47, p<0.01). Limbic LBD appeared to also moderate the association between MBI and incident AD (Limbic LBD+ HR: 4.64, CI: 2.05-10.50, p<0.001; Limbic LBD- HR: 1.87, CI: 1.46-2.40, p<0.001). Antecedent MBI was strongly associated with AD pathology but not with other neurodegenerative dementias. Inclusion of MBI in research and clinical frameworks for dementia may aid in identification of early stages of neurodegenerative disease, which may be helpful for selecting patients for treatment with AD disease-modifying drugs.","PeriodicalId":9063,"journal":{"name":"Brain","volume":"48 1","pages":""},"PeriodicalIF":14.5,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143875946","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 of sodium channel mutations in sensory neurons reverses aberrant properties","authors":"Jaehoon Shim, Brian Tanaka, Daniel G Taub, Malgorzata A Mis, Betsy R Schulman, Andrew Snavely, Yung-Chih Cheng, Cedric Laedermann, Elizabeth D Buttermore, Alexander Ren, Crystal Hermawan, Dan Dou, Riki Kawaguchi, Daniel H Geschwind, Sulayman Dib-Hajj, Stephen G Waxman, Clifford J Woolf","doi":"10.1093/brain/awaf155","DOIUrl":"https://doi.org/10.1093/brain/awaf155","url":null,"abstract":"Inherited erythromelalgia, small fiber neuropathy and paroxysmal extreme pain disorder are caused by gain-of-function mutations in the voltage gated sodium channel Nav1.7. How different mutations in the same channel enhancing electrogenesis in sensory neurons results in such distinct disease presentations remains unknown. Most of the work analysing the impact of these mutations on electrophysiological properties has utilized over-expression systems in cell lines and rodent sensory neurons, which may differ from the natural context. We have differentiated sensory neurons from iPSCs derived from patient samples that have the Nav1.7 A1632G mutation. This strategy reveals changes in electrophysiological properties not previously observed in cell lines, that may be important for disease presentation. Further, using CRISPR/Cas9, we corrected this mutation which reduced the underlying hyperexcitability, providing a path for personalized medicine to treat these disorders and introduced the mutation into control iPSCs which generated hyperexcitability providing causality. iPSC sensory neurons are a robust, scalable, and relevant model to study the effects of gain-of-function mutations in ion channels in pain-related disorders.","PeriodicalId":9063,"journal":{"name":"Brain","volume":"7 1","pages":""},"PeriodicalIF":14.5,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143875945","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":"A mouse model of GRIN2D developmental and epileptic encephalopathy recapitulates the human disease","authors":"Mor Yam, Jolan Nassir, Danielle Galber, Shir Quinn, Roni Gal, Mor Ovadia, Mor Bordeynik-Cohen, Eden Peled, Christopher D Makinson, Moran Hausman Kedem, Aviva Fattal-Valevski, Wayne N Frankel, Karen B Avraham, Moran Rubinstein","doi":"10.1093/brain/awaf149","DOIUrl":"https://doi.org/10.1093/brain/awaf149","url":null,"abstract":"Pathogenic variants in GRIN2D, encoding one of the subunits of the NMDA receptor (NMDAR), are associated with developmental and epileptic encephalopathies (DEEs). Unusual for de novo mutations, the recurrent, de-novo, gain of function, missense mutation c.1999G>A (p.Val667Ile) was discovered in multiple patients. We characterized a mouse model carrying the orthologous Grin2d mutation, using behavioral paradigms, electrophysiological recordings in acute brain slices focusing mainly on the activity of Purkinje neurons (PNs) in the cerebellum, and electrocorticography (ECoG) recordings monitoring brain activity and the response to several drugs. Grin2d mutant mice exhibit a range of phenotypes that closely mirror the human disease, including premature mortality, spontaneous seizures, and early onset of motor deficits followed by cognitive impairment. In addition, we observed complex developmental changes in PNs with reduced spontaneous firing in immature mice and augmented synaptic response to NMDA application in older mice. ECoG recordings demonstrated profound and continuous abnormal brain activity, with altered spectral properties and a prominent narrowband activity in the theta, alpha, and beta bands, paralleling the patterns seen in a patient with the same GRIN2D pathogenic variant. Acute administration of ketamine at a low dose (0.5 mg/kg) had a limited effect on the spectral properties, and higher dosages (4 or 10 mg/kg) caused seizures. Conversely, memantine (10 mg/kg) and phenytoin (30 mg/kg) demonstrated a small corrective effect on ECoG properties. Together, Grin2d mutant mice recapitulate key phenotypes of patients with pathogenic GRIN2D variants, including unique, abnormal brain oscillations, which may serve as a biomarker for quantifying drug responses and guiding future research efforts.","PeriodicalId":9063,"journal":{"name":"Brain","volume":"37 1","pages":""},"PeriodicalIF":14.5,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143875943","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":"Shedding light on a novel circuit within primary motor cortex as a target for neuromodulation.","authors":"Caroline Tscherpel,Christian Grefkes","doi":"10.1093/brain/awaf128","DOIUrl":"https://doi.org/10.1093/brain/awaf128","url":null,"abstract":"","PeriodicalId":9063,"journal":{"name":"Brain","volume":"37 1","pages":""},"PeriodicalIF":14.5,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143866499","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":"Disease-modifying effects of TMEM106B in genetic frontotemporal dementia: a longitudinal GENFI study.","authors":"Saira S Mirza,Maurice Pasternak,Andrew D Paterson,Ekaterina Rogaeva,Maria C Tartaglia,Sara B Mitchell,Sandra E Black,Morris Freedman,David Tang-Wai,Arabella Bouzigues,Lucy L Russell,Phoebe H Foster,Eve Ferry-Bolder,Martina Bocchetta,David M Cash,Henrik Zetterberg,Aitana Sogorb-Esteve,John van Swieten,Lize C Jiskoot,Harro Seelaar,Raquel Sanchez-Valle,Robert Laforce,Caroline Graff,Daniela Galimberti,Rik Vandenberghe,Alexandre de Mendonça,Pietro Tiraboschi,Isabel Santana,Alexander Gerhard,Johannes Levin,Sandro Sorbi,Markus Otto,Florence Pasquier,Simon Ducharme,Chris Butler,Isabelle Le Ber,Elizabeth Finger,James B Rowe,Matthis Synofzik,Fermin Moreno,Barbara Borroni,Jonathan D Rohrer,Mario Masellis,","doi":"10.1093/brain/awaf019","DOIUrl":"https://doi.org/10.1093/brain/awaf019","url":null,"abstract":"Common variants within TMEM106B are associated with risk for frontotemporal lobar degeneration with TDP-43 pathology (FTLD-TDP). The G allele of the top single nucleotide polymorphism, rs1990622, confers protection against FTLD-TDP, including genetic cases due to GRN mutations or C9orf72 hexanucleotide repeat expansions. However, the effects of interaction between TMEM106B-rs1990622 and frontotemporal dementia (FTD) mutations on disease endophenotypes in genetic FTD are unknown. This longitudinal cohort study was embedded within the GENetic Frontotemporal dementia Initiative (GENFI). We included 518 participants from 222 families [209 non-carriers; 222 presymptomatic carriers (C9orf72 = 79; GRN = 101, MAPT = 42); 87 symptomatic carriers (C9orf72 = 45; GRN = 29; MAPT = 13)] followed for up to 7 years. Using linear mixed-effects models, we examined the effects of a triple interaction between TMEM106B-rs1990622G allele dosage (additive model: 0, 1 or 2 alleles) and autosomal dominant FTD mutations with clinical status, and time from baseline on (i) grey matter volume using a voxel-based analysis; (ii) serum neurofilament light chain (NfL) levels; and (iii) cognitive and behavioural measures. Mean age of participants was 47.9 ± 13.8 years, 58.1% were female and 61% had at least one G allele. C9orf72: rs1990622G allele dosage was associated with less atrophy within the right occipital region in presymptomatic carriers at baseline, and reduced atrophy rate within putamen and caudate nucleus, right frontotemporal regions, left cingulate and bilateral insular cortices in symptomatic carriers over time; lower NfL levels in presymptomatic carriers at baseline; better executive functions and language abilities in presymptomatic carriers; and maintained overall cognitive functions and behaviour in symptomatic carriers over time. GRN: rs1990622G allele dosage was associated with reduced grey matter atrophy rate within the right temporal and occipital regions in presymptomatic carriers, and within the right frontal cortex and insula over time in symptomatic carriers; lower serum NfL levels over time in presymptomatic carriers and lower NfL levels at both baseline and over time in symptomatic carriers; and better global cognitive performance at baseline and higher attention/processing speed scores over time in symptomatic carriers. MAPT: rs1990622G allele dosage was associated with reduced grey matter atrophy rate within the right inferior frontal gyrus in symptomatic carriers, but no effects on serum NfL or cognitive/behavioural measures. TMEM106B-rs1990622G allele dosage showed protective effects on multiple endophenotypes predominantly in GRN and C9orf72 groups. Therefore, TMEM106B genotype should be assessed in clinical trials, particularly of GRN- and C9orf72-related genetic FTD, due to its modifying effects on biomarker, imaging, cognitive and clinical outcomes.","PeriodicalId":9063,"journal":{"name":"Brain","volume":"8 1","pages":""},"PeriodicalIF":14.5,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143866739","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":"CSF amyloid-β40 levels are not associated with efficacy outcomes in Alzheimer's disease trials.","authors":"Jesus Thomas Abanto,Alok K Dwivedi,Bruno P Imbimbo,Alberto J Espay","doi":"10.1093/brain/awaf143","DOIUrl":"https://doi.org/10.1093/brain/awaf143","url":null,"abstract":"","PeriodicalId":9063,"journal":{"name":"Brain","volume":"5 1","pages":""},"PeriodicalIF":14.5,"publicationDate":"2025-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143853086","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":"Abreaction: a humble suggestion","authors":"Norman A Poole","doi":"10.1093/brain/awaf142","DOIUrl":"https://doi.org/10.1093/brain/awaf142","url":null,"abstract":"Abreaction was once a common treatment for functional neurological disorder (FND) but has since fallen out of use. Norman Poole argues that abreaction is compatible with many findings from modern neuroscience, and should be studied and tested as a treatment for FND.","PeriodicalId":9063,"journal":{"name":"Brain","volume":"34 1","pages":""},"PeriodicalIF":14.5,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143841640","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}