Brain最新文献

{"title":"Reward circuit local field potential modulations precede risk taking","authors":"Natasha C Hughes, Helen Qian, Derek J Doss, Ghassan S Makhoul, Michael Zargari, Zixiang Zhao, Balbir Singh, Zhengyang Wang, Jenna N Fulton, Graham W Johnson, Rui Li, Benoit M Dawant, Dario J Englot, Christos Constantinidis, Shawniqua Williams Roberson, Sarah K Bick","doi":"10.1093/brain/awaf107","DOIUrl":"https://doi.org/10.1093/brain/awaf107","url":null,"abstract":"Risk-taking behaviour is a symptom of multiple neuropsychiatric disorders and often lacks effective treatments. Reward circuitry regions including the amygdala, orbitofrontal cortex, insula, and anterior cingulate have been implicated in risk-taking, but electrophysiological activity predictive of risk taking in these regions is not well understood in humans. Identifying local field potential frequency signatures of risk-taking may provide therapeutic insight into disorders associated with risk-taking. Eleven patients with medically refractory epilepsy who underwent stereotactic electroencephalography with electrodes in the amygdala, orbitofrontal cortex, insula, and/or anterior cingulate participated in this experiment. Patients completed a gambling task where they wagered on a visible playing card being higher than a hidden card, betting $5 or $20 on this outcome, while local field potentials were recorded from implanted electrodes. We used linear regression models and cluster-based permutation testing to identify oscillatory power modulations associated with reward prediction error signal. We also computed a risk-taking value for each trial using card number and bet choice and similarly used linear regression and cluster-based permutation testing to identify power changes associated with risk-taking value. We then used two-way ANOVA with bet and risk level to identify power clusters predictive of risky decisions. We used linear mixed effects models to evaluate the relationship between reward prediction error and risky decision signals across trials. Time-frequency clusters associated with reward prediction error were identified in the amygdala (2 clusters: all p<0.001) and orbitofrontal cortex (4 clusters: all p<0.001). Risky decisions were predicted by increased oscillatory power in theta-to-beta frequency range during card presentation in the orbitofrontal cortex (p=0.00053; η2bet=0.15, η2risk=0.27, η2bet*risk=0.017), and by high beta power in the insula (p=0.0003; η2bet=0.15, η2risk=0.20, η2bet*risk=0.0018). Subsequent analysis localized these signals to lateral orbitofrontal cortex and posterior insula respectively. The power within an insula cluster associated with risky decisions was associated with a theta-alpha reward prediction error signal in the orbitofrontal cortex (p=0.023). In addition, an amygdala reward prediction error signal was associated with overall percentage of high bets (p=0.0015) and a lateral OFC risky decision signal was associated with high bets in risky scenarios (p=0.028). Our findings identify and help characterize reward circuitry activity predictive of risk-taking in humans. These findings identify oscillatory power signatures within these regions preceding risky decisions, which may serve as potential biomarkers to inform the development of novel treatment strategies such as closed loop neuromodulation for disorders of risk taking.","PeriodicalId":9063,"journal":{"name":"Brain","volume":"6 1","pages":""},"PeriodicalIF":14.5,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143653471","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":"Genome-wide association study of neuropathological features in Lewy body disease","authors":"Rebecca R Valentino, Shunsuke Koga, Alexandra I Soto-Beasley, Daisuke Ono, Mikolaj A Wieczorek, Patrick W Johnson, Launia J White, Molly M Watkins, Melissa E Murray, Koji Kasanuki, Pamela J McLean, Wolfdieter Springer, Ryan J Uitti, Julie A Fields, Hugo Botha, Vijay K Ramanan, Kejal Kantarci, Val J Lowe, Clifford R Jack, Jose Bras, Rita Guerreiro, Nilufer Ertekin-Taner, Rodolfo Savica, Jonathan Graff-Radford, Ronald C Petersen, Joseph E Parisi, R Ross Reichard, Neill R Graff-Radford, Tanis J Ferman, Bradley F Boeve, Zbigniew K Wszolek, Dennis W Dickson, Michael G Heckman, Owen A Ross","doi":"10.1093/brain/awaf105","DOIUrl":"https://doi.org/10.1093/brain/awaf105","url":null,"abstract":"Studies assessing genetic associations with neuropathological features in Lewy body disease (LBD) have been limited to candidate gene investigations, and therefore information is lacking regarding the genetic architecture of the neuropathology of LBD. In the current study, we examined a large series of neuropathologically-confirmed LBD cases (N=980 in the discovery series, N=503 in the replication series) and performed genome-wide association studies (GWAS’s) of 11 different neuropathological outcome measures. The 11 neuropathological outcomes included Braak neurofibrillary tangle (NFT) stage, Thal amyloid phase, LBD subtype, Lewy body (LB) counts in five different brain regions, dorsolateral and ventromedial putaminal tyrosine hydroxylase immunoreactivity (TH-ir), and neuronal loss in the ventrolateral part of the substantia nigra (SN). Associations between variants and outcomes were assessed using regression models appropriate for the nature of the given neuropathological outcome and that were adjusted for age at death, sex, and top principal components of genetic data. In the discovery series, APOE rs429358 (i.e., APOE ε4) was associated with a greater severity of each of Braak NFT stage (OR=3.07, P=2.34 x 10-32), Thal amyloid phase (OR=3.57, P=3.28 x 10-29), and LBD subtype (OR=1.78, P=9.85 x 10-9), with similar findings observed in the independent replication series (Braak NFT stage, OR=2.30, P=2.70 x 10-11; Thal amyloid phase, OR=3.17, P=6.39 x 10-18; LBD subtype, OR=2.68, P=3.85 x 10-10). In the subgroup of cases with lower levels of AD pathology (Braak NFT stage ≤III and Thal amyloid phase ≤2), there was a strong association between APOE rs429358 and LBD subtype in even when adjusting for Braak stage and Thal phase in the discovery series (N=218, OR=2.47, P=0.007) and the replication series (N=141, OR=3.60, P=0.006). Although additional genome-wide significant associations were identified in the discovery series between LINC01581/MCTP2 rs547411734 and lower middle frontal LB counts, between TLE3 rs3743309 and lower cingulate LB counts, and between GRIN2A/ATF7IP2 rs1097915 and lower parahippocampal LB counts, these findings were not observed in the replication series. Our results indicate that the APOE ε4 allele is the most prominent genetic determinant of severity of neuropathology in LBD. These findings represent a key step forward in our understanding of genetic drivers of neuropathological features in LBD. Future studies utilizing meta-analytical approaches will be important to more precisely assess other associations that were not quite genome-wide significant in the discovery series.","PeriodicalId":9063,"journal":{"name":"Brain","volume":"90 1","pages":""},"PeriodicalIF":14.5,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143641107","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":"Activated αβ T- and reduced mucosa-associated invariant T cells in LGI1- and CASPR2-encephalitis.","authors":"Daniela Esser, Louisa Müller-Miny, Michael Heming, Manuela Paunovic, Martijn van Duijn, Ligia Abrante Cabrera, Katharina M Mair, Christine Strippel, Saskia Räuber, Justina Dargvainiene, Stjepana Kovac, Catharina C Gross, Nina Fransen, Robin van Steenhoven, Péter Körtvélyessy, Werner Stenzel, Romana Höftberger, Eric Bindels, Christian G Bien, Heinz Wiendl, Sven G Meuth, Jan Bauer, Nico Melzer, Maarten J Titulaer, Frank Leypoldt, Gerd Meyer Zu Hörste","doi":"10.1093/brain/awaf096","DOIUrl":"https://doi.org/10.1093/brain/awaf096","url":null,"abstract":"<p><p>Anti-Leucine-rich glioma inactivated-1 (LGI1) and anti-contactin-associated-protein-2 (CASPR2) autoimmune encephalitis (AIE) are common and characterized by pathogenic antibodies targeting neuronal autoantigens. However, the drivers of the antibody-secreting cells (ASC) and involvement of T cells remain unresolved. We performed single cell RNA-sequencing of fresh cerebrospinal fluid (CSF) and parallel blood samples of 15 patients with LGI1- (n=9) and CASPR2-AIE (n=6) compared to control patients (multiple sclerosis (MS) n=15, idiopathic intracranial hypertension (IIH) n=18). We validated our observations in independent cohorts using flow cytometry of CSF and blood. We confirmed autoantibody specificity using recombinant human monoclonal antibodies. Compared to IIH and MS controls, we observed clonal CSF-specific ASC expansion in LGI1/CASPR2-AIE despite mostly normal CSF findings. ASCs were dominantly plasmablasts and transcribed IgG4 and IgG1/2 heavy chains. Expanded clones showed signs of affinity maturation and bound the respective neuronal autoantigen. Within CD4 and CD8 T cell clusters, CD4 and CD8 central memory T cells were activated, clonally restricted and expanded. T cell clones were often shared between CSF and blood. We also observed a shift of NK cells and loss of mucosa-associated invariant T (MAIT) cells in the CSF of LGI1- and blood of LGI1- and CASPR2-AIE compared to IIH and MS controls. Indeed, MAIT-like T cells were detected in autopsy brains of LGI1 and CASPR2-AIE patients and mice lacking MAIT cells displayed an increased antibody seroconversion and higher titers following active LGI1-/CASPR2 immunization. Our data (1) confirms the intrathecal antigen-specific plasma cell expansion in LGI1- and CASPR2-AIE in a large cohort of untreated AIE patients, (2) suggests that activated and expanded central memory CD4 and CD8 T cells in the CSF participate in disease pathogenesis and (3) for the first time implicates invariant T cell receptor expressing lymphocytes in the brain, CSF and blood in disease pathogenesis.</p>","PeriodicalId":9063,"journal":{"name":"Brain","volume":" ","pages":""},"PeriodicalIF":10.6,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647114","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":"Large-scale profiling of antibody reactivity to glycolipids in patients with Guillain-Barré syndrome.","authors":"Robin C M Thomma, Susan K Halstead, Laura C de Koning, Evelin E J A Wiegers, Dawn S Gourlay, Anne P Tio-Gillen, Wouter van Rijs, Henning Andersen, Giovanni Antonini, Samuel Arends, Shahram Attarian, Fabio A Barroso, Kathleen J Bateman, Luana Benedetti, Peter Van den Bergh, Jan Bürmann, Mark Busby, Carlos Casasnovas, Efthimios Dardiotis, Amy Davidson, Thomas E Feasby, Janev Fehmi, Giuliana Galassi, Tania Garcia-Sobrino, Volkan Granit, Gerardo Gutiérrez-Gutiérrez, Robert D M Hadden, Thomas Harbo, Hans-Peter Hartung, Imran Hasan, James K L Holt, Zhahirul Islam, Summer Karafiath, Hans D Katzberg, Noah Kolb, Susumu Kusunoki, Satoshi Kuwabara, Motoi Kuwahara, Helmar C Lehmann, Sonja E Leonhard, Lorena Martín-Aguilar, Soledad Monges, Eduardo Nobile-Orazio, Julio Pardo, Yann Pereon, Luis Querol, Ricardo C Reisin, Simon Rinaldi, Paolo Ripellino, Rhys C Roberts, Olivier Scheidegger, Nortina Shahrizaila, Kazim A Sheikh, Nicholas J Silvestri, Soren H Sindrup, Beth Stein, Cheng Y Tan, Hatice Tankisi, Leo H Visser, Waqar Waheed, Ruth Huizinga, Bart C Jacobs, Hugh J Willison","doi":"10.1093/brain/awaf102","DOIUrl":"https://doi.org/10.1093/brain/awaf102","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Guillain-Barré syndrome is an acute polyradiculoneuropathy in which preceding infections often elicit the production of antibodies that target peripheral nerve antigens, principally gangliosides. Anti-ganglioside antibodies are thought to play a key role in the clinical diversity of the disease and can be helpful in clinical practice. Extensive research into clinical associations of individual anti-ganglioside antibody specificities has been performed. Recent research has highlighted glycolipid complexes, glycolipid combinations that may alter antibody binding, as targets. In this study, we investigated antibody reactivity patterns to glycolipids and glycolipid complexes using combinatorial array, in relation to clinical features in Guillain-Barré syndrome. In total, 1413 patients from the observational International Guillain-Barré syndrome Outcome Study (0-91 years, 60.3% male) and 1061 controls (healthy, family, infectious, vaccination, other neurological disease) were included. Acute-phase sera from patients were screened for IgM, IgG, and IgA reactivity against 15 glycolipids and one phospholipid and their heteromeric complexes, similarly to archived control sera. Antibody specificities and reactivity patterns were analysed in relation to clinical features. Of all patients, 1309 (92.6%) were positive for at least one anti-glycolipid (complex) antibody. Anti-GM1 and anti-GQ1b (complex) antibodies best distinguished motor Guillain-Barré syndrome and Miller Fisher syndrome from controls, with antibodies to glycolipid complexes outperforming antibodies to single glycolipids. Three models consisting of anti-glycolipid (complex) antibodies distinguished patients with Guillain-Barré syndrome, the motor variant, and Miller Fisher syndrome from controls with high sensitivity and specificity, performing better than antibodies to single glycolipids used in clinical practice. Seven patient clusters with particular antibody reactivity patterns were identified. These clusters were distinguished by geographical region, clinical variants, preceding Campylobacter jejuni infection, electrophysiological subtypes, the Medical Research Council sum score at study entry, and the ability to walk 10 meters unaided at 26 weeks. Two patient clusters with distinct anti-GM1 (complex) reactivity (broad versus restricted) differed in frequency of the axonal subtype. In cumulative incidence analyses, 15 anti-glycolipid (complex) antibodies were associated with the time required to regain the ability to walk 10 meters unaided. After adjustment for known prognostic factors, IgG anti-GQ1b:GM4, GQ1b:PS, and GQ1b:Sulphatide remained associated with faster recovery. Addition of anti-glycolipid antibodies to clinical prognostic models slightly improved their discriminative capacity, though insufficiently to improve the models. Measurement of anti-glycolipid antibodies by combinatorial array increases the diagnostic yield compared to assaying single glycolipids, identifies cl","PeriodicalId":9063,"journal":{"name":"Brain","volume":" ","pages":""},"PeriodicalIF":10.6,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647116","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":"How modular are modules in visual cortex?","authors":"Martin N Hebart","doi":"10.1093/brain/awaf100","DOIUrl":"https://doi.org/10.1093/brain/awaf100","url":null,"abstract":"This scientific commentary refers to ‘Visual feature processing in a large stroke cohort: evidence against modular organization’ by Lugtmeijer, Sobolewska et al. (https://doi.org/10.1093/brain/awaf009).","PeriodicalId":9063,"journal":{"name":"Brain","volume":"3 1","pages":""},"PeriodicalIF":14.5,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143618478","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":"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":"https://doi.org/10.1093/brain/awaf082","url":null,"abstract":"<p><p>Ischemic 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. In order 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 fibers 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 72h, 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":""},"PeriodicalIF":10.6,"publicationDate":"2025-03-12","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":"Modulating inhibitory synaptic plasticity to restore basal ganglia dynamics in Parkinson’s disease","authors":"Kiah A Spencer, Alexandra Boogers, Srdjan Sumarac, David B J Crompton, Leon A Steiner, Luka Zivkovic, Yijinmide Buren, Alexandre Boutet, Andres M Lozano, Suneil K Kalia, William D Hutchison, Alfonso Fasano, Luka Milosevic","doi":"10.1093/brain/awaf103","DOIUrl":"https://doi.org/10.1093/brain/awaf103","url":null,"abstract":"Parkinson’s disease is characterized, in part, by hypoactivity of direct pathway inhibitory projections from striatum to the globus pallidus internus (GPi) and indirect pathway inhibitory projections from globus pallidus externus (GPe) to the subthalamic nucleus (STN). In people with Parkinson’s disease (n=32), we explored the potential use of intracranial stimulation for eliciting long-term potentiation (LTP) of these underactive pathways to produce improvement of symptoms that persists beyond stimulation cessation. During GPi deep brain stimulation (DBS) surgery, we found strong evidence (p&amp;lt;.05; BF10&amp;gt;10) of increased amplitudes of hand movements and striato-GPi evoked potentials before versus after high-frequency microstimulation. In a small sample of outpatients with sensing-enabled GPi-DBS, we found anecdotal evidence (p&amp;lt;.10; BF10&amp;gt;1) of improved hand movements and attenuated beta frequency oscillations. In STN, enduring behavioural effects, potentiation of GPe-STN projections (intraoperative), and decreases to beta oscillations (extraoperative) were not observed. Our findings support that LTP-like effects in GPi may produce motor improvements that extend beyond stimulation cessation, while the lack of effects in STN suggests the need for optimizing stimulation paradigms for effective LTP induction. These findings nevertheless highlight the potential of LTP-based strategies for sustained therapeutic benefits, which may be useful for mitigating DBS side-effects and optimizing battery usage.","PeriodicalId":9063,"journal":{"name":"Brain","volume":"31 1","pages":""},"PeriodicalIF":14.5,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143607988","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":"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":"https://doi.org/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":""},"PeriodicalIF":10.6,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcallosal inhibition does not influence subacute motor recovery in mild-to-moderate stroke","authors":"Emily Fokas, Myriam Taga, Leticia Hayes, Charalambos C Charalambous, Sharmila Raju, Ziyue Wang, Yongzhao Shao, Pietro Mazzoni, Valentin Stepanov, Els Fieremans, Heidi Schambra","doi":"10.1093/brain/awaf095","DOIUrl":"https://doi.org/10.1093/brain/awaf095","url":null,"abstract":"After stroke, upper extremity (UE) motor recovery may be mediated in part by transcallosal projections between hemispheres. The interhemispheric competition model posits that transcallosal inhibition (TI) from the contralesional hemisphere is abnormally strengthened following stroke and interferes with motor recovery. This model has recently been questioned. In this longitudinal study, we aimed to definitively confirm or refute a maladaptive role of contralesional TI in subacute motor recovery. We assessed 30 mild-to-moderately impaired subjects over the six months following ischemic stroke. We tracked contralesional TI and motor functions in the proximal and distal segments of the paretic UE. We used transcranial magnetic stimulation to examine the ipsilateral silent period (iSP) in an arm and hand muscle. We used quantitative and clinical testing to examine deficits in muscle strength, motor control, and individuation; UE segmental impairment; and UE activity limitation. We assessed the relationships of contralesional TI to motor functions in the subacute period. Despite recovery of most motor functions in the proximal and distal UE, contralesional TI was largely static and unrelated to recovery of any motor function. There were inconsistent associations between stronger TI, less hand impairment, and less activity limitation in the subacute period overall. We found no compelling evidence to suggest a maladaptive role of contralesional TI in UE motor recovery in mild-to-moderately impaired stroke subjects. The scattered associations between stronger TI and better levels of paretic UE function suggest a potential supportive role rather than a limiting one. These findings challenge the validity of the interhemispheric competition model in the subacute recovery period, and prompt reconsideration of neuromodulatory strategies that subacutely target contralesional TI.","PeriodicalId":9063,"journal":{"name":"Brain","volume":"2 1","pages":""},"PeriodicalIF":14.5,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143599800","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: Why the threat of psychosocial reductionism to patients in psychiatry and medicine is rather ignored.","authors":"Thomas A Pollak","doi":"10.1093/brain/awaf092","DOIUrl":"https://doi.org/10.1093/brain/awaf092","url":null,"abstract":"","PeriodicalId":9063,"journal":{"name":"Brain","volume":" ","pages":""},"PeriodicalIF":10.6,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143595753","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}