Brain communications最新文献

{"title":"Sexual dimorphisms in innate immune activation markers in predementia Alzheimer's disease.","authors":"Stephanie Knudtzon, Kaja Nordengen, Lene Pålhaugen, Berglind Gísladóttir, Jonas Jarholm, Geir Bråthen, Ragnhild Eide Skogseth, Knut Waterloo, Per Selnes, Tormod Fladby, Bjørn-Eivind Kirsebom","doi":"10.1093/braincomms/fcaf161","DOIUrl":"https://doi.org/10.1093/braincomms/fcaf161","url":null,"abstract":"<p><p>Females have an increased risk of developing Alzheimer's disease (AD). The innate immune system plays a key role in AD pathology, and sex differences in innate immune responses may contribute to differences in disease risk and progression. This study investigated sex differences in innate immune responses among participants without cerebrospinal fluid (CSF) determined amyloid pathology [A-; cognitively normal (CN), <i>n</i> = 83] and those with amyloid pathology (A+, <i>n</i> = 202), further stratified into preclinical (CN with A+, <i>n</i> = 72) and mild cognitive impairment (MCI with A+, <i>n</i> = 130). Participants were drawn from the Norwegian Dementia Disease Initiation cohort (<i>n</i> = 285). We measured plasma glial fibrillary acidic protein (GFAP) and CSF concentrations of nine innate immune markers: soluble triggering receptor expressed on myeloid cells 2 (sTREM2), monocyte chemoattractant protein 1 (MCP-1), fractalkine, chitinase 3-like 1 (YKL-40), clusterin, interferon gamma (IFN-γ), interleukin-6 (IL-6), IL-10, and IL-18. Linear regression was used, adjusted for multiple comparisons using the false discovery rate. In A+ cases (<i>n</i> = 202, females = 105), females had lower MCP-1 (<i>P</i>  <i><</i> 0.01), IL-6 and IL-18 (both <i>P</i>  <i><</i> 0.05) than males, while no sex differences were observed in A- cases (<i>n</i> = 83, females = 39). Among A+ participants, no sex differences were observed in CN cases (<i>n</i> = 72, females = 37), but females (<i>n</i> = 68) with MCI had lower MCP-1 and IL-6 (both <i>P</i>  <i><</i> 0.05) than males (<i>n</i> = 62) with MCI. Moreover, A+ females exhibited stronger positive associations between sTREM2 and clusterin with CSF total tau (<i>P</i> < 0.001; <i>P</i> < 0.05) and Neurofilament light chain (<i>P</i> < 0.01; <i>P</i> < 0.01) than males. These findings suggest sex-specific differences in innate immune responses, which may contribute to disease progression in amyloid-positive individuals.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 3","pages":"fcaf161"},"PeriodicalIF":4.1,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12046404/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144055475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aberrant preparation of hand movement in schizophrenia spectrum disorder: an fMRI study.","authors":"Harun A Rashid, Tilo Kircher, Benjamin Straube","doi":"10.1093/braincomms/fcaf148","DOIUrl":"https://doi.org/10.1093/braincomms/fcaf148","url":null,"abstract":"<p><p>Schizophrenia spectrum disorder is linked to impaired self-other distinction and action feedback monitoring, largely stemming from sensory-motor predictive mechanisms. However, the neural correlates of these predictive processes during movement preparation are unknown. Here, we investigated whether patients with schizophrenia spectrum disorder exhibit aberrant sensory-motor predictive processes reflected in neural activation patterns prior to hand movement onset. Functional MRI data from patients with schizophrenia spectrum disorder (<i>n</i> = 20) and healthy controls (<i>n</i> = 20) were acquired during actively performed or passively induced hand movements. The task required participants to detect temporal delays between their movements and video feedback, which either displayed their own (self) or someone else's (other) hand moving in accordance with their own hand movements. Patients compared with healthy controls showed reduced preparatory blood-oxygen-level-dependent activation (active > passive) in clusters comprising the left putamen, left insula, left thalamus and lobule VIII of the right cerebellum. Reduced activation in the left insula and putamen was specific to own-hand feedback. Additionally, patients with schizophrenia spectrum disorder revealed reduced suppression (passive > active) in bilateral and medial parietal (including the right angular gyrus) and occipital areas, the right postcentral gyrus, cerebellum crus I, as well as the left medial superior frontal gyrus. Ego-disturbances were negatively correlated with left insula and putamen activation during active conditions and with right angular gyrus activation patterns during passive conditions when own-hand feedback was presented. These functional MRI findings suggest that group differences are primarily evident during preparatory processes. Our results show that this preparatory neural activation is further linked to symptom severity, supporting the idea that the preparation of upcoming events as internal predictive mechanisms may underlie severe symptoms in patients with schizophrenia spectrum disorder. These findings could improve our understanding of deficits in action planning, self-monitoring and motor dysfunction in various psychiatric, neurological and neurodegenerative disorders.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 2","pages":"fcaf148"},"PeriodicalIF":4.1,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12022610/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144044123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low-grade gliomas do not grow along white matter tracts: evidence from quantitative imaging.","authors":"Philip Rauch, Matthias Gmeiner, Martin Aichholzer, Matthias Sterrer, Helga Wagner, Stefan Katletz, Carlo Serra, Petra Böhm, Michael Sonnberger, Nico Stroh, Stefan Aspalter, Kathrin Aufschnaiter-Hiessböck, Tobias Rossmann, Francisco Ruiz-Navarro, Maria Gollwitzer, Annette Leibetseder, Josef Pichler, Wolfgang Thomae, Raimund Kleiser, Andreas Gruber, Harald Stefanits","doi":"10.1093/braincomms/fcaf157","DOIUrl":"https://doi.org/10.1093/braincomms/fcaf157","url":null,"abstract":"<p><p>Low-grade gliomas are infiltrative brain tumors that can lead to significant neurological deficits due to their invasive nature. The prevailing belief is that low-grade gliomas primarily disseminate along white matter tracts, but quantitative <i>in vivo</i> evidence supporting this concept is lacking. Clarifying their true growth patterns is essential for optimizing therapeutic strategies. We conducted a quantitative analysis of tumor growth patterns in a longitudinal cohort of 43 untreated patients with unigyral World Health Organization grade 2 or 3 gliomas, stratified by their anatomical locations within the neocortex, mesocortex and allocortex. Serial MRI scans were used to generate vector deformation fields, providing detailed three-dimensional representations of tumor evolution over time. These vector deformation fields were compared with diffusion tensor imaging data to assess the alignment of tumor growth with white matter pathways. Quantitative analysis revealed that low-grade gliomas do not predominantly expand along white matter tracts. Instead, they remain confined within specific anatomical boundaries, in respect to their topology of origin. Angular measurements and heat map analysis indicated that tumor growth is directed towards the subventricular zone and may follow their respective radial units. These consistent observations across different anatomical regions challenge the traditional model of glioma progression, suggesting that early-stage glioma expansion is closely governed by ontogenetic factors. In conclusion, this study provides the first quantitative evidence that phenotypical low-grade gliomas do not primarily follow white matter tracts but may instead be influenced by ontogenetic mechanisms. These insights necessitate a re-evaluation of existing models of glioma progression and underscore the importance of incorporating developmental aspects into treatment planning to enhance patient outcomes.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 3","pages":"fcaf157"},"PeriodicalIF":4.1,"publicationDate":"2025-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12053163/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144031405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"White matter tract correlations with spoken language in cerebrovascular disease.","authors":"Dana N Broberg, Seyyed M H Haddad, Katharine Aveni, Alexander Havens, Paula M McLaughlin, Malcolm A Binns, Joseph B Orange, Stephen R Arnott, Courtney Berezuk, Leanne K Casaubon, Dar Dowlatshahi, Ayman Hassan, Nuwan D Nanayakkara, Alicia J Peltsch, Joel Ramirez, Gustavo Saposnik, Christopher J M Scott, Richard H Swartz, Sean Symons, Angela K Troyer, Angela C Roberts, Robert Bartha","doi":"10.1093/braincomms/fcaf145","DOIUrl":"https://doi.org/10.1093/braincomms/fcaf145","url":null,"abstract":"<p><p>Assessment of spoken language is a promising marker for cognitive impairment in individuals with cerebrovascular disease. However, the underlying neurological basis for spoken language beyond single words and sentences remains poorly defined in this cohort, particularly with respect to white matter. This study aimed to examine and compare white matter hyperintensity volumes and diffusion tensor metrics in normal-appearing white matter (NAWM) as potential correlates of spoken language performance. Baseline imaging and spoken language data were obtained from the cerebrovascular disease cohort of the Ontario Neurodegenerative Disease Research Initiative (<i>n</i> = 127; age: 55-85 years). Most participants had subclinical or very mild strokes, with very little to no aphasia symptoms. Spoken language samples were analysed to compute 10 different measures related to syntax, productivity, lexical diversity, fluency, and information content. Structural and diffusion MRI data were analysed to segment white matter hyperintensities and tracts. Normalized white matter hyperintensity volume, as well as average fractional anisotropy and mean diffusivity in the normal-appearing portion of eight white matter tracts, were correlated with the 10 spoken language measures using canonical correlation analyses. White matter and spoken language variate scores for individual participants then were correlated separately in male (<i>n</i> = 86) and female (<i>n</i> = 41) participants to probe potential sex differences. Spoken language performance was significantly associated with the fractional anisotropy (<i>r_c</i> = 0.51, <i>P</i>  <i>=</i> 0.041) and mean diffusivity (<i>r_c</i> = 0.56, <i>P</i>  <i>=</i> 0.011) of NAWM, particularly in the left superior longitudinal fasciculus, but not with white matter hyperintensity volumes (<i>r_c</i> = 0.41, <i>P</i>  <i>=</i> 0.80) in the same tracts. Measures related to syntax, fluency, and information content loaded most strongly in the spoken language variate. No significant sex differences were found in NAWM microstructure, and female and male participants exhibited similarly strong associations between spoken language and NAWM microstructure (fractional anisotropy: <i>z</i> = 1.44, <i>P</i> = 0.15; mean diffusivity: <i>z</i> = 1.03, <i>P</i> = 0.30). These results suggest that diffusion MRI in NAWM may be superior to white matter hyperintensity volumetrics when evaluating the role of white matter tract integrity on cognitive outcomes in people with relatively mild cerebrovascular pathology. These results also demonstrate that multi-domain spoken language analysis is sensitive to underlying white matter microstructure in participants with cerebrovascular disease without significant aphasia, supporting its value as a tool for assessing cognitive status.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 3","pages":"fcaf145"},"PeriodicalIF":4.1,"publicationDate":"2025-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12062522/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144065396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Onset ages of cerebrovascular disease and amyloid and effects on cognition in risk-enriched cohorts.","authors":"Lianlian Du, Elizabeth M Planalp, Tobey J Betthauser, Erin M Jonaitis, Bruce P Hermann, Leonardo A Rivera-Rivera, Karly A Cody, Nathaniel A Chin, Robert V Cadman, Kevin M Johnson, Aaron Field, Howard A Rowley, Kimberly D Mueller, Sanjay Asthana, Laura Eisenmenger, Bradley T Christian, Sterling C Johnson, Rebecca E Langhough","doi":"10.1093/braincomms/fcaf158","DOIUrl":"https://doi.org/10.1093/braincomms/fcaf158","url":null,"abstract":"<p><p>The temporal relationship between cerebrovascular disease (V), indicated by white matter hyperintensities, and beta-amyloid (A) in Alzheimer's disease remains unclear, prompting speculation about their potential interdependence. Longitudinal data were employed to estimate onset ages and corresponding disease chronicity for A and V (where disease chronicity is calculated as age at measurement minus estimated age of biomarker abnormality onset). In a large, predominantly cognitively unimpaired dataset (<i>n</i> = 877, ages 43-93 years), a V+ threshold was identified, and Sampled Iterative Local Approximation (SILA) was utilized to illustrate the predictable accumulation trajectory of V post-onset. Investigating the temporal association between A and V onset ages and accumulation trajectories in preclinical years, four operationalizations of time were examined across two initially cognitively unimpaired samples (<i>n</i> = 240 primary sample from Wisconsin Registry for Alzheimer's Prevention; <i>n</i> = 123 replication sample from Wisconsin Alzheimer's Disease Research Center): (i) chronological age, (ii) estimated V+ chronicity, (iii) years since baseline scan, and (iv) estimated A+ chronicity. Results indicated that while both diseases are age-related, their onsets and trajectories are independent of each other. In addition, results indicated that V and A accumulation trajectories were highly predictable relative to onset of positivity for each biomarker. Cognitive decline across multiple cognitive domains was fastest when both V and A were present based on last available amyloid PET and MRI scan, with greater A chronicity being a more salient predictor of cognitive decline in these samples.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 3","pages":"fcaf158"},"PeriodicalIF":4.1,"publicationDate":"2025-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12056727/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144046383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predicting cognitive change using functional, structural, and neuropsychological predictors.","authors":"Laurie Décarie-Labbé, Samira Mellah, Isaora Z Dialahy, Sylvie Belleville","doi":"10.1093/braincomms/fcaf155","DOIUrl":"https://doi.org/10.1093/braincomms/fcaf155","url":null,"abstract":"<p><p>To effectively address Alzheimer's disease, it is crucial to understand its earliest manifestations, underlying mechanisms and early markers of progression. Recent findings of very early brain activation anomalies highlight their potential for early disease characterization and predicting future cognitive decline. Our objective was to evaluate the value of brain activation-both individually and in combination with structural and neuropsychological measures-for predicting cognitive change. The study included 105 individuals from the Consortium for the Early Identification of Alzheimer's Disease-Quebec cohort who exhibited subjective cognitive decline or mild cognitive impairment. Cognitive decline was assessed by calculating the slope of Montreal Cognitive Assessment scores using regression models across successive assessments, and individuals were characterized as either decliners or stable based on clinically reliable change. We evaluated cognitive decline predictions using unimodal models for each class of predictors and multimodal models that combined these predictors. Functional activation emerged as a strong predictor of cognitive change (R²=52.5%), with 87.6% accuracy and 98.7% specificity, performing comparably to structural and neuropsychological measures. Although the unimodal functional model exhibited high specificity, indicating that functional abnormalities frequently predict future decline, it had low sensitivity (60%), meaning that the absence of abnormalities does not rule out future decline. Multimodal models provided greater explanatory power than unimodal models and greater sensitivity than the functional model. These findings highlight the potential role of early brain activation anomalies in the early detection of future cognitive changes, offering valuable insights for clinicians and researchers in assessing cognitive decline risk and refining clinical trial criteria.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 3","pages":"fcaf155"},"PeriodicalIF":4.1,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12056721/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144045043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brain age in multiple sclerosis: a study with deep learning and traditional machine learning.","authors":"Lars Skattebøl, Gro O Nygaard, Esten H Leonardsen, Tobias Kaufmann, Thomas Moridi, Leszek Stawiarz, Russel Ouellette, Benjamin V Ineichen, Daniel Ferreira, J Sebastian Muehlboeck, Mona K Beyer, Piotr Sowa, Ali Manouchehrinia, Eric Westman, Tomas Olsson, Elisabeth G Celius, Jan Hillert, Ingrid Kockum, Hanne F Harbo, Fredrik Piehl, Tobias Granberg, Lars T Westlye, Einar A Høgestøl","doi":"10.1093/braincomms/fcaf152","DOIUrl":"https://doi.org/10.1093/braincomms/fcaf152","url":null,"abstract":"<p><p>'Brain age' is a numerical estimate of the biological age of the brain and an overall effort to measure neurodegeneration, regardless of disease type. In multiple sclerosis, accelerated brain ageing has been linked to disability accrual. Artificial intelligence has emerged as a promising tool for the assessment and quantification of the impact of neurodegenerative diseases. Despite the existence of numerous AI models, there is a noticeable lack of comparative imaging data for traditional machine learning versus deep learning in conditions such as multiple sclerosis. A retrospective observational study was initiated to analyse clinical and MRI data (4584 MRIs) from various scanners in a large longitudinal cohort (<i>n</i> = 1516) of people with multiple sclerosis collected from two institutions (Karolinska Institute and Oslo University Hospital) using a uniform data post-processing pipeline. We conducted a comparative assessment of brain age using a deep learning simple fully convolutional network and a well-established traditional machine learning model. This study was primarily aimed to validate the deep learning brain age model in multiple sclerosis. The correlation between estimated brain age and chronological age was stronger for the deep learning estimates (<i>r</i> = 0.90, <i>P</i> < 0.001) than the traditional machine learning estimates (<i>r</i> = 0.75, <i>P</i> < 0.001). An increase in brain age was significantly associated with higher expanded disability status scale scores (traditional machine learning: <i>t</i> = 5.3, <i>P</i> < 0.001; deep learning: <i>t</i> = 3.7, <i>P</i> < 0.001) and longer disease duration (traditional machine learning: <i>t</i> = 6.5, <i>P</i> < 0.001; deep learning: <i>t</i> = 5.8, <i>P</i> < 0.001). No significant inter-model difference in clinical correlation or effect measure was found, but significant differences for traditional machine learning-derived brain age estimates were found between several scanners. Our study suggests that the deep learning-derived brain age is significantly associated with clinical disability, performed equally well to the traditional machine learning-derived brain age measures, and may counteract scanner variability.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 3","pages":"fcaf152"},"PeriodicalIF":4.1,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12056726/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144048465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ongoing loss of viable neurons for weeks after mild hypoxia-ischaemia.","authors":"Melanie A McNally, Lauren A Lau, Simon Granak, David Hike, Xiaochen Liu, Xin Yu, Rachel A Donahue, Lori B Chibnik, John V Ortiz, Alicia Che, Raul Chavez-Valdez, Frances J Northington, Kevin J Staley","doi":"10.1093/braincomms/fcaf153","DOIUrl":"https://doi.org/10.1093/braincomms/fcaf153","url":null,"abstract":"<p><p>Mild hypoxic-ischaemic encephalopathy is common in neonates, and there are no evidence-based therapies. By school age, 30-40% of those patients experience adverse neurodevelopmental outcomes. The nature and progression of mild injury is poorly understood. We studied the evolution of mild perinatal brain injury using longitudinal two-photon imaging of transgenic fluorescent calcium-sensitive and insensitive proteins to provide a novel readout of neuronal viability and activity at cellular resolution <i>in vitro</i> and <i>in vivo</i>. <i>In vitro</i>, perinatal organotypic hippocampal cultures underwent 15-20 min of oxygen-glucose deprivation. <i>In vivo</i>, mild hypoxia-ischaemia was completed at post-natal day 10 with carotid ligation and 15 min of hypoxia (FiO₂, 0.08). Consistent with a mild injury, minimal immediate neuronal death was seen <i>in vitro</i> or <i>in vivo,</i> and there was no volumetric evidence of injury by <i>ex vivo</i> MRI 2.5 weeks after injury (<i>n</i> = 3 pups/group). However, in both the hippocampus and neocortex, these mild injuries resulted in delayed and progressive neuronal loss by the second week after injury compared to controls; measured by fluorophore quenching (<i>n</i> = 6 slices/group <i>in vitro</i>, <i>P</i> < 0.001; <i>n</i> = 8 pups/group <i>in vivo</i>, <i>P</i> < 0.01). Mild hypoxia-ischaemia transiently suppressed cortical network calcium activity <i>in vivo</i> for over 2 h after injury (versus sham, <i>n</i> = 13 pups/group; <i>P</i> < 0.01). No post-injury seizures were seen. By 24 h, network activity fully recovered, and there was no disruption in the development of normal cortical activity for 11 days (<i>n</i> = 8 pups/group). The participation in network activity of individual neurons destined to die <i>in vivo</i> was indistinguishable from those that survived up to 4 days post-injury (<i>n</i> = 8 pups/group). Despite a lack of significant immediate neuronal death and only transient disruptions of network activity, mild perinatal brain injury resulted in a delayed and progressive increase of neuronal death in the hippocampus and neocortex. Neurons that died late were functioning normally for days after injury, suggesting a new pathophysiology of neuronal death after mild injury. Critically, the neurons destined to die late demonstrated multiple biomarkers of viability long after mild injury, suggesting their later death may be modified with neuroprotective interventions.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 2","pages":"fcaf153"},"PeriodicalIF":4.1,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12034461/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144000193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lymphocyte signatures correspond to clinical phenotypes in autoimmune limbic encephalitis.","authors":"Saskia Räuber, Andreas Schulte-Mecklenbeck, Kelvin Sarink, Christoph Müller, Manoj Mannil, Lisa Langenbruch, Andre Dik, Sumanta Barman, Christine Strippel, Marco Gallus, Kristin S Golombeck, Christina B Schroeter, Alice Willison, Christopher Nelke, Fatme Seval Ismail, Wolfram Schwindt, Norbert Goebels, Stjepana Kovac, Heinz Wiendl, Gerd Meyer Zu Hörste, Thomas Duning, Michael Hanke, Tobias Ruck, Walter Heindel, Udo Dannlowski, Tim Hahn, Catharina C Gross, Sven G Meuth, Nico Melzer","doi":"10.1093/braincomms/fcaf156","DOIUrl":"https://doi.org/10.1093/braincomms/fcaf156","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Autoimmune limbic encephalitis is an inflammatory condition confined to the limbic system of the brain that is deemed to be due to a dysregulated immune response. However, the exact pathophysiological mechanisms remain elusive. Diagnosis of autoimmune limbic encephalitis currently relies on clinical consensus criteria. However, diagnostic workup can be challenging, potentially delaying treatment initiation associated with poor clinical outcomes. We retrospectively identified 640 patients (81 autoimmune limbic encephalitis, 148 relapsing-remitting multiple sclerosis, 197 Alzheimer's disease, 67 frontotemporal dementia, 37 temporal lobe epilepsy with hippocampal sclerosis and 110 somatic symptom disorder patients). Applying multidimensional flow-cytometry together with novel computational approaches, we analysed the peripheral blood and cerebrospinal fluid immune cell profiles at different disease stages and performed correlations with clinical parameters (i.e. neuropsychological performance, EEG and MRI). We were able to identify a shared immune signature of autoimmune limbic encephalitis showing similarities in adaptive B and T cell response with other inflammatory central nervous system diseases and in T cell patterns with neurodegenerative disorders. Antibody-negative autoimmune limbic encephalitis showed a pronounced T cell response in peripheral blood similar to temporal lobe epilepsy and hippocampal sclerosis and neurodegenerative disorders differentiating from antibody-positive autoimmune limbic encephalitis and classical inflammatory central nervous system diseases with regard to B and plasma cell response. Longitudinal immune cell phenotyping in autoimmune limbic encephalitis revealed dynamic changes over time mainly affecting the innate, B and plasma cell compartment. Correlation analysis indicated associations between the baseline immune cell profile, especially lymphocytes, and neuropsychological performance, as well as EEG and MRI abnormalities. Applying novel computational approaches, we found that multidimensional flow cytometry together with routine CSF parameters could reliably distinguish autoimmune limbic encephalitis from controls and clinical differential diagnoses. Incorporation of multidimensional flow cytometry parameters showed superior discriminatory ability compared with CSF routine parameters alone. Taken together, autoimmune limbic encephalitis is characterized by a B and T cell dominated intrathecal immune-cell signature corresponding to changes reported in the brain parenchyma and showing similarities with classical inflammatory central nervous system diseases and neurodegenerative disorders. Incorporating clinical parameters and applying novel computational approaches, we could show that multidimensional flow cytometry might be a beneficial complement to the established diagnostic workup of autoimmune limbic encephalitis promoting early diagnosis and facilitating outcome prediction to enhance individualized tr","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 2","pages":"fcaf156"},"PeriodicalIF":4.1,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12038345/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144055230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elevated circulating cell-free mitochondrial DNA level in cerebrospinal fluid of narcolepsy type 1.","authors":"Monica Moresco, Concetta Valentina Tropeano, Martina Romagnoli, Giulia Neccia, Alessandro Rapone, Fabio Pizza, Stefano Vandi, Emmanuel Mignot, Alessandra Maresca, Valerio Carelli, Giuseppe Plazzi","doi":"10.1093/braincomms/fcaf125","DOIUrl":"https://doi.org/10.1093/braincomms/fcaf125","url":null,"abstract":"<p><p>Narcolepsy type 1 (NT1) is a rare neurological disorder characterized by excessive daytime sleepiness and cataplexy, thought to result from an autoimmune process targeting the hypothalamic hypocretin-producing neurons. Aiming to add clues to the latter hypothesis, we investigated circulating cell-free mitochondrial DNA (ccf-mtDNA) levels in cerebrospinal fluid (CSF), a possible biomarker for neurodegeneration, neuroinflammation or immune activation, from 46 NT1 patients with low CSF hypocretin-1, compared with 32 controls. We found significantly increased ccf-mtDNA levels in NT1 patients compared with controls, which negatively correlated with CSF hypocretin-1 concentrations. Additionally, higher ccf-mtDNA levels were observed in patients with elevated number of sleep onset rapid eye movement periods. These observations imply that increased levels of ccf-mtDNA associate with reduced CSF hypocretin-1 concentrations leading to greater alteration in sleep architecture. Furthermore, cytokine profiling in CSF revealed significant changes in interleukins 6 and 18 in NT1 patients, suggesting an active neuroinflammatory process possibly linked to ccf-mtDNA release, thus pointing to a specific inflammatory signature in NT1. These findings hint a potential mitochondrial dysfunction and neuroinflammation in NT1. Further studies are needed to elucidate the underlying mechanisms and how this may reflect on therapy.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 2","pages":"fcaf125"},"PeriodicalIF":4.1,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12003949/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144060831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}