Brain communications最新文献

{"title":"Distinct changes in the morphology of cortical and subcortical grey matter associated with age-related hearing loss and tinnitus in the UK Biobank participants.","authors":"Fatin N Zainul Abidin, Francesca Biondo, Andre Altmann, Sally J Dawson","doi":"10.1093/braincomms/fcaf203","DOIUrl":"10.1093/braincomms/fcaf203","url":null,"abstract":"<p><p>Prevalence of both hearing loss and tinnitus increases with age. However, neuroimaging studies of both conditions report inconsistent changes in brain morphology likely due to small sample size and variable methodology. Structural and functional neuroimaging studies in hearing loss and tinnitus have revealed distinct neural correlates, and further replication is needed to confirm these findings. This study aims to investigate the effects of hearing loss and tinnitus on the brain morphology in a well-powered sample. We utilized self-reported hearing difficulty and tinnitus in participants with magnetic resonance imaging (MRI) in the UK Biobank cohort. Control participants without hearing difficulty and tinnitus were age and sex matched leading to total sample sizes of 13 074 and 6242 for self-reported hearing difficulty and tinnitus, respectively. We utilized the rich UK Biobank dataset (i) to reveal these brain changes in a well-powered large study of hearing loss and tinnitus, (ii) to document the effect of confounding factors on these associations, (iii) to discriminate the effects of tinnitus versus hearing difficulty on the brain and (iv) to estimate the brain-age gap in hearing difficulty and tinnitus subjects compared with controls. Hearing difficulty is significantly associated with smaller grey matter volumes exclusively in the bilateral transverse temporal regions, whereas tinnitus is associated with larger volumes of bilateral hippocampi and thalami when compared with the control group. Furthermore, correcting for confounders (i.e. diabetes, cardiovascular disease, age, sex, smoking, alcohol consumption and Townsend deprivation index) during statistical analysis helped to better delineate the impact of hearing status on brain structural changes. The brain-age gap analysis showed that participants with tinnitus appeared to have significantly younger brains than controls, whereas participants with hearing difficulty did not differ significantly from the control group. Altogether, our results confirmed previous findings and suggest the enlargement of bilateral thalami as the main effect in people with tinnitus. We also established that there are independent and distinct brain pathologies between hearing difficulty and tinnitus. Therefore, the self-reported measure is a reasonable approach to assess the hearing loss and tinnitus pathologies.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 3","pages":"fcaf203"},"PeriodicalIF":4.1,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12149739/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144268165","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":"Ion concentrations in CSF and serum are differentially and precisely regulated.","authors":"Tim Lyckenvik, My Forsberg, Kalle Johansson, Markus Axelsson, Henrik Zetterberg, Kaj Blennow, Sebastian Illes, Pontus Wasling, Eric Hanse","doi":"10.1093/braincomms/fcaf201","DOIUrl":"10.1093/braincomms/fcaf201","url":null,"abstract":"<p><p>Fluctuations of extracellular brain ion concentrations have been associated with transitions between brain states such as sleep and wakefulness, and disturbances have been implicated in a variety of neurological conditions, including dementia, epilepsy and migraine. This study aims to define the normal CSF ion profile and identify key factors influencing its regulation. In this cross-sectional study, we analysed samples from 42 individuals (16 men), including 28 healthy participants and 14 patients with medically unexplained neurological symptoms. Age spanned between 20 and 55 years. Using validated clinical assays, we measured paired CSF and serum concentrations of Ca²⁺, Cl⁻, K⁺, Mg²⁺ and Na⁺. We examined their interrelationships and assessed the impact of blood-brain barrier permeability (the albumin quotient), age, sampling time and sex. CSF ion concentrations were highly stable and maintained within distinct, narrow ranges, separate from serum ranges for all ions measured (<i>P</i> < 0.0001), with no overlapping. Cl^- (+25%), Na⁺ (+5%) and Mg²⁺ (+37%) concentrations were higher, while K⁺ (-30%) and Ca²⁺ (-50%) concentrations were lower. Consistent with an independent and active CNS homeostatic control, CSF concentrations of K⁺, Cl^- or Mg²⁺ showed no significant correlation with their serum counterparts, while Na⁺ and Ca²⁺ displayed moderate associations with serum levels. Moreover, blood-brain barrier permeability had no significant impact on CSF ion concentrations. Small, but significant, age-related declines were observed for Cl^-, Mg²⁺ and Ca²⁺ in CSF, and circadian fluctuations affected K⁺, which increased slightly in the afternoon. Minor sex differences were noted, with men exhibiting slightly higher Mg²⁺ and Ca²⁺ levels. Our findings demonstrate that CSF ion concentrations are precisely regulated at the barriers of the CNS, largely independent of serum levels and with low interindividual variation, reinforcing the concept of a highly controlled CNS environment. This distinct ion composition may help modulate neuronal excitability, supporting brain state transitions such as sleep-wake cycling. Identification of hydration status as a potential confounding factor suggests that normalization to CSF-Na⁺ may improve the detection of pathological disruptions in CSF ion homeostasis. These insights reinforce the foundation for using CSF ion profiles as biomarkers for neurological disorders.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 3","pages":"fcaf201"},"PeriodicalIF":4.1,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12129886/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144217820","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":"Intra-amniotic infection with <i>Ureaplasma parvum</i> causes serovar-dependent white matter damage in preterm fetal sheep.","authors":"Dima Abdu, Graeme R Polglase, Sharmony B Kelly, Sinead Murphy, Ilias Nitsos, Claudia A Nold-Petry, Suhas G Kallapur, Alan H Jobe, John P Newnham, Timothy J Moss, Robert Galinsky","doi":"10.1093/braincomms/fcaf182","DOIUrl":"10.1093/braincomms/fcaf182","url":null,"abstract":"&lt;p&gt;&lt;p&gt;&lt;i&gt;Ureaplasma parvum&lt;/i&gt; is commonly isolated from the amniotic fluid of pregnancies complicated by infection. While some studies have shown an association between intra-amniotic &lt;i&gt;Ureaplasma&lt;/i&gt; species infection and brain injury and/or adverse neurodevelopment, others have not. The relationship between antenatal exposure to microbial infection and risk of poor neurological outcome is complex and multifactorial and may reflect diversities in microbial pathogenicity along with the duration and severity of the fetal inflammatory response to microbial infection. This study aimed to determine the impact of chronic intra-amniotic infection with &lt;i&gt;Ureaplasma parvum&lt;/i&gt; serovars 3 and 6, which are among the most common serovars isolated in pregnancies complicated by infection/inflammation, on white matter development in preterm fetal sheep. Pregnant ewes carrying singleton or twin fetuses (55 days gestational age, term = 145 days) were randomly allocated to receive an ultrasound-guided intra-amniotic injection of &lt;i&gt;Ureaplasma parvum&lt;/i&gt; serovars 3 (&lt;i&gt;n&lt;/i&gt; = 11), 6 (&lt;i&gt;n&lt;/i&gt; = 16) or media (control, &lt;i&gt;n&lt;/i&gt; = 6). At 125 days of gestation, the ewe and foetus were euthanized and the fetal brain was collected for immunohistochemistry. Total numbers of oligodendrocytes (oligodendrocyte transcription factor 2-positive cells) in the periventricular white matter tract were higher in &lt;i&gt;Ureaplasma parvum&lt;/i&gt; serovar 6-exposed fetuses than control. Numbers of mature oligodendrocytes [anti-adenomatous polyposis coli clone (CC) 1-positive cells] and myelin density (% area fraction of myelin basic protein-positive) in the periventricular and intragyral white matter tracts were lower in &lt;i&gt;Ureaplasma parvum&lt;/i&gt; serovar 6-exposed fetuses than control. Myelin anisotropy was lower in serovar 6-exposed fetuses than control. There were no differences in numbers of total or mature oligodendrocytes, myelin density and anisotropy in &lt;i&gt;Ureaplasma parvum&lt;/i&gt; serovar-3-exposed fetuses compared to control. Cell death, numbers of neurons, total and reactive (signal transducer and activator of transcription 3-positive) microglia and astrocytes did not differ between &lt;i&gt;Ureaplasma parvum&lt;/i&gt;-exposed fetuses and controls within the premotor cortex and striatum. Chronic intra-amniotic infection with &lt;i&gt;Ureaplasma parvum&lt;/i&gt; serovar 6, but not 3, impaired oligodendrocyte maturation and myelination within the large white matter tracts of the preterm sheep brain. These data suggest that the impact &lt;i&gt;Ureaplasma parvum&lt;/i&gt; infection on white matter development may be serovar dependant, which may help to explain why some fetuses exposed to intra-amniotic &lt;i&gt;Ureaplasma&lt;/i&gt; infection have adverse neurodevelopmental outcomes while others do not. Overall, this study demonstrates that greater emphasis needs to be placed on the taxonomy of &lt;i&gt;Ureaplasma&lt;/i&gt; infection when designing and interpreting clinical and preclinical studies of fetal infection and neurodevelopmental outcomes","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 3","pages":"fcaf182"},"PeriodicalIF":4.1,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12130620/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144217819","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":"Differential tractography: an imaging marker for tissue degeneration in neurodegenerative diseases.","authors":"Connor J Lewis, Zeynep Vardar, Anna Luisa Kühn, Jean M Johnston, Precilla D'Souza, Muhammad H Yousef, William A Gahl, Mohammed Salman Shazeeb, Cynthia J Tifft, Maria T Acosta","doi":"10.1093/braincomms/fcaf198","DOIUrl":"10.1093/braincomms/fcaf198","url":null,"abstract":"<p><p>GM1 gangliosidosis is an ultra-rare inherited neurodegenerative lysosomal storage disorder caused by biallelic mutations in the <i>GLB1</i> gene. GM1 is uniformly fatal and has no approved therapies, although clinical trials investigating gene therapy as a potential treatment for this condition are underway. Novel outcome measures or markers demonstrating the longitudinal effects of GM1 and potential recovery due to therapeutic intervention are urgently needed to establish efficacy of potential therapeutics. One promising tool is differential tractography, a novel imaging modality utilizing serial diffusion tensor imaging to quantify longitudinal changes in white matter microstructure. In this study, we present the novel use of differential tractography in quantifying the progression of GM1 alongside age-matched neurotypical controls. We analysed 113 diffusion tensor imaging scans from 16 GM1 patients and 32 age-matched neurotypical controls to investigate longitudinal changes in white matter pathology. GM1 patients showed white matter degradation evident by both the number and size of fibre tract loss. In contrast, neurotypical controls showed longitudinal white matter improvements as evident by both the number and size of fibre tract growth. We also corroborated these findings by documenting significant correlations between clinical global impression scores of clinical presentations and our differential tractography derived metrics in our GM1 cohort. Specifically, GM1 patients who lost more neuronal fibre tracts also had a worse clinical presentation. This result demonstrates the utility of differential tractography as a marker for disease progression in GM1 patients with potential extension to other neurodegenerative diseases and therapeutic intervention.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 3","pages":"fcaf198"},"PeriodicalIF":4.5,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12130619/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144217818","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":"A compilation of reported alterations in the cerebrospinal fluid proteome in Alzheimer's disease.","authors":"Matthijs B de Geus, Angus C Nairn, Steven E Arnold, Becky C Carlyle","doi":"10.1093/braincomms/fcaf202","DOIUrl":"10.1093/braincomms/fcaf202","url":null,"abstract":"<p><p>Alzheimer's disease is a multifaceted neurodegenerative disorder, with diverse underlying pathophysiological processes extending beyond amyloid-β and tau accumulation. The heterogeneity of Alzheimer's disease necessitates the identification of a broad array of biomarkers that capture the diverse mechanisms contributing to disease onset and progression. In this study, we systematically compiled and analysed cerebrospinal fluid proteomics data from omics studies utilizing mass spectrometry, Olink, or SomaScan platforms. Systematic literature searches for each platform revealed a total of 264 studies. From this, a set of 18 studies were selected based on sample size, number of markers analysed, and open data availability. We found a total of 1,448 differentially expressed proteins between Alzheimer's disease and amyloid negative controls across these datasets, with 635 being found in more than one study. A 'top' set of 61 differentially expressed proteins were consistently reported in at least six studies. Clustering and functional enrichment analysis of the top differentially expressed proteins indicated involvement in metabolic regulation, glutathione metabolism and proteins of the 14-3-3 family, reflecting importance of reactive oxygen species (ROS) response. Synaptic signalling processes were found to generally be downregulated. We further integrated the top differentially expressed proteins with results from a study on familial Alzheimer's disease cerebrospinal fluid to assess at which stage of disease progression these proteins change, highlighting markers shared between sporadic and familial Alzheimer's disease datasets. Lastly, we examine the overlap of the top differentially expressed proteins between cerebrospinal fluid and brain tissue using a publicly available database. This analysis provides a comprehensive overview of the Alzheimer's disease cerebrospinal fluid proteomic landscape, indicating changes in key pathways and cellular processes associated with Alzheimer's disease pathology. By integrating data from different platforms, we highlight reproducible protein changes that may serve as promising candidates for further biomarker research aimed at improving patient stratification, tracking disease progression, and assessing therapeutic interventions.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 3","pages":"fcaf202"},"PeriodicalIF":4.1,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12146149/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144259566","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 glymphatic fluid mapping in Alzheimer's disease: a human MRI and PET study.","authors":"Liangdong Zhou, Thanh D Nguyen, Gloria C Chiang, Samantha A Keil, Xiuyuan Hugh Wang, Tsung-Wei Hu, Haoyu Lan, Ke Xi, Ana Paula Costa, Emily B Tanzi, Lidia Glodzik, Jarek Wegiel, Tracy Butler, Mony J de Leon, Yi Li","doi":"10.1093/braincomms/fcaf200","DOIUrl":"10.1093/braincomms/fcaf200","url":null,"abstract":"<p><p>Glymphatic system has been identified as a fluid exchange network in brain parenchymal for removal of toxic metabolites in Alzheimer's disease. However, a clinically feasible, accurate, and non-invasive imaging technique for mapping global glymphatic fluid distribution throughout the entire brain and monitoring its dysfunction in Alzheimer's disease is currently lacking. This cross-sectional retrospective study aims to compare three MRI-based measures of the glymphatic system structural alterations, a novel multi-echo T2 relaxometry-based parenchymal CSF (pCSF) mapping, T2 weighted-based segmented perivascular space burden, and diffusion tensor imaging-based free-water mapping. We evaluated their cross-correlation and investigated their respective association with PET measured beta-amyloid deposition using ¹¹C-PiB PET. A total of 29 subjects (18 Female, age: 70.07 ± 8.73 years old), among them, 16 were cognitively normal and 13 were mild cognitive impairment or Alzheimer's disease, underwent both MRI and ¹¹C-PiB PET scans. Parenchymal CSF mapping, diffusion-based free-water mapping and perivascular spaces burden were generated from their respective MRI. Age and sex effects and group differences of these biomarkers were evaluated. The associations among these measures and Aβ deposition on ¹¹C-PiB PET were analysed and compared. Our analysis demonstrated moderate correlations between pCSF, diffusion-based free-water mapping and perivascular space burden, suggesting these biomarkers capture overlapping yet distinct aspects of glymphatic fluid distribution. Importantly, linear regression analyses revealed that pCSF exhibited a significantly stronger positive association with beta-amyloid deposition (white matter: <i>t</i> = 3.536, <i>P</i> = 0.002, <i>R</i> ² = 0.446; Alzheimer's disease-related meta regions: <i>t</i> = 4.510, <i>P</i> < 0.001, <i>R</i> ² = 0.541), compared with diffusion-based free-water mapping in white matter (<i>t</i> = 0.843, <i>P</i> = 0.407, <i>R</i> ² = 0.191) and perivascular space burden (<i>t</i> = 0.422, <i>P</i> = 0.677, <i>R</i> ² = 0.174), after adjusting for age and sex. This study identifies pCSF mapping, derived from multi-echo T2 data with clinically feasible 5 mins scan FAST-T2 sequence, as a potential non-invasive imaging biomarker for assessing glymphatic dysfunction in Alzheimer's disease. The superior sensitivity of pCSF mapping arises from its direct quantification of glymphatic fluid at the water molecular level based on free CSF-specific T2 relaxation properties. These results suggest that pCSF could be useful in the monitoring of Alzheimer's disease progression as beta-amyloid accumulating and predicting response to anti-amyloid therapies, potentially leading to better diagnostic strategies and therapeutic interventions of Alzheimer's disease.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 3","pages":"fcaf200"},"PeriodicalIF":4.1,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12130685/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144217817","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":"Evidence that minocycline treatment confounds the interpretation of neurofilament as a biomarker.","authors":"Juliana E Gentile, Christina N Heiss, Taylor L Corridon, Meredith A Mortberg, Stefanie Fruhwürth, Kenia Guzman, Lana Grötschel, Laia Montoliu-Gaya, Kwan Chan, Neil C Herring, Timothy Janicki, Rajaa Nhass, Janani Manavala Sarathy, Brian Erickson, Ryan Kunz, Alison Erickson, Craig Braun, Katherine T Henry, Lynn Bry, Steven E Arnold, Eric Vallabh Minikel, Henrik Zetterberg, Sonia M Vallabh","doi":"10.1093/braincomms/fcaf175","DOIUrl":"10.1093/braincomms/fcaf175","url":null,"abstract":"<p><p>Neurofilament light (NfL) concentration in CSF and blood serves as an important biomarker in neurology drug development. Changes in NfL are generally assumed to reflect changes in neuronal damage, while little is known about the clearance of NfL from biofluids. In a study of asymptomatic individuals at risk for prion disease, both blood and CSF NfL spiked in one participant following a 6-week course of minocycline, absent any other biomarker changes and without subsequent onset of symptoms. We subsequently observed high NfL after minocycline treatment in discarded clinical plasma samples from inpatients, in mouse plasma and in conditioned media from neuron-microglia co-cultures. The specificity and kinetics of NfL response lead us to hypothesize that minocycline does not cause or exacerbate neuronal damage, but instead affects NfL by inhibiting its clearance, posing a potential confounder for the interpretation of this important biomarker.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 3","pages":"fcaf175"},"PeriodicalIF":4.1,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12100619/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144980","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":"Sensitivity of diffusion tensor imaging to regional mixed cerebrovascular pathology.","authors":"Jennifer K Ferris, Julia Dahlby, Shie Rinat, Brian Greeley, Joel Ramirez, Sandra E Black, Lara A Boyd","doi":"10.1093/braincomms/fcaf193","DOIUrl":"10.1093/braincomms/fcaf193","url":null,"abstract":"<p><p>Diffusion tensor imaging is a candidate biomarker in cerebrovascular disease. Yet, little is known about the sensitivity of diffusion tensor imaging to mixed forms of cerebrovascular pathology: stroke and white matter hyperintensities. We evaluated the sensitivity of diffusion tensor imaging to regional lesion load, considering both stroke and white matter hyperintensity lesions. 65 older adults and 39 individuals with chronic stroke underwent diffusion tensor imaging and comprehensive cerebrovascular lesion segmentation. We tested relationships between fractional anisotropy or mean diffusivity and cerebrovascular lesions with linear mixed effects regression. In older adults, tract microstructure related to white matter hyperintensity lesion load (fractional anisotropy: <i>b</i> = -0.003, <i>P</i> = 0.003; mean diffusivity: <i>b</i> = 0.071 × 10^-4, <i>P</i> < 0.001). In individuals with chronic stroke, tract microstructure related to stroke lesion load (fractional anisotropy: <i>b</i> = -0.041, <i>P</i> < 0.001; mean diffusivity: <i>b</i> = 1.460 × 10^-4, <i>P</i> < 0.001), with a significant interaction between stroke and white matter hyperintensity lesion load (fractional anisotropy: <i>b</i> = 0.019, <i>P</i> < 0.001; mean diffusivity: <i>b</i> = -0.727 × 10^-4, <i>P</i> < 0.001). Among both groups, whole-brain normal appearing white matter microstructure did not relate to whole-brain lesion volumes. Our findings provide foundational evidence for the use and interpretation of diffusion tensor imaging as a biomarker in cerebrovascular disease.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 3","pages":"fcaf193"},"PeriodicalIF":4.1,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12120440/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144181557","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":"Differentiating sporadic frontotemporal dementia from late-onset primary psychiatric disorders.","authors":"Sterre C M de Boer, Lina Riedl, Simon Braak, Chiara Fenoglio, David Foxe, James Carrick, Ramón Landin-Romero, Sophie Matis, Zac Chatterton, Ishana Rue, Marie-Paule E van Engelen, Jay L P Fieldhouse, Mardien Oudega, Sigfried N T M Schouws, Welmoed A Krudop, Argonde C van Harten, Flora H Duits, Sven J van der Lee, Daniela Galimberti, Janine Diehl-Schmid, Glenda M Halliday, Simon Ducharme, Yolande A L Pijnenburg, Olivier Piguet","doi":"10.1093/braincomms/fcaf199","DOIUrl":"10.1093/braincomms/fcaf199","url":null,"abstract":"<p><p>Sporadic behavioural variant frontotemporal dementia (bvFTD) is often misdiagnosed as late-onset primary psychiatric disorder (PPD) due to overlapping symptoms and lack of biomarkers. We aimed to identify clinical features that distinguish sporadic bvFTD from PPD. Multi-centre baseline data were retrospectively retrieved and categorized into neuropsychological domains. Logistic regression models and receiver operating characteristic curves were conducted to determine discriminators. Data from 508 sporadic bvFTD and 152 PPD cases were included. Higher scores in cognitive screening [odds ratio (OR): 1.23], facial emotion processing (OR: 1.69), episodic memory (OR: 1.09), animal fluency (OR: 1.17), working memory (OR: 1.18), letter fluency (OR: 1.17) and depressive symptoms (OR: 7.41) were significantly associated with PPD (all <i>P</i>s ≤ 0.010). Within a combined model, higher scores of letter fluency (OR: 1.47), cognitive screening (OR: 1.72) and lower attention (OR: 0.77) were significantly (all <i>P</i>s ≤ 0.05) associated with PPD (area under the curve = 0.771). Neuropsychological measurements-letter fluency, cognitive screening and attention-can help distinguish sporadic bvFTD from late-onset PPD. Depressive symptoms and facial emotion processing emerged as potential discriminators, warranting further exploration.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 3","pages":"fcaf199"},"PeriodicalIF":4.1,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12141780/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144251312","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":"Delineating network integration and segregation in the pathophysiology of functional neurological disorder.","authors":"Christiana Westlin, Andrew J Guthrie, Cristina Bleier, Sara A Finkelstein, Julie Maggio, Jessica Ranford, Julie MacLean, Ellen Godena, Daniel Millstein, Sara Paredes-Echeverri, Jennifer Freeburn, Caitlin Adams, Christopher D Stephen, Ibai Diez, David L Perez","doi":"10.1093/braincomms/fcaf195","DOIUrl":"10.1093/braincomms/fcaf195","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Functional neurological disorder (FND) is a neuropsychiatric condition that is framed as a multi-network brain problem. Despite this conceptualization, studies have generally focused on specific regions or connectivity features, under-characterizing the complex and nuanced role of resting-state networks in FND pathophysiology. This study employed three complementary graph theory analyses to delineate the functional network architecture in FND. Specifically, we investigated whole-brain weighted-degree, isocortical integration and isocortical segregation extracted from resting-state functional MRI data prospectively collected from 178 participants: 61 individuals with mixed FND; 58 psychiatric controls matched on age, sex, depression, anxiety and post-traumatic stress disorder severity; and 59 age- and sex-matched healthy controls. All analyses were adjusted for age, sex and antidepressant use and focused on differences between FND versus psychiatric controls, with individual-subject maps normalized to healthy controls. Compared to psychiatric controls, patients with mixed FND exhibited increased weighted-degree in the right dorsal anterior cingulate and superior frontal gyrus and the left inferior frontal gyrus and supplementary motor area. Isocortical integration analyses revealed increased &lt;i&gt;between-network&lt;/i&gt; connectivity for somatomotor network areas, with widespread heightened connections to regions of the default mode, frontoparietal and salience networks. Isocortical segregation analyses revealed increased &lt;i&gt;within-network&lt;/i&gt; connectivity for the frontoparietal network. Secondary analyses of functional motor disorder (&lt;i&gt;n&lt;/i&gt; = 46) and functional seizure (&lt;i&gt;n&lt;/i&gt; = 23) subtypes (versus psychiatric controls) revealed both shared and unique patterns of altered connectivity across subtypes, including increased weighted-degree and integrated connectivity in the left posterior insula and anterior/mid-cingulate in functional motor disorder and increased segregated connectivity in the right angular gyrus for functional seizures. In &lt;i&gt;post hoc&lt;/i&gt; between-group analyses, findings remained significant adjusting for depression, anxiety and post-traumatic stress disorder severity, as well as for childhood maltreatment. &lt;i&gt;Post hoc&lt;/i&gt; correlations revealed significant relationships between connectivity metrics in several of these regions and somatic symptom severity across FND and psychiatric control participants. Notably, individual connectivity values were predominantly within the range of healthy controls (with patients with FND generally showing tendencies for increased connectivity and psychiatric controls showing tendencies towards decreased connectivity), indicating subtle shifts in the network architecture rather than gross abnormalities. This study provides novel mechanistic insights (i.e. increased somatomotor integration) and specificity regarding the neurobiology of FND, highlighting both shared mechanisms across subtypes and ","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 3","pages":"fcaf195"},"PeriodicalIF":4.1,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12107243/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144164291","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}