Brain communicationsPub Date : 2025-07-22eCollection Date: 2025-01-01DOI: 10.1093/braincomms/fcaf276
Ke Wu, Yaya Jiang, Junhao Luo, Yijun Chen, Shaoling Peng, Xiangyu Kong, Gaolang Gong
{"title":"Latent dimension linking functional connectivity with post-stroke deficits across multiple domains.","authors":"Ke Wu, Yaya Jiang, Junhao Luo, Yijun Chen, Shaoling Peng, Xiangyu Kong, Gaolang Gong","doi":"10.1093/braincomms/fcaf276","DOIUrl":"10.1093/braincomms/fcaf276","url":null,"abstract":"<p><p>Stroke often leads to multiple behavioural impairments. Understanding the neural basis of these deficits is essential for elucidating the mechanisms of functional impairments and optimising therapeutic strategies for stroke patients. Although many studies have revealed that specific behavioural deficits are related to disruptions in distributed functional connectivity across brain networks, these studies typically focus on single behavioural traits, overlooking the multivariate characteristics of deficits after stroke. Recent studies have demonstrated that deficits within and across domains are highly correlated, suggesting a complex many-to-many mapping between brain and behaviour following stroke. Thus, the present study aims to identify meaningful multivariate patterns of functional connectivity-behaviour covariation following stroke. Specifically, we employed a multivariate data-driven approach, partial least squares correlation, to examine the relationships between whole-brain functional connectivity and an extensive array of neurological scores (including motor, attention, verbal memory, spatial memory and language domains) in a large cohort of stroke patients at 2 weeks (<i>n</i> = 81), 3 months (<i>n</i> = 78) and 12 months (<i>n</i> = 74) post-injury. This multivariate analysis revealed a significant latent component (LC) from 2-week post-stroke data, capturing a unique pattern of cognitive deficits across multiple domains. This pattern was strongly associated with widespread network dysfunction, characterized by decreased interhemispheric connectivity and increased intrahemispheric connectivity. Notably, the identified LC was replicated and generalized to stroke data at the 3-month and 12-month time points. Furthermore, we examined whether structural lesion features, including structural disconnection of white matter pathways and grey matter damage, could explain variance in the identified LC. Structural disconnection outperformed grey matter damage, highlighting its critical role in the functional connectivity-behaviour relationship following stroke. Mediation analysis confirmed that structural disconnection serves as the neuroanatomical basis for the association between functional connectivity and deficits. Overall, this study suggests that stroke-induced white matter disconnections are associated with widespread and consistent disruptions in brain network connectivity, which are reflected in a highly correlated behavioural profile. These results provide an integrative insight into the complex relationships among lesions, functional networks, and behavioural outcomes following stroke.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 4","pages":"fcaf276"},"PeriodicalIF":4.5,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12308281/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144755424","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}
Brain communicationsPub Date : 2025-07-22eCollection Date: 2025-01-01DOI: 10.1093/braincomms/fcaf280
Stephen Krieger, Thibo Billiet, Nuno Pedrosa de Barros, Thanh Vân Phan, Wim Van Hecke, Annemie Ribbens, Karin Cook, Tim Wang, Kain Kyle, Linda Ly, Justin Garber, Michael Barnett
{"title":"Depicting multiple sclerosis disease course using lesion parenchymal fraction: a quantified expression of the topographical model of multiple sclerosis.","authors":"Stephen Krieger, Thibo Billiet, Nuno Pedrosa de Barros, Thanh Vân Phan, Wim Van Hecke, Annemie Ribbens, Karin Cook, Tim Wang, Kain Kyle, Linda Ly, Justin Garber, Michael Barnett","doi":"10.1093/braincomms/fcaf280","DOIUrl":"10.1093/braincomms/fcaf280","url":null,"abstract":"<p><p>The topographical model of multiple sclerosis proposes that functional reserve compensates for multiple sclerosis lesions, and that disability accumulation is the result of an insidious unmasking of deficits referable to lesion burden. To utilize topographical principles to establish an imaging metric-lesion parenchymal fraction (LPF)-defined as lesion volume divided by parenchymal volume in the same regional compartment, and to assess the relationship of LPF with disability. One hundred patients with relapsing-remitting or secondary progressive multiple sclerosis were evaluated; clinical and MRI data were longitudinally acquired from 2011-19. Lesion and parenchymal volumes in brain and cervical cord were processed using icobrain/icospine pathways, parsed into topographical compartments, and regional LPF was computed. Performance of LPF-based linear models was evaluated using Pearson correlation and root mean squared error between measured and estimated disability scores (expanded disability status score). To establish relative contributions of LPF in cervical, infratentorial and cerebral compartments, a density plot of weight distributions was generated. Individual disability scores and compartment-weighted LPF trajectories were rendered using matplotlib in Python. MRI and clinical data from 78 patients were sufficient for modelling: 39 remaining relapsing-remitting and 39 progressing to secondary progressive multiple sclerosis. The LPF model had the best performance in decoding the disability score using root mean squared error (1.638) and ranked second in Pearson correlation (0.275). Setting the mean coefficient of cerebral LPF to 1, the cervical compartment had the largest coefficient (3.8), followed by infratentorial (2.5). Compartment-weighted cumulative LPF values depict multiple sclerosis disease trajectory longitudinally on a per-patient basis. This visualization is shown for patients who transitioned from relapsing-remitting to secondary progressive phenotypes; non-progressing patients; and outliers where the LPF model does not approximate the disability score trajectory. We developed and evaluated LPF as an MRI-quantified expression of the topographical model of multiple sclerosis, a first effort to operationalize this model to depict individual disease course. That LPF from spinal cord and infratentorial compartments conferred respectively 3.8 and 2.5 more impact on the expanded disability status score than the cerebral hemispheres emphasizes the importance of lesion topography. Implications of outliers are instructive regarding current model limitations; refinement using additional clinical and imaging metrics could allow application to individual patients.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 4","pages":"fcaf280"},"PeriodicalIF":4.5,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12308131/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144755423","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}
Brain communicationsPub Date : 2025-07-22eCollection Date: 2025-01-01DOI: 10.1093/braincomms/fcaf236
Michael C B David, Emma-Jane Mallas, Lucia M Li, Magdalena A Kolanko, Ramin Nilforooshan, Man Lai Tsoi, Hanim Karakoc, Karen Hoang, Johanna Brandt, Charikleia Triantafyllou, Dragos C Gruia, Darije Custovic, Peter J Lally, Karl A Zimmerman, Paresh A Malhotra, Gregory Scott, David J Sharp
{"title":"Pupil-linked arousal, cortical activity, and cognition in Alzheimer's disease.","authors":"Michael C B David, Emma-Jane Mallas, Lucia M Li, Magdalena A Kolanko, Ramin Nilforooshan, Man Lai Tsoi, Hanim Karakoc, Karen Hoang, Johanna Brandt, Charikleia Triantafyllou, Dragos C Gruia, Darije Custovic, Peter J Lally, Karl A Zimmerman, Paresh A Malhotra, Gregory Scott, David J Sharp","doi":"10.1093/braincomms/fcaf236","DOIUrl":"10.1093/braincomms/fcaf236","url":null,"abstract":"<p><p>Arousal dysfunction contributes to impairments seen in Alzheimer's disease. However, the nature and degree of this dysfunction have not been studied in detail. We investigated changes in tonic and phasic arousal using simultaneous pupillometry-EEG, relating these changes to locus coeruleus integrity, a key arousal nucleus. Forty Alzheimer's disease participants and 30 controls underwent neuropsychological testing using the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), MRI designed to show contrast in the locus coeruleus as a measure of integrity and simultaneous pupillometry-EEG during 5 min of eyes-open resting-state. Pupillometry-EEG was then also applied during an oddball task which included a passive session and sessions in which responses to target stimuli were required, to test the effect of salience. Alzheimer's disease had lower locus coeruleus integrity (<i>b</i> = -0.26, <i>P</i> = 0.02) and lower peak alpha frequency (tonic arousal) (<i>b</i> = -1.09, <i>P</i> < 0.001). Both were related to ADAS-Cog. There was a very strong relationship between pupil size and both periodic and aperiodic EEG power. Cortical slowing in Alzheimer's disease affected this relationship, particularly at low frequencies. During the attentionally demanding oddball task, Alzheimer's disease participants' behavioural performance was impaired, with reduced accuracy and slower and more variable reaction times. They also had reduced pupil responses to salient stimuli (phasic arousal) (estimate = -0.19, <i>P</i> < 0.001). EEG and pupil measures of pre-stimulus tonic arousal were strongly correlated and predicted behavioural responses in both groups. Arousal fluctuations at rest and in response to stimuli are abnormal in Alzheimer's disease as measured by combined pupillometry and EEG. Salient stimuli that require a behavioural response are accompanied by a phasic increase in arousal, demonstrated by pupil dilation to oddball stimuli. This response is slower and of smaller magnitude in Alzheimer's disease patients. Cortical slowing (reduced peak alpha frequency) is seen in Alzheimer's disease, and this is modulated by arousal level and relates to overall cognition. Pupil-linked arousal responses and alpha EEG fluctuations are tightly coupled, but cortical slowing in Alzheimer's disease influences this coupling. The tools used here to measure neurophysiological arousal level have potential in understanding the nature of arousal system dysfunction in Alzheimer's disease at the group level. These tools may also be used as biomarkers at the individual level in order to target patients most likely to benefit from arousal-modulating medications.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 4","pages":"fcaf236"},"PeriodicalIF":4.1,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12280328/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144692766","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}
Brain communicationsPub Date : 2025-07-21eCollection Date: 2025-01-01DOI: 10.1093/braincomms/fcaf272
Lakshmi Balaji, Didu Kariyawasam, Karen Herbert, Hugo A Sampaio, Anita Cairns, Brittany C McGill, Lauren Kelada, Susan Woolfenden, Nancy Briggs, Michelle A Farrar
{"title":"Neurodevelopmental screening in children with early-onset spinal muscular atrophy in the treatment era: a strengths-based cohort study.","authors":"Lakshmi Balaji, Didu Kariyawasam, Karen Herbert, Hugo A Sampaio, Anita Cairns, Brittany C McGill, Lauren Kelada, Susan Woolfenden, Nancy Briggs, Michelle A Farrar","doi":"10.1093/braincomms/fcaf272","DOIUrl":"10.1093/braincomms/fcaf272","url":null,"abstract":"<p><p>With transformative advances in diagnostic and therapeutic approaches in spinal muscular atrophy, the long-term neurodevelopmental outcomes of children with, or predicted to have, spinal muscular atrophy type 1 are essential to evaluate. In this single-centre cross-sectional study, development in children with/at-risk of spinal muscular atrophy type 1, aged 1-66 months, was assessed using parent-reported Ages and Stages Questionnaires® (ASQ-3™). Risk of autism spectrum disorder (ASD), parental distress, sociodemographic and clinical characteristics were also evaluated. Associations between exploratory variables and developmental risk were analysed within a bioecological model of health. Adaptive least absolute shrinkage and selection operator (LASSO) was used to identify variables most predictive of developmental acquisition. Thirty-seven children with spinal muscular atrophy participated (response rate: 90.2%, girls: 54.0%). Clinical characteristics varied with modality of diagnosis, survival motor neuron 2 (<i>SMN2</i>) copies and clinical status at initiation of survival motor neuron (SMN)-augmenting therapy. ASQ-3 scores were indicative of no/low developmental risk in 16/37 (43.2%), isolated gross-motor delay consistent with spinal muscular atrophy phenotype in 8/37 (21.6%), isolated non-gross-motor delay in 3/37 (8.1%), and global developmental delay (≥2 domains) in 10/37 (27.0%). The majority of children (21/24, 87.5%) screened negative on Modified Checklist for Autism in Toddlers Revised (M-CHAT-R), indicating low risk of autism spectrum disorder. Almost one-third (32.4%) of parents reported high levels of distress. Factors associated with better developmental performance included three <i>SMN2</i> copies, diagnosis through newborn bloodspot screening and clinical silent status, absence of bulbar dysfunction, higher motor function at the time of initiation of SMN-augmenting therapy, parental well-being (absence of mental health condition and no distress) and parental attainment of tertiary education. An absence of a mental health condition in parents and three <i>SMN2</i> copy genotype in the child were identified as the strongest predictors of no/low developmental risk, with odds ratios of 4.7 and 1.4, respectively. The study findings demonstrate diverse neurodevelopmental profiles in treated children with/at-risk of spinal muscular atrophy type 1 associated with the magnitude and duration of SMN deficiency. The SMN-associated neurodevelopmental disorders may be amenable to modification by targeting bioecological factors of health. Namely, newborn screening and expedient initiation of SMN-augmenting therapies are central to targeting the neurodevelopmental window in children with/at-risk of spinal muscular atrophy type 1. Best practice includes the incorporation of proactive developmental screening for all children with/at-risk of spinal muscular atrophy type 1, with an integrated model of psychosocial support provided for families.","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 4","pages":"fcaf272"},"PeriodicalIF":4.5,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12341873/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144839383","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}
Brain communicationsPub Date : 2025-07-17eCollection Date: 2025-01-01DOI: 10.1093/braincomms/fcaf278
Hui Zhang, Jingrao Zhang, Chun Liang Hsu, Edward S Hui, Kai-Hei Tse, Henry Ka-Fung Mak, David H K Shum
{"title":"Longitudinal effects of sex differences and apolipoprotein E genotype on white matter engagement among elderly.","authors":"Hui Zhang, Jingrao Zhang, Chun Liang Hsu, Edward S Hui, Kai-Hei Tse, Henry Ka-Fung Mak, David H K Shum","doi":"10.1093/braincomms/fcaf278","DOIUrl":"10.1093/braincomms/fcaf278","url":null,"abstract":"<p><p>The apolipoprotein E (<i>APOE</i>) ɛ4 allele is the primary genetic risk factor that influences lipid metabolism and contributes to distinctive Alzheimer's disease pathologies, including increased hippocampal atrophy and accelerated cognitive decline. Synaptic dysfunction can occur in <i>APOE4</i> carriers even before the appearance of any clinical symptoms. Recent evidence has suggested that this genetic risk factor impacts males and females differently. The sex-specific vulnerability for females to cognitive decline, particularly memory, intensifies post-menopause and emphasizes the need for further investigation. White matter abnormalities, <i>APOE4</i> allele and disruptions in default mode network connectivity serve as early indicators that are crucial for better understanding Alzheimer's disease progression. This study aims to explore relationships between biological sex, <i>APOE4</i>, default mode network-white matter activity and memory function as measured by the Selective Reminding Test. Participants were categorized by risk level on their <i>APOE4</i> status. Using longitudinal data from the Harvard Aging Brain Study, we examined sex differences in default mode network-white matter engagement among older individuals with and without the <i>APOE4</i> allele. Our findings demonstrated a significant reduction in default mode network-white matter activity in the right posterior corona radiata in the high-risk group compared to the low-risk group. High-risk females showed reduction in default mode network-white matter activity in the right superior longitudinal fasciculus, which positively correlated with free recall performance, compared to their low-risk counterparts. Unlike females, males showed no significant changes between the low- and high-risk groups. These results underscore the effectiveness of white matter engagement mapping in differentiating longitudinal changes in memory function related to the genetic risk factor <i>APOE4</i> and biological sex.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 4","pages":"fcaf278"},"PeriodicalIF":4.5,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12308282/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144755425","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}
Brain communicationsPub Date : 2025-07-16eCollection Date: 2025-01-01DOI: 10.1093/braincomms/fcaf222
Raihaan Patel, Grace Gillis, Clare E Mackay, Ludovica Griffanti, Congxiyu Wang, Klaus P Ebmeier, Sana Suri
{"title":"The lifetime accumulation of multimorbidity and its influence on dementia risk: a UK Biobank study.","authors":"Raihaan Patel, Grace Gillis, Clare E Mackay, Ludovica Griffanti, Congxiyu Wang, Klaus P Ebmeier, Sana Suri","doi":"10.1093/braincomms/fcaf222","DOIUrl":"10.1093/braincomms/fcaf222","url":null,"abstract":"<p><p>The number of people living with dementia worldwide is projected to reach 150 million by 2050, making prevention a crucial priority for health services. The co-occurrence of two or more chronic health conditions, termed multimorbidity, occurs in up to 80% of dementia patients, making multimorbidity an important risk factor for dementia. However, we lack an understanding of the specific health conditions, and their age of onset, that drive the link between multimorbidity and dementia. Using data from 282 712 participants of the UK Biobank, we defined the sequential patterns of accumulation of 46 chronic conditions over the life course. By grouping individuals based on their life history of chronic illness, we show here that the risk of incident dementia can be stratified by both the type and timing of their accumulated chronic conditions. We identified several distinct clusters of multimorbidity throughout the lifespan (cardiometabolic, mental health, neurovascular, peripheral vascular, eye diseases and low/no multimorbidity). We observed that the odds of developing dementia varied based on when these comorbidities were diagnosed. Until midlife (age 55), the accumulation of cardiometabolic conditions, such as coronary heart disease, atrial fibrillation, and diabetes, was most strongly associated with dementia risk. However, from 55 to 70 years, the accumulation of mental health conditions, such as anxiety and depression, as well as neurovascular conditions, such as stroke and transient ischaemic attack, was associated with an over 2-fold increase in dementia risk compared with low multimorbidity. Importantly, individuals who continuously and sequentially accumulate cardiometabolic, mental health, and neurovascular conditions were at greatest risk. The age-dependent role of multimorbidity in predicting dementia risk could be used for early stratification of individuals into high- and low-risk groups and could inform targeted prevention strategies based on a person's prior history of chronic disease.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 4","pages":"fcaf222"},"PeriodicalIF":4.1,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12266833/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144651519","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}
Brain communicationsPub Date : 2025-07-16eCollection Date: 2025-01-01DOI: 10.1093/braincomms/fcaf258
Sarah L Martin, Carme Uribe, Kimberly L Desmond, Lucas Narciso, Bayla Dolman, Edgardo Torres-Carmona, Isabelle Boileau, Ariel Graff-Guerrero, Neil Vasdev, Antonio P Strafella
{"title":"[<sup>18</sup>F]SynVest-1 PET imaging in people with Parkinson's disease.","authors":"Sarah L Martin, Carme Uribe, Kimberly L Desmond, Lucas Narciso, Bayla Dolman, Edgardo Torres-Carmona, Isabelle Boileau, Ariel Graff-Guerrero, Neil Vasdev, Antonio P Strafella","doi":"10.1093/braincomms/fcaf258","DOIUrl":"10.1093/braincomms/fcaf258","url":null,"abstract":"<p><p>The [<sup>18</sup>F]SynVest-1 radiotracer targets the synaptic vesicle glycoprotein 2A (SV2A) and is a proxy of presynaptic density. Parkinson's disease is associated with synaptic dysfunction. Here we investigated synaptic density via the [<sup>18</sup>F]SynVest-1 radiotracer in people with PD compared with healthy controls, with reference to how it compares to the previous SV2A radiotracer, [11C]UCB-J. Ten Parkinson's patients and 12 healthy subjects underwent a [<sup>18</sup>F]SynVest-1 PET scan. We compared non-displaceable binding potential via voxel-wise and volume of interest analysis to investigate group differences. Volume-of-interest-analyses reported lower non-displaceable binding potential in key a priori regions associated with Parkinson's disease, namely the substantia nigra and caudate nucleus (<i>P</i> < 0.05). Follow-up exploratory volume-of-interest-analyses reported widespread reduction in non-displaceable binding potential within all brain lobes, cerebellum, hippocampus, thalamus and insula; however, these findings did not survive correction for multiple comparisons (<i>P</i> < 0.004). In addition, voxel-wise analyses with family-wise error correction, highlighted significantly lower non-displaceable binding potential in the PD cohort within the putamen and cerebellum. We did not observe any relationships between clinical metrics and non-displaceable binding potential. The results are in line with differences observed using the [<sup>11</sup>C]UCB-J radiotracer. The [<sup>18</sup>F]SynVest-1 radiotracer confirmed lower synaptic density in the Parkinson's disease cohort and adds to the growing evidence of synaptic dysfunction in Parkinson's disease pathology.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 4","pages":"fcaf258"},"PeriodicalIF":4.1,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12264488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144651516","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}
Brain communicationsPub Date : 2025-07-16eCollection Date: 2025-01-01DOI: 10.1093/braincomms/fcaf271
Peirong Liu, Dina Zemlyanker, Karthik Gopinath, You Cheng, Yingnan He, David Izquierdo-Garcia, Teresa Gomez-Isla, Sudeshna Das, Shahin Nasr, Kevin N Sheth, Matthew S Rosen, W Taylor Kimberly, Adam de Havenon, Francis X Shen, Juan Eugenio Iglesias
{"title":"The normalizing properties of intracranial volume across race and sex.","authors":"Peirong Liu, Dina Zemlyanker, Karthik Gopinath, You Cheng, Yingnan He, David Izquierdo-Garcia, Teresa Gomez-Isla, Sudeshna Das, Shahin Nasr, Kevin N Sheth, Matthew S Rosen, W Taylor Kimberly, Adam de Havenon, Francis X Shen, Juan Eugenio Iglesias","doi":"10.1093/braincomms/fcaf271","DOIUrl":"10.1093/braincomms/fcaf271","url":null,"abstract":"<p><p>In volumetric analysis of the human brain with MRI, intracranial volume is an important covariate as it has a strong correlation with the volume of regions of interest in the brain. Therefore, accurate adjustment for intracranial volume (e.g. by division) is essential to mitigate the impact of head size on brain measurements. In this study, we assess the effects of intracranial volume normalization on differences across sex and racial groups, using a diverse cohort with 5977 subjects from three different (self-reported) races. We show that (i) differences in intracranial volume across sex are consistent across race and vice versa; and (ii) intracranial volume normalization almost completely accounts for differences by race and sex. These results suggest that subjects of different sexes and races can be safely aggregated in volumetric studies by normalizing the volume of regions of interest to intracranial volume.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 4","pages":"fcaf271"},"PeriodicalIF":4.5,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12315546/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144777257","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}
Brain communicationsPub Date : 2025-07-16eCollection Date: 2025-01-01DOI: 10.1093/braincomms/fcaf273
Sofiati Dian, Valerie A C M Koeken, Edwin Ardiansyah, Ahmad R Ganiem, Kirsten van Abeelen, Raúl Aguirre-Gamboa, Feby Purnama, Sofia Imaculata, Jessi Annisa, Lidya Chaidir, Rovina Ruslami, Leo A B Joosten, Mihai G Netea, Bachti Alisjahbana, Reinout van Crevel, Arjan van Laarhoven, Vinod Kumar
{"title":"Inflammatory markers in the cerebrospinal fluid linked to mortality in tuberculous meningitis.","authors":"Sofiati Dian, Valerie A C M Koeken, Edwin Ardiansyah, Ahmad R Ganiem, Kirsten van Abeelen, Raúl Aguirre-Gamboa, Feby Purnama, Sofia Imaculata, Jessi Annisa, Lidya Chaidir, Rovina Ruslami, Leo A B Joosten, Mihai G Netea, Bachti Alisjahbana, Reinout van Crevel, Arjan van Laarhoven, Vinod Kumar","doi":"10.1093/braincomms/fcaf273","DOIUrl":"10.1093/braincomms/fcaf273","url":null,"abstract":"<p><p>This study examines the role of host inflammation in the high mortality of tuberculous meningitis (TBM) and identifies potential biomarkers associated with improved survival. We conducted a case-control study involving 131 patients in a discovery cohort, 81 TBM patients in a validation cohort, and 43 non-infected controls from a referral hospital in Indonesia. We measured 94 inflammation-related proteins in cerebrospinal fluid (CSF) and performed genome-wide quantitative trait loci (QTL) mapping. Sixty-seven proteins were found to be differentially expressed between TBM patients and controls, with 64 proteins elevated in patients. Five proteins, including vascular endothelial growth factor (VEGF) and matrix metalloproteinase-10 (MMP-10), were identified as predictors of 180-day mortality in TBM patients. The validation cohort confirmed that MMP-10, but not VEGF, was predictive of mortality. Genome-wide QTL mapping identified two genome-wide significant and four suggestive genetic loci associated with CSF MMP-10, which also predicted survival in an additional cohort of 218 patients. High CSF concentrations of MMP-10, along with specific genetic loci, may be associated with survival in TBM patients, suggesting a potential role for MMP-10 in disease pathogenesis and warranting further investigation into its utility in host-directed therapies.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 4","pages":"fcaf273"},"PeriodicalIF":4.5,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12284393/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144700649","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":"Hyperuricaemia is associated with smaller volumes in the caudate nucleus head and putamen.","authors":"Naoki Omori, Manabu Ishida, Masahiro Takamura, Satoshi Abe, Atsushi Nagai","doi":"10.1093/braincomms/fcaf263","DOIUrl":"10.1093/braincomms/fcaf263","url":null,"abstract":"<p><p>Hyperuricaemia is a risk factor for gout, kidney diseases, and cerebrovascular diseases. Uric acid (UA) is also known as an antioxidant and has been suggested to inhibit the progression of neurodegenerative diseases, such as Parkinson's disease. However, only a few studies have focused on the potential effects of UA on the basal ganglia. This study aimed to measure UA levels and basal ganglia volumes in community-dwelling adults and to evaluate the association thereof. Blood UA levels and brain MRI data were collected from individuals who underwent brain health checkups between January 2015 and March 2022 at Shimane Institute of Health Science. Participants were classified into three groups based on their UA levels: normal-low UA (< 5.0 mg/dL), normal-high UA (5.0-7.0 mg/dL), and hyperuricaemia (> 7.0 mg/dL). MRI was used to assess the presence of asymptomatic infarcts, microbleeds, and the severity of enlarged perivascular spaces in the basal ganglia. The volumes of the caudate nucleus, globus pallidus, putamen, substantia nigra, and subthalamic nucleus were calculated using voxel-based morphometry (VBM) as <i>Z</i>-scores adjusted for participant age, sex, and total intracranial volume. Analysis of covariance and smooth-curve fitting models were used to examine the association between UA levels and basal ganglia volumes. In total, 981 participants were included in the analysis. Analysis of covariance revealed that the hyperuricaemia group had significantly higher <i>Z</i>-scores (indicating smaller volumes) in the bilateral caudate nucleus head and putamen than those of the normal-high UA group. The smooth-curve model showed U-shaped associations with smaller volumes for both high and low UA levels, whereas piecewise linear regression analysis confirmed significant regression lines only in the group with higher UA levels. Although UA is thought to have a neuroprotective effect in adults, our findings indicate that hyperuricaemia may contribute to smaller volumes in the caudate nucleus head and putamen. This suggests that excessive UA levels could negatively affect basal ganglia structure and neurological health.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 4","pages":"fcaf263"},"PeriodicalIF":4.1,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12260223/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144644377","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}