Brain communications最新文献

{"title":"The causal association between resting state intrinsic functional networks and neurodegeneration.","authors":"Malik Nassan, Iyas Daghlas, Bram R Diamond, Adam Martersteck, Emily Rogalski","doi":"10.1093/braincomms/fcaf098","DOIUrl":"10.1093/braincomms/fcaf098","url":null,"abstract":"<p><p>Alterations of resting state intrinsic functional networks have been associated with neurodegenerative diseases even before the onset of cognitive symptoms. Emerging hypotheses propose a role of resting state intrinsic functional networks alterations in the risk or vulnerability to neurodegeneration. It is unknown whether intrinsic functional network alterations can be causal for neurodegenerative diseases. We sought to answer this question using two-sample Mendelian randomization. Using the largest genome-wide association study of resting state intrinsic functional connectivity (<i>n</i> = 47 276), we generated genetic instruments (at the significance level 2.8 ×10^-11) to proxy resting state intrinsic functional network features. Based on the known brain regions implicated in different neurodegenerative diseases, we generated genetically proxied resting state intrinsic functional features and tested their association with their paired neurodegenerative outcomes: features in parieto-temporal regions and Alzheimer dementia (111 326 cases, 677 663 controls); frontal region and frontotemporal dementia (2154 cases, 4308 controls); temporal pole region and semantic dementia (308 cases, 616 controls), and occipital region with Lewy body dementia (LBD) (2591 cases, 4027 controls). Major depressive disorder outcome (170 756 cases, 329 443 controls) was included as a positive control and tested for its association with genetically proxied default mode network (DMN) exposure. Inverse-variance weighted analysis was used to estimate the association between the exposures (standard deviation units) and outcomes. Power and sensitivity analyses were completed to assess the robustness of the results. None of the genetically proxied functional network features were significantly associated with neurodegenerative outcomes (adjusted <i>P</i> value >0.05), despite sufficient calculated power. Two resting state features in the visual cortex showed a nominal level of association with LBD (<i>P</i> = 0.01), a finding that was replicated using a different instrument (<i>P</i> = 0.03). The genetically proxied DMN connectivity was associated with the risk of depression (<i>P</i> = 0.024), supporting the validity of the genetic instruments. Sensitivity analyses were supportive of the main results. This is the first study to comprehensively assess the potential causal effect of resting state intrinsic functional network features on the risk of neurodegeneration. Overall, the results do not support a causal role for the tested associations. However, we report a nominal association between visual network connectivity and Lewy body dementia that requires further evaluation.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 2","pages":"fcaf098"},"PeriodicalIF":4.1,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11913654/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660127","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":"Uncovering atrophy progression pattern and mechanisms in individuals at risk of Alzheimer's disease.","authors":"Christina Tremblay, Shady Rahayel, Alexandre Pastor-Bernier, Frédéric St-Onge, Andrew Vo, François Rheault, Véronique Daneault, Filip Morys, Natasha Rajah, Sylvia Villeneuve, Alain Dagher","doi":"10.1093/braincomms/fcaf099","DOIUrl":"https://doi.org/10.1093/braincomms/fcaf099","url":null,"abstract":"<p><p>Alzheimer's disease is associated with pre-symptomatic changes in brain morphometry and accumulation of abnormal tau and amyloid-beta pathology. Studying the development of brain changes prior to symptoms onset may lead to early diagnostic biomarkers and a better understanding of Alzheimer's disease pathophysiology. Alzheimer's disease pathology is thought to arise from a combination of protein accumulation and spreading via neural connections, but how these processes influence brain atrophy progression in the pre-symptomatic phases remains unclear. Individuals with a family history of Alzheimer's disease (FHAD) have an elevated risk of Alzheimer's disease, providing an opportunity to study the pre-symptomatic phase. Here, we used structural MRI from three databases (Alzheimer's Disease Neuroimaging Initiative, Pre-symptomatic Evaluation of Experimental or Novel Treatments for Alzheimer Disease and Montreal Adult Lifespan Study) to map atrophy progression in FHAD and Alzheimer's disease and assess the constraining effects of structural connectivity on atrophy progression. Cross-sectional and longitudinal data up to 4 years were used to perform atrophy progression analysis in FHAD and Alzheimer's disease compared with controls. PET radiotracers were also used to quantify the distribution of abnormal tau and amyloid-beta protein isoforms at baseline. We first derived cortical atrophy progression maps using deformation-based morphometry from 153 FHAD, 156 Alzheimer's disease and 116 controls with similar age, education and sex at baseline. We next examined the spatial relationship between atrophy progression and spatial patterns of tau aggregates and amyloid-beta plaques deposition, structural connectivity and neurotransmitter receptor and transporter distributions. Our results show that there were similar patterns of atrophy progression in FHAD and Alzheimer's disease, notably in the cingulate, temporal and parietal cortices, with more widespread and severe atrophy in Alzheimer's disease. Both tau and amyloid-beta pathology tended to accumulate in regions that were structurally connected in FHAD and Alzheimer's disease. The pattern of atrophy and its progression also aligned with existing structural connectivity in FHAD. In Alzheimer's disease, our findings suggest that atrophy progression results from pathology propagation that occurred earlier, on a previously intact connectome. Moreover, a relationship was found between serotonin receptor spatial distribution and atrophy progression in Alzheimer's disease. The current study demonstrates that regions showing atrophy progression in FHAD and Alzheimer's disease present with specific connectivity and cellular characteristics, uncovering some of the mechanisms involved in pre-clinical and clinical neurodegeneration.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 2","pages":"fcaf099"},"PeriodicalIF":4.1,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11906971/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143652402","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":"Sleep on it!","authors":"Laurent Sheybani","doi":"10.1093/braincomms/fcaf072","DOIUrl":"10.1093/braincomms/fcaf072","url":null,"abstract":"<p><p>Our Associate Editor, Laurent Sheybani, discusses some very old and very recent findings on sleep physiology and function, hoping to raise further interest and publications in the field.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 2","pages":"fcaf072"},"PeriodicalIF":4.1,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11879451/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143569137","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":"Unraveling the role of proteins in dementia: insights from two UK cohorts with causal evidence.","authors":"Jessica Gong, Dylan M Williams, Shaun Scholes, Sarah Assaad, Feifei Bu, Shabina Hayat, Paola Zaninotto, Andrew Steptoe","doi":"10.1093/braincomms/fcaf097","DOIUrl":"10.1093/braincomms/fcaf097","url":null,"abstract":"<p><p>Population-based proteomics offers a groundbreaking avenue to predict future disease risks, enhance our understanding of disease mechanisms, and discover novel therapeutic targets and biomarkers. The role of plasma proteins in dementia, however, requires further exploration. This study investigated 276 protein-dementia associations in 229 incident all-cause dementia, 89 Alzheimer's disease, and 41 vascular dementia among 3249 participants (55% women, 97.2% white ethnicity) from the English Longitudinal Study of Ageing (ELSA) over a median 9.8-year follow-up. We used Cox proportional hazard regression for the analysis. Receiver operating characteristic analyses were conducted to assess the precision of the identified proteins from the fully adjusted Cox regression models in predicting incident all-cause dementia, both individually and in combination with demographic predictors, <i>APOE</i> genotype, and memory score, to estimate the area under the curve. Additionally, the eXtreme Gradient Boosting machine learning algorithm was used to identify the most important features predictive of future all-cause dementia onset. These associations were then validated in 1506 incident all-cause dementia, 732 Alzheimer's disease, 281 vascular dementia, and 111 frontotemporal dementia cases among 52 745 individuals (53.9% women, 93.3% White ethnicity) from the UK Biobank over a median 13.7-year follow-up. Two-sample bi-directional Mendelian randomization and drug target Mendelian randomization were further employed to determine the causal direction between protein concentration and dementia. NEFL (hazard ratio [HR] [95% confidence intervals (CIs)]: 1.54 [1.29, 1.84]) and RPS6KB1 (HR [95% CI]: 1.33 [1.16, 1.52]) were robustly associated with incident all-cause dementia; MMP12 (HR [95% CI]: 2.06 [1.41, 2.99]) was associated with vascular dementia in ELSA, after correcting for multiple testing. Additional markers EDA2R and KIM1 were identified from subgroup and sensitivity analyses. Combining NEFL and RPS6KB1 with other predictors yielded high predictive accuracy (area under the curve = 0.871) for incident all-cause dementia. The eXtreme Gradient Boosting machine learning algorithm also identified RPS6KB1, NEFL, and KIM1 as the most important protein features for predicting future all-cause dementia. Sex difference was evident for the association between RPS6KB1 and all-cause dementia, with stronger association in men (<i>P</i> for interaction = 0.037). Replication in the UK Biobank confirmed the associations between the identified proteins and various dementia subtypes. The results from Mendelian randomization in the reverse direction indicated that several proteins serve as early markers for dementia, rather than being direct causes of the disease. These findings provide insights into putative mechanisms for dementia. Future studies are needed to validate the findings on RPS6KB1 in relation to dementia risk.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 2","pages":"fcaf097"},"PeriodicalIF":4.1,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11906402/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143652403","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":"Influence of apolipoprotein E genotype on the proteomic profile in cerebral microdialysis after human severe traumatic brain injury: a prospective observational study.","authors":"Caroline Lindblad, Andrea Klang, David Bark, Cristina Bellotti, Anders Hånell, Per Enblad, Anders Lewén, Elham Rostami","doi":"10.1093/braincomms/fcaf096","DOIUrl":"10.1093/braincomms/fcaf096","url":null,"abstract":"<p><p>Patient-tailored treatment, also known as precision-medicine, has been emphasized as a prioritized area in traumatic brain injury research. In fact, pre-injury patient genetic factors alone account for almost 26% of outcome prediction variance following traumatic brain injury. Among implicated genetic variants single-nucleotide polymorphism in apolipoprotein E has been linked to worse prognosis following traumatic brain injury, but the underlying mechanism is still unknown. We hypothesized that apolipoprotein E genotype would affect the levels of pathophysiology-driving structural, or inflammatory, proteins in cerebral microdialysate following severe traumatic brain injury. We conducted a prospective observational study of patients with severe traumatic brain injury treated with invasive neuromonitoring including cerebral microdialysis at Uppsala University Hospital. All patients were characterized regarding apolipoprotein E genotype. Utilizing fluid- and plate-based antibody arrays, we quantified 101 proteins (of which 89 were eligible for analysis) in cerebral microdialysate at 1 day and 3 days following trauma. Statistical analysis included clustering techniques, as well as uni- and multi-variate linear mixed modelling. In total, 26 patients were included, and all relevant genotypes of apolipoprotein E were represented in the data. Among all proteins tested, 41 proteins showed a time-dependent expression level. There was a weak clustering tendency in the data, and not primarily to genotype, either depicted through t-distributed stochastic neighbour embedding or hierarchical clustering. Using linear mixed models, two proteins [the inflammatory protein CD300 molecule like family member f (CLM-1) and the neurotrophic protein glial-derived neurotrophic factor family receptor α1] were found to have protein levels concomitantly dependent upon time and genotype, albeit this effect was not seen following multiple testing corrections. Apart from amyloid-β-40 (Aβ) and Microtubule-associated protein tau, neither Aβ peptide levels nor the Aβ42/40 ratio were seen related to time from trauma or apolipoprotein E genotype. This is the first study in clinical severe traumatic brain injury examining the influence of apolipoprotein E genotype on microdialysate protein expression. Protein levels in cerebral microdialysate following trauma are seen to be strongly dependent on time from trauma, corroborating previous work on protein expression longitudinally following traumatic brain injury. We also identified protein expression level alterations dependent on apolipoprotein E genotype, which might indicate that apolipoprotein E affects ongoing pathophysiology in the injured brain at the proteomic level.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 2","pages":"fcaf096"},"PeriodicalIF":4.1,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11920868/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143665632","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":"Whole-brain volumetric analysis in adult Moyamoya patients reveals significant atrophy compared to healthy controls.","authors":"Patrick Haas, Alexander Debolski, Benjamin Bender, Leonie Zerweck, Ulrike Ernemann, Marcos Tatagiba, Till-Karsten Hauser, Nadia Khan, Constantin Roder","doi":"10.1093/braincomms/fcaf100","DOIUrl":"10.1093/braincomms/fcaf100","url":null,"abstract":"<p><p>Moyamoya disease (MMD) may lead to perfusion deficits, stroke and brain atrophy in the long-term. Our aim was to analyse whole-brain volumetry of a large cohort of Moyamoya disease patients compared to healthy controls. 3D T1w MRI sequences of adult Moyamoya disease patients treated at our centre between 2016 and 2022 without prior revascularization were analysed for whole-brain volumetry (AssemblyNet) and compared age-controlled to healthy controls. A total of 133 different regions of interest were examined retrospectively for each patient separately by localization, structure and tissue type. All segmentations were subjected to automated and manual quality control. After quality control, 149 hemispheres from 80 Moyamoya disease patients were compared to 258 hemispheres from 129 healthy controls. A significant brain volume loss was observed in Moyamoya disease patients with increasing age, with the greatest reduction seen in bilaterally affected patients with Suzuki grade >3. As direct signs of brain atrophy, significant differences were seen across all regions of interests, emphasized in cortical grey matter with a reduction of 4.4% (95% CI 2.7-6.1%; <i>P</i> < 0.001) in patients aged 30-45 years and 3.4% (95% CI 2.1-4.7%; <i>P</i> < 0.001) aged 46-60 years. As indirect sign for atrophy, external CSF spaces increased up to 26.4% (95% CI 17.0-35.9%; <i>P</i> < 0.001) for 30-45 years and 28.4% (95% CI 17.1-39.7%; <i>P</i> < 0.001) for 46-60 years compared to healthy controls. Infratentorial, significant volume loss was observed for patients aged 46-60 years with 11.6% for cerebellar white matter (95% CI 3.7-19.5%; <i>P</i> = 0.0025) and with 8.5% (95% CI 3.5-13.5%; <i>P</i> = 0.0006) for the brainstem, likely due to secondary neurodegeneration. Moyamoya disease patients >45 year without ischaemia also had significantly less grey matter and white matter volume, with accordingly enlarged CSF spaces. Moyamoya disease may lead to significant differences in brain volume of local and global regions of interest as a sign of brain atrophy, even in the absence of infarctions. These findings might be useful for the understanding of the disease burden and in decision-making for timely revascularization.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 2","pages":"fcaf100"},"PeriodicalIF":4.1,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934919/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143712497","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":"Correction to: The role of brain white matter in depression resilience and response to sleep interventions.","authors":"","doi":"10.1093/braincomms/fcaf064","DOIUrl":"https://doi.org/10.1093/braincomms/fcaf064","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1093/braincomms/fcad210.].</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 1","pages":"fcaf064"},"PeriodicalIF":4.1,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11879035/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143560388","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":"Longitudinal alterations in brain networks and thalamocortical connectivity in paediatric focal epilepsy: a structural connectomics pilot study.","authors":"Aswin Chari, Rory J Piper, Rachel Wilson-Jeffers, Michelle Ruiz-Perez, Kiran Seunarine, M Zubair Tahir, Chris A Clark, Richard Rosch, Rod C Scott, Torsten Baldeweg, Martin M Tisdall","doi":"10.1093/braincomms/fcaf081","DOIUrl":"10.1093/braincomms/fcaf081","url":null,"abstract":"<p><p>Epilepsy is an archetypal brain network disorder characterized by recurrent seizures and associated psychological, cognitive and behavioural sequelae. Progressive brain network dysfunction may contribute to poorer outcomes following treatment, but this has never been tested in humans. In this structural connectomics pilot study, we assess whether there is progressive brain network dysfunction in a cohort of 23 children undergoing repeated multi-shell diffusion tensor imaging as part of their pre-surgical evaluation of focal epilepsy prior to epilepsy surgery. We analyse global and nodal graph metrics and thalamocortical connectivity, comparing the longitudinal changes to a cross-sectional cohort of 57 healthy controls. We identify no robust longitudinal changes in global or nodal network properties over a median of 1.15 years between scans. We also do not identify robust longitudinal changes in thalamic connectivity between scans. On sensitivity analyses, we identify increases in weighted degree at higher scales of brain parcellation and a decrease in the proportion of nodes with a low participation coefficient, suggesting progressive increases in intermodular connections. These findings of no or subtle structural longitudinal brain network changes over a relatively short timeframe indicate that either there are no progressive structural brain network changes over time in epilepsy or the changes appear over longer timescales. Larger studies with longer timeframes between scans may help clarify these findings.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 1","pages":"fcaf081"},"PeriodicalIF":4.1,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11878571/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143560391","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":"Vulnerability of the entorhinal cortex II to neurodegeneration in Alzheimer's disease.","authors":"Aldelmo Emmanuel Reyes-Pablo, Nabil Itzi Luna-Viramontes, José Francisco Montiel-Sosa, Miguel Ángel Ontiveros-Torres, Linda Garcés-Ramírez, Fidel de la Cruz-López, Ricardo Apátiga-Pérez, Ignacio Villanueva-Fierro, Mario Hernandes-Alejandro, Blanca Estela Jaramillo-Loranca, Genaro Vargas-Hernández, Mar Pacheco-Herrero, José Luna-Muñoz","doi":"10.1093/braincomms/fcaf091","DOIUrl":"10.1093/braincomms/fcaf091","url":null,"abstract":"<p><p>Alzheimer's disease is characterized by progressive memory loss and deterioration of cognitive functions. The presence of neurofibrillary tangles in the hippocampal areas (perforant pathway) correlates with cognitive impairment. Pathological processing of tau protein is characterized by post-translational changes such as hyperphosphorylation and truncation, which favour conformational changes within tau. These conformational changes can be regional (dependent on phosphorylation) or structural (depending on regional conformational changes and truncation). Through immunohistochemical and immunofluorescence staining in hippocampus Alzheimer disease brains and quantification in tissue stained with TG3 antibody and analysed by confocal microscopy, we have been able to demonstrate that TG3 correlates with cognitive impairment. In the process of tangle evolution, TG3 is present in pre-tangle. This epitope of the TG3 antibody was very stable to proteolytic processing by caspase-3; truncation is evidenced by the TauC-3 antibody. The entorhinal cortex showed high sensitivity to neurodegeneration and pathological tau processing.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 2","pages":"fcaf091"},"PeriodicalIF":4.1,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11897590/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143618057","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":"Neural correlates of fatigue after traumatic brain injury.","authors":"Annina E Anliker, Léa A S Chauvigné, Leslie Allaman, Adrian G Guggisberg","doi":"10.1093/braincomms/fcaf082","DOIUrl":"10.1093/braincomms/fcaf082","url":null,"abstract":"<p><p>Fatigue is the main cause of disability after traumatic brain injury and has negative impact on social, physical and cognitive functions, participation in daily activities, and ability to work. Since the neural underpinnings are largely unknown, few causal treatments are currently available. This study therefore aimed to investigate the neural correlates of subjective fatigue after traumatic brain injury, controlling for differences in cognitive performance, motor performance and subjective psychological covariates such as depression, anxiety and apathy. Seventeen chronic traumatic brain injury patients (10 with and seven without fatigue) and 11 age, sex, and education-matched healthy controls participated in the study. The dependent variable, overall fatigue, was quantified as the sum of the subscales of the multivariate fatigue inventory. Subjective psychological covariates were extracted from appropriate questionnaires. Brain activation during a two-back task and functional connectivity at rest were reconstructed from high-density EEG. Cortical excitability was quantified from motor evoked potentials induced by transcranial magnetic stimulation over the primary motor cortex. Cognitive performance was assessed with a two-back task as well as with a comprehensive neuropsychological test battery. Motor performance was quantified with Jamar dynamometer. Beside the between-group differences in most fatigue subscales resulting from the group attribution, participants also differed in subjective memory functions, depression, anxiety and apathy. Conversely, objective neuropsychological performance was similar across groups in most domains, except for alertness and divided attention (<i>P</i> ≤ 0.039). At the neural level, we observed no difference in corticospinal excitability, but a significant disruption of global resting-state alpha-band functional connectivity between cortical midline structures and the rest of the brain in patients with fatigue (<i>P</i> = 0.006). Furthermore, individuals with fatigue exhibited reduced signs of overall brain activation compared with healthy controls throughout the cognitive task (<i>P</i> = 0.032) without time-on-task effect. In a multivariate regression model, resting-state functional connectivity (<i>P</i> = 0.013) and subjective psychological questionnaire scores (<i>P</i> < 0.0001) were independent predictors of fatigue. In conclusion, our results suggest that disrupted network interactions are the primary independent neural predictor of fatigue. This may serve as a new target for therapy.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 2","pages":"fcaf082"},"PeriodicalIF":4.1,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11891517/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143598601","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}