Brain communications最新文献

{"title":"Neuronal and glial dysfunction, white matter hyperintensities and cognition in ageing and Alzheimer's disease.","authors":"Ann J Lee, Erica Howard, Nicole Saltiel, Jasmeet P Hayes, Scott M Hayes","doi":"10.1093/braincomms/fcaf068","DOIUrl":"10.1093/braincomms/fcaf068","url":null,"abstract":"<p><p>This cross-sectional study examined associations between multiple fluid biomarkers of neuronal and glial dysfunction (plasma neurofilament light chain, CSF growth-associated protein 43 and CSF soluble triggering receptor expressed on myeloid cells 2), total white matter hyperintensity volume and episodic memory and executive function performance in the context of Alzheimer's disease biomarker status. A total of 563 participants (mean age = 71.9 years, standard deviation = 7.2) from the Alzheimer's Disease Neuroimaging Initiative were classified by the amyloid-β/tau/neurodegeneration framework into no Alzheimer's disease pathology (<i>n</i> = 176), suspected non-Alzheimer's disease pathophysiology (<i>n</i> = 87) or Alzheimer's disease continuum (<i>n</i> = 300) groups. Participants completed baseline neuropsychological assessment, plasma/CSF biomarker collection and MRI. Analyses explored the relative contributions of biomarkers to episodic memory and executive function performance and whether relationships varied by amyloid-β/tau/neurodegeneration group status. Across all participants, neurofilament light chain ( <math> <mrow><mover><mi>β</mi> <mo>^</mo></mover> </mrow> </math> <b>=</b> -0.14, <i>P</i> < 0.001) and growth-associated protein 43 ( <math> <mrow><mover><mi>β</mi> <mo>^</mo></mover> </mrow> </math> <b>=</b> -0.13, <i>P</i> < 0.001) were the strongest biomarkers associated with episodic memory performance, such that greater levels were associated with worse episodic memory. There was a group by growth-associated protein 43 interaction with episodic memory: greater growth-associated protein 43 was associated with lower episodic memory performance in participants classified as Alzheimer's disease continuum relative to the no Alzheimer's disease pathology group ( <math> <mrow><mover><mi>β</mi> <mo>^</mo></mover> </mrow> </math> <b>=</b> -0.26, <i>P</i> < 0.001). No robust associations between biomarkers and executive function performance or between soluble triggering receptor expressed on myeloid cells 2, white matter hyperintensity volume and cognition were observed. Biomarkers of neuro-axonal injury and synaptic dysfunction may independently contribute to episodic memory performance across participants with differing amyloid-β/tau/neurodegeneration profiles. Growth-associated protein 43 may predict worse episodic memory performance in participants with greater Alzheimer's disease pathology. These biomarkers of neuronal dysfunction may serve as domain-specific cognitive correlates in the context of Alzheimer's disease biomarker status.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 1","pages":"fcaf068"},"PeriodicalIF":4.1,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11848269/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143495031","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":"Speech outcomes in cochlear implant users depend on visual cross-modal cortical activity measured before or after implantation.","authors":"Brandon T Paul, Vincent Trinh, Joseph Chen, Trung Le, Vincent Lin, Andrew Dimitrijevic","doi":"10.1093/braincomms/fcaf071","DOIUrl":"10.1093/braincomms/fcaf071","url":null,"abstract":"<p><p>Cochlear implants can partially restore hearing function in deaf individuals, but long-term speech listening outcomes vary widely across cochlear implant users. Visual cross-modal plasticity, where auditory cortical neurons upregulate visual inputs to assist visual processing, is one factor proposed to worsen cochlear implant users' speech outcomes because it may limit auditory processing capability. However, evidence for this view is conflicting, and the relationship of cross-modal activity to speech perception may depend on other variables such as the type of visual activity and when it is assessed. To clarify, we measured visual cross-modal activity during a silent lip reading task using EEG in a cross-sectional, observational study. The study tested visual brain activation in 14 individuals prior to receiving a cochlear implant, 15 individuals tested at least 1 year after receiving and using a cochlear implant and 13 typical hearing controls who did not use a cochlear implant or hearing aid. Cross-modal responses to the onset of a visual event were positively correlated to speech outcomes in cochlear implant users tested after surgery but were negatively correlated in those tested prior to cochlear implant surgery. In addition, cross-modal increases in neural oscillatory power in the alpha band (8-12 Hz) arising in the lip reading task were associated with worse speech outcomes in both cochlear implant user groups. Taken together, results redress claims that cross-modal plasticity is maladaptive for speech outcomes and instead suggest that this relationship depends on the time point of testing, stage of sensory processing and likely the relevance of the stimulus for speech. In addition, findings form the basis for new neural markers that are predictive of cochlear implant users' long-term speech ability.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 1","pages":"fcaf071"},"PeriodicalIF":4.1,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11851104/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143506597","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":"High-frequency oscillations in epileptic and non-epileptic Alzheimer's disease patients and the differential effect of levetiracetam on the oscillations.","authors":"M C Vishnu Shandilya, Kwaku Addo-Osafo, Kamalini G Ranasinghe, Mohamad Shamas, Richard Staba, Srikantan S Nagarajan, Keith Vossel","doi":"10.1093/braincomms/fcaf041","DOIUrl":"10.1093/braincomms/fcaf041","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Alzheimer's disease increases the risk of developing epilepsy together with cognitive decline. Early diagnosis or prediction of parameters associated with epileptic activity can greatly help in managing disease outcomes. Network hyperexcitability is a candidate of interest as a neurophysiological biomarker of Alzheimer's disease. High-frequency oscillations are increasingly recognized as potential biomarkers of hyperexcitability and epileptic activity. However, they have not yet been identified in Alzheimer's disease. In this study, we measured high-frequency oscillations via magnetoencephalography recordings in Alzheimer's disease patients with and without epileptic activity, as part of a Phase 2a randomized, double blind clinical trial of the efficacy of levetiracetam to improve cognitive functions in Alzheimer's disease. To measure the high-frequency oscillations, we used 10-min magnetoencephalography recordings (275-channel and sampling rate 1200-4000 Hz) during awake resting periods in participants with Alzheimer's disease and healthy controls. Recordings from 14 Alzheimer's disease participants, with six having non-epileptic Alzheimer's disease (median age: 60.8, 2 M/4 F), eight having sub-clinical epileptic activity (median age: 54.9, 5 M/3 F) and eight as control (median age: 71, 5 M/3 F), were analysed using two software scripts: Delphos and a custom-made script, for detecting high-frequency oscillations. Levetiracetam 125 mg twice-a-day or placebo was administered for 4 weeks in between two magnetoencephalography recordings, and 4 weeks of washout before switching levetiracetam/placebo phases for each participant. High-frequency oscillations were categorized into ripples (80 to 250 Hz) and fast ripples (250 to 500 Hz). At baseline, Alzheimer's disease participants, both epileptic and non-epileptic had higher rate of ripples and fast ripples than controls in several left/right hemispheric sensor regions (&lt;i&gt;P&lt;/i&gt; &lt; 0.05). Additionally, compared to epileptic, non-epileptic had higher rate of ripples in left-frontal, left-temporal and cerebral fissure regions and higher rate of fast ripples in left-frontal regions (&lt;i&gt;P&lt;/i&gt; &lt; 0.05). In epileptic type, levetiracetam decreased ripples in bilateral-frontal, bilateral-occipital regions and cerebral fissure, whereas in non-epileptic type, levetiracetam increased both ripples and fast ripples in right central and left parietal regions, and ripples in the right parietal region (&lt;i&gt;P&lt;/i&gt; &lt; 0.05). Additionally, we found hemisphere asymmetry in epileptic type, with right temporal/occipital having more high-frequency oscillations than their counterpart region. Overall, Alzheimer's disease had a high level of high-frequency oscillations, with higher numbers observed in non-epileptic type. Levetiracetam decreased high-frequency oscillations in epileptic but increased high-frequency oscillations in non-epileptic. Thus, high-frequency oscillations can function as a biomarker of hyperexcitability in","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 1","pages":"fcaf041"},"PeriodicalIF":4.1,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11822293/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143415543","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":"Cortico-hippocampal networks underpin verbal memory encoding in temporal lobe epilepsy.","authors":"Giorgio Fiore, Davide Giampiccolo, Fenglai Xiao, Matthias J Koepp, Juan E Iglesias, Sjoerd B Vos, Jane de Tisi, Andrew W McEvoy, Giulio A Bertani, Marco Locatelli, Roisin Finn, Lorenzo Caciagli, Meneka Sidhu, Marian Galovic, Sallie Baxendale, John S Duncan, Anna Miserocchi","doi":"10.1093/braincomms/fcaf067","DOIUrl":"10.1093/braincomms/fcaf067","url":null,"abstract":"<p><p>Knowledge of the structural underpinnings of human verbal memory is scarce. Understanding the human verbal memory network at a finer anatomical scale will have important clinical implications for the management of patients with verbal memory impairment. In this cross-sectional study, we aimed to assess the contributions of cerebral cortex and hippocampal subfields to verbal memory encoding in temporal lobe epilepsy. We included consecutive patients (<i>n</i> = 84) with radiologically and pathologically defined hippocampal sclerosis (HS) (44 left-sided) and unilateral temporal lobe epilepsy, and healthy volunteers (<i>n</i> = 43) who were comparable regarding age and sex. The morphometric and volumetric measures of cerebral cortex and hippocampal subfields were extracted from high-resolution MRI scans. People included in this study underwent standardized neuropsychological evaluation, including measures of verbal memory assessed through the Adult Memory and Information Processing Battery. Verbal memory performances were <i>Z</i>-scores corrected by using means and standard deviations published for sample standardization. Associations between verbal learning <i>Z</i>-scores and the grey matter volume of the cerebral cortex and hippocampal subfields were investigated. Reduction of grey matter volumes in the left and right medial and dorsolateral prefrontal cortex (<i>P</i> _corr < 0.0001), superior and middle temporal gyri (<i>P</i> _corr < 0.0001), anterior and posterior cingulate cortex (<i>P</i> _corr < 0.0001) and of the left ventrolateral prefrontal cortex (<i>P</i> _corr < 0.0001) and parietal-temporal-occipital junction (<i>P</i> _corr < 0.0001) were associated with worse verbal learning. These findings were consistent across both the entire cohort and in a subgroup analysis focused exclusively on HS patients. Within hippocampi, smaller volumes of the left dentate gyrus (<i>P</i> = 0.003), cornu ammonis 4 (<i>P</i> = 0.005) and cornu ammonis 3 (<i>P</i> = 0.03) were associated with worse verbal learning <i>Z</i>-scores. This study demonstrates that verbal learning in patients with temporal lobe epilepsy is strongly related to the volume of distinct regions of the prefrontal, temporal and cingulate cortices and left dentate gyrus, cornu ammonis 4 and cornu ammonis 3 hippocampal subfields. It provides the basis to suggest a corticohippocampal network for verbal learning in these patients, improving our understanding of human verbal memory. These biomarkers may inform attractive targets for forthcoming modulating therapies. Future work may also analyse the impact of sparing part of the left dentate gyrus, cornu ammonis 4 and cornu ammonis 3 as a protective measure against verbal memory impairment after surgery for temporal lobe epilepsy.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 2","pages":"fcaf067"},"PeriodicalIF":4.1,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11922552/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143665617","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":"Structural brain changes in post-COVID condition and its relationship with cognitive impairment.","authors":"Laura Pacheco-Jaime, Carla Garcia-Vicente, Mar Ariza, Neus Cano, Maite Garolera, Lourdes Carreras-Vidal, Ignacio Roura, Clara Capdevila-Lacasa, Javier Oltra, Jèssica Pardo, Cristina Martín-Barceló, Anna Campabadal, Roser Sala-Llonch, Núria Bargalló, Cristian Barrué, Javier Bejar, Claudio U Cortés, Carme Junqué, Bàrbara Segura","doi":"10.1093/braincomms/fcaf070","DOIUrl":"10.1093/braincomms/fcaf070","url":null,"abstract":"<p><p>It has been estimated that ∼4% of individuals infected with SARS-CoV-2 will be diagnosed with post-COVID condition. Previous studies have evidenced the presence of cognitive dysfunction and structural brain changes in infected individuals; however, the relationship between structural changes and cognitive alterations in post-COVID condition is still not clear. Consequently, the aim of this work is to study structural brain alterations in post-COVID condition patients after almost 2 years of infection and their likely relationship with patients' cognitive impairment. Additionally, the association with blood biomarkers and clinical variables was also explored. One hundred and twenty-eight individuals with post-COVID condition and 37 non-infected healthy controls from the Nautilus Project (ClinicalTrials.gov IDs: NCT05307549 and NCT05307575) underwent structural brain magnetic resonance imaging and a comprehensive neuropsychological assessment. A subsample of 66 post-COVID participants also underwent blood extraction to obtain levels of blood biomarkers. Cortical thickness and subcortical volumes were obtained and analysed using FreeSurfer (v7.1). FMRIB Software Library software (v6.0.4) was used to perform grey matter voxel-based analysis and to study microstructural white matter integrity. Patients with post-COVID performed significantly worse in working and verbal memory, processing speed, verbal fluency and executive functions, compared to healthy controls. Moreover, patients with post-COVID showed increased cortical thickness in the right superior frontal and the right rostral middle frontal gyri that negatively correlated with working memory performance. Diffusion tensor imaging data showed lower fractional anisotropy in patients in the right superior longitudinal fasciculus, the splenium and genu of the corpus callosum, the right uncinate fasciculus and the forceps major, that negatively correlated with subjective memory failures. No differences in blood biomarkers were found. Once patients were classified according to their cognitive status, post-COVID clinically cognitively altered presented increased cortical thickness compared to those classified as non-cognitively altered. In conclusion, our study showed that grey and white matter brain changes are relevant in this condition after almost 2 years of infection and partly explain long-term cognitive sequelae. These findings underscore the critical importance of monitoring this at-risk population over time.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 1","pages":"fcaf070"},"PeriodicalIF":4.1,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11851114/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143506598","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":"Distinct spatiotemporal atrophy patterns in corticobasal syndrome are associated with different underlying pathologies.","authors":"William J Scotton, Cameron Shand, Emily G Todd, Martina Bocchetta, Christopher Kobylecki, David M Cash, Lawren VandeVrede, Hilary W Heuer, Annelies Quaegebeur, Alexandra L Young, Neil Oxtoby, Daniel Alexander, James B Rowe, Huw R Morris, Adam L Boxer, Jonathan D Rohrer, Peter A Wijeratne","doi":"10.1093/braincomms/fcaf066","DOIUrl":"10.1093/braincomms/fcaf066","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Although the corticobasal syndrome was originally most closely linked with the pathology of corticobasal degeneration, the 2013 Armstrong clinical diagnostic criteria, without the addition of aetiology-specific biomarkers, have limited positive predictive value for identifying corticobasal degeneration pathology in life. Autopsy studies demonstrate considerable pathological heterogeneity in corticobasal syndrome, with corticobasal degeneration pathology accounting for only ∼50% of clinically diagnosed individuals. Individualized disease stage and progression modelling of brain changes in corticobasal syndrome may have utility in predicting this underlying pathological heterogeneity, and in turn improve the design of clinical trials for emerging disease-modifying therapies. The aim of this study was to jointly model the phenotypic and temporal heterogeneity of corticobasal syndrome, to identify unique imaging subtypes based solely on a data-driven assessment of MRI atrophy patterns and then investigate whether these subtypes provide information on the underlying pathology. We applied Subtype and Stage Inference, a machine learning algorithm that identifies groups of individuals with distinct biomarker progression patterns, to a large cohort of 135 individuals with corticobasal syndrome (52 had a pathological or biomarker defined diagnosis) and 252 controls. The model was fit using volumetric features extracted from baseline T1-weighted MRI scans and then used to subtype and stage follow-up scans. The subtypes and stages at follow-up were used to validate the longitudinal consistency of the baseline subtype and stage assignments. We then investigated whether there were differences in associated pathology and clinical phenotype between the subtypes. Subtype and Stage Inference identified at least two distinct and longitudinally stable spatiotemporal subtypes of atrophy progression in corticobasal syndrome; four-repeat-tauopathy confirmed cases were most commonly assigned to the &lt;i&gt;Subcortical&lt;/i&gt; subtype (83% of individuals with progressive supranuclear palsy pathology and 75% of individuals with corticobasal-degeneration pathology), whilst those with Alzheimer's pathology were most commonly assigned to the &lt;i&gt;Fronto-parieto-occipital subtype&lt;/i&gt; (81% of individuals). Subtype assignment was stable at follow-up (98% of cases), and individuals consistently progressed to higher stages (100% stayed at the same stage or progressed), supporting the model's ability to stage progression. By jointly modelling disease stage and subtype, we provide data-driven evidence for at least two distinct and longitudinally stable spatiotemporal subtypes of atrophy in corticobasal syndrome that are associated with different underlying pathologies. In the absence of sensitive and specific biomarkers, accurately subtyping and staging individuals with corticobasal syndrome at baseline has important implications for screening on entry into clinical trials, as well as f","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 2","pages":"fcaf066"},"PeriodicalIF":4.1,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11894806/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143607582","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":"Frontotemporal dementia subtyping using machine learning, multivariate statistics and neuroimaging.","authors":"Amelie Metz, Yashar Zeighami, Simon Ducharme, Sylvia Villeneuve, Mahsa Dadar","doi":"10.1093/braincomms/fcaf065","DOIUrl":"10.1093/braincomms/fcaf065","url":null,"abstract":"<p><p>Frontotemporal dementia (FTD) is a prevalent form of early-onset dementia characterized by progressive neurodegeneration and encompasses a group of heterogeneous disorders. Due to overlapping symptoms, diagnosis of FTD and its subtypes still poses a challenge. Magnetic resonance imaging (MRI) is commonly used to support the diagnosis of FTD. Using machine learning and multivariate statistics, we tested whether brain atrophy patterns are associated with severity of cognitive impairment, whether this relationship differs between the phenotypic subtypes and whether we could use these brain patterns to classify patients according to their FTD variant. A total of 136 patients (70 behavioural variant FTD, 36 semantic variant primary progressive aphasia and 30 non-fluent variant primary progressive aphasia) from the frontotemporal lobar degeneration neuroimaging initiative (FTLDNI) database underwent brain MRI and clinical and neuropsychological examination. Deformation-based morphometry, which offers increased sensitivity to subtle local differences in structural image contrasts, was used to estimate regional cortical and subcortical atrophy. Atlas-based associations between atrophy values and performance across different cognitive tests were assessed using partial least squares. We then applied linear regression models to discern the group differences regarding the relationship between atrophy and cognitive decline in the three FTD phenotypes. Lastly, we assessed whether the combination of atrophy and cognition patterns in the latent variables identified in the partial least squares analysis could be used as features in a machine learning model to predict FTD subtypes in patients. Results revealed four significant latent variables that combined accounted for 86% of the shared covariance between cognitive and brain atrophy measures. Partial least squares-based atrophy and cognitive patterns predicted the FTD phenotypes with a cross-validated accuracy of 89.12%, with high specificity (91.46-97.15%) and sensitivity (84.19-93.56%). When using only MRI measures and two behavioural tests in the partial least squares and classification algorithms, ensuring clinical feasibility, our model was equally precise in the same participant sample (87.18%, specificity 76.14-92.00%, sensitivity 86.93-98.26%). Here, including only atrophy or behaviour patterns in the analysis led to prediction accuracies of 69.76% and 76.54%, respectively, highlighting the increased value of combining MRI and clinical measures in subtype classification. We demonstrate that the combination of brain atrophy and clinical characteristics and multivariate statistical methods can serve as a biomarker for disease phenotyping in FTD, whereby the inclusion of deformation-based morphometry measures adds to the classification accuracy in the absence of extensive clinical testing.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 1","pages":"fcaf065"},"PeriodicalIF":4.1,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11844796/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143485050","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":"Tracking the neurophysiological effects of proteinopathy into the pre-clinical stage of Alzheimer's disease.","authors":"Alex I Wiesman, Santiago I Flores-Alonso","doi":"10.1093/braincomms/fcaf069","DOIUrl":"10.1093/braincomms/fcaf069","url":null,"abstract":"<p><p>This scientific commentary refers to 'Amyloid-β deposition predicts oscillatory slowing of magnetoencephalography signals and a reduction of functional connectivity over time in cognitively unimpaired adults', by Scheijbeler <i>et al</i>. (https://doi.org/10.1093/braincomms/fcaf018).</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 1","pages":"fcaf069"},"PeriodicalIF":4.1,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11851007/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143506600","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":"Putaminal-cortical circuits predict response of bilateral deep brain stimulation of the subthalamic nucleus in the primary Meige syndrome after 5 years.","authors":"Ning Wang, Yifeng Wu, Chen Yao, Dawei Meng, Haoran Zhang, Qinxiu Cheng, Xiaodong Zhang, Hailiang Shen, Yingqi Lu, Lin Wang, Jinping Xu","doi":"10.1093/braincomms/fcaf042","DOIUrl":"10.1093/braincomms/fcaf042","url":null,"abstract":"<p><p>The deep brain stimulation (DBS) in the subthalamic nucleus (STN) has attracted more attention for primary Meige syndrome due to easier target location and lower power consumption. However, potential and reliable preoperative predictors of longitudinal outcomes of STN-DBS to guide therapeutic decisions remain largely unexplored. Herein, we used preoperative structural MRI and Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) from 55 patients with primary Meige syndrome who finished STN-DBS after 5 years. They were further classified into response (<i>n</i> = 23) and super-response (<i>n</i> = 32) based on the improvement rates of BFMDRS. Voxel-based morphology, partial correlation analyses, receiver operating characteristic (ROC) analyses and support vector machine were performed. We identified that improved rates of BFMDRS were 63, 71.97, 76.64, 79.51, 81.02, 81.36, 81.16, 80.80 and 80.93% at 1, 3, 6, 12, 18, 24, 36, 48 and 60 months after STN-DBS, respectively, and remained steady across 1-5 years. Further voxel-based morphology analyses revealed significantly lower grey-matter volume in the right hippocampus, left putamen, right supramarginal gyrus and left superior frontal gyrus in response when compared with super-response. The grey-matter volumes in the left putamen, right supramarginal gyrus and left superior frontal gyrus were not only positively correlated with improvement rates of BFMDRS after STN-DBS for 5 years in the primary Meige syndrome, but also presented a reliable classification ability in distinguishing response and super-response (area under curve = 0.855). These results suggested that STN-DBS is an effective treatment for primary Meige syndrome, and preoperative grey-matter volume of putaminal-cortical circuits could be used as potential biomarkers to predict longitudinal outcomes.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 1","pages":"fcaf042"},"PeriodicalIF":4.1,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11814497/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412004","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":"An open-label Phase 2a study to assess the safety and tolerability of trimetazidine in patients with amyotrophic lateral sclerosis.","authors":"Ruben P A van Eijk, Frederik J Steyn, Mark R Janse van Mantgem, Angela Schmidt, Myrte Meyjes, Sally Allen, Dara V Daygon, Jean-Philippe Loeffler, Ammar Al-Chalabi, Leonard H van den Berg, Robert D Henderson, Shyuan T Ngo","doi":"10.1093/braincomms/fcaf063","DOIUrl":"10.1093/braincomms/fcaf063","url":null,"abstract":"<p><p>Metabolic imbalance is associated with amyotrophic lateral sclerosis progression. Impaired glucose oxidation and increased reliance on fatty acid oxidation contribute to reduced metabolic flexibility and faster disease progression in amyotrophic lateral sclerosis. We sought to evaluate the safety and tolerability, and explore the pharmacodynamic response of trimetazidine, a partial fatty acid oxidation inhibitor, on oxidative stress markers and energy expenditure in amyotrophic lateral sclerosis. The study was conducted between June 29, 2021 and May 24, 2023. People living with amyotrophic lateral sclerosis, recruited in Australia and the Netherlands, received open-label oral trimetazidine for 12 weeks after an initial 4-week lead-in period. The primary outcome measures were safety and tolerability, as well as the change from baseline in oxidative stress markers malondialdehyde (MDA) and 8-hydroxy-2'-deoxyguanosine (8-OHdG). Secondary outcome measures were change from baseline in energy expenditure, amyotrophic lateral sclerosis functional rating scale-revised, and slow vital capacity (SVC). Linear mixed effects were used to estimate the mean difference in MDA and 8-OHdG between the on- and off-treatment periods. This trial is registered under ClinicalTrial.gov National Clinical Trial (NCT) number NCT04788745 and European Union Drug Regulating Authorities Clinical Trials (EudraCT) number 2020-005018-17. Twenty-one participants received trimetazidine; 19 (90%) completed the treatment period. Trimetazidine was well tolerated; there were 57 adverse events reported, of which 7 (11%) were deemed potentially drug-related, including hot flushes (2), nausea (2), paraesthesia (2) and fatigue (1). MDA was numerically lower during treatment [-0.29 uM; 95% confidence interval (CI) -0.90 to 0.33, <i>P</i>  <i>=</i> 0.36]; 8-OHdG was significantly lower during treatment (-0.12 nM; 95% CI -0.23 to -0.01, <i>P</i> = 0.0245). The decrease in oxidative stress markers was accompanied by a reduction in resting energy expenditure (95 kcal, 95% CI 36.8-154, <i>P</i> = 0.0014). The absence of a placebo group prevented the interpretation of the clinical parameters. Oral trimetazidine was safe and well tolerated among patients with amyotrophic lateral sclerosis. This, combined with the significant reduction in markers of oxidative stress and resting energy expenditure, warrants a larger double-blind placebo-controlled efficacy study.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 1","pages":"fcaf063"},"PeriodicalIF":4.1,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11851067/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143506056","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}