Brain communications最新文献

{"title":"Statin use is associated with higher white matter hyperintensity volumes and lower grey matter volumes.","authors":"Mélissa Gentreau, Maud Miguet, Oreste Affatato, Gull Rukh, Helgi Birgir Schiöth","doi":"10.1093/braincomms/fcae417","DOIUrl":"https://doi.org/10.1093/braincomms/fcae417","url":null,"abstract":"<p><p>While statins are routinely prescribed to prevent cardiovascular diseases, their effects on brain alterations remain largely unknown. Very few studies have examined the differences in brain volumes between statin users and non-users, and existing research has yielded inconsistent results. This cross-sectional study aims to investigate the association between statin use at baseline and global and specific brain volumes measured 9 years later in a large population-based sample of middle-aged and older adults. Participants from the UK Biobank without neurological and psychiatric disorders consisted of 3285 statin users (mean 60 years and 69% males) and 36 229 non-users (mean 55 years and 46% males). We used linear models to estimate the mean volumetric differences between statin users and non-users while adjusting for UK Biobank assessment centre, age, sex, ethnicity, education, apolipoprotein E ɛ4 status, Townsend deprivation index, antidepressant use, intracranial volume, lifestyle factors (alcohol intake frequency, smoking and physical activity) and health-related conditions (body mass index, blood pressure, diabetes, coronary heart disease, stroke, head injury, depression and insomnia). Moreover, mediation analysis was performed to evaluate whether the association between statin use and global brain volumes was mediated by total serum cholesterol concentration. Statin use was associated with lower grey matter volume [β = -1575 mm³ (-2358, -791)], with 20% of this association mediated by total serum cholesterol concentration. Statin use was also associated with lower peripheral cortical grey matter volumes [β = -1448 mm³ (-2227, -668)] and higher white matter hyperintensity [β = 0.11 mm³ (0.07, 0.15)]. However, white matter volume did not differ significantly between statin users and non-users. Further analyses revealed that volumes of thalamus, pallidum, hippocampus, nucleus accumbens and other regions of the temporal lobe were smaller among statin users compared with non-users. This study showed that statin use is associated with higher white matter hyperintensity volumes and lower total and peripheral cortical grey matter volumes 9 years later, indicative of the brain's ageing process. Moreover, the observed grey matter alterations were partially explained by statin-induced total serum cholesterol reduction. This study emphasizes the potential direct and indirect effects of statins on brain volume.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"6 6","pages":"fcae417"},"PeriodicalIF":4.1,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11606650/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142775694","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":"Corticotropin-releasing hormone as a candidate biomarker for parkinsonian disorders.","authors":"Bárbara Fernandes Gomes, Atul Kumar, Nicholas J Ashton, Sara Hall, Erik Stomrud, Ruben Smith, Henrik Zetterberg, Kaj Blennow, Niklas Mattsson-Carlgren, Oskar Hansson","doi":"10.1093/braincomms/fcae414","DOIUrl":"10.1093/braincomms/fcae414","url":null,"abstract":"<p><p>Disease-specific fluid biomarkers are in demand for parkinsonian syndromes (PS). Corticotropin-releasing hormone (CRH) was proposed as a biomarker for Lewy body disease. As such, this project aimed to confirm CRH as a potential biomarker for different PS. CRH and misfolded α-synuclein (αSyn) were measured in CSF. The primary cohort included Lewy body disease patients (i.e. Parkinson's disease or dementia with Lewy bodies, <i>n</i> = 77), atypical PS (<i>n</i> = 37) and non-parkinsonian neurodegenerative diseases (<i>n</i> = 164), as well as controls (<i>n</i> = 354). A replication cohort included Lewy body disease (<i>n</i> = 27), atypical PS (<i>n</i> = 58) and controls (<i>n</i> = 58). CRH was downregulated in αSyn positive Lewy body disease, αSyn positive controls and in all atypical PS compared with αSyn negative controls (<i>P</i> = 3.3e-05, <i>P</i> = 3.1e-10, <i>P</i> = 2.9e-03). CRH was also decreased in αSyn positive Lewy body disease compared with αSyn negative non-PS (<i>P</i> = 2e-03) and correlated with cognitive impairment and inflammation in αSyn positive Lewy body disease. We show that CRH is a promising biomarker for Lewy body disease and atypical PS and its association with inflammation and cognitive decline. Reductions in CRH in Lewy body disease and other PS suggest this decrease may relate to dopaminergic degeneration instead of αSyn pathology.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"6 6","pages":"fcae414"},"PeriodicalIF":4.1,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11601160/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142740866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brain age gap, dementia risk factors and cognition in middle age.","authors":"James D Stefaniak, Elijah Mak, Li Su, Stephen F Carter, Maria-Eleni Dounavi, Graciela Muniz Terrera, Katie Bridgeman, Karen Ritchie, Brian Lawlor, Lorina Naci, Ivan Koychev, Paresh Malhotra, Craig W Ritchie, John T O'Brien","doi":"10.1093/braincomms/fcae392","DOIUrl":"10.1093/braincomms/fcae392","url":null,"abstract":"<p><p>Brain Age Gap has been associated with dementia in old age. Less is known relating brain age gap to dementia risk-factors or cognitive performance in middle-age. Cognitively healthy, middle-aged subjects from PREVENT-Dementia had comprehensive neuropsychological, neuroimaging and genetic assessments. Brain Ages were predicted from T1-weighted 3T MRI scans. Cognition was assessed using the COGNITO computerized test battery. 552 middle-aged participants (median [interquartile range] age 52.8 [8.7] years, 60.0% female) had baseline data, of whom 95 had amyloid PET data. Brain age gap in middle-age was associated with hypertension (<i>P</i> = 0.007) and alcohol intake (<i>P</i> = 0.008) but not apolipoprotein E epsilon 4 allele (<i>P</i> = 0.14), amyloid centiloids (<i>P</i> = 0.39) or cognitive performance (<i>P</i> = 0.74). Brain age gap in middle-age is associated with modifiable dementia risk-factors, but not with genetic risk for Alzheimer's disease, amyloid deposition or cognitive performance. These results are important for understanding brain-age in middle-aged populations, which might be optimally targeted by future dementia-preventing therapies.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"6 6","pages":"fcae392"},"PeriodicalIF":4.1,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11601159/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142740488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential functional change in olfactory bulb and olfactory eloquent areas in Parkinson's disease.","authors":"Yu Luo, Xinyuan Miao, Suraj Rajan, Adrian G Paez, Xinyi Zhou, Liana S Rosenthal, Alexander Pantelyat, Vidyulata Kamath, Jun Hua","doi":"10.1093/braincomms/fcae413","DOIUrl":"10.1093/braincomms/fcae413","url":null,"abstract":"<p><p>Olfactory dysfunction, or hyposmia, frequently occurs as a prodromal symptom and ongoing sign of Parkinson's disease. Functional MRI is a powerful tool for studying functional changes in the olfactory brain regions in patients with Parkinson's disease. However, existing studies show inconsistent results and no study has measured olfactory functional MRI abnormalities in the human olfactory bulb directly. This is mainly due to the well-known susceptibility artefacts in conventional functional MRI images that affect several key olfactory-eloquent brain regions, and especially the olfactory bulb. In this study, olfactory functional MRI was performed using a recently developed functional MRI approach that can minimize susceptibility artefacts and measure robust functional MRI signals in the human olfactory bulb during olfactory stimulation. Experiments were performed on high magnetic field (7 T) in 24 early (<5 years of parkinsonian symptoms) Parkinson's disease patients and 31 matched healthy controls. Our data showed increased functional MRI signal changes (ΔS/S) in the olfactory bulb in patients with early Parkinson's disease, which correlated with behavioural olfactory measures. Temporally, functional MRI signals in the olfactory bulb returned to the pre-stimulus state earlier after reaching peak amplitude in patients with early Parkinson's disease, implicating a faster olfactory habituation effect. The piriform cortex showed reduced numbers of activated voxels in patients with early Parkinson's disease, which correlated with behavioural olfactory assessment. Several secondary olfactory regions including the orbitofrontal cortex, temporal pole and amygdala exhibited reduced numbers of activated voxels and increased functional MRI signal changes in patients with early Parkinson's disease. Our data also showed that functional MRI results are highly dependent on voxel selection in the functional analysis. In summary, we demonstrate differential spatial and temporal characteristics of olfactory functional MRI signals between the primary and secondary olfactory regions in patients with early Parkinson's disease. These results may assist the development of novel quantitative biomarkers (especially in the early stages of Parkinson's disease) to track and predict disease progression, as well as potential treatment targets for early intervention.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"6 6","pages":"fcae413"},"PeriodicalIF":4.1,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11589462/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142735381","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":"Loss of tissue-type plasminogen activator causes multiple developmental anomalies.","authors":"Kevin Uguen, Tanja Frey, Osama Muthaffar, Jean-Claude Décarie, Najim Ameziane, Sarah Boissel, Yalda Baradaran-Heravi, Anita Rauch, Gabriela Oprea, Aboulfazl Rad, Katharina Steindl, Jacques L Michaud","doi":"10.1093/braincomms/fcae408","DOIUrl":"10.1093/braincomms/fcae408","url":null,"abstract":"<p><p>Hydrocephalus and Dandy-Walker malformation are amongst the most common congenital brain anomalies. We identified three consanguineous families with both obstructive hydrocephalus and Dandy-Walker malformation. To understand the molecular basis of these anomalies, we conducted genome-wide sequencing in these families. We identified three homozygous truncating variants in the <i>PLAT</i> gene in the four affected family members. All of them showed tetraventricular hydrocephalus. In two individuals, a membrane at the inferior aspect of the fourth ventricle was likely the cause of their hydrocephalus. Three cases exhibited Dandy-Walker malformation, whereas the two oldest individuals displayed intellectual disability. <i>PLAT</i> encodes the tissue-type plasminogen activator, a serine protease whose main function is to cleave the proenzyme plasminogen to produce active plasmin. Interestingly, plasminogen deficiency has also been shown to cause obstructive hydrocephalus and Dandy-Walker malformation, suggesting that loss of <i>PLAT</i> causes these defects by disrupting plasmin production. In summary, we describe a recessive disorder characterized by obstructive hydrocephalus, Dandy-Walker malformation and intellectual disability in individuals with loss-of-function variants in <i>PLAT</i>. This discovery further strengthens the involvement of the plasminogen pathway in the pathogenesis of these developmental disorders.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"6 6","pages":"fcae408"},"PeriodicalIF":4.1,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11580217/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142690083","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":"Cerebral white matter myelination is associated with longitudinal changes in processing speed across the adult lifespan.","authors":"Zhaoyuan Gong, Murat Bilgel, Yang An, Christopher M Bergeron, Jan Bergeron, Linda Zukley, Luigi Ferrucci, Susan M Resnick, Mustapha Bouhrara","doi":"10.1093/braincomms/fcae412","DOIUrl":"10.1093/braincomms/fcae412","url":null,"abstract":"<p><p>Myelin's role in processing speed is pivotal, as it facilitates efficient neural conduction. Its decline could significantly affect cognitive efficiency during ageing. In this work, myelin content was quantified using our advanced MRI method of myelin water fraction mapping. We examined the relationship between myelin water fraction at the time of MRI and retrospective longitudinal change in processing speed among 121 cognitively unimpaired participants, aged 22-94 years, from the Baltimore Longitudinal Study of Aging and the Genetic and Epigenetic Signatures of Translational Aging Laboratory Testing (a mean follow-up duration of 4.3 ± 6.3 years) using linear mixed-effects models, adjusting for demographics. We found that higher myelin water fraction values correlated with longitudinally better-maintained processing speed, with particularly significant associations in several white matter regions. Detailed voxel-wise analysis provided further insight into the specific white matter tracts involved. This research underscores the essential role of myelin in preserving processing speed and highlights its potential as a sensitive biomarker for interventions targeting age-related cognitive decline, thereby offering a foundation for preventative strategies in neurological health.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"6 6","pages":"fcae412"},"PeriodicalIF":4.1,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11653079/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142857280","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":"Outcome prediction comparison of ischaemic areas' radiomics in acute anterior circulation non-lacunar infarction.","authors":"Xiang Zhou, Jinxi Meng, Kangwei Zhang, Hui Zheng, Qian Xi, Yifeng Peng, Xiaowen Xu, Jianjun Gu, Qing Xia, Lai Wei, Peijun Wang","doi":"10.1093/braincomms/fcae393","DOIUrl":"10.1093/braincomms/fcae393","url":null,"abstract":"<p><p>The outcome prediction of acute anterior circulation non-lacunar infarction (AACNLI) is important for the precise clinical treatment of this disease. However, the accuracy of prognosis prediction is still limited. This study aims to develop and compare machine learning models based on MRI radiomics of multiple ischaemic-related areas for prognostic prediction in AACNLI. This retrospective multicentre study consecutively included 372 AACNLI patients receiving MRI examinations and conventional therapy between October 2020 and February 2023. These were grouped into training set, internal test set and external test set. MRI radiomics features were extracted from the mask diffusion-weighted imaging, mask apparent diffusion coefficient (ADC) and mask ADC620 by AACNLI segmentations. Grid search parameter tuning was performed on 12 feature selection and 9 machine learning algorithms, and algorithm combinations with the smallest rank-sum of area under the curve (AUC) was selected for model construction. The performances of all models were evaluated in the internal and external test sets. The AUC of radiomics model was larger than that of non-radiomics model with the same machine learning algorithm in the three mask types. The radiomics model using least absolute shrinkage and selection operator-random forest algorithm combination gained the smallest AUC rank-sum among all the algorithm combinations. The AUC of the model with ADC620 was 0.98 in the internal test set and 0.91 in the external test set, and the weighted average AUC in the three sets was 0.96, the largest among three mask types. The Shapley additive explanations values of the maximum of National Institute of Health Stroke Scale score within 7 days from onset (7-d NIHSS_max), stroke-associated pneumonia and admission Glasgow coma scale score ranked top three among the features in AACNLI outcome prediction. In conclusion, the random forest model with mask ADC620 can accurately predict the AACNLI outcome and reveal the risk factors leading to the poor prognosis.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"6 6","pages":"fcae393"},"PeriodicalIF":4.1,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11580218/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142690086","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":"Mutant huntingtin protein decreases with CAG repeat expansion: implications for therapeutics and bioassays.","authors":"Christian Landles, Georgina F Osborne, Jemima Phillips, Maria Canibano-Pico, Iulia M Nita, Nadira Ali, Konstantin Bobkov, Jonathan R Greene, Kirupa Sathasivam, Gillian P Bates","doi":"10.1093/braincomms/fcae410","DOIUrl":"10.1093/braincomms/fcae410","url":null,"abstract":"<p><p>Huntington's disease is an inherited neurodegenerative disorder caused by a CAG repeat expansion that encodes a polyglutamine tract in the huntingtin (HTT) protein. The mutant CAG repeat is unstable and expands in specific brain cells and peripheral tissues throughout life. Genes involved in the DNA mismatch repair pathways, known to act on expansion, have been identified as genetic modifiers; therefore, it is the rate of somatic CAG repeat expansion that drives the age of onset and rate of disease progression. In the context of an expanded CAG repeat, the <i>HTT</i> pre-mRNA can be alternatively processed to generate the <i>HTT1a</i> transcript that encodes the aggregation prone and highly pathogenic HTT1a protein. This may be a mechanism through which somatic CAG repeat expansion exerts its pathogenic effects, as the longer the CAG repeat, the more <i>HTT1a</i> and HTT1a is produced. The allelic series of knock-in mouse models, <i>Hdh</i>Q20, <i>Hdh</i>Q50, <i>Hdh</i>Q80, <i>Hdh</i>Q111, CAG140 and zQ175 with polyglutamine expansions of 20, 50, 80, 111, 140 and ∼190, can be used to model the molecular and cellular consequences of CAG repeat expansion within a single neuron. By western blot of cortical lysates, we found that mutant HTT levels decreased with increasing CAG repeat length; mutant HTT was only 23 and 10% of wild-type levels in CAG140 and zQ175 cortices, respectively. To identify the optimal bioassays for detecting the full-length HTT and HTT1a isoforms, we interrogated the pairwise combinations of seven well-characterized antibodies on both the 'homogeneous time-resolved fluorescence' and 'Meso Scale Discovery' platforms. We tested 32 assays on each platform to detect 'full-length mutant HTT', HTT1a, 'total mutant HTT' (full-length HTT and HTT1a) and 'total full-length HTT' (mutant and wild type). None of these assays recapitulated the full-length mutant HTT levels as measured by western blot. We recommend using isoform- and species-specific assays that detect full-length mutant HTT, HTT1a or wild-type HTT as opposed to those that detect more than one isoform simultaneously. Our finding that as the CAG repeat expands, full-length mutant HTT levels decrease, while <i>HTT1a</i> and HTT1a levels increase has implications for therapeutic strategies. If mutant HTT levels in cells containing (CAG)₂₀₀ are only 10% of wild-type, HTT-lowering strategies targeting full-length <i>HTT</i> at sequences 3' to Intron 1 <i>HTT</i> will predominantly lower wild-type HTT, as mutant HTT levels in these cells are already depleted. These data support a therapeutic strategy that lowers <i>HTT1a</i> and depletes levels of the HTT1a protein.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"6 6","pages":"fcae410"},"PeriodicalIF":4.1,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11660907/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142878887","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":"Mapping sentence comprehension and syntactic complexity: evidence from 131 stroke survivors.","authors":"Nicoletta Biondo, Maria V Ivanova, Alexis L Pracar, Juliana Baldo, Nina F Dronkers","doi":"10.1093/braincomms/fcae379","DOIUrl":"10.1093/braincomms/fcae379","url":null,"abstract":"<p><p>Understanding and interpreting how words are organized in a sentence to convey distinct meanings is a cornerstone of human communication. The neural underpinnings of this ability, known as syntactic comprehension, are far from agreed upon in current neurocognitive models of language comprehension. Traditionally, left frontal regions (e.g. left posterior inferior frontal gyrus) were considered critical, while more recently, left temporal regions (most prominently, left posterior middle temporal gyrus) have been identified as more indispensable to syntactic comprehension. Syntactic processing has been investigated by using different types of non-canonical sentences i.e. those that do not follow prototypical word order and are considered more syntactically complex. However, non-canonical sentences can be complex for different linguistic reasons, and thus, their comprehension might rely on different neural underpinnings. In this cross-sectional study, we explored the neural correlates of syntactic comprehension by investigating the roles of left hemisphere brain regions and white matter pathways in processing sentences with different levels of syntactic complexity. Participants were assessed at a single point in time using structural MRI and behavioural tests. Employing lesion-symptom mapping and indirect structural disconnection mapping in a cohort of 131 left hemisphere stroke survivors, our analysis revealed the following left temporal regions and underlying white matter pathways as crucial for general sentence comprehension: the left mid-posterior superior temporal gyrus, middle temporal gyrus and superior temporal sulcus and the inferior longitudinal fasciculus, the inferior fronto-occipital fasciculus, the middle longitudinal fasciculus, the uncinate fasciculus and the tracts crossing the most posterior part of the corpus callosum. We further found significant involvement of different white matter tracts connecting the left temporal and frontal lobes for different sentence types. Spared connections between the left temporal and frontal regions were critical for the comprehension of non-canonical sentences requiring long-distance retrieval (spared superior longitudinal fasciculus for both subject and object extraction and spared arcuate fasciculus for object extraction) but not for comprehension of non-canonical passive sentences and canonical declarative sentences. Our results challenge traditional language models that emphasize the primary role of the left frontal regions, such as Broca's area, in basic sentence structure comprehension. Our findings suggest a gradient of syntactic complexity, rather than a clear-cut dichotomy between canonical and non-canonical sentence structures. Our findings contribute to a more nuanced understanding of the neural architecture of language comprehension and highlight potential directions for future research.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"6 6","pages":"fcae379"},"PeriodicalIF":4.1,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11565230/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142649589","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":"Overcoming genetic neuromuscular diagnostic pitfalls in a middle-income country.","authors":"Rodrigo Siqueira Soares Frezatti, Pedro José Tomaselli, Christopher J Record, Lindsay A Wilson, Gustavo Maximiano Alves, Natalia Dominik, Stephanie Efthymiou, Krutik Patel, Jana Vandrovcova, Roope Männikkö, Robert D S Pitceathly, Claudia Ferreira da Rosa Sobreira, Robert McFarland, Robert W Taylor, Henry Houlden, Michael G Hanna, Mary M Reilly, Wilson Marques","doi":"10.1093/braincomms/fcae342","DOIUrl":"10.1093/braincomms/fcae342","url":null,"abstract":"<p><p>Neuromuscular disorders affect almost 20 million people worldwide. Advances in molecular diagnosis have provided valuable insights into neuromuscular disorders, allowing for improved standards of care and targeted therapeutic approaches. Despite this progress, access to genomic diagnosis remains scarce and inconsistent in middle-income countries such as Brazil. The lack of public health policies to enable feasible genetic diagnosis and the shortage of neuromuscular disorders specialists are the main reasons in this process. We report our experience in a transcontinental genomic consortium for neuromuscular disorders highlighting how collaborative efforts have helped overcome various obstacles in diagnosing our patients. We describe several challenging cases categorized into three major themes, underlining significant gaps in genetic diagnosis: (i) reverse phenotyping and variant validation, (ii) deep phenotyping and identifying a bespoke molecular approach, and (iii) exploring the use of genomic tests beyond whole exome sequencing. We applied a qualitative case-based approach to exemplify common pitfalls in genomic diagnosis in a middle-income country. Our experience has shown that establishing a virtual transcontinental partnership is viable, offering effective exchange of scientific experiences, providing both guidance for rational decision-making and specialized training on a local level and access to diverse molecular diagnosis strategies and functional analyses. Collaborative efforts such as these have the potential to overcome local obstacles, strengthen scientific capabilities, foster diverse multi-ethnic cohorts, and ultimately provide improved care for patients.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"6 6","pages":"fcae342"},"PeriodicalIF":4.1,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11562110/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634398","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}