Brain communications最新文献

{"title":"Abnormal brain functional networks in systemic lupus erythematosus: a graph theory, network-based statistic and machine learning study.","authors":"Yifan Yang, Ru Bai, Shuang Liu, Shu Li, Ruotong Zhao, Xiangyu Wang, Yuqi Cheng, Jian Xu","doi":"10.1093/braincomms/fcaf130","DOIUrl":"https://doi.org/10.1093/braincomms/fcaf130","url":null,"abstract":"<p><p>Systemic lupus erythematosus patients' brain functional network impairments are incompletely clarified. This study investigates the brain functional network topological alterations in systemic lupus erythematosus and the application of machine learning to the classification of systemic lupus erythematosus and healthy controls. Resting-state functional MRI data from 127 systemic lupus erythematosus patients and 102 healthy controls were used. The pre-processing process involved using automated anatomical labelling atlas to compute time series data for 116 brain regions. A functional connectivity network was then created by assessing the Pearson correlation between the time series of these brain regions. The GRETNA toolbox was used to compute the difference in topological attributes between groups. Variations in regional networks among groups were evaluated using non-parametric permutation tests that rely on network-based statistical analysis. With the functional connectivity network metrics as features and network-based statistical analysis as the feature selection method, network-based statistical analysis Predict software was used to classify systemic lupus erythematosus from controls by support vector machine. The subnets that contributed the most to systemic lupus erythematosus classification were also identified. For global indicators, the systemic lupus erythematosus group exhibited significantly lower values for the normalized clustering coefficient (<i>P</i> = 0. 0317) and small-world index (<i>P</i> = 0.0364) compared to the healthy controls group. After false discovery rate correction, the differences in Betweeness Centrality, Degree Centrality, Node Efficiency, Node Local Efficiency and other local indexes between the two groups were not retained. No correlation was found between clinical data and network indicators. Systemic lupus erythematosus group had a significantly reduced connection with a 12-node, 11-edge subnetwork (<i>P</i> = 0.024). In conclusion, systemic lupus erythematosus patients exhibit suboptimal global brain functional connectivity network topology and the presence of a subnetwork with abnormally reduced connectivity.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 2","pages":"fcaf130"},"PeriodicalIF":4.1,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11979335/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144034000","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":"Novel insights into the molecular nature of neurofilament light polypeptide species in cerebrospinal fluid.","authors":"Bruno Becker, Johan Gobom, Gunnar Brinkmalm, Ulf Andreasson, Francisco J Meda, Henrik Zetterberg, Kaj Blennow","doi":"10.1093/braincomms/fcaf129","DOIUrl":"https://doi.org/10.1093/braincomms/fcaf129","url":null,"abstract":"<p><p>The quantification of neurofilament light polypeptide (NFL) in biofluids is being clinically used to detect and grade general neuronal damage in neurodegenerative diseases and quantify neuronal injury during acute events like traumatic brain injury. Specific assays that target only particular molecular breakdown products of neurofilaments have the potential to distinguish between various pathologies. Nevertheless, the molecular structure of neurofilament light polypeptide in cerebrospinal fluid remains to be elucidated. We characterized neurofilament light polypeptide in cerebrospinal fluid by size-exclusion chromatography, Western blotting and mass spectrometry. Neurofilament light polypeptide in cerebrospinal fluid was found to be composed of aggregates of fragments of the full-length molecule. These aggregates were sensitive to reduction by dithiothreitol and dissociated to monomeric fragments of 6-12 kDa (Western blot), covering most of the coiled-coil domains of neurofilament light polypeptide. Since only cysteine residues can form disulfide bonds, this points to a role of the single cysteine 322 for maintaining the stability of the aggregates. The sequence region covered by the identified fragments ended just a few amino acids C-terminally of the coiled-coil region at a site which had been previously mapped to a calpain cleavage site in the glial fibrillary acidic protein, which is highly homologous to neurofilament light polypeptide in the coiled-coil region. This cleavage site was also confirmed to be present in bovine neurofilament light polypeptide by <i>in vitro</i> digestion of purified neurofilament light polypeptide with calpain-1. The difference of the molecular weights of the reduced and non-reduced forms of neurofilament light polypeptide suggests that neurofilament light polypeptide in CSF consists of disulfide-linked aggregated fragments, most likely tetramers, or alternately dimers in a complex with another binding partner.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 2","pages":"fcaf129"},"PeriodicalIF":4.1,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12003950/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144038100","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":"Beyond the cerebellum: perivascular space burden in spinocerebellar ataxia type 3 extends to multiple brain regions.","authors":"Yonghua Huang, Zhiming Zhen, Lihua Deng, Peiling Ou, Linfeng Shi, Feng Shi, Rui Hua, Jiaojiao Wu, Wei Chen, Ru Wen, Jian Wang, Chen Liu","doi":"10.1093/braincomms/fcaf118","DOIUrl":"10.1093/braincomms/fcaf118","url":null,"abstract":"<p><p>Spinocerebellar ataxia type 3 (SCA3) is an uncommon inherited (autosomal dominant) neurodegenerative disorder caused by abnormal accumulation of ataxin-3 protein. The perivascular space (PVS) burden reflects protein clearance and may worsen in SCA3 disease. This study aimed to quantify the PVS burden and investigate the relationship between the PVS burden and clinical characteristics in individuals with SCA3. This study enrolled 43 SCA3 patients and 43 age- and sex-matched healthy controls (HCs). The cross-sectional study assessed the severity of ataxia in SCA3 patients using the Scale for the Assessment and Rating of Ataxia (SARA) and the International Cooperative Ataxia Rating Scale (ICARS). Various cognitive functions were evaluated in all subjects using the Montreal Cognitive Assessment (MoCA), Rapid Verbal Retrieval (RAR) and Digital Span Test (DST) scales. MRI was used to automatically segment the PVS in all subjects and quantify the PVS burden in 15 brain regions. Compared with the HCs, the SCA3 patients showed a significantly higher PVS burden in the basal ganglia, temporal lobe, right parietal lobe and right cerebellum. There was a positive correlation in motor dysfunction between the PVS volume in the left parietal lobe, right cerebellum and PVS number in the right cerebellum with the SARA and ICARS scores. This study showed that SCA3 patients have an increased PVS burden in many brain regions, leading to motor impairment. The PVS burden could be a new imaging biomarker for disease monitoring and a therapeutic target for SCA3.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 2","pages":"fcaf118"},"PeriodicalIF":4.1,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11969673/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143797189","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":"Absence of GluN2A in hippocampal CA1 neurons leads to altered dendritic structure and reduced frequency of miniature excitatory synaptic events.","authors":"Farhana Yasmin, Katie F M Marwick, Daniel W Hunter, Sarfaraz Nawaz, Grant F Marshall, Sam A Booker, Giles E Hardingham, Peter C Kind, David J A Wyllie","doi":"10.1093/braincomms/fcaf124","DOIUrl":"https://doi.org/10.1093/braincomms/fcaf124","url":null,"abstract":"<p><p>GluN2A is a NMDA receptor subunit postulated as important for learning and memory. In humans, heterozygous loss of function variants in the gene encoding it (<i>GRIN2A</i>) increase the risk of epilepsy, intellectual disability and schizophrenia. Haploinsufficient mouse models show electrophysiological abnormalities and thus to improve and widen understanding of the pathogenesis of <i>GRIN2A</i>-associated disorders in humans, this study aimed to assess the impact of <i>Grin2a</i> absence and haploinsufficiency on core neuronal and synaptic properties in genetically modified rats. Electrophysiological whole-cell current- and voltage-clamp recordings were made from CA1 pyramidal neurons in acute hippocampal slices from wild-type and <i>Grin2a</i> heterozygous (<i>Grin2a^+/-</i> ) and homozygous (<i>Grin2a^-/-</i> ) knock out rats aged postnatal day 27-34. While reduced levels or absence of GluN2A did not affect neuronal excitability or intrinsic membrane properties in both <i>Grin2a^+/-</i> and <i>Grin2a^-/-</i> rats, we found a reduced frequency of miniature excitatory post synaptic currents and a reduced density of proximal dendrites suggestive of a reduced number of excitatory synapses. Recordings from CA1 neurons in slices prepared from <i>Grin2a^+/-</i> and <i>Grin2a^-/-</i> rats revealed there was a reduced ratio of the current mediated by NMDA receptors compared to AMPA receptors, while in <i>Grin2a^-/-</i> recordings, there was a slowing of the decay time-constant of the NMDA receptor-mediated excitatory postsynaptic currents. Moreover, neither summation of sub-threshold excitatory postsynaptic potentials nor summation of supra-threshold excitatory postsynaptic potentials to initiate action potential firing in CA1 pyramidal neurons indicated any dependence on GluN2A. We conclude that reduced levels of GluN2A alters the kinetics of NMDA receptor-mediated synaptic events and dendritic structure of CA1 neurons, but do not affect several other core neuronal functions. These relatively subtle changes are consistent with the largely intact neural functioning of the majority of humans carrying <i>GRIN2A</i> loss of function variants. Further research could explore whether the changes in synaptic properties we observed contribute to alterations in higher level circuit dynamics and computation, which may manifest as disorders of cognition and excitability in humans.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 2","pages":"fcaf124"},"PeriodicalIF":4.1,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11986202/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144059893","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":"Regional brain volume changes in Hakim's disease versus Alzheimer's and mild cognitive impairment.","authors":"Shigeki Yamada, Takuya Yuzawa, Hirotaka Ito, Chifumi Iseki, Toshiyuki Kondo, Tomoyasu Yamanaka, Motoki Tanikawa, Tomohiro Otani, Satoshi Ii, Yasuyuki Ohta, Yoshiyuki Watanabe, Shigeo Wada, Marie Oshima, Mitsuhito Mase","doi":"10.1093/braincomms/fcaf122","DOIUrl":"https://doi.org/10.1093/braincomms/fcaf122","url":null,"abstract":"<p><p>Idiopathic normal-pressure hydrocephalus (Hakim's disease) is characterized by ventricular enlargement and disproportionately enlarged subarachnoid space hydrocephalus, leading to localized brain deformation. Differentiating regional brain volume changes in Hakim's disease from those in Alzheimer's disease, Hakim's disease with Alzheimer's disease, and mild cognitive impairment provides insights into disease-specific mechanisms. This study aimed to identify disease-specific patterns of brain volume changes in Hakim's disease, Alzheimer's disease, Hakim's disease with Alzheimer's disease, and mild cognitive impairment and compare them with those in cognitively healthy individuals using an advanced artificial intelligence-based brain segmentation tool. The study included 970 participants, comprising 52 patients with Hakim's disease, 256 with Alzheimer's disease, 25 with Hakim's disease with Alzheimer's disease, 163 with mild cognitive impairment, and 474 healthy controls. The intracranial spaces were segmented into 100 brain and 7 CSF subregions from 3D T1-weighted MRIs using brain subregion analysis. The volume ratios of these regions were compared among the groups using Glass's Δ, referencing 400 healthy controls aged ≥50 years. Hakim's disease exhibited significant volume reduction in the supramarginal gyrus of the parietal lobe and the paracentral gyrus of the frontal lobe. Alzheimer's disease exhibited prominent volume loss in the hippocampus and temporal lobe, particularly in the entorhinal cortex, fusiform gyrus, and inferior temporal gyrus. Hakim's disease with Alzheimer's disease showed significant volume reductions in the supramarginal gyrus of the parietal lobe, similar to Hakim's disease, whereas temporal lobe volumes were relatively preserved compared with those in Alzheimer's disease. Patients with mild cognitive impairment aged ≥70 years had comparable regional brain volume ratios with healthy controls in the same age group. The Hakim's disease and Hakim's disease with Alzheimer's disease groups were characterized by volume reductions in the frontal and parietal lobes caused by disproportionately enlarged subarachnoid space hydrocephalus-related compression compared with temporal lobe atrophy observed in the Alzheimer's disease group. These disease-specific morphological changes highlight the need for longitudinal studies to clarify the causes of compression and atrophy.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 2","pages":"fcaf122"},"PeriodicalIF":4.1,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11997787/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144052039","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":"Current and prospective roles of magnetic resonance imaging in mild traumatic brain injury.","authors":"Matilde Sassani, Tara Ghafari, Pradeepa R W Arachchige, Iman Idrees, Yidian Gao, Alice Waitt, Samuel R C Weaver, Ali Mazaheri, Hannah S Lyons, Olivia Grech, Mark Thaller, Caroline Witton, Andrew P Bagshaw, Martin Wilson, Hyojin Park, Matthew Brookes, Jan Novak, Susan P Mollan, Lisa J Hill, Samuel J E Lucas, James L Mitchell, Alexandra J Sinclair, Karen Mullinger, Davinia Fernández-Espejo","doi":"10.1093/braincomms/fcaf120","DOIUrl":"https://doi.org/10.1093/braincomms/fcaf120","url":null,"abstract":"<p><p>There is unmet clinical need for biomarkers to predict recovery or the development of long-term sequelae of mild traumatic brain injury, a highly prevalent condition causing a constellation of disabling symptoms. A substantial proportion of patients live with long-lasting sequelae affecting their quality of life and ability to work. At present, symptoms can be assessed through clinical tests; however, there are no imaging or laboratory tests fully reflective of pathophysiology routinely used by clinicians to characterize post-concussive symptoms. Magnetic resonance imaging has potential to link subtle pathophysiological alterations to clinical outcomes. Here, we review the state of the art of MRI research in adults with mild traumatic brain injury and provide recommendations to facilitate transition into clinical practice. Studies utilizing MRI can inform on pathophysiology of mild traumatic brain injury. They suggest presence of early cytotoxic and vasogenic oedema. They also show that mild traumatic brain injury results in cellular injury and microbleeds affecting the integrity of myelin and white matter tracts, all processes that appear to induce delayed vascular reactions and functional changes. Crucially, correlates between MRI parameters and post-concussive symptoms are emerging. Clinical sequences such as T₁-weighted MRI, susceptibility-weighted MRI or fluid attenuation inversion recovery could be easily implementable in clinical practice, but are not sufficient, in isolation for prognostication. Diffusion sequences have shown promises and, although in need of analysis standardization, are a research priority. Lastly, arterial spin labelling is emerging as a high-utility research as it could become useful to assess delayed neurovascular response and possible long-term symptoms.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 2","pages":"fcaf120"},"PeriodicalIF":4.1,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12001801/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144044695","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":"Association of blood-based glial fibrillary acidic protein level with depression and suicidal ideation following traumatic brain injury with Glasgow Coma Scale score 13 to 15: a TRACK-TBI study.","authors":"Shawn R Eagle, Raquel C Gardner, Sonia Jain, Xiaoying Sun, Ava Puccio, David Brent, Lindsay D Nelson, Michael A McCrea, Joseph T Giacino, David O Okonkwo, John K Yue, Geoffrey T Manley, Murray B Stein","doi":"10.1093/braincomms/fcaf123","DOIUrl":"10.1093/braincomms/fcaf123","url":null,"abstract":"<p><p>Blood-based glial fibrillary acidic protein (GFAP) level within 24 h of traumatic brain injury (TBI) has been inversely associated with post-traumatic stress disorder at 6 months in the Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study. We sought to assess the relationship between day-of-injury GFAP and cumulative prevalence (CI) of depression or suicidal ideation in the first year after injury among patients presenting with Glasgow Coma Scale 13-15 who participated in Transforming Research and Clinical Knowledge in Traumatic Brain Injury (<i>n</i> = 1511). Multivariable logistic regression models were used to assess the association of day-of-injury GFAP levels with year 1 CI of depression or suicidal ideation adjusting for age, sex, prior TBI, psychiatric history and acute intracranial trauma on head computed tomography (CT) scan. Subgroup analyses categorized into 'high' and 'low' risk for mental health problems based upon a history of psychiatric disorder or TBI. Overall, 20.4% reported depression and 11.3% reported suicidal ideation in the first year. Participants with depression had significantly lower GFAP compared with participants without depression overall (median = 149.9 pg/mL versus 306.9 pg/mL, <i>P</i> < 0.001) and CT-negative high risk and CT-negative low risk subgroups. Participants with suicidal ideation had lower GFAP in the overall sample (155.8 pg/mL versus 299.1 pg/mL, <i>P</i> = 0.001). We found an interaction between GFAP and CT status, reflecting an inverse association of GFAP with cumulative depression among CT- subjects (adjusted odds ratio = 0.84, 95% CI: 0.77-0.92), but not among CT+ subjects. Blood biomarkers may warrant future investigation as potential predictors of depression following TBI in patients without evidence of acute intracranial trauma on CT scan.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 2","pages":"fcaf123"},"PeriodicalIF":4.1,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11968334/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143797271","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":"Stratifying risk of Alzheimer's disease in healthy middle-aged individuals with machine learning.","authors":"Raghav Tandon, Liping Zhao, Caroline M Watson, Neel Sarkar, Morgan Elmor, Craig Heilman, Katherine Sanders, Chadwick M Hales, Huiying Yang, David W Loring, Felicia C Goldstein, John J Hanfelt, Duc M Duong, Erik C B Johnson, Aliza P Wingo, Thomas S Wingo, Blaine R Roberts, Nicholas T Seyfried, Allan I Levey, James J Lah, Cassie S Mitchell","doi":"10.1093/braincomms/fcaf121","DOIUrl":"https://doi.org/10.1093/braincomms/fcaf121","url":null,"abstract":"<p><p>Alzheimer's disease has a prolonged asymptomatic phase during which pathological changes accumulate before clinical symptoms emerge. This study aimed to stratify the risk of clinical disease to inform future disease-modifying treatments. Cerebrospinal fluid analysis from participants in the Emory Healthy Brain Study was used to classify individuals based on amyloid beta 42 (Aβ42), total tau (tTau) and phosphorylated tau (pTau) levels. Cognitively normal (CN), biomarker-positive (CN)/BM+individuals were identified using a tTau: Aβ42 ratio > 0.24, determined by Gaussian mixture models. CN/BM+ individuals (<i>n</i> = 134) were classified as having asymptomatic Alzheimer's disease (AsymAD), while CN, biomarker-negative (CN/BM-) individuals served as controls (<i>n</i> = 134). Cognitively symptomatic, biomarker-positive individuals with an Alzheimer's disease diagnosis confirmed by the Emory Cognitive Neurology Clinic were labelled as Alzheimer's disease (<i>n</i> = 134). Study groups were matched for age, sex, race and education. Cerebrospinal fluid samples from these matched Emory Healthy Brain Study groups were analysed using targeted proteomics via selected reaction monitoring mass spectrometry. The targeted cerebrospinal fluid panel included 75 peptides from 58 unique proteins. Machine learning approaches identified a subset of eight peptides (ADQDTIR, AQALEQAK, ELQAAQAR, EPVAGDAVPGPK, IASNTQSR, LGADMEDVCGR, VVSSIEQK, YDNSLK) that distinguished between CN/BM- and symptomatic Alzheimer's disease samples with a binary classifier area under the curve performance of 0.98. Using these eight peptides, Emory Healthy Brain Study AsymAD cases were further stratified into 'Control-like' and 'Alzheimer's disease-like' subgroups, representing varying levels of risk for developing clinical disease. The eight peptides were evaluated in an independent dataset from the Alzheimer's Disease Neuroimaging Initiative, effectively distinguishing CN/BM- from symptomatic Alzheimer's disease cases (area under the curve = 0.89) and stratifying AsymAD individuals into control-like and Alzheimer's disease-like subgroups (area under the curve = 0.89). In the absence of matched longitudinal data, an established cross-sectional event-based disease progression model was employed to assess the generalizability of these peptides for risk stratification. In summary, results from two independent modelling methods and datasets demonstrate that the identified eight peptides effectively stratify the risk of progression from asymptomatic to symptomatic Alzheimer's disease.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 2","pages":"fcaf121"},"PeriodicalIF":4.1,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11986205/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144065395","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 neural correlates of morphosyntactic and thematic comprehension processes in aphasia.","authors":"Sabrina Beber, Rita Capasso, Chiara Maffei, Marco Tettamanti, Gabriele Miceli","doi":"10.1093/braincomms/fcaf093","DOIUrl":"10.1093/braincomms/fcaf093","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Functional neuroimaging studies in neurotypical subjects correlate sentence comprehension to a left fronto-temporo-parietal network. Recent voxel-based lesion-symptom mapping (VLSM) studies of aphasia confirm the link between sentence comprehension and a left posterior region including the angular gyrus, the supra-marginal gyrus and the postero-superior division of the temporal lobe but support left pre-frontal involvement inconsistently. However, these studies focus on thematic role assignment without considering morphosyntactic processes. Hence, available VLSM evidence could provide a partial view of the neurofunctional substrate of sentence comprehension. In the present VLSM study, both morphosyntactic and thematic processes were evaluated systematically and in the same sentence types in each participant, to provide a more detailed picture of the sentence comprehension network. Participants (33 patients with post-stroke aphasia and 90 healthy controls) completed a sentence-picture matching task in which active and passive, declarative reversible sentences were paired with morphosyntactic, thematic and lexical-semantic alternatives. Phonological short-term memory tasks were also administered. Aphasic participants were selected from an initial pool of 70 because they scored below norm on thematic foils (&lt;i&gt;n&lt;/i&gt; = 18) or on thematic and morphological foils (&lt;i&gt;n&lt;/i&gt; = 15), but within the norm on lexical-semantic foils. The neurofunctional correlates of morphosyntactic and thematic processes were starkly distinguishable. Pre-frontal areas including the inferior and middle frontal gyrus were involved directly in processing local morphosyntactic features and only indirectly in thematic processes. When these areas were damaged, morphosyntactic errors always co-occurred with thematic errors, probably because morphosyntactic damage disrupts the assignment of grammatical roles and ultimately that of thematic roles. Morphosyntactic errors were not influenced by word order canonicity. In contrast, selective thematic role reversals were linked to temporal and parietal damage and were significantly influenced by word order, occurring on passive more than on active sentences. An area including the angular and supra-marginal gyrus was critical for processing non-canonical word order. In sentence comprehension, pre-frontal regions are critical for processing local morphosyntactic features (at least in simple declarative sentences). Temporal and parietal regions are critical for thematic processes. Postero-superior temporal areas are involved in retrieving verb argument structure. Parietal areas are critical for assigning morphosyntactically analysed constituents to the appropriate thematic role, thus serving a crucial function in thematic re-analysis. Each area plays a prevailing but not exclusive role in these processes, interacting with other areas in the network and possibly providing both the language-specific and the domain-general resources needed","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 2","pages":"fcaf093"},"PeriodicalIF":4.1,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11930358/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701411","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":"Enduring differential patterns of neuronal loss and myelination along 6-month pulsatile gonadotropin-releasing hormone therapy in individuals with Down syndrome.","authors":"Michela Adamo, Mihaly Gayer, An Jacobs, Quentin Raynaud, Raphael Sebbah, Giulia di Domenicantonio, Adeliya Latypova, Nathalie Vionnet, Ferath Kherif, Antoine Lutti, Nelly Pitteloud, Bogdan Draganski","doi":"10.1093/braincomms/fcaf117","DOIUrl":"10.1093/braincomms/fcaf117","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Despite major progress in understanding the impact of the triplicated chromosome 21 on the brain and behaviour in Down syndrome, our knowledge of the underlying neurobiology in humans is still limited. We sought to address some of the pertinent questions about the drivers of brain structure differences and their associations with cognitive function in Down syndrome. To this aim, in a pilot magnetic resonance imaging (MRI) study, we monitored brain anatomy in individuals with Down syndrome receiving pulsatile gonadotropin-releasing hormone (GnRH) therapy over 6 months in comparison with typically developed age- and sex-matched healthy controls. We analysed cross-sectional (Down syndrome/healthy controls &lt;i&gt;n&lt;/i&gt;  &lt;i&gt;=&lt;/i&gt; 11/27; Down syndrome-2 females/9 males, age 26.7 ± 5.0 years old; healthy controls-8 females/19 males, age 24.1 ± 2.5 years old) and longitudinal (Down syndrome/healthy controls &lt;i&gt;n&lt;/i&gt;  &lt;i&gt;=&lt;/i&gt; 8&lt;i&gt;/&lt;/i&gt;13; Down syndrome-1 female/7 males, age 26.4 ± 5.3 years old; healthy controls-4 females/9 males, 24.7 ± 2.2 years old) relaxometry and diffusion-weighted MRI data alongside standard cognitive assessment. The statistical tests looked for cross-sectional baseline differences and for differential changes over time between Down syndrome and healthy controls. The &lt;i&gt;post hoc&lt;/i&gt; analysis confined to the Down syndrome group, tested for potential time-dependent interactions between individuals' overall cognitive performance and associated brain anatomy changes. The brain MRI statistical analyses covered both grey and white matter regions across the whole brain allowing for investigation of regional volume, macromolecular/myelin and iron content, additionally to diffusion tensor and neurite orientation and dispersion density characterization across major white matter tracts. The cross-sectional analysis showed reduced frontal, temporal and cerebellar volumes in Down syndrome with only the cerebellar differences remaining significant after adjustment for the presence of microcephaly (&lt;i&gt;P&lt;/i&gt; &lt;sub&gt;family-wise-corrected&lt;/sub&gt; &lt; 0.05). The volume reductions were paralleled by decreased cortical and subcortical macromolecular/myelin content confined to the cortical motor system, thalamus and basal ganglia (&lt;i&gt;P&lt;/i&gt; &lt;sub&gt;family-wise-corrected&lt;/sub&gt; &lt; 0.05). All major white matter tracts showed a ubiquitous mean diffusivity and intracellular volume fraction reduction contrasted with no differences in magnetization transfer saturation metrics (&lt;i&gt;P&lt;/i&gt; &lt;sub&gt;family-wise-corrected&lt;/sub&gt; &lt; 0.05). Compared with healthy controls over the same period, Down syndrome individuals under GnRH therapy showed cognitive improvement (Montreal Cognitive Assessment from 11.4 ± 5.5 to 15.1 ± 5.6; &lt;i&gt;P&lt;/i&gt; &lt; 0.01) on the background of stability of the observed differential neuroanatomical patterns. Despite the lack of adequate Down syndrome control group, we interpret the obtained cross-sectional and longitudinal findings in young adults as evidence for ","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 2","pages":"fcaf117"},"PeriodicalIF":4.1,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11969670/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143797191","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}