Brain communications最新文献

{"title":"Hyperuricaemia is associated with smaller volumes in the caudate nucleus head and putamen.","authors":"Naoki Omori, Manabu Ishida, Masahiro Takamura, Satoshi Abe, Atsushi Nagai","doi":"10.1093/braincomms/fcaf263","DOIUrl":"10.1093/braincomms/fcaf263","url":null,"abstract":"<p><p>Hyperuricaemia is a risk factor for gout, kidney diseases, and cerebrovascular diseases. Uric acid (UA) is also known as an antioxidant and has been suggested to inhibit the progression of neurodegenerative diseases, such as Parkinson's disease. However, only a few studies have focused on the potential effects of UA on the basal ganglia. This study aimed to measure UA levels and basal ganglia volumes in community-dwelling adults and to evaluate the association thereof. Blood UA levels and brain MRI data were collected from individuals who underwent brain health checkups between January 2015 and March 2022 at Shimane Institute of Health Science. Participants were classified into three groups based on their UA levels: normal-low UA (< 5.0 mg/dL), normal-high UA (5.0-7.0 mg/dL), and hyperuricaemia (> 7.0 mg/dL). MRI was used to assess the presence of asymptomatic infarcts, microbleeds, and the severity of enlarged perivascular spaces in the basal ganglia. The volumes of the caudate nucleus, globus pallidus, putamen, substantia nigra, and subthalamic nucleus were calculated using voxel-based morphometry (VBM) as <i>Z</i>-scores adjusted for participant age, sex, and total intracranial volume. Analysis of covariance and smooth-curve fitting models were used to examine the association between UA levels and basal ganglia volumes. In total, 981 participants were included in the analysis. Analysis of covariance revealed that the hyperuricaemia group had significantly higher <i>Z</i>-scores (indicating smaller volumes) in the bilateral caudate nucleus head and putamen than those of the normal-high UA group. The smooth-curve model showed U-shaped associations with smaller volumes for both high and low UA levels, whereas piecewise linear regression analysis confirmed significant regression lines only in the group with higher UA levels. Although UA is thought to have a neuroprotective effect in adults, our findings indicate that hyperuricaemia may contribute to smaller volumes in the caudate nucleus head and putamen. This suggests that excessive UA levels could negatively affect basal ganglia structure and neurological health.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 4","pages":"fcaf263"},"PeriodicalIF":4.1,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12260223/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144644377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Whole-brain functional connectivity predicts regional tau PET in preclinical Alzheimer's disease.","authors":"Hamid Abuwarda, Anne Trainer, Corey Horien, Xilin Shen, Sophia Moret, Suyeon Ju, R Todd Constable, Carolyn Fredericks","doi":"10.1093/braincomms/fcaf274","DOIUrl":"10.1093/braincomms/fcaf274","url":null,"abstract":"<p><p>Preclinical Alzheimer's disease, characterized by the abnormal accumulation of amyloid-β prior to cognitive symptoms, presents a critical opportunity for early intervention. Past work has described functional connectivity (FC) changes in preclinical Alzheimer's disease, yet the predictive <i>nature</i> between the functional connectome and Alzheimer's disease pathology during this window remains unexplored. We applied connectome-based predictive modelling to investigate the ability of resting-state whole-brain FC to predict tau (18F-flortaucipir) and amyloid-β (18F-florbetapir) PET binding in preclinical Alzheimer's disease (A4, <i>n</i> = 342 amyloid-β-positive, age 65-85). Separate models were developed to predict amyloid PET signal in the posterior cingulate, precuneus, and cortical composite regions, and to predict tau PET signal in each of 14 cortical regions that demonstrated meaningful tau elevation as identified through a Gaussian mixture model approach. Model performance was assessed using a Spearman's correlation between predicted and observed PET binding standard uptake value ratios. We assessed the validity of significant models by applying them to an external dataset and visualized the underlying connectivity that was positively and negatively correlated to regional tau. We found that whole-brain FC predicts regional tau PET, outperforming FC-amyloid-β PET models. The best-performing tau models were for regions affected in Braak stage IV-V regions (posterior cingulate, precuneus, lateral occipital cortex, middle temporal, inferior temporal, and banks of the superior temporal sulcus), while models for regions of earlier tau pathology (entorhinal, parahippocampal, fusiform, and amygdala) performed poorly. Importantly, FC-based models predicted tau PET signal in the Alzheimer's Disease Neuroimaging Intitative-3 dataset (amyloid-β-positive, <i>n</i> = 211, age 55-90) in tau-elevated but not tau-negative individuals. For the posterior cingulate tau model, the most accurate model in A4, the predictive edges positively correlated with posterior cingulate tau predominantly came from nodes within temporal, limbic, and cerebellar regions. The most predictive edges negatively associated with tau were from nodes of heteromodal association areas, particularly within the prefrontal and parietal cortices. These findings reveal that whole-brain FC meaningfully predicts tau PET in preclinical Alzheimer's disease, particularly in regions affected in advanced disease, and are relevant across the Alzheimer's disease clinical spectrum in individuals with elevated tau PET burden. This suggests that functional connectivity, likely in conjunction with other factors, may play a key role in early processes that facilitate later-stage tau spread. These models highlight the potential of the functional connectome for the early detection and monitoring of Alzheimer's disease pathology, especially in later-stage target regions.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 4","pages":"fcaf274"},"PeriodicalIF":4.5,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12305425/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144746526","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":"Beta burst-driven adaptive deep brain stimulation for gait impairment and freezing of gait in Parkinson's disease.","authors":"Kevin B Wilkins, Matthew N Petrucci, Emilia F Lambert, Jillian A Melbourne, Aryaman S Gala, Pranav Akella, Laura Parisi, Chuyi Cui, Yasmine M Kehnemouyi, Shannon L Hoffman, Sudeep Aditham, Cameron Diep, Hannah J Dorris, Jordan E Parker, Jeffrey A Herron, Helen M Bronte-Stewart","doi":"10.1093/braincomms/fcaf266","DOIUrl":"10.1093/braincomms/fcaf266","url":null,"abstract":"<p><p>Freezing of gait is a debilitating symptom of Parkinson's disease that is often refractory to medication. Prolonged beta bursts within the subthalamic nucleus are associated with worse impairment and freezing, which are improved with deep brain stimulation. The goal of the study was to investigate the feasibility, safety and tolerability of beta burst-driven adaptive deep brain stimulation for gait impairment and freezing of gait in Parkinson's disease. Seven individuals with Parkinson's disease were implanted with the investigational Summit™ RC + S deep brain stimulation system (Medtronic, PLC, Dublin, Ireland). A PC-in-the-loop architecture adjusted stimulation in real-time based on beta burst durations in the subthalamic nucleus. A rigorous calibration procedure was employed to find participant-specific adaptive deep brain stimulation parameters. In a double-blind design, participants performed a harnessed stepping-in-place task, a free walking turning and barrier course, instrumented measures of bradykinesia and clinical motor assessments in four conditions: OFF stimulation, on adaptive, continuous or randomly adapting deep brain stimulation. Adaptive deep brain stimulation was successfully implemented and deemed safe and tolerable in all participants. Gait metrics such as overall percent time freezing and mean peak shank angular velocity improved on adaptive deep brain stimulation compared to OFF and showed similar efficacy as continuous deep brain stimulation. Similar improvements were also seen for overall clinical motor impairment, including tremor and quantitative metrics of bradykinesia. The current pilot study demonstrated initial safety, tolerability, and feasibility of adaptive deep brain stimulation for freezing of gait in Parkinson's disease in the acute laboratory setting, supporting the future investigation of its longer-term efficacy in the at-home setting.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 4","pages":"fcaf266"},"PeriodicalIF":4.1,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12268161/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144661257","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":"Vasomotor fluctuations are increased in primary central nervous system lymphoma: a case-control study with fast functional MRI.","authors":"Valter Poltojainen, Matti Järvelä, Janette Kemppainen, Nina Keinänen, Michaela Bode, Juha-Matti Isokangas, Hanne Kuitunen, Juha Nikkinen, Eila Sonkajärvi, Vesa Korhonen, Timo Tuovinen, Niko Huotari, Lauri Raitamaa, Janne Kananen, Heta Helakari, Tommi-Kalevi Korhonen, Sami Tetri, Outi Kuittinen, Vesa Kiviniemi","doi":"10.1093/braincomms/fcaf262","DOIUrl":"10.1093/braincomms/fcaf262","url":null,"abstract":"<p><p>Primary CNS lymphoma is an aggressive brain tumour. An accumulation of malignant cells around cerebral blood vessels may potentially impair the convection of cerebrospinal fluid within perivascular spaces. Recent evidence links an increased variation of the blood oxygen level-dependent signal, a marker for haemodynamic changes, to risk of mortality in lymphoma. In this study, we aimed to characterize the physiological source(s) of increased blood oxygen level-dependent signal variation in lymphoma and characterize the link between altered physiological pulsations and mortality. Thirty lymphoma patients (median age 66 years; 9 females) and 40 healthy age-matched controls (median age 62 years; 29 females) were scanned using an ultrafast functional MRI sequence. We extracted physiological brain pulsation frequency bands from functional MRI data: full band (0.008-5 Hz), very low frequency (0.008-0.1 Hz), respiratory (0.1-0.5 Hz) and cardiac (0.7-2 Hz). We compared the respective pulsation amplitudes between groups using non-parametric covariate-adjusted permutation tests and studied the link between region-specific pulsation amplitudes and mortality in receiver-operating characteristic (ROC) and survival analyses. The lymphoma group showed higher amplitudes in all brain pulsation bands (<i>P</i> ≤ 0.05), with a global increase in the very-low-frequency band. Additionally, we detected increased fluctuation amplitudes in regions extending beyond the macroscopically visible tumour areas. The very-low-frequency and respiratory bands showed a link to mortality in the lymphoma patients, very-low-frequency band being independent of other predictive markers. Increased very-low-frequency amplitude, reflecting propagating vasomotor waves, was the main source for the increased blood oxygen level-dependent signal variation in lymphoma. The patients dying during follow-up showed higher very-low-frequency and respiratory amplitudes compared with the surviving patients, implicating them as a potential prognostic marker.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 4","pages":"fcaf262"},"PeriodicalIF":4.1,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12268500/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144661258","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":"Morphometric characteristics of tibial nerve and their relationship with age.","authors":"Shahram Oveisgharan, Armand Collin, Jingyun Yang, Sue E Leurgans, Veronique VanderHorst, David A Bennett, Julien Cohen-Adad, Osvaldo Delbono, Aron S Buchman","doi":"10.1093/braincomms/fcaf267","DOIUrl":"10.1093/braincomms/fcaf267","url":null,"abstract":"<p><p>Peripheral nerve comprises a crucial component of the distributed motor/sensory system. However, there is a paucity of data on peripheral nerve morphology derived from large numbers of older adults. This study aimed to quantify the morphometric characteristics of myelinated nerve fibres of the tibial nerve obtained from deceased community-dwelling older adults and examine their association with age. The tibial nerves were obtained from consecutive autopsies of older adults without a history of diabetes who were participants of the Rush Memory and Aging Project, an ongoing longitudinal clinical-autopsy study. A nerve fascicle, obtained from a fixed popliteal segment of the tibial nerve, was separated from the blood vessels and adipose tissue for postmortem examination under an optical microscope. Morphometric characteristics of the myelinated nerve fibres were automatically segmented and quantified using our open-source software <i>AxonDeepSeg</i>. The participants (<i>N</i> = 140) had a mean age of 92.0 years (SD = 5.4) at death, and 72.1% (<i>N</i> = 101) were women. We examined 754 247 myelinated nerve fibres, with an average 5387 (SD = 3436) nerve fibres per participant. The average diameter of myelinated nerve fibres was 4.9 µm (SD = 3.1), axon diameter was 2.0 µm (SD = 1.4), myelin thickness was 1.4 µm (SD = 0.96) and the <i>g</i>-ratio (ratio of axon diameter to myelinated nerve fibre diameter) was 0.45 (SD = 0.17). The relationship between axon diameter and myelin thickness was nonlinear. Myelin was thicker in larger axons up to a diameter of 8 µm, beyond which myelin thickness plateaued. Older age at death was associated with smaller myelinated nerve fibres, smaller axons and thinner myelin. However, age at death was not correlated with myelinated nerve fibre density and was not associated with the average of <i>g</i>-ratio. The association between older age and smaller myelinated nerve fibres was largely attributable to a lower percentage of myelinated nerve fibres >8 µm. We conclude that the smaller tibial myelinated nerve fibres observed in older adults may reflect axonal atrophy rather than degeneration and regeneration of the myelinated nerve fibres. Further research is needed to investigate the pathologies and molecular mechanisms underlying these age-related morphometric changes and their clinical implications in older adults.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 4","pages":"fcaf267"},"PeriodicalIF":4.1,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12272163/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144676845","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":"Deep learning to predict progression independent of relapse activity at a first demyelinating event.","authors":"Llucia Coll, Deborah Pareto, Francisco Aparicio-Serrano, Susana Otero-Romero, Alvaro Cobo-Calvo, Evy Reinders, Manel Alberich, María Jesús Arévalo, Georgina Arrambide, Cristina Auger, Joaquín Castilló, Manuel Comabella, Ingrid Galán, Luciana Midaglia, Carlos Nos, Frederik Novak, Arnau Oliver, Jordi Río, Breogán Rodríguez-Acevedo, Jaume Sastre-Garriga, Ángela Vidal-Jordana, Ana Zabalza, Xavier Montalban, Àlex Rovira, Mar Tintoré, Xavier Lladó, Carmen Tur","doi":"10.1093/braincomms/fcaf243","DOIUrl":"10.1093/braincomms/fcaf243","url":null,"abstract":"<p><p>Progression independent of relapse activity is the main cause of irreversible disability in multiple sclerosis and is strongly associated with older age at symptom onset. Early and accurate prediction, at symptom onset, of which patients are at highest risk of progression independent of relapses, is an unmet need. This study aimed to develop a deep learning survival model using only routine MRI acquired at the first demyelinating attack to predict the risk of progression independent of relapses, and assess its ability to improve classical age-adjusted predictions. We analysed a prospective cohort of patients under 50, clinically assessed within three months of symptom onset, with available MRI (T1- and T2-Fluid-Attenuated Inversion Recovery sequences). An independent early multiple sclerosis cohort (≤1 year from symptom onset) from the Multiple Sclerosis Partners Advancing Technology and Health Solutions database (<i>N</i> = 32) was used for external validation. Patients were assessed for progression independent of relapse activity, defined as a 6-month confirmed increase in the Expanded Disability Status Scale without relapses. Our deep learning model used EfficientNet to estimate the cumulative probability of progression independent of relapses at 1-year intervals. We employed 5-fold cross-validation for model training and testing, assessing performance with the time-dependent concordance index. We also investigated the optimal cumulative probability threshold for binary risk stratification. The model's ability to improve a classical Cox regression model was evaluated. Additionally, we identified brain regions most relevant to deep learning-based progression independent of relapse activity predictions using an interpretability algorithm. A total of 259 patients were evaluated, 58 (22%) of whom experienced at least one event of progression independent of relapse activity over a median follow-up of 4.2 years. The deep learning model demonstrated high performance (time-dependent concordance index = 0.72) with an accuracy of 78% in the original cohort and 72% in the external cohort for predicting the risk of progression independent of relapse activity. Incorporating the deep learning-derived cumulative probability of progression independent of relapses significantly improved an age-adjusted Cox regression model, raising Harrell's C index from 0.62 to 0.74. Interpretability revealed the frontoparietal cortex as a key region in predicting progression independent of relapse activity. In conclusion, our deep learning survival model, based on routine MRI at the first demyelinating attack, can accurately identify patients at high risk of progression independent of relapses and may serve as a valuable tool in clinical practice.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 4","pages":"fcaf243"},"PeriodicalIF":4.1,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12226453/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144577237","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":"Associations between night/shift working and late-life brain health.","authors":"Josh King-Robson, Jennifer M Nicholas, Sarah-Naomi James, Ashvini Keshavan, Dylan M Williams, James Groves, Carole H Sudre, Kirsty Lu, Josephine Barnes, William Coath, David M Cash, Sarah E Keuss, Marcus Richards, Jason D Warren, Jonathan M Schott","doi":"10.1093/braincomms/fcaf264","DOIUrl":"10.1093/braincomms/fcaf264","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Sleep and circadian disturbances are associated with increased dementia risk. The mechanism remains poorly understood. We aimed to examine the relationship between night/shift working at age 31 and biomarkers of late-life brain health and to estimate the extent to which these relationships are mediated by unhealthy lifestyle behaviours. A prospective longitudinal cohort study, Insight 46, recruited participants from the Medical Research Council National Survey of Health and Development (NSHD) 1946 British Birth cohort. All born in the same week in 1946, participants were assessed at age 70 with multi-modal structural and molecular brain imaging and fluid biomarkers, from which whole-brain and hippocampal volumes, white matter hyper-intensity volume (WMHV), &lt;sup&gt;18&lt;/sup&gt;F-florbetapir amyloid-β PET Centiloids and plasma phosphorylated tau (p-tau)217 were derived. Prospective data collection included night/shift working at age 31, alongside smoking, alcohol intake, body mass index, exercise, blood pressure, Framingham risk score (FRS) at multiple timepoints from age 20 to 70 and dementia diagnosis or death by age 78. Analyses were adjusted for sex, age, education, socioeconomic position and, where appropriate, total intracranial volume or apolipoprotein E (&lt;i&gt;APOE&lt;/i&gt;) genotype. Night/shift working data were available for 431 Insight 46 participants {50% female, mean age 70.7 years [standard deviation (SD) 0.6]}. Night/shift workers had lower whole-brain volume [-19.9 mL, 95% confidence interval (CI) -31.9, -7.9, &lt;i&gt;P =&lt;/i&gt; 0.001], lower amyloid PET Centiloids (-9.45, 95% CI -14.7, -4.1, &lt;i&gt;P =&lt;/i&gt; 0.0008) and lower plasma p-tau217 concentration (-0.05 pg/mL, 95% CI -0.10, -0.001, &lt;i&gt;P =&lt;/i&gt; 0.04), without significant difference in hippocampal volume or WMHV. p-tau217 concentrations were also lower in night/shift workers from a wider sample from the NSHD cohort [&lt;i&gt;n&lt;/i&gt; = 1067, mean age 69.9 (SD 0.7), -0.05 pg/mL, 95% CI -0.08, -0.02, &lt;i&gt;P =&lt;/i&gt; 0.004]. By age 78, night/shift workers in the NSHD cohort (&lt;i&gt;n&lt;/i&gt; = 3040) had lower rates of all-cause (excluding vascular) dementia (hazard ratio 0.33, 95% CI 0.12, 0.92, &lt;i&gt;P&lt;/i&gt; = 0.03). Night/shift workers had 0.6% higher FRS (&lt;i&gt;P =&lt;/i&gt; 0.01) at age 36, smoked 5.9 more pack-years by age 53 (&lt;i&gt;P =&lt;/i&gt; 0.005), consumed 10.7 g/day more alcohol by age 63 (&lt;i&gt;P =&lt;/i&gt; 0.006) and had higher rates of &lt;i&gt;APOE&lt;/i&gt; ɛ4 allele carriage. Lifestyle behaviours mediated 28% of the lower brain volume in night/shift workers. Despite less healthy lifestyles, higher rates of &lt;i&gt;APOE&lt;/i&gt; ɛ4 allele carriage and smaller brains, night/shift workers had lower levels of Alzheimer's disease pathology as measured by amyloid PET and plasma p-tau217 and approximately one-third of the risk of dementia by age 78 compared with non-night/shift workers. Lower brain volume in night/shift workers was partially mediated by unhealthy behaviours. Reduced dementia risk in night/shift workers is unexpected and will require further stud","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 4","pages":"fcaf264"},"PeriodicalIF":4.1,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12268499/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144661256","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":"The importance of translational neuroscience in troubled times.","authors":"Tara L Spires-Jones","doi":"10.1093/braincomms/fcaf226","DOIUrl":"10.1093/braincomms/fcaf226","url":null,"abstract":"<p><p>Our editor discusses the importance of translational neuroscience, continued funding and international collaboration.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 4","pages":"fcaf226"},"PeriodicalIF":4.1,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12225673/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144577240","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":"Downregulation of <i>NEAT1</i> due to loss of TDP-43 function exacerbates motor neuron degeneration in amyotrophic lateral sclerosis.","authors":"Yu Kawakami, Yohei Iguchi, Jiayi Li, Yoshinobu Amakusa, Takashi Yoshimura, Ryo Chikuchi, Satoshi Yokoi, Madoka Iida, Yuichi Riku, Yasushi Iwasaki, Tetsuro Hirose, Shinichi Nakagawa, Masahisa Katsuno","doi":"10.1093/braincomms/fcaf261","DOIUrl":"10.1093/braincomms/fcaf261","url":null,"abstract":"<p><p>TAR DNA-binding protein 43 (TDP-43) is of particular interest in the pathogenesis of amyotrophic lateral sclerosis (ALS). It has been speculated that loss of nuclear TDP-43 and its cytoplasmic aggregation contributes to neurodegeneration. Although considerable attention has been paid to RNA metabolism in TDP-43 function, TDP-43 is also known to act as a transcription factor. This study found that the expression of Nuclear-enriched abundant transcript 1 (<i>NEAT1</i>), a long-non-coding RNA, was substantially downregulated in motor neurons with nuclear TDP-43 loss, but upregulated in those with preserved nuclear TDP-43, in the postmortem spinal cords of patients with sporadic ALS. TDP-43 depletion induced <i>Neat1</i> downregulation in Neuro2a cells, primary cortical neurons, and mouse spinal motor neurons. Furthermore, TDP-43 was found to positively regulate <i>NEAT1</i> at the transcriptional level. Finally, <i>Neat1</i> knockout exacerbates neurodegeneration of hSOD1^G93A mice accompanied by increased misfolded superoxide dismutase 1 (SOD1) aggregations. Transcriptome analysis revealed that <i>Neat1</i> knockout reduced protein folding-related genes, such as heat shock protein family A member 1A (<i>Hspa1a</i>), in the spinal cords of hSOD1^G93A mice. Our results indicated that the loss of TDP-43 function enhances ALS neurodegeneration by losing the protective effect of <i>NEAT1</i>.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 4","pages":"fcaf261"},"PeriodicalIF":4.1,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12256815/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144638887","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":"Motor network organization in healthy development and chronic tic disorders.","authors":"Theresa V Heinen, Julia Schmidgen, Theresa Paul, Lukas Hensel, Gereon R Fink, Lukas J Volz, Christian Grefkes, Stephan Bender, Kerstin Konrad","doi":"10.1093/braincomms/fcaf260","DOIUrl":"10.1093/braincomms/fcaf260","url":null,"abstract":"<p><p>Tic disorders (TD) are childhood-onset neurodevelopmental disorders characterized by sudden, repetitive motor and vocal tics, often with partial or complete remission by the time young adulthood is reached. We here investigated motor control and compensatory neural processes in drug-naïve children and adolescents with chronic Motor Tic Disorder or Tourette Syndrome (TD) by examining motor network activity and connectivity compared to healthy controls. Using a reaction time (RT) task under varying cueing conditions, combined with functional magnetic resonance imaging (fMRI) and dynamic causal modelling (DCM), we explored how TD-related motor networks adapt to support volitional movement control. Participants with TD demonstrated enhanced task accuracy across internally and externally cued conditions despite deficits in sustained motor inhibition (blink suppression). Relative to controls, individuals with TD exhibited increased task-related activation in ipsilateral motor regions, particularly in the primary motor cortex, and somatosensory cortex, and enhanced interhemispheric connectivity between parietal sensory-motor hubs. Notably, while in typically developing participants, age-related increases in parietal lobe activation and modulatory connectivity between primary motor and premotor regions were linked to improved task accuracy, working memory and visuomotor coordination, TD patients deviated from this normative developmental trajectory with distinct, atypical but neither delayed nor accelerated neural activation and connectivity patterns. Our data suggest that TD involves compensatory neuroplastic adaptations that leverage additional sensorimotor resources to improve motor control but do not extend to motor inhibition processes. Moreover, the findings emphasize the intricate interplay between motor control and neural plasticity in TD, highlighting how compensatory mechanisms may serve as adaptive responses to motor challenges. These findings open avenues for therapeutic strategies that harness the brain's compensatory capacities to enhance motor control and facilitate TD management.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 4","pages":"fcaf260"},"PeriodicalIF":4.1,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12264489/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144651517","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}