Brain communications最新文献

{"title":"Cerebellum mitochondrial DNA copy number is increased in Parkinson's disease.","authors":"Talia Beglarian, David R Tyrpak, J Raphael Gibbs, John Andrew MacKay, Sonja W Scholz, Bryan J Traynor, Marilyn S Albert, Liana S Rosenthal, Ted M Dawson, Juan C Troncoso, Dena G Hernandez, Mark R Cookson, Charles H Adler, Geidy Serrano, Andrew B Singleton, Thomas G Beach, Brooke E Hjelm","doi":"10.1093/braincomms/fcaf296","DOIUrl":"10.1093/braincomms/fcaf296","url":null,"abstract":"<p><p>Bioinformatics methods can be used to quantify mitochondrial DNA copy number from whole genome sequencing (WGS) data. We evaluated mitochondrial DNA copy number from human brain-derived WGS data using the fastMitoCalc tool. 341 Parkinson's Disease cerebellum samples were compared with 74 age-matched controls from the North American Brain Expression Consortium. Parkinson's Disease cerebellum had significantly higher mitochondrial DNA copy number compared with controls (<i>P</i> = 4.15e-7), and this effect was reproducible in four of five brain banks when analysis was restricted to each resource that contributed Parkinson's Disease samples to this genetic dataset. Follow-on analyses of 128 Parkinson's Disease cerebellum samples and 33 controls that had paired neuropathology data and clinical scores demonstrated a significant increase in mitochondrial DNA copy number with Unified Staging System for Lewy Body disorders stages and Unified Parkinson's Disease Rating Scale (off meds) motor scores. Analysis of Lewy Body scores from ten brain regions showed cerebellum mitochondrial DNA copy number increased upon pathological infestation of α-synuclein aggregates in the brainstem and limbic system but did not increase after late-stage neocortical involvement. This genetics dataset supports previous observations of cerebellum activation in Parkinson's Disease and suggests mitochondrial DNA copy number may increase to support this regional activation as a compensatory mechanism to pathology or motor symptoms.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 4","pages":"fcaf296"},"PeriodicalIF":4.5,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12378876/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144982317","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":"Striatal dopaminergic patterns and clinical features in frontotemporal dementia.","authors":"Daniele Urso, Antonio Anastasia, Valentina Gnoni, Alessia Giugno, Davide Vilella, Alessandra Vitulli, Chiara Zecca, José A Pineda-Pardo, Guglielmo Foffani, José A Obeso, Giancarlo Logroscino","doi":"10.1093/braincomms/fcaf284","DOIUrl":"10.1093/braincomms/fcaf284","url":null,"abstract":"<p><p>Frontotemporal dementia is a group of neurodegenerative disorders mainly characterized by behavioural and language impairments. While the precise pathophysiology remains elusive, emerging evidence points to an important role of dopamine dysfunction, particularly within the caudate nucleus. Moreover, a theoretical model proposes that frontotemporal dementia manifestations result from a deficit in goal-directed behaviour, which may be related to altered dopamine control of the frontostriatal circuitry. However, no study has investigated the gradient of striatal dopamine transporter levels in frontotemporal dementia using neuroimaging and their correlation with clinical features. This study used ¹²³I-Ioflupane Single Photon Emission Computed Tomography imaging to measure striatal dopamine transporter levels and their distribution patterns in frontotemporal dementia, compared to Parkinson's disease and healthy controls. Additionally, we explored the correlation between dopamine transporter uptake and two key domains affected in frontotemporal dementia: social cognition and language abilities. We hypothesized that frontotemporal dementia would show a predominant dopaminergic deficit in the caudate, and that this would correlate with the severity of clinical core features. The study comprised 139 participants, including 34 sporadic and genetic frontotemporal dementia, 68 Parkinson's disease individuals, and 37 age- and sex-matched healthy controls. Among the frontotemporal dementia group, 22 cases had clinically probable behavioural variant frontotemporal dementia, and 12 had primary progressive aphasia. Social cognition was assessed with the abbreviated version of the Social and Emotional Assessment, which includes a Theory of Mind test and a Facial Emotion Recognition Task. Language skills were evaluated with the Screening for Aphasia in NeuroDegeneration battery. We found that dopamine transporter levels were reduced in frontotemporal dementia compared to healthy controls (<i>P</i> < 0.001) and that frontotemporal dementia showed a higher putamen-to-caudate ratio than Parkinson's disease (<i>P</i> < 0.001), particularly notable in patients with identified disease-causing mutation. We also found that dopamine transporter levels were correlated with parkinsonian motor features and general cognition in frontotemporal dementia. Notably, both social cognition-especially facial emotion recognition-and language abilities exhibited associations with dopamine transporter levels in both the putamen and the caudate. These findings suggest that the pattern of dopamine transporter uptake could serve as a valuable biomarker for frontotemporal dementia, shedding light on the role of the dopaminergic system and the striatum in some fundamental clinical aspects. This opens new avenues for further investigating the underlying mechanisms and potential therapeutic targets of the dopaminergic projections in frontotemporal dementia.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 4","pages":"fcaf284"},"PeriodicalIF":4.5,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12365758/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144982404","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":"Phase 1, randomized trials of MEDI1341: cerebrospinal fluid free α-synuclein lowered by >50.","authors":"Craig Shering, Michael Pomfret, Robert J Kubiak, Isabelle J Pouliquen, Wei Yin, Arthur Simen, Elena Ratti, Zubair Hussain, Michael Perkinton, Keith Tan, Kirsten M Scott, Thor Ostenfeld, Iain Chessell","doi":"10.1093/braincomms/fcaf304","DOIUrl":"10.1093/braincomms/fcaf304","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Accumulation of pathological forms of α-synuclein is a hallmark of Parkinson's disease. MEDI1341 (also known as TAK-341) is a high-affinity, α-synuclein-specific, fully human monoclonal antibody that binds the C-terminal region of human α-synuclein. Pre-clinical studies of MEDI1341 demonstrated significant reductions in α-synuclein accumulation and propagation along axons. Two randomized, double-blind, placebo-controlled, Phase 1 studies administering MEDI1341 intravenously were conducted; a single ascending dose study (NCT03272165) of MEDI1341 (70, 210, 400, 1200, 2400 or 4500 mg; &lt;i&gt;n&lt;/i&gt; = 6 each) or placebo (&lt;i&gt;n&lt;/i&gt; = 13 total) in healthy participants and a multiple ascending dose study (NCT04449484) of 4-weekly MEDI1341 (1200 or 2000 mg; &lt;i&gt;n&lt;/i&gt; = 9 each) or placebo (&lt;i&gt;n&lt;/i&gt; = 7 total) in participants with Parkinson's disease. Both studies assessed the safety and tolerability of MEDI1341 versus placebo, with MEDI1341 pharmacokinetics, pharmacodynamics and immunogenicity as secondary objectives. Pharmacokinetic (MEDI1341 in serum and CSF) and pharmacodynamic (total α-synuclein in plasma, and free α-synuclein in CSF) concentrations were determined using validated electrochemiluminescence assays. Overall, 49 healthy participants (67.3% male; mean [standard deviation] age 43.4 [9.5] years) were included in the single ascending dose study and 25 participants with Parkinson's disease (72.0% male; mean [standard deviation] age 63.0 [9.0] years; 88% Hoehn and Yahr stage 2) were included in the multiple ascending dose study. Treatment-emergent adverse events were reported in 23 healthy participants (MEDI1341, &lt;i&gt;n&lt;/i&gt; = 17; placebo, &lt;i&gt;n&lt;/i&gt; = 6) and 10 participants with Parkinson's disease (MEDI1341, &lt;i&gt;n&lt;/i&gt; = 9; placebo, &lt;i&gt;n&lt;/i&gt; = 1). The most common treatment-related treatment-emergent adverse events were headache, fall and nausea. Dose proportional increases were observed for maximum concentration in serum and area under the curve (AUC) in both studies, with the exception of a supra-proportional increase in AUC&lt;sub&gt;0-∞&lt;/sub&gt; from 2400 to 4500 mg (single ascending dose study). Median time to maximum concentration was 1 h after intravenous administration and geometric mean terminal elimination half-life ranged from 16.6 to 24.3 days across both studies. Suppression of α-synuclein in CSF was greatest at the highest doses investigated: -53.6% median change from baseline on Day 15 [4500 mg (healthy participants)] and -59.0% median change from baseline on Day 85 [2000 mg (participants with Parkinson's disease)]. Across all doses and time points, individual participant CSF MEDI1341 concentrations were &lt;1% of their respective serum concentrations. MEDI1341 had favourable safety, tolerability, pharmacokinetic and pharmacodynamic profiles in healthy participants and those with Parkinson's disease, supporting further clinical development. MEDI1341 is the first monoclonal antibody targeted against α-synuclein to demonstrate a &gt; 50% reduction in CS","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 5","pages":"fcaf304"},"PeriodicalIF":4.5,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12421129/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145042515","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":"Superficial and deep white matter abnormalities in temporal lobe epilepsy.","authors":"Gerard R Hall, Sarah J Gascoigne, Jonathan J Horsley, Yujiang Wang, Csaba Kozma, Jane de Tisi, Sjoerd B Vos, Gavin P Winston, John S Duncan, Peter N Taylor","doi":"10.1093/braincomms/fcaf305","DOIUrl":"10.1093/braincomms/fcaf305","url":null,"abstract":"<p><p>Non-invasive neuroimaging is important in epilepsy to help identify cerebral abnormalities. Abnormally reduced fractional anisotropy (FA) in deep white matter (WM) from diffusion-weighted imaging (DWI) is widely reported in large multi-cohort studies across all types of epilepsies. However, abnormalities in FA for superficial WM are rarely investigated in epilepsy. To gain a greater understanding of the nature of WM abnormality at different WM depths, we investigated DWI abnormalities at a range of superficial and deep WM in two separate temporal lobe epilepsy (TLE) cohorts. The first cohort (TLE = 81, Healthy Control; HC = 67) underwent a high angular resolution multi-shell DWI, whilst the second cohort (TLE = 70, HC = 29) had a single-shell acquisition. We registered FA maps to a standard template, and analysed temporal WM within 8 mm of the temporal lobe grey matter, amygdala and hippocampus. We standardised FA measures at different depths, and compared ipsi-versus contralateral temporal WM, and MRI-positive versus MRI-negative groups. We report three major findings: First, superficial WM had greater FA reductions than deep WM in TLE (<i>P</i> < 0.001). Second, this effect was more prominent in the ipsilateral than contralateral temporal lobe WM (<i>P</i> < 0.001). Third, these effects were present to a similar degree in patients who reported an MRI negative. All results are held in both TLE cohorts. These findings suggest that, in the temporal lobe, superficial WM is more abnormal than deep WM in TLE, with potential clinical use for lateralisation even in MRI-negative patients. These findings motivate further investigation of the importance of superficial WM in epilepsy.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 5","pages":"fcaf305"},"PeriodicalIF":4.5,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12402771/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144994769","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":"Activation metrics for structural connectivity recruitment in deep brain stimulation.","authors":"Konstantin Butenko, Jan Roediger, Bassam Al-Fatly, Ningfei Li, Till A Dembek, Yifei Gan, Guan-Yu Zhu, Jianguo Zhang, Andrea A Kühn, Andreas Horn","doi":"10.1093/braincomms/fcaf301","DOIUrl":"10.1093/braincomms/fcaf301","url":null,"abstract":"<p><p>Comparatively high excitability of myelinated fibres suggests that they represent a major mediator of deep brain stimulation effects. Such effects can be modelled using different levels of abstraction, ranging from simple electric field estimates to complex multicompartment axon models. In this study, we explored three metrics to evaluate axonal activation: electric field magnitudes, electric field projections and pathway activation modelling. Furthermore, in order to account for variability in axonal morphology, these metrics were computed in a probabilistic fashion. To showcase and illustrate their relevance, we retrospectively analysed a dataset of 15 Parkinson's disease patients, who were stimulated in the subthalamic nucleus in bipolar mode. High similarity of activation patterns was observed for the electric field metrics, but not for pathway activation modelling, which might be attributed to its ability to capture stimulation's polarity. Nevertheless, all three metrics associated motor improvement with activation of motor pallidosubthalamic and hyperdirect pathways. To make these probabilistic approaches accessible to the community, the modelling and statistical framework was implemented in the openly available Lead-DBS toolbox.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 5","pages":"fcaf301"},"PeriodicalIF":4.5,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12402687/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144994773","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":"Unilateral focused ultrasound thalamotomy for tremor-dominant Parkinson's disease: blinded evaluation and imaging correlation.","authors":"James Peters, Joel Maamary, Kain Kyle, Isabelle Osborne, Duncan Wilson, Lyndsey Jones, Sam Bolitho, Michael Barnett, Chenyu Wang, Yael Barnett, Benjamin Jonker, Stephen Tisch","doi":"10.1093/braincomms/fcaf303","DOIUrl":"10.1093/braincomms/fcaf303","url":null,"abstract":"<p><p>There have been promising outcomes from the use of unilateral High-intensity focused ultrasound (HiFUS) thalamotomy in tremor-dominant Parkinson's disease. However, the reliability of this treatment has been questioned due to the high rate of tremor relapse. Authors have hypothesized that treatment failure is due to insufficient HiFUS lesion size, though detailed volumetric lesion analyses are lacking. To report the blinded tremor outcomes of unilateral HiFUS thalamotomy in tremor-dominant Parkinson's disease and correlate these outcomes with lesion characteristics, including the dentatorubrothalamic tract ablation overlap, which may provide valuable insights into the mechanisms behind tremor relapse and ultimately refine the optimal HiFUS target for tremor in Parkinson's disease. Retrospective review of consecutively treated tremor-dominant Parkinson's disease patients followed under a uniform protocol. Blinded tremor analysis was completed on pre- and post-operative videos. Patients were classified into two groups: 'responder' (≥50% improvement in Hand Tremor Score) or 'suboptimal responder' (<50% improvement in Hand Tremor Score) at the last follow-up. 17 patients with tremor-dominant Parkinson's disease underwent a unilateral HiFUS thalamotomy at our centre. Pre- and post-operative videos were available in 15 patients for analysis. Baseline median Hand Tremor Score was 11.0 (9.5-14.5), improving to 6.0 (1-13.5) over a median 24-month (3-36) follow-up period (<i>P</i> = 0.098). Seven patients had ≥50% improvement in Hand Tremor Score, while eight patients had <50% improvement in Hand Tremor Score at the last follow-up. At the final follow-up, the median change in Hand Tremor Score from baseline was 91% in responders, compared to an 8% increase in the suboptimal responders (<i>P</i> < 0.002). Levodopa daily dose equivalent increased by 17% in responders (<i>P</i> = 0.043), and the difference between responders and suboptimal responders was significant at the final follow-up (<i>P</i> = 0.024). There was a trend for larger lesions in the suboptimal responders, 157.5mm³ (113.4-215) compared to 119.7mm³ (111.6-237.6) in responders. Further, the dentatorubrothalamic core lesion overlap was greater in the suboptimal responders, 41.7% (40.5-48.8%), compared to the responders, 27.1% (13.8-39.3%), (<i>P</i> = 0.010), and was associated with a higher Hand Tremor Score at the final follow-up. We found that unilateral HiFUS thalamotomy in tremor-dominant Parkinson's Disease resulted in sustained tremor reduction in approximately 50% of patients but was also in the context of higher levodopa replacement. These favourable outcomes did not correlate with DRTT ablation overlap or lesion size, providing indirect evidence that the most efficacious HiFUS thalamic tremor target differs between essential tremor and tremor-dominant Parkinson's Disease.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 4","pages":"fcaf303"},"PeriodicalIF":4.5,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12392903/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144982407","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":"Pontocerebellar hypoplasia: a review from 1912 to 2022.","authors":"Natalie A Kukulka, Shriya Singh, Matthew T Whitehead, William B Dobyns, Taeun Chang, Youssef A Kousa","doi":"10.1093/braincomms/fcaf298","DOIUrl":"10.1093/braincomms/fcaf298","url":null,"abstract":"<p><p>Pontocerebellar hypoplasia is a rare neurodevelopmental disorder that results from differences in formation and function of the pons, cerebellum and cerebrum. It can be diagnosed prenatally or postnatally with a combination of clinical, neuroimaging and genetic data obtained over time. The diagnosis of pontocerebellar hypoplasia usually portends severe developmental delay, epilepsy and/or neurodegeneration in childhood. Here we perform a comprehensive review with the primary goal of evaluating published evidence addressing the clinical and genetic features of pontocerebellar hypoplasia by type and subtype. Secondly, we summarize neurodiagnostic patterns of pontocerebellar hypoplasia and demonstrate its spectrum. Finally, we provide recommendations in diagnosis, prognosis and management for the neurologist. To address these goals, we performed an extensive review of published literature from 1912 to 2022. We identified 191 publications by combining search results from PubMed, OMIM and cross-referenced bibliographies. Publications on developmental neuroanatomy, not pertaining to pontocerebellar hypoplasia or published in a foreign language were excluded. We performed both qualitative (1912-1993) and quantitative (1993-2022) analyses to understand the current classification of this disease as it pertains to genetic and neurodiagnostic features of pontocerebellar hypoplasia by type and subtype. Our review shows that the most reported types of pontocerebellar hypoplasia are 1, 2 and 6; less frequently described are 3, 4 and 9. Very few cases are described for all other subsequent pontocerebellar hypoplasia types. Mutations in <i>TSEN54</i>, <i>RARS2</i>, <i>EXOSC3</i> and <i>AMPD2</i> (genes that regulate RNA processing and basic cellular metabolism) are the most frequently reported pathological mutations in pontocerebellar hypoplasia. The neuroradiographic features of pontocerebellar hypoplasia are complex and evolve over time, affecting the pons, cerebellum, vermis, cortex and cerebral white matter. In conclusion, pontocerebellar hypoplasia is a rare neurodevelopmental disorder, often the result of genetic dysfunction in basic neural metabolism. The diagnosis conveys significant implications for the affected individual and their families and requires a combination of clinical, neuroradiographic, and genetic testing to best inform type/subtype categorization of pontocerebellar hypoplasia.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 5","pages":"fcaf298"},"PeriodicalIF":4.5,"publicationDate":"2025-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12422213/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145042445","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":"Pathological beta power increase in the subthalamic nucleus is absent in essential tremor.","authors":"Halen Baker Erdman, Hagai Bergman, Juan F Leon, Sami Heymann, Yara Atamna, Muneer Abu Snineh, Omer Zarchi, Idit Tamir, Zvi Israel","doi":"10.1093/braincomms/fcaf297","DOIUrl":"10.1093/braincomms/fcaf297","url":null,"abstract":"<p><p>Parkinson's disease and essential tremor are common movement disorders characterized by distinct motor symptoms. Deep brain stimulation targeting the subthalamic nucleus has shown efficacy in managing Parkinson's disease symptoms, whereas the posterior subthalamic area is an emerging target for essential tremor. This analytical cross-sectional study investigates the electrophysiological activity of the subthalamic nucleus in Parkinson's disease and essential tremor patients from deep brain stimulation surgeries to understand the underlying neural oscillatory mechanisms. Microelectrode recordings during deep brain stimulation surgery from 35 Parkinson's disease patients targeting the subthalamic nucleus and 21 essential tremor patients simultaneously targeting the posterior subthalamic area and subthalamic nucleus using a novel dual electrode technique were analysed for the main analysis. Additionally, subthalamic nucleus data from a subgroup of 12 Parkinson's disease patients was compared with seven essential tremor patients who were matched based on the <i>y</i>-coordinate of the electrode. A final comparison was made between a third subgroup of nine Parkinson's disease patients with satisfactory subthalamic nucleus recordings in the posterior BenGun location and 21 essential tremor patients. Recordings were collected from two medical centres with a common electrophysiology team. Root mean square and spectral analysis were employed as well as statistical analysis of demographic and recorded subthalamic nucleus anatomical dimensions. Relative dimensions of subthalamic nucleus physiological regions did not differ between the main groups. The motor subregion of the subthalamic nucleus in Parkinson's disease patients exhibited significantly increased beta frequency power (13-30 Hz). Conversely, essential tremor patients did not show this increase, suggesting distinct pathophysiological mechanisms. Additionally, the subthalamic nucleus spiking activity, as measured by RMS analysis, was higher in Parkinson's disease patients. <i>y</i>-coordinate matched, and posterior subthalamic nucleus Parkinson's disease patient comparisons confirmed the higher beta frequency power in Parkinson's disease patients only. These findings underscore the different neural dynamics between Parkinson's disease and essential tremor. They highlight the role of beta oscillations in Parkinson's disease's motor symptoms and raise questions about the absence of beta oscillations in essential tremor, whether it reflects a normal lack of beta activity or an active suppression of a normal beta stop signal.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 5","pages":"fcaf297"},"PeriodicalIF":4.5,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12402545/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144994679","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":"Epidemiology and diagnostic challenges in neuromyelitis optica spectrum disorder in Taiwan: a hospital-based surveillance accompanied by a nationwide study.","authors":"Jung Lung Hsu, Jen Jen Su, Mei-Yun Cheng, Ming-Feng Liao, Hung-Chou Kuo, Chun-Che Chu, Chiung-Mei Chen, Kuo-Hsuan Chang, Chun-Wei Chang, Yih-Ru Wu, Chin-Chang Huang, Chyi-Huey Bai, Long-Sun Ro","doi":"10.1093/braincomms/fcaf293","DOIUrl":"10.1093/braincomms/fcaf293","url":null,"abstract":"<p><p>Neuromyelitis optica spectrum disorder is a rare autoimmune inflammatory demyelinating disease that must be differentiated from multiple sclerosis. The impact of misclassification on these patients in Taiwan remains unclear. We conducted a hospital-based retrospective cohort study of neuromyelitis optica spectrum disorder patients using the Chang Gung Research Database from 2005 to 2021. This cohort included diagnostic serostatus data from anti-Aquaporin 4 antibody testing, providing insights into incidence, demographics, annual relapse rate, and initial misclassification as multiple sclerosis. To extend these findings, we applied the same methodology to a nationwide neuromyelitis optica spectrum disorder cohort (2006-2020) using Taiwan's National Health Insurance Research Database, which does not include aquaporin 4 serostatus information; thus, the data made it impossible to distinguish seropositive from seronegative nationwide neuromyelitis optica spectrum disorder cases. Misclassification was calculated as the ratio of nationwide neuromyelitis optica spectrum disorder patients initially diagnosed with multiple sclerosis (MS) to the total nationwide neuromyelitis optica spectrum disorder cases in each cohort. In the Chang Gung Research Database cohort, we identified 193 seropositive nationwide neuromyelitis optica spectrum disorder patients, including four (2.1%) paediatric cases. Hospital incidence increased from 0.08 to 1.19 per 100 000 persons (2006-2021). Comorbidities were present in 32% of adults, with Sjögren's syndrome as the most common (21.2%). Median annualized relapse rate in adults was 0.49 (range, 0.26-0.85) and was higher in the first 3 years post-diagnosis (0.67 versus 0.00; <i>P</i> < 0.01). The National Health Insurance Research Database cohort included 1892 neuromyelitis optica spectrum disorder patients, 92 (4.9%) paediatric. Incidence in adults rose from 0.25 to 0.84 per 100 000 persons, with a prevalence of 8.01 per 100 000 in 2020. Median annualized relapse rate was 0.36 (range, 0.07-60.83) for adults and 0.44 (range, 0.07-6.40) for paediatric patients. Misclassification as multiple sclerosis occurred in 55.0% Chang Gung Research Database and 63.5% National Health Insurance Research Database cohort. Misclassified patients were more likely to be younger, female, experience delayed antibody testing, have frequent hospitalizations, and suffer more relapses. Both hospital-based and nationwide cohorts revealed increasing neuromyelitis optica spectrum disorder incidence and prevalence in Taiwan. This early-phase elevation in relapse activity highlights the critical therapeutic window where intervention may most effectively prevent long-term disability. Greater clinical awareness and close follow-up may improve neuromyelitis optica spectrum disorder diagnosis and management.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 4","pages":"fcaf293"},"PeriodicalIF":4.5,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12392899/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144982270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Longitudinal brain ageing after stroke: a marker for neurodegeneration and its relevance for upper limb motor outcome.","authors":"Raphael B Takyi, Jeanette Plantin, Sylvain Charron, Marc A Maier, Jean-Claude Baron, Guillaume Turc, Charlotte Rosso, Clément Debacker, Påvel G Lindberg","doi":"10.1093/braincomms/fcaf299","DOIUrl":"10.1093/braincomms/fcaf299","url":null,"abstract":"<p><p>Brain age, as distinct from chronological age, may reveal post-stroke recovery mechanisms, but longitudinal studies tracking brain age are lacking. We explored longitudinal change of brain age post-stroke and its relation to upper limb sensorimotor outcome. T₁-weighted MRI at baseline (∼3 weeks) and follow-up (3-7 months) post-stroke was used to estimate brain age. Difference to chronological age was calculated as brain age gap (BAG). Grey and white matter changes and lesion location related to increased brain ageing were investigated, controlling for lesion volume. Association between BAG change and upper limb sensorimotor outcome was studied using linear mixed effects regression. Totally, 114 stroke patients with arm/hand hemiparesis were pooled from three studies. BAG significantly increased from baseline to follow-up, a period of ∼6 months, by a mean of 3.62 years (<i>t</i> = -7.31; <i>P</i> < 0.001). Voxel-based morphometry showed that high BAG change was related to reduced grey and white matter volume ipsilesionally, extending beyond the stroke lesion. Voxel-based lesion symptom mapping showed that lesion to thalamocortical projections, internal capsule and corona radiata related to accelerated brain ageing. BAG change was significantly associated with motor outcomes in the sub-acute to chronic phase, as expressed by Fugl-Meyer assessment (<i>β</i> = -5.62, SE = 2.81, <i>t</i> = -2.00, <i>P</i> = 0.05), maximum grip strength (<i>β</i> = -0.14, SE = 0.04, <i>t</i> = -3.36, <i>P</i> = 0.001) and dexterity assessment (<i>β</i> = -0.09, SE = 0.04, <i>t</i> = -2.17, <i>P</i> = 0.03). We demonstrate increased brain ageing within the first few months post-stroke. This secondary neurodegeneration was negatively related to motor outcome. Brain age may be a valid whole-brain probe of individual secondary post-stroke degeneration, relevant for predicting recovery and identifying targets of neural plasticity.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 5","pages":"fcaf299"},"PeriodicalIF":4.5,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12399367/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144994730","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}