Brain Research Bulletin最新文献

{"title":"Abnormal dynamic connectivity patterns in self-limited epilepsy with centrotemporal spikes","authors":"Xu Chen ,&nbsp;Linfeng Song ,&nbsp;Jiaren Zhang ,&nbsp;Xuejin Ma ,&nbsp;Binlin Tian ,&nbsp;Yongzhe Li ,&nbsp;Anjie Zhang ,&nbsp;Xiyao Yang ,&nbsp;Yiyun Zhang ,&nbsp;Tijiang Zhang ,&nbsp;Lin Jiang","doi":"10.1016/j.brainresbull.2025.111669","DOIUrl":"10.1016/j.brainresbull.2025.111669","url":null,"abstract":"<div><h3>Objective</h3><div>To characterize the dynamic functional network connectivity (dFNC) patterns in children with self-limited epilepsy with centrotemporal spikes (SeLECTS) and to uncover potential abnormalities in neural regulation and related functional impairments.</div></div><div><h3>Materials and methods</h3><div>Resting-state functional magnetic resonance imaging (rs-fMRI) data were collected from 61 children with SeLECTS and 69 healthy controls (HCs). Independent component analysis (ICA), the sliding window approach and hidden markov modeling (HMM) were employed to systematically investigate potential differences in dFNC properties between the two groups.</div></div><div><h3>Results</h3><div>The dFNC analysis identified four dynamic states, with State 1 occurring most frequently. State 1 and State 3 represented two polarized connectivity patterns, with State 1 characterized by weak/negative connections and State 3 by widespread strong connections. In both states, children with SeLECTS showed significantly reduced connectivity within the dorsal attention network (DAN) compared with HCs (<em>p</em> &lt; 0.001, FDR-corrected). In the connectivity-balanced State 2, children with SeLECTS showed significantly reduced fractional windows (<em>p</em> = 0.009) and mean dwell time (<em>p</em> = 0.018) compared with HCs, whereas no significant differences were observed in State 4. In addition, temporal variability of functional connectivity between the DAN and visual network (VIS) was significantly reduced in SeLECTS (<em>p</em> &lt; 0.001, FDR-corrected), and this variability was positively correlated with full-scale intelligence quotient (FIQ) (<em>p</em> &lt; 0.05). HMM results from another dynamic perspective further confirmed and echoed the above abnormalities.</div></div><div><h3>Conclusion</h3><div>This study revealed abnormal dynamic connectivity patterns of brain networks in children with SeLECTS from a multidimensional dynamic perspective. These macroscopic abnormalities may reflect an underlying excitation–inhibition imbalance in neural networks and provide new insights into brain functional reorganization and the potential neurobiological mechanisms of SeLECTS.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"234 ","pages":"Article 111669"},"PeriodicalIF":3.7,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145676631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A critical appraisal of drug transport across the blood-brain barrier: Evaluation using new-age microfluidic technique","authors":"Kiran Marathe ,&nbsp;Dhruv Sanjay Gupta ,&nbsp;Kalyani Barve ,&nbsp;Dhananjay Bodas","doi":"10.1016/j.brainresbull.2025.111662","DOIUrl":"10.1016/j.brainresbull.2025.111662","url":null,"abstract":"<div><div>Research over the past few decades has focused on elucidating the role of the blood-brain barrier (BBB) in neuroprotection, regulation of the brain microenvironment, and mediation of the selective permeability of substances, including drug molecules. This has highlighted its significance in preclinical research, particularly in the screening of novel chemical entities with neuromodulatory properties. The BBB is not a static barrier but a dynamic, multicellular interface known as the neurovascular unit (NVU), which actively regulates brain homeostasis. A persistent challenge in neurotherapeutics is the translatability crisis, where promising results from traditional preclinical models fail to materialize in human trials. Current <em>in vivo</em> models, such as those using rodents and zebrafish, replicate the complexity of the human BBB and demonstrate satisfactory reproducibility, but are limited by their cost, time-consuming nature, and critical issues of interspecies translatability, particularly in the expression and function of key drug transporters. This has driven the development of <em>in vitro</em> models. In recent years, organ-on-a-chip technologies, which utilize the principles of microfluidics, have emerged at the forefront. These models are robust, cost-effective, and enable high-throughput screening of experimental results. By incorporating human-derived cells, physiological shear stress, and 3D architecture, these platforms are evolving from simple permeability-screening tools into sophisticated \"pathophysiology-in-a-dish\" systems. They combine the advantages of both <em>in vivo</em> and <em>in vitro</em> systems and offer promising scalability for modeling neurodegenerative diseases, neuroinflammation, and cancer, thereby enabling more predictive screening of therapeutic candidates. This review aims to provide a perspective on the current understanding of the BBB and its associated transport mechanisms, followed by a discussion of various contemporary models with the potential to transform the drug discovery landscape. The application of microfluidics in designing these models, along with noteworthy case studies in disease modeling, is explored. Finally, a brief overview of current challenges in the field, including the need for standardization, and exciting future directions spurred by regulatory shifts toward non-animal alternative methods is presented.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"234 ","pages":"Article 111662"},"PeriodicalIF":3.7,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145676599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DHX9 aggravates epilepsy by promoting STAT1 phosphorylation to increase oxidative stress and apoptosis","authors":"Hong Chen ,&nbsp;Qiannan Song ,&nbsp;Da-Qing Feng","doi":"10.1016/j.brainresbull.2025.111650","DOIUrl":"10.1016/j.brainresbull.2025.111650","url":null,"abstract":"<div><h3>Background</h3><div>DEAH-box helicase 9 (DHX9), as a member of the RNA helicase family, plays important roles in various diseases, but its specific function and molecular mechanisms in epilepsy remain unclear. This study aims to investigate the role of DHX9 in epilepsy and its interaction mechanisms with STAT1.</div></div><div><h3>Methods</h3><div>Acute and chronic epilepsy mouse models induced by pentylenetetrazole (PTZ) and kainic acid (KA)-induced epilepsy mouse models were established to detect DHX9 expression levels in hippocampal tissue. In vitro epilepsy models were established using HT22 mouse hippocampal neuronal cell lines and BV2 microglial cell lines to analyze DHX9 expression changes. Co-immunoprecipitation was employed to detect protein-protein interactions between DHX9 and STAT1. STAT1-specific inhibitors were used in rescue experiments to validate the critical role of STAT1 in DHX9-mediated pathogenic effects. Western blot and immunofluorescence staining were used to detect oxidative stress markers and apoptosis-related indicators.</div></div><div><h3>Results</h3><div>DHX9 expression was upregulated in hippocampal tissue from PTZ-induced acute and chronic epilepsy mice and KA-induced epilepsy mice. In vitro experiments confirmed that DHX9 expression was similarly increased in epilepsy models constructed with HT22 neurons and BV2 microglia. Functional studies demonstrated that DHX9 overexpression aggravated neuronal injury, including increased apoptosis rate, elevated oxidative stress levels, and promoted inflammatory responses. Conversely, silencing DHX9 through shRNA reduced neuronal injury in KA-induced epilepsy mouse models. Mechanistic studies revealed that DHX9 silencing exerted neuroprotective effects by inhibiting the STAT1 signaling pathway, reducing oxidative stress and apoptosis. Co-immunoprecipitation experiments confirmed direct protein-protein interactions between DHX9 and STAT1. Rescue experiments further demonstrated that STAT1-specific inhibitors could reverse DHX9 overexpression-induced neuronal injury, proving that STAT1 is a key downstream molecule mediating DHX9's pathogenic effects.</div></div><div><h3>Conclusion</h3><div>This study reveals the important role of DHX9 in epilepsy pathogenesis and elucidates the molecular mechanism by which DHX9 directly interacts with STAT1 and promotes its phosphorylation, thereby activating downstream oxidative stress and apoptotic signaling pathways, ultimately aggravating epileptic neuronal injury.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"233 ","pages":"Article 111650"},"PeriodicalIF":3.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145586080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prefrontal neurophysiological changes associated with subanesthetic esketamine accelerating mice emergence from propofol anesthesia","authors":"Yinying Sun ,&nbsp;Bo Li ,&nbsp;Yiting Wang ,&nbsp;Xuliang Jiang ,&nbsp;Su Tang ,&nbsp;Jiayi Zhang ,&nbsp;Jun Zhang","doi":"10.1016/j.brainresbull.2025.111648","DOIUrl":"10.1016/j.brainresbull.2025.111648","url":null,"abstract":"<div><h3>Background</h3><div>Recent studies have demonstrated that subanesthetic dose of ketamine or its S-enantiomer, esketamine, can paradoxically accelerate the recovery of consciousness in rodents following general anesthesia. However, the neural mechanisms underlying this \"awakening-promoting\" effect remain poorly understood.</div></div><div><h3>Methods</h3><div>Adult C57BL/6 J mice were anesthetized with propofol, 0and a low dose of esketamine (2 mg/kg) was administered intravenously to assess its awakening effects through behavioral tests. In vivo multichannel electrophysiological recordings, calcium imaging, and two-photon imaging combined with neurotransmitter probes targeting 5-hydroxytryptamine(5-HT) and acetylcholine (ACh) were employed to investigate electrophysiological and neurochemical dynamics in the prefrontal cortex (PFC) during the awakening process.</div></div><div><h3>Results</h3><div>Subanesthetic esketamine significantly accelerated awakening from propofol anesthesia in mice. In the PFC, esketamine hastened the emergence of γ oscillations and triggered earlier activation of neuronal somata and dendrites in layer V, while delaying activation in layer II/III neurons. Additionally, subanesthetic esketamine induced inter-layer phase desynchronization and a premature increase in ACh and 5-HT levels in the PFC during the awakening process.</div></div><div><h3>Conclusion</h3><div>Our findings suggest that low-dose esketamine facilitates mice awakening from propofol anesthesia may by orchestrating a sequence of neural events in the PFC. This study provides novel mechanistic insight into the paradoxical emergence from anesthesia induced by subanesthetic esketamine/ketamine.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"233 ","pages":"Article 111648"},"PeriodicalIF":3.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145596178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ATF3 promotes ferroptosis by transcriptional repression of SLC7A11 in ischemic stroke","authors":"Ying He ,&nbsp;Ying Zhao ,&nbsp;Ruitao Mao ,&nbsp;Wangxiang Li ,&nbsp;Tengmin Gui ,&nbsp;Huanhuan Ren ,&nbsp;Shuxian Zhang ,&nbsp;Yuan Song ,&nbsp;Liqing Yao","doi":"10.1016/j.brainresbull.2025.111659","DOIUrl":"10.1016/j.brainresbull.2025.111659","url":null,"abstract":"<div><div>Activating transcription factor 3 (ATF3) and solute carrier family 7 member 11 (SLC7A11) have been implicated in ferroptosis following ischemic stroke. However, the precise regulatory mechanisms between ATF3 and SLC7A11 remain incompletely understood. This study aims to investigate the regulatory mechanism of ATF3 and SLC7A11 in ferroptosis during ischemic stroke. The stroke-related microarray dataset GSE58294 was downloaded from the GEO database. Differential gene expression analysis was performed to identify ferroptosis-related differentially expressed genes (FRDEGs). Bioinformatics analyses, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, and protein-protein interaction (PPI) network construction, were conducted. Key hub genes were validated in both a rat model of middle cerebral artery occlusion/reperfusion (MCAO/R) and a cellular model of oxygen-glucose deprivation/reoxygenation (OGD/R) using BV2 microglia. Cell viability was assessed by CCK-8 assay. Ferroptosis-related proteins were analyzed by Western blot, and apoptosis was detected by flow cytometry. Levels of reactive oxygen species (ROS) and Fe²⁺ were measured using immunofluorescence and ELISA, respectively. Bioinformatic analysis identified SLC7A11 as a significantly altered gene in stroke. The PPI network predicted ATF3 as a key transcription factor regulating SLC7A11. In vitro, transfection with si-ATF3 downregulated GPX4 and FTH1 levels while upregulating IREB2 and ALOX15. Furthermore, si-ATF3 transfection reduced ROS levels and iron concentration in microglia, effects that were reversed by the ferroptosis inducer erastin. Notably, SLC7A11 expression was significantly increased following ATF3 knockdown. Our findings demonstrate that ATF3 preliminarily promotes ferroptosis by binding to the SLC7A11 promoter and inhibiting its expression, providing a novel mechanistic insight into ischemic stroke pathology.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"233 ","pages":"Article 111659"},"PeriodicalIF":3.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145615112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multifunctionality of tissue inhibitor of metalloproteinase-1 in central nervous system diseases","authors":"Linke Zhong ,&nbsp;Liuyang Zhao ,&nbsp;Qiaoyan Tang ,&nbsp;Xiaohua Zhang ,&nbsp;Mingchao Zhou ,&nbsp;Jiao Luo ,&nbsp;Yulong Wang","doi":"10.1016/j.brainresbull.2025.111647","DOIUrl":"10.1016/j.brainresbull.2025.111647","url":null,"abstract":"<div><div>Central nervous system (CNS) diseases are characterized by high morbidity, long disease courses, and irreversible neurological impairment, often resulting from damage to the neurovascular unit (NVU). Tissue inhibitor of metalloproteinase-1 (TIMP-1), the endogenous inhibitor of matrix metalloproteinase-9 (MMP-9), plays a pivotal role in maintaining extracellular matrix (ECM) homeostasis and regulating NVU integrity. Beyond its canonical MMP-inhibitory function, TIMP-1 exerts a wide spectrum of MMP-independent effects as a multifunctional cytokine that interacts with cell surface receptors such as CD63/β1-integrin and low-density lipoprotein receptor-related protein-1 (LRP-1). Through activation of FAK/PI3K–Akt and MAPK signaling pathways, TIMP-1 modulates astrocyte proliferation, neural stem cell adhesion and migration, endothelial barrier stability, and myelin regeneration. Altered TIMP-1 expression is closely associated with the onset, progression, and prognosis of major CNS disorders, including ischemic stroke, epilepsy, multiple sclerosis, and neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease. Accumulating evidence highlights its dual, context-dependent roles—protective in acute neuroinflammatory and ischemic injury, yet potentially profibrotic or maladaptive under chronic pathological conditions. This review comprehensively summarizes recent advances in understanding the molecular mechanisms and biological functions of TIMP-1 in CNS diseases, emphasizing its regulatory networks in neuroinflammation, neuroprotection, and neuroregeneration. A deeper understanding of TIMP-1 signaling dynamics will accelerate its translational application as a diagnostic biomarker and therapeutic target for restoring neurovascular unit function in CNS disorders.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"233 ","pages":"Article 111647"},"PeriodicalIF":3.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145630009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of combined entacapone and rTMS therapy on pain severity and serum inflammatory biomarkers (IL-6 and TNF-α) in Parkinson's disease","authors":"Yifan Yang ,&nbsp;Jianglin Wang ,&nbsp;Li Gao ,&nbsp;Jiaodan Miao ,&nbsp;Fuwei Shen ,&nbsp;Hua Liu","doi":"10.1016/j.brainresbull.2025.111652","DOIUrl":"10.1016/j.brainresbull.2025.111652","url":null,"abstract":"<div><h3>Objective</h3><div>To evaluate the efficacy of entacapone (EN) combined with high-frequency repetitive transcranial magnetic stimulation (rTMS) in treating pain in patients with Parkinson's disease (PD), with the primary outcome defined as the change in pain severity assessed by the Visual Analog Scale (VAS).Secondary outcomes included motor function (UPDRS), other pain dimensions (KPPS), depressive symptoms (HAMD), and levels of inflammatory markers (TNF-α and IL-6).</div></div><div><h3>Methods</h3><div>A total of 72 PD patients with pain were enrolled and randomly assigned to three groups: Group 1 (LD + sham stimulation), Group 2 (LD + EN + sham stimulation), and Group 3 (LD + EN + rTMS) and assessed via motor, pain, and depression scales (UPDRS/VAS/KPPS/HAMD) to evaluate the efficacy of the treatment, and also to observe the changes in the levels of interleukin (IL-6) and tumor necrosis factor (TNF-α), which are associated with pain in PD.</div></div><div><h3>Results</h3><div>After six months of combined pharmacotherapy and rTMS, the primary outcome, VAS score, demonstrated a significantly greater reduction in Group 3 compared to Group 2 (2.86 ± 1.25 vs. 8.22 ± 1.31, P &lt; 0.05).In addition, from the indexes of inflammatory factors, this study found that after six months of regular and systematic treatment, the reduction in serum IL-6 and TNF-α levels was most pronounced in the combined therapy group (LD+EN+rTMS), with statistically significant differences compared to Group 2 (P = 0.003 for TNF-α).</div></div><div><h3>Conclusions</h3><div>High-frequency rTMS, as a non-invasive neuromodulation technique combined with EN, improves muscle rigidity, alleviates depressive symptoms, reduces pain, and attenuates inflammatory factor secretion in PD patients, can improve muscle tension, regulate depression, relieve pain, and reduce the secretion of inflammatory factors in Parkinson's patients.This combined therapy was clinically effective and demonstrated a favorable safety profile, with no serious adverse events reported and only mild, transient side effects (e.g., scalp discomfort, headache) observed in the rTMS group. However, its long-term efficacy requires further investigation.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"233 ","pages":"Article 111652"},"PeriodicalIF":3.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145602602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abnormal functional integration and effective connectivity in striatal-cortical networks with neurotransmitter system correlates in migraine without aura: A resting-state fMRI study","authors":"Zhiyang Zhang ,&nbsp;Chaorong Xie ,&nbsp;Linglin Dong ,&nbsp;Xu Ouyang ,&nbsp;Xixiu Ni ,&nbsp;Mingsheng Sun ,&nbsp;Qixuan Fu ,&nbsp;Qinyi Yan ,&nbsp;Qiang Zhang ,&nbsp;Xiao Wang ,&nbsp;Ling Zhao","doi":"10.1016/j.brainresbull.2025.111653","DOIUrl":"10.1016/j.brainresbull.2025.111653","url":null,"abstract":"<div><h3>Background</h3><div>Migraine without aura (MWoA) is linked to abnormal subcortical/cortical network activity and neurotransmitter dysregulation. However, the alteration of functional integration and the information flow between brain networks participated in pain sensory pathway and the patterns of neurotransmitter dysregulation during the interictal period remain unclear.</div></div><div><h3>Methods</h3><div>This cross-sectional study compared 53 interictal MWoA patients and 51 healthy controls using resting-state fMRI. Whole-brain functional integration (degree centrality, DC) and effective connectivity (EC) were analyzed. JuSpace toolbox mapped spatial correlation between functional alterations and neurotransmitter systems.</div></div><div><h3>Results</h3><div>MWoA patients showed decreased DC in the left putamen and increased DC in the left angular gyrus. Altered EC from subcortical to cortical regions included pathways from the left putamen to right medial superior frontal gyrus, supramarginal gyrus, dorsolateral superior frontal gyrus, and postcentral gyrus, as well as bilateral caudate to left angular gyrus. Cortical-to-subcortical EC changes involved right dorsolateral superior frontal gyrus to left putamen and left angular gyrus to left caudate. EC from left putamen to right postcentral gyrus inversely correlated with headache frequency, while right caudate to left angular gyrus EC positively correlated with disease duration. Altered DC patterns spatially overlapped with serotonergic, dopaminergic, and glutamate pathways and correlated with quality-of-life impairments (MSQ scores).</div></div><div><h3>Conclusion</h3><div>MWoA involves disrupted functional integration and bidirectional subcortical-cortical connectivity during interictal periods, associated with headache severity and neurotransmitter system imbalances. These findings highlight network-level pathophysiology and neurochemical dysregulation underlying migraine.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"233 ","pages":"Article 111653"},"PeriodicalIF":3.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145615563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MultiEpilepsyNet: An EEG and MRI data based multimodal seizure detection model using hybrid deep learning model","authors":"Mohd Abdul Rahim Khan ,&nbsp;Nasser Ali AlJarallah ,&nbsp;Ashit Kumar Dutta ,&nbsp;Shtwai Alsubai ,&nbsp;Seyed Jalaleddin Mousavirad ,&nbsp;Sunil Kumar Sharma ,&nbsp;Ghanshyam G. Tejani ,&nbsp;David BASSIR","doi":"10.1016/j.brainresbull.2025.111645","DOIUrl":"10.1016/j.brainresbull.2025.111645","url":null,"abstract":"<div><div>Epilepsy is a critical neurological disorder that requires accurate and privacy-preserving diagnostic solutions to enable early detection and effective management. However, existing approaches face key challenges, including reliance on centralized data, poor generalizability across modalities, suboptimal feature extraction, and vulnerability to noise. To address these issues, we propose MultiEpilepsyNet, a novel multimodal seizure detection framework that integrates federated learning with hybrid deep learning models. At its core, the system introduces SeizureFed-Net, a federated architecture that enables collaborative learning from EEG and MRI data while safeguarding patient privacy. For detection, we design SeizureShieldNet, a hybrid model that fuses the temporal learning capabilities of BBIDNet (Boosted BiLSTM Intrusion Detector Network) with the adaptive decision-making of FD-TMS (Fuzzy-DQN Threat Mitigation System) under uncertainty. To further enhance model efficiency, a Jackal-Wolf Hybrid Optimizer (JWHO)—a novel combination of Golden Jackal Optimization and Grey Wolf Optimizer—is employed for optimal feature subset selection. On the imaging side, MRI preprocessing is improved through EpiSkullNet+ +, a modified 3D UNet+ + architecture tailored for precise brain segmentation. Extensive experiments on two benchmark datasets demonstrate the superiority of our approach, achieving 99.36 % accuracy on the CHB-MIT EEG dataset and 99.38 % accuracy on an epilepsy MRI dataset. Beyond accuracy, MultiEpilepsyNet demonstrates improved robustness to missing modalities, reduced training overhead via federated aggregation, and enhanced privacy preservation compared to centralized deep learning models, thereby addressing critical barriers in practical clinical deployment. These outcomes highlight the effectiveness, scalability, and real-world clinical potential of the proposed framework for epilepsy diagnosis and management.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"233 ","pages":"Article 111645"},"PeriodicalIF":3.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145562868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A comprehensive analysis of differential RNA m6A methylation modifications across the entire transcriptome in PTSD through high-throughput MeRIP sequencing","authors":"Luodong Yang ,&nbsp;Jiaying Lu ,&nbsp;Keke Lu ,&nbsp;Min Hu ,&nbsp;Guiqing Zhang","doi":"10.1016/j.brainresbull.2025.111665","DOIUrl":"10.1016/j.brainresbull.2025.111665","url":null,"abstract":"<div><div>In recent years, the increasing frequency of traumatic events has drawn greater attention to post-traumatic stress disorder (PTSD). However, its underlying biological mechanisms remain poorly understood. N6-methyladenosine (m6A) methylation is among the most common RNA modifications, yet to our knowledge, no studies to date have reported alterations in m6A methylation in PTSD. We enrolled 27 individuals with PTSD and 32 healthy controls. Quantitative real-time PCR (qRT-PCR) was used to examine expression differences of m6A methyltransferases. MeRIP-seq and RNA-seq were employed to investigate m6A methylation modifications and differentially expressed genes between PTSD patients and controls, followed by bioinformatic analysis. Our findings revealed decreased expression of METTL3 and FTO in peripheral blood mononuclear cells of PTSD patients, along with reduced global m6A methylation levels. MeRIP-seq analysis identified 1243 differentially expressed m6A peaks between groups. These peaks were annotated to 1054 differentially m6A-methylated genes, among which 183 exhibited hypermethylation and 871 showed hypomethylation in the PTSD group. RNA-seq analysis detected 662 differentially expressed genes, including 449 up-regulated and 213 down-regulated genes. In the differentially expressed lncRNA profile, 818 genes were identified, comprising 562 up-regulated and 256 down-regulated genes. GO and KEGG analyses indicated that the differentially methylated genes, mRNAs, and lncRNAs were primarily associated with inflammatory response, myelination alterations, and autonomic nervous system activation. In summary, m6A modification plays a critical role in the development and progression of PTSD. This study provides new insights into the biological mechanisms underlying the disorder.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"233 ","pages":"Article 111665"},"PeriodicalIF":3.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145647332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}