Brain Research Bulletin最新文献

{"title":"Machine learning and deep learning in clinical practice: Advancing neurodegenerative disease diagnosis with multimodal markers","authors":"Omid Zarei ,&nbsp;Maryam Talebi moghaddam ,&nbsp;Sadegh Moradi Vastegani","doi":"10.1016/j.brainresbull.2025.111667","DOIUrl":"10.1016/j.brainresbull.2025.111667","url":null,"abstract":"<div><div>Neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and multiple sclerosis, present major global health challenges due to their progressive and incurable nature. Early and accurate diagnosis is critical to slow disease progression and optimize therapeutic interventions, yet conventional diagnostic approaches, such as neuroimaging, cerebrospinal fluid biomarker analysis, and clinical evaluation are often inadequate at the prodromal stage. Recent advances in artificial intelligence, particularly machine learning (ML), have provided new opportunities for precision diagnosis and treatment in neurology, using large data and multimodal biomarkers. Applications of ML to data from neuroimaging, electrophysiology, behavioral functions, speech and handwriting analysis, and molecular biomarkers have shown promising improvements in diagnostic accuracy, patient classification, and therapeutic recommendations. However, significant challenges remain, including data heterogeneity, model interpretability, population diversity, and ethical concerns surrounding patients’ privacy. The purpose of this review is to examine current applications of ML in the diagnosis and management of neurodegenerative diseases through various data, highlight its strengths and limitations, and discuss future directions for using these approaches in clinical practice. We also outline emerging directions, including multimodal fusion with longitudinal data, federated and privacy-preserving learning, and the potential of explainable AI (XAI) and large language models (LLMs) in clinical decision support.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"234 ","pages":"Article 111667"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145667113","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":"Exogenous Aβ1–42 monomers rescue memory deficits in presenilin-1 and presenilin-2 conditional double knockout mice","authors":"Jinnan Chen ,&nbsp;Bo Wang ,&nbsp;Zhidong Chen ,&nbsp;Fan Ding,&nbsp;Jiayue Wang,&nbsp;Chaoyang Ding,&nbsp;Xiaohua Cao","doi":"10.1016/j.brainresbull.2026.111715","DOIUrl":"10.1016/j.brainresbull.2026.111715","url":null,"abstract":"<div><div>Emerging evidence challenges the direct causal relationship between amyloid-β (Aβ) deposition and cognitive decline in Alzheimer's disease (AD), as exemplified in presenilin-1 and presenilin-2 conditional double knockout (cDKO) mice which exhibit no amyloid plaques and reduced soluble Aβ_1–42 monomers, but paradoxically display AD-like memory deficits. In this study, we hypothesize that reduced soluble Aβ_1–42 monomers critically underlie memory dysfunction in cDKO mice. Combining behavioral assessments and <em>in vivo</em> multichannel electrophysiology, we show that cDKO mice exhibit impaired spatial and episodic memory, accompanied by reduced theta oscillation power and theta-gamma phase-amplitude coupling in the dorsal hippocampal CA1. Remarkably, exogenous supplementation of physiological level Aβ_1–42 monomers rescued memory deficits and restored neural oscillatory dynamics, while co-administration of the α7-nicotinic acetylcholine receptors (α7-nAChRs) antagonist methyllycaconitine blocked these rescuing effects. Our findings reveal that soluble Aβ_1–42 monomers help to sustain hippocampal memory through α7-nAChRs-dependent pathways, thereby contributing toa revised perspective on the roles of Aβ_1–42 monomers in cognition and suggesting potential avenues for Aβ-targeted AD treatments.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"234 ","pages":"Article 111715"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145920919","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 repetitive transcranial magnetic stimulation on apoptosis and MAPK/PI3K-AKT signaling pathways in rats with spinal cord injury","authors":"Qingqin Xu ,&nbsp;Junhong Su ,&nbsp;Qian Lei ,&nbsp;Jinxiu Liu ,&nbsp;Jing Wang ,&nbsp;Mengyu Yang ,&nbsp;Juan Song ,&nbsp;Hemu Chen ,&nbsp;Jianwei Lu","doi":"10.1016/j.brainresbull.2025.111687","DOIUrl":"10.1016/j.brainresbull.2025.111687","url":null,"abstract":"<div><h3>Background</h3><div>Repetitive transcranial magnetic stimulation (rTMS) is a promising non-invasive neuromodulation technique, but its mechanisms in spinal cord injury (SCI) remain unclear. This study investigated the effects and potential mechanisms of rTMS on motor recovery in SCI rats.</div></div><div><h3>Methods</h3><div>A rat SCI model was established using the modified Allen's method. rTMS treatment was initiated on postoperative Day 2 and administered daily for 56 days. Bioinformatics analysis was first conducted to identify SCI-related genes and signaling pathways. Western blotting, immunofluorescence staining, TUNEL assay, NeuN staining, motor evoked potential (MEP) measurement, hematoxylin-eosin staining, and Basso-Beattie-Bresnahan (BBB) score were performed to evaluate molecular and functional outcomes.</div></div><div><h3>Results</h3><div>Bioinformatics analysis identifies MAPK-, PI3K/AKT-, and Bcl-2-related genes as potentially involved in SCI pathology. Western blotting reveals that rTMS is associated with lower levels of p-JNK, p-p38 MAPK, Bax, and caspase-3, and with higher levels of p-ERK, p-PI3K, p-AKT, and Bcl-2 (<em>P</em> &lt; 0.001). Immunofluorescence staining shows that rTMS is accompanied by reduced p-JNK and p-p38 MAPK positive cells and increased p-ERK, p-PI3K and p-AKT positive cells (<em>P</em> &lt; 0.001). TUNEL and NeuN staining further suggest reduced neuronal apoptosis in the injured spinal cord. Behavioral and electrophysiological assessments show that rTMS is associated with shorter MEP latencies, higher MEP amplitudes, reduced spinal tissue damage, attenuated muscle atrophy, and improved BBB score (<em>P</em> &lt; 0.001).</div></div><div><h3>Conclusion</h3><div>rTMS is associated with improvements in motor function and anti-apoptotic molecular changes in SCI rats, possibly via modulation of MAPK and PI3K/AKT signaling pathways, including upregulation of Bcl-2 and downregulation of Bax and caspase-3.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"234 ","pages":"Article 111687"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145762154","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":"TRIM37 regulates HMGB1 ubiquitination to inhibit ferroptosis in Schwann cells and alleviate peripheral nerve injury","authors":"Xiang Zhou ,&nbsp;Yazhu You ,&nbsp;Liangying Zhong ,&nbsp;Wenfu Peng ,&nbsp;Yi Yang ,&nbsp;Jian Qi","doi":"10.1016/j.brainresbull.2025.111701","DOIUrl":"10.1016/j.brainresbull.2025.111701","url":null,"abstract":"<div><div>Peripheral nerve injury (PNI) is a common neurological disorder. Despite advances in surgical and non-surgical interventions, therapeutic outcomes remain suboptimal, necessitating the identification of novel molecular targets. TRIM37, an E3 ubiquitin ligase, has not been investigated in the context of peripheral nerve injury. To address this gap, we first established a rat sciatic nerve injury model to explore whether PNI is associated with ferroptosis and to characterize TRIM37 expression levels in this context. Using DHE staining, immunofluorescence, and ELISA, we quantified ROS levels, GPX4 expression, and oxidative stress markers. Meanwhile, TRIM37 expression was analyzed via qPCR, Western blot, and immunofluorescence. To clarify the direct role of TRIM37 in ferroptosis, we further performed in vitro experiments using H₂O₂-induced ferroptosis in RSC96 cells. Given that TRIM37 functions as an E3 ubiquitin ligase, we then used co-immunoprecipitation and ubiquitination assays to investigate its potential interaction with HMGB1 and the underlying mechanism. Finally, to validate the in vivo relevance, SFI, von Frey test, and histopathological analyses were used to evaluate the impact of TRIM37 on functional recovery after nerve injury. In summary, PNI significantly induced ferroptosis, which was accompanied by reduced TRIM37 expression. Mechanistically, TRIM37 directly interacted with HMGB1 and promoted its ubiquitination and degradation, thereby inhibiting ferroptosis. TRIM37 overexpression reversed these pathological changes by alleviating ferroptosis, enhancing functional recovery, reducing structural damage, and modulating oxidative stress markers in injured sciatic nerves. Thus, TRIM37 is a potential therapeutic target for improving functional recovery in PNI.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"234 ","pages":"Article 111701"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145809964","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":"Chronic suppression of monoacylglycerol lipase restores adult neurogenesis in the septal but not the temporal DG in Ts65Dn mouse model of Down syndrome","authors":"Donya Fozoonmayeh,&nbsp;Mathangi Sankaran,&nbsp;Jessica Yu,&nbsp;Meriel Walsh,&nbsp;Anna Tyrtyshnaia,&nbsp;Alexander M. Kleschevnikov","doi":"10.1016/j.brainresbull.2026.111721","DOIUrl":"10.1016/j.brainresbull.2026.111721","url":null,"abstract":"<div><div>Down syndrome (DS) is a genetic disorder characterized by cognitive impairment and varying degrees of changes in emotion-related behaviors. A deficiency in adult hippocampal neurogenesis is among the cellular mechanisms implicated in both abnormalities. Previously, we observed that chronic inhibition of monoacylglycerol lipase (MAGL) with the selective inhibitor JZL184 increased brain levels of the endocannabinoid 2-arachidonoylglycerol (2-AG), improved hippocampal synaptic plasticity and long-term memory, but did not affect anxiety-related thigmotactic behavior in Ts65Dn mice, a genetic model of DS. In this study, we tested the hypothesis that these effects of JZL184 might be associated with changes in adult hippocampal neurogenesis. Ts65Dn mice and their normosomic (2 N) littermates were injected daily for 3 weeks with JZL184 or vehicle, and bromodeoxyuridine (BrdU) was co-administered during the chronic phase of the treatment. BrdU-immunopositive cells were quantified in the septal, medial, and temporal segments of the dentate gyrus (DG). It was observed that both the total number and the density of BrdU-positive cells were significantly reduced in Ts65Dn mice compared to their 2 N littermate controls. Strikingly, JZL184 treatment effects exhibited a profound septo-temporal bias: the BrdU-immunopositive cell density was restored to near control levels in the septal DG (a region presumably linked to cognitive function), but it was largely unaffected in the temporal DG (presumably associated with emotion-related behaviors). These results suggest that chronic MAGL inhibition may provide a targeted region-specific therapeutic strategy for cognitive impairment in Down syndrome, potentially independent of its effects on emotional behavior.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"234 ","pages":"Article 111721"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145920916","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":"Research on the syntax of EEG microstates: A comprehensive analysis of epilepsy and psychosis of epilepsy","authors":"Wei Shi ,&nbsp;Fangni Chen ,&nbsp;Yina Cao ,&nbsp;Lei Zhang ,&nbsp;Jian Wan","doi":"10.1016/j.brainresbull.2026.111720","DOIUrl":"10.1016/j.brainresbull.2026.111720","url":null,"abstract":"<div><div>Growing evidence suggests that abnormalities within the microstate sequence are associated with a wide range of mental illnesses. In this study, we aimed to evaluate the impact of higher-order microstate sequence syntax on brain cognitive processes. We first refined the microstate sequences obtained from the EEG recordings of individuals with epilepsy (EP) and those with psychosis of epilepsy (POE) into subdivisions in terms of microstate words. Subsequently, the microstate word characteristics and clustering degree features of different microstate word sizes were computed and compared. Finally, the correlation between word characteristics and the severity of POE was analyzed using Pearson's correlation coefficient and linear regression analysis. Our study showed that microstate B and the combined microstates {C, D} switch frequently in patients with POE compared to those with EP, whereas microstate A rarely switches directly with the combination {B, D}. In patients with higher Positive and Negative Syndrome Scale (PANSS) negative factor scores, we observed numerous continuous transitions involving {B, D}, {A, D}, and microstate C. Conversely, fewer continuous transitions of {B, C}, {C, D}, and microstate A could exacerbate psychiatric symptoms. Furthermore, while verifying the high-cohesion properties of microstate words on the time scale, patterns of \"binary loop words\" and \"mirror word pairs\" within brain microstate sequences were observed. Overall, the results demonstrate that mining higher-order syntax within microstate sequences provides novel methodological tools to understand brain cognitive processes and POE’s pathological mechanisms, while offering clinical biomarkers for POE severity assessment.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"234 ","pages":"Article 111720"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145921016","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":"Lipidomics reveals dysregulated lipid profiles in lipopolysaccharide administration-induced cognitive impairments","authors":"Yali Lu ,&nbsp;Yuanyuan Chen ,&nbsp;Liangqian Ye ,&nbsp;Jun Zhong","doi":"10.1016/j.brainresbull.2025.111655","DOIUrl":"10.1016/j.brainresbull.2025.111655","url":null,"abstract":"<div><div>Sepsis-associated encephalopathy is a frequent complication in critically ill patients and is associated with long-term cognitive impairments. However, the pathophysiology of septic encephalopathy underlying cerebral metabolism, cognition, learning, and memory capabilities is poorly understood. In this study, LC/MS-MS-based metabolomics was used to investigate the cognitive deficit mechanism underlying bacterial lipopolysaccharide (LPS)-induced sepsis-associated encephalopathy. Mice were randomly divided into the vehicle (control), LPS, and LPS + minocycline (LPS+Mino) groups. Minocycline was administered 30 min after the LPS administration and daily afterward for 2 days. Behavioral tests were performed starting from day 6 with open field, fear conditioning tests, and T-maze, respectively. LPS-induced sepsis caused a profound alteration of the lipid profile in multiple brain regions. Analyses of lipid profiles revealed that the lipidome was differentially affected among the different brain areas in the LPS-induced septic brain. Following the injection of LPS, more lipid categories were impacted in the cerebral cortex. And glycerophospholipids contributed to a large proportion of those significantly modified lipids in the nucleus accumbens (NAc) and hippocampus. Furthermore, the length and unsaturation of fatty acids were also differentially affected in the LPS-induced septic brain. After being treated with minocycline, the dysregulated lipidomic profiles can be partially reversed, demonstrating the critical roles of dysregulated lipidome in sepsis-associated encephalopathy. Collectively, our results show that sepsis-associated encephalopathy differentially reprograms the lipidomic metabolism among the brain areas, which may underlie its cognitive deficits.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"234 ","pages":"Article 111655"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145630036","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":"Alternations of gray matter lateralization and structural covariation in the children with developmental dyslexia and isolated spelling deficit","authors":"Huanhuan Liu ,&nbsp;Qian Shen ,&nbsp;Xiaodong He ,&nbsp;Jiaxin Ding ,&nbsp;Bing Xiong ,&nbsp;Feng Li","doi":"10.1016/j.brainresbull.2026.111718","DOIUrl":"10.1016/j.brainresbull.2026.111718","url":null,"abstract":"<div><h3>Background</h3><div>Spelling components in developmental dyslexia (DD) have been marginally reported, and there has been controversy over to what extent reading and spelling deficits share a common neuroanatomical mechanism. This study aims to explore the pattern of gray matter alteration in children with dyslexia and isolated spelling disorders (SpD).</div></div><div><h3>Method</h3><div>This study included 22 children with typically developing (TD), 20 children with DD, and 16 children with SpD. Voxel-based lateralization analysis was performed to calculate lateralization index (LI) and investigate the structural asymmetry of gray matter. Furthermore, the structural covariance network (SCN) was utilized to describe the changes of structural covariation network in the brain regions of interest among the DD, SpD and TD groups.</div></div><div><h3>Result</h3><div>The results demonstrated that compared with the TD group, the lateralization patterns of the middle frontal gyrus (MFG) and superior frontal gyrus (SFG) in the DD and SpD groups were changed. Additionally, SCN results revealed that compared with the TD group, the structural covariation of the left MFG to the Frontal_Mid_L, Occipital_Sup_R, Lingual_R, Precuneus_L and Cuneus_R were weakened in the DD group. The structural covariation between the left SFG and the Occipital_Mid_L and Occipital_Sup_L was enhanced. In contrast, the structural covariance between the left SFG and the Cuneus_R, Cingulum_Ant_R, Precuneus_L, and Precentral_L was weakened. In addition, the structural covariation of left MFG with the Supp_Motor_Area_R was increased and the structural covariation with Temporal_Sup_L was decreased in the SpD group. The structural covariation between left SFG and bilateral postcentral gyrus was increased, while that between left SFG and Parietal_Sup_L was decreased.</div></div><div><h3>Conclusion</h3><div>This study displayed lateralization patterns of gray matter in children with DD and SpD, and proved that both types of dysfunctions have shared and distinct neural signatures.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"234 ","pages":"Article 111718"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145920918","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":"Resting-state fMRI reveals cerebellar-temporal lobe network remodeling in hyperlipidemia: A graph theoretical analysis","authors":"Jian-Hui He ,&nbsp;Jia-Jia Wu ,&nbsp;Ling-Ling Li ,&nbsp;Shuang He ,&nbsp;Xin Xue ,&nbsp;Jie Ma ,&nbsp;Mou-Xiong Zheng ,&nbsp;Yu-Xin Zheng ,&nbsp;Jian-Guang Xu","doi":"10.1016/j.brainresbull.2025.111697","DOIUrl":"10.1016/j.brainresbull.2025.111697","url":null,"abstract":"<div><div>Hyperlipidemia (HLP) is a major risk factor for cardiovascular diseases and has a significant impact on the nervous system, potentially leading to cognitive decline. This study uses resting-state functional magnetic resonance imaging (fMRI) to analyze the brain network characteristics of HLP patients and explore their relationship with cognitive performance.This study collected fMRI data from 50 patients with HLP and 54 healthy controls. Graph theory analysis was employed to examine differences in brain functional networks between the two groups. Compared with the healthy control group, the HLP group did not exhibit abnormal global properties at the whole-brain level (all <em>P</em> &gt; 0.05). At the nodal level, patients showed abnormal local network topology, characterized by decreased local efficiency, degree centrality, and clustering coefficient in several brain regions, while increased local efficiency, nodal efficiency, degree centrality (<em>P</em> &lt; 0.05), and clustering coefficient were observed in multiple nodes located in the cerebellum (<em>P</em> &lt; 0.05). Patients with hyperlipidemia demonstrate cognitive decline and aberrant activity in several brain regions, most prominently in areas essential for cognition and memory, such as the cerebellum, temporal lobe, and basal ganglia. These findings enhance understanding of brain function in hyperlipidemia and offer a novel framework for exploring disease progression.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"234 ","pages":"Article 111697"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145803120","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":"The functional connectivity status of DMN and its anti-correlated networks across cognitive loads in clinical high risk for psychosis","authors":"Ling Quan ,&nbsp;Xiaoying Sun ,&nbsp;Chuan He ,&nbsp;Xiao Guo ,&nbsp;Ting Ye ,&nbsp;Hanxi Wu ,&nbsp;Gujing Li ,&nbsp;Maria Luisa Bringas-Vega ,&nbsp;Sisi Jiang ,&nbsp;Dezhong Yao ,&nbsp;Cheng Luo","doi":"10.1016/j.brainresbull.2025.111709","DOIUrl":"10.1016/j.brainresbull.2025.111709","url":null,"abstract":"<div><div>The abnormal functional integration of DMN was widely observed in the psychosis. However, few studies focused on DMN in individuals at Clinical High Risk for Psychosis (CHR), especially under different cognitive loads. The present research predominantly focused on DMN and its antagonism with other networks using the functional MRI. To characterize the specificity of cognitive load-dependent antagonism between DMN and its anti-correlated networks in CHR, this study simulated a graded cognitive load continuum by implementing resting-state fMRI (Minimal cognitive load), passive SSVEP task (low cognitive load), and Emotional Face-Matching Task (high cognitive load). There were 36 CHR individuals and 39 healthy controls (HC) enrolled. Static and dynamic functional connectivity (sFC and dFC) were analyzed. The CHR subjects exhibited significantly reduced antagonism between higher-order cortices and DMN under low cognitive condition. Conversely, they demonstrated enhanced antagonism with greater fluctuation under high cognitive condition, likely a compensatory mechanism to maintain cognitive performance. Concurrently, the primary cortex demonstrated compensatory fluctuations during low cognitive load task. The neural signature reflects inefficient neural resource allocation and cognitive flexibility deficits, suggesting that dynamic brain network indicators based on cognitive load may become sensitive biomarkers for the early identification and intervention of CHR.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"234 ","pages":"Article 111709"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145848822","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}