Brain Research Bulletin最新文献

{"title":"Mapping structural disconnection and transcriptomic signatures in Alzheimer’s disease with MIND networks","authors":"Yongsheng Wu ,&nbsp;Hao Zhang ,&nbsp;Junyu Qu ,&nbsp;Rui Zhu ,&nbsp;Guihua Xu ,&nbsp;Wenwen Xu ,&nbsp;Guizhen Yan ,&nbsp;Jianhong Yang ,&nbsp;Jiaxiang Xin ,&nbsp;Yi Li ,&nbsp;Dawei Wang ,&nbsp;for Alzheimer’s Disease Neuroimaging Initiative","doi":"10.1016/j.brainresbull.2026.111737","DOIUrl":"10.1016/j.brainresbull.2026.111737","url":null,"abstract":"<div><h3>Background</h3><div>Alzheimer’s disease (AD) is increasingly conceptualized as a disconnection syndrome involving widespread alterations in large-scale brain networks. Previous studies using morphometric similarity networks (MSNs) have revealed broad structural and transcriptomic changes, yet vertex-level structural disconnection and its molecular basis remain poorly understood. We applied morphometric inverse divergence (MIND), an innovative approach for fine-grained mapping of structural disconnection and its transcriptomic correlates in AD.</div></div><div><h3>Methods</h3><div>Utilizing two independent datasets: [ADNI (219 AD, 219 cognitively normal, CN) and the Qilu dataset (100 AD, 137 CN)], we mapped robust MIND network alterations in AD patients and examined their associations with cognitive performance and biomarker quantifications. Additionally, we linked MIND connectome to spatial gene expression using partial least squares regression, followed by gene enrichment analysis to identify relevant biological pathways. Finally, to validate the clinical utility of MIND, a residual deep neural network (ResDNN) was developed to compare its diagnostic performance against MSNs in distinguishing AD from CN.</div></div><div><h3>Results</h3><div>Significantly decreased MIND degree was identified in the bilateral frontal, lateral occipital, and posterior temporal lobes (P _FDR &lt; 0.05), positively correlating with MMSE score and FDG-PET SUVR (all P &lt; 0.001). Conversely, increased MIND degree was observed in the bilateral cuneus, entorhinal, lingual, and parahippocampal regions (P _FDR &lt; 0.05), negatively correlating with cognition assessment, CSF Aβ-42 levels and FDG-PET SUVR (all P &lt; 0.001). These AD-related MIND alterations were spatially correlated with gene expression profiles crucial for synaptic function, neurotransmission, and metabolic regulation. Importantly, MIND achieved superior diagnostic efficacy (AUC=0.90/0.88 in ADNI/Qilu) over MSNs.</div></div><div><h3>Conclusions</h3><div>We mapped a robust pattern of structural disconnection in Alzheimer's disease with MIND approach and associate it with particular transcriptomic signatures. These findings not only improve our mechanistic understanding of AD as a disconnection syndrome but also demonstrate MIND as a sensitive tool for identifying disease-specific alterations, holding promise for future mechanistic and clinical investigations into AD pathology.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"235 ","pages":"Article 111737"},"PeriodicalIF":3.7,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145997323","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":"Cell-type-specific reorganization of VGSCs in auditory cortex and therapeutic potential of Nav1.6 blockade for tinnitus","authors":"Miao Zhao ,&nbsp;Shichu Sun ,&nbsp;Shiqi Jing ,&nbsp;Zifei Ma ,&nbsp;Zihan Zhang ,&nbsp;Yonghua Ji ,&nbsp;Chenchen Xia ,&nbsp;You Zhou","doi":"10.1016/j.brainresbull.2026.111733","DOIUrl":"10.1016/j.brainresbull.2026.111733","url":null,"abstract":"<div><div>Neuronal hyperexcitability resulting from an inhibitory-excitatory imbalance in the primary auditory cortex (A1) is a key pathological feature of tinnitus. Voltage-gated sodium channels (VGSCs) are crucial in regulating neuronal excitability by facilitating action potential generation and propagation. However, the specific involvement of VGSC subtypes in tinnitus-related hyperexcitability within the A1 cortex remains poorly understood. Previous studies have shown that acute and chronic salicylate administration can induce stable tinnitus in rats. In this study, we investigated the distribution and expression profiles of four VGSC subtypes (Nav1.1, Nav1.2, Nav1.3, and Nav1.6) in the A1 cortex of rats following systemic salicylate administration. Immunohistochemical staining and quantitative PCR analyses revealed dynamic and subtype-specific changes in VGSC expression. Notably, while the expression of Nav1.1 and Nav1.2 was significantly reduced in GAD67-immunoreactive GABAergic neurons, both Nav1.3 and Nav1.6 showed substantial upregulation, particularly in VGLUT2-immunoreactive glutamatergic neurons in the A1 cortex. Among these, Nav1.6 exhibited the most pronounced changes, suggesting it could be a key player in the altered excitatory-inhibitory balance observed in tinnitus. Furthermore, Nav1.6 knockout mice displayed reduced central gain enhancement following salicylate administration, further implicating Nav1.6 in tinnitus pathology. Treatment with NBI-921352, a selective Nav1.6 inhibitor, alleviated tinnitus-like behaviors induced by both acute and chronic salicylate treatments, concomitant with a suppression of salicylate-induced central gain enhancement. These findings suggest that the bidirectional regulation of VGSC subtypes contributes to tinnitus-associated excitatory-inhibitory imbalances in the A1 cortex, with Nav1.6 representing a promising therapeutic target for tinnitus.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"235 ","pages":"Article 111733"},"PeriodicalIF":3.7,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145975647","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":"MAF1 loss protects against ischemic cerebral injury by attenuating NLRP3-mediated pyroptosis","authors":"Xue Gao,&nbsp;Hanzhi Wang,&nbsp;Lingting Jin,&nbsp;Shumeng Li,&nbsp;Gang Li,&nbsp;Can Cui,&nbsp;Yingying Han","doi":"10.1016/j.brainresbull.2026.111732","DOIUrl":"10.1016/j.brainresbull.2026.111732","url":null,"abstract":"<div><h3>Background</h3><div>Acute ischemic stroke (AIS) is the second leading cause of death worldwide and is associated with high rates of disability and mortality. Emerging evidence indicates that the transcriptional regulator MAF1 may play an important role in neurological diseases by modulating the NLRP3 signaling pathway. Previous studies suggest the transcriptional regulator MAF1 may play an important role in neurological diseases through regulating NLRP3 pathway. However, its role in ischemic cerebral injury remains unclear. This study aims to reveal the key role and mechanisms of MAF1 in AIS.</div></div><div><h3>Methods</h3><div>Using transient middle cerebral artery occlusion (tMCAO) model, the sensorimotor function of mice after modeling was evaluated by behavioral methods and changes of MAF1 expression were investigated by Polymerase Chain Reaction (PCR), Western blot and Immunofluorescence (IF) staining. The oxygen glucose deprivation/reperfusion (OGD/R) model was used as cell model for in vitro verification. Stereotactic injection of AAV-hsyn-shMAF1 was used to assess the effect of MAF1 knockdown on the improvement of neurological function and infarct volume in stroke mice. RNA sequencing was performed to identify differentially expressed genes between OGD/R-Lenti-shMAF1 and OGD/R-Lenti-SCR groups. Western blot analysis was further applied to examine molecular alterations in the downstream NLRP3 pathway.</div></div><div><h3>Results</h3><div>Expression of the transcription factor MAF1 was upregulated in AIS and conditional Conditional knockdown of MAF1 in the tMCAO mouse model alleviated neurological deficits and reduced infarct volume. RNA sequencing revealed altered expression of NLRP3-related pyroptosis proteins and pathways following MAF1 knockdown in OGD/R-treated primary neurons. Downregulation of MAF1 led to expression changes of NLRP3 inflammasome/pyroptosis pathways in both tMCAO mouse and OGD/R cell models.</div></div><div><h3>Conclusions</h3><div>MAF1 expression was significantly increased in animal and cellular models of AIS. Knockdown of MAF1 improved neurological function after AIS and the protective effect is related to the regulation of the NLRP3 inflammasome/pyroptosis pathway. These findings elucidated a critical role and mechanistic insight for MAF1 in AIS pathogenesis, highlighting its potential as a therapeutic target for ischemic stroke treatment.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"235 ","pages":"Article 111732"},"PeriodicalIF":3.7,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145975644","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":"Suppression of the PI3K/AKT/mTOR signaling pathway by PDYN alleviates sepsis-associated encephalopathy in mice","authors":"Ao Li ,&nbsp;Shujuan Qu ,&nbsp;Shengfeng Wang ,&nbsp;Qiong Guo ,&nbsp;Sinian Tan ,&nbsp;Mao Peng ,&nbsp;Lin Liu","doi":"10.1016/j.brainresbull.2026.111734","DOIUrl":"10.1016/j.brainresbull.2026.111734","url":null,"abstract":"<div><h3>Background</h3><div>Microglial pyroptosis-mediated neuroinflammation is a key pathogenic mechanism in Sepsis-Associated Encephalopathy (SAE). However, the role of prodynorphin (PDYN) in SAE and the relationship between PDYN and microglial pyroptosis remain unknown.</div></div><div><h3>Methods</h3><div>Mice were subjected to cecal ligation and puncture (CLP) or sham surgery. Microglial cells were treated with lipopolysaccharide (LPS) <em>in vitro</em>. Cognitive function was assessed using the Morris water maze, novel object recognition, and open field tests. Transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) staining was used to observe glial apoptosis; Nissl staining was used to observe microglial infiltration; H&amp;E staining was used to detect histopathological changes. Pyroptosis and the expression levels of relevant signaling molecules were assessed by Western blot analysis.</div></div><div><h3>Results</h3><div>PDYN protected against neuronal damage and cognitive impairment in septic mice. PDYN inhibits microglial pyroptosis and secretion of inflammatory cytokines <em>in vivo</em> and <em>in vitro</em>. Further examination revealed that PDYN inhibits microglial pyroptosis by inhibiting the PI3K/AKT/mTORC pathway. Moreover, the PI3K activator 740Y-P promoted microglial pyroptosis by activating the PI3K/AKT/mTORC pathway.</div></div><div><h3>Conclusion</h3><div>This study reveals, for the first time, that PDYN exerts neuroprotective effects in SAE by suppressing microglial pyroptosis through inhibition of the PI3K/AKT/mTOR signaling pathway. These findings identify PDYN and the PI3K/AKT/mTOR-pyroptosis axis as novel therapeutic targets for SAE, providing a mechanistic foundation for developing adjunctive neuroprotective strategies alongside standard sepsis care.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"235 ","pages":"Article 111734"},"PeriodicalIF":3.7,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145975645","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":"Alkaloids and flavonoids of Solanaceae: Mechanisms of action in neurodegenerative diseases","authors":"Qiushi Yin ,&nbsp;Mingzhen Hu ,&nbsp;Wei Li ,&nbsp;Peng Cheng ,&nbsp;Yuqing Liu ,&nbsp;Long Liu ,&nbsp;Lin Chen ,&nbsp;Qin Ru ,&nbsp;Yuxiang Wu","doi":"10.1016/j.brainresbull.2026.111716","DOIUrl":"10.1016/j.brainresbull.2026.111716","url":null,"abstract":"<div><div>Neurodegenerative diseases (e.g., Alzheimer's disease [AD], Parkinson's disease [PD], Huntington's disease [HD]) pose a serious threat to human health. Current therapeutic approaches have limitations such as significant side effects and limited efficacy, making natural plant active ingredients an emerging research focus in this field. Solanaceae plants are widely distributed worldwide, rich in secondary metabolites such as alkaloids and flavonoids, and have long been used in traditional medicine. This review systematically summarizes the structural characteristics of Solanaceae-derived alkaloids (e.g., nicotine[NI], atropine[ATP], scopolamine[SCO]) and flavonoids (e.g., quercetin[QR], luteolin[LUT], kaempferol[KAE], anthocyanidin[ACN]), as well as their therapeutic potential and core mechanisms of action against the three major neurodegenerative diseases — including multi-target regulatory pathways such as antioxidative stress, inhibiting neuroinflammation, regulating neurotransmitter balance, preventing abnormal protein aggregation, and suppressing neuronal apoptosis. Additionally, this review analyzes the challenges faced by these natural products in extraction and purification, bioavailability, target selectivity, and clinical translation, and prospects the potential of promoting their clinical application through technological breakthroughs such as synthetic biology and nanodelivery systems. This review indicates that Solanaceae-derived secondary metabolites provide an important resource for the development of safe and effective therapeutic drugs for neurodegenerative diseases, with broad application value.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"235 ","pages":"Article 111716"},"PeriodicalIF":3.7,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145976335","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":"Purα overexpression mitigates neonatal hypoxic-ischemic brain damage by inhibiting neuronal pyroptosis via the P2X7R/NLRP3/Caspase-1 pathway","authors":"Da Zheng ,&nbsp;Hui Zhang ,&nbsp;Yi-Kai Zou ,&nbsp;Jiao-Yang Yang ,&nbsp;Shu-Yi He ,&nbsp;Hai-Jing Peng ,&nbsp;Jian-Xia Liu ,&nbsp;Shao-Hua Qi ,&nbsp;Jia-Wei Min","doi":"10.1016/j.brainresbull.2026.111726","DOIUrl":"10.1016/j.brainresbull.2026.111726","url":null,"abstract":"<div><div>Hypoxic-ischemic brain damage (HIBD) is a common neonatal disorder that often leads to permanent neurological sequelae. Neuronal pyroptosis, a pro-inflammatory form of programmed cell death, has been increasingly recognized as a key contributor to neuronal damage and subsequent neurological deficits in HIBD. However, effective therapeutic strategies for HIBD remain limited, highlighting the urgent need to identify novel therapeutic targets. Purine-rich element-binding protein α (Purα) is a multifunctional DNA/RNA-binding protein involved in gene transcription and nervous system regulation. However, its role in neonatal HIBD has not been defined. Here, we investigated the neuroprotective effects of Purα in both <em>in vivo</em> and <em>in vitro</em> models of HIBD. We found that endogenous Purα protein levels were markedly reduced in brain tissue from HI-challenged neonatal mice and in primary cortical neurons subjected to oxygen-glucose deprivation/reoxygenation (OGD/R). Purα overexpression effectively reduced cerebral infarction, alleviated neuronal injury, attenuated brain atrophy, and improved neurological outcomes in neonatal HIBD mice. In cultured neurons, Purα overexpression significantly increased cell viability and reduced cell death following OGD/R. RNA sequencing identified purinergic 2X7 receptor (P2X7R) as a potential downstream target of Purα, consistent with P2X7R’s established role in pyroptosis regulation. Mechanistic studies further demonstrated that Purα overexpression suppressed P2X7R expression and inhibited activation of the NLRP3/Caspase-1 pathway, as indicated by reduced levels of P2X7R, NLRP3, Caspase-1, cleaved Caspase-1, GSDMD-N, and IL-1β. Collectively, these findings reveal a novel role for Purα in mitigating neuronal pyroptosis via regulation of the P2X7R/NLRP3/Caspase-1 pathway and support Purα as a promising therapeutic target for neonatal HIBD.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"235 ","pages":"Article 111726"},"PeriodicalIF":3.7,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145976336","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":"TCF7L2 transcriptionally regulates C1QB to exacerbate synaptic pruning-dependent neuronal injury in the epileptic hippocampus","authors":"Lulu Wu ,&nbsp;Yuping Huang ,&nbsp;Xinyu Wang ,&nbsp;Ting Tian ,&nbsp;Dandan Feng ,&nbsp;Guoping Zhou","doi":"10.1016/j.brainresbull.2026.111730","DOIUrl":"10.1016/j.brainresbull.2026.111730","url":null,"abstract":"<div><div>Epilepsy represents one of the most prevalent and debilitating chronic neurological disorders. While the complement component 1q subcomponent B (C1QB) has been implicated in synaptic pruning and is associated with various neurological diseases, including epilepsy, the transcriptional regulatory mechanisms of the <em>C1QB</em> gene in epilepsy remain poorly understood. Here, we identified transcription factor 7-like 2 (<em>TCF7L2</em>) as a novel upstream transcriptional regulator of <em>C1QB</em> gene. Chromatin immunoprecipitation (ChIP) and luciferase reporter assays confirmed the direct binding of <em>TCF7L2</em> to the <em>C1QB</em> promoter region and its positive regulatory effect on <em>C1QB</em> expression in vitro. Using a kainic acid-induced epilepsy model in male C57BL/6 mice, we demonstrated a significant upregulation of both <em>Tcf7l2</em> and <em>C1qb</em> in the hippocampal region, which was accompanied by microglial activation and neuronal damage. Notably, the lentivirus-mediated specific knockdown of <em>Tcf7l2</em> effectively reversed the overexpression of <em>C1qb</em>, attenuated microglial activation, and ameliorated neuronal injury in epileptic mice. Our study establishes the <em>TCF7L2-C1QB</em> regulatory axis and demonstrates its pathogenic role in epilepsy, suggesting that targeting this pathway may offer a novel therapeutic strategy for epilepsy treatment.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"235 ","pages":"Article 111730"},"PeriodicalIF":3.7,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145975646","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":"Altered brain dynamic in cirrhotic patients without overt hepatic encephalopathy: State and trait features","authors":"Chao Ju ,&nbsp;Longtao Yang ,&nbsp;Zhongshang Dai ,&nbsp;Yisong Wang ,&nbsp;Yingxia Zhou ,&nbsp;Jun Liu","doi":"10.1016/j.brainresbull.2026.111724","DOIUrl":"10.1016/j.brainresbull.2026.111724","url":null,"abstract":"<div><div>Neurocognitive impairment, a prevalent complication in cirrhosis, correlates with disruptions in static functional connectivity(FC) of the brain. This study aims to explore altered spatiotemporal properties of blood oxygen-level dependent(BOLD) signals and elucidate their association with neurocognitive changes in cirrhotic patients. Between March 2023 and February 2025, we recruited 77 cirrhotic patients and 66 healthy controls(HCs) accompanied by resting-state functional magnetic resonance imaging(rs-fMRI) acquisition. Neurocognitive function was evaluated by psychometric hepatic encephalopathy score(PHES). The hidden Markov model(HMM) was used to explain variations in rs-fMRI averaged functional activity(AFA) and FC across the whole-brain by using a set of 5 unique recurring states. This study assessed the stability between different groups by comparing the time spent in each state and the mean duration of visits to each state. Mann<img>Whitney U tests, Kruskal Wallis H test, chi-squared test, correlation analysis. After Bonferroni correction, cirrhotic patients with minimal hepatic encephalopathy(MHE) showed significantly higher temporal stability and proportional time spent in state#1 characterized by lower AFA of frontoparietal network(FPN) and subcortical network and higher AFA of visual network (VN), as well as have lower fractional occupancy(FO) and averaged lifetime(ALT) in state#5, which is characterized by weaker within-network FC and lower AFA of limbic network(LN), salience network(SN), somatosensory motor network(SMN), and default mode network(DMN). We observed a significant positive correlation(Bonferroni corrected) between dynamic properties in state#5 and PHES performance. These findings suggest that disrupted brain functional synchrony across time is present in MHE and is linked to cognitive impairment.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"235 ","pages":"Article 111724"},"PeriodicalIF":3.7,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145951553","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":"Functional connectivity-based searchlight multivariate pattern analysis for discriminating Parkinson’s disease patients and predicting clinical variables","authors":"Jingjing Xu ,&nbsp;Sijia Tan ,&nbsp;Jiaqi Wen,&nbsp;Weijin Yuan,&nbsp;Minming Zhang,&nbsp;Xiaojun Xu","doi":"10.1016/j.brainresbull.2026.111723","DOIUrl":"10.1016/j.brainresbull.2026.111723","url":null,"abstract":"<div><h3>Objectives</h3><div>Disruptions in brain functional connectivity (FC) have been verified to be one of the characteristics of Parkinson’s disease (PD) and PD patients with mild cognitive impairment (MCI). This study aims to differentiate PD patients from healthy controls (HCs), distinguish PD-MCI from PD patients with normal cognition (PD-NC), and evaluate the extent to which connectivity-based searchlight multivariate pattern analysis (CBS-MVPA) could provide predictive information on clinical severity.</div></div><div><h3>Methods</h3><div>A cohort of 261 participants from the Parkinson’s Progression Markers Initiative (PPMI) was included (98 PD-MCI patients, 98 PD-NC patients, and 65 HCs). Resting-state functional magnetic resonance imaging was used to examine whole-brain FC subnetworks. CBS-MVPA, a novel unbiased whole-brain analysis capable of capturing distributed predictive signals, was applied to identify subnetworks that contributed to group discrimination, and to assess their predictive effects on clinical measures.</div></div><div><h3>Result</h3><div>CBS-MVPA identified 20 FC subnetworks that reliably differentiated PD patients from HCs. Classification accuracy was moderate for PD vs HC (71.25 % to 75.48 %) and modest for PD-MCI vs PD-NC (57.21 % to 62.74 %). Specifically, four subnetworks centered on the posterior cingulate cortex, hippocampus, pallidum, and central postcentral gyrus showed modest predictive value for motor severity (MDS-UPDRS I-III scores). Additional subnetworks involving the paracentral lobule, lingual gyrus, and medial orbital superior frontal gyrus showed modest associations with cognitive performance. It should be noted, however, that this accuracy is only modestly above chance level, reflecting the complexity and heterogeneity of PD.</div></div><div><h3>Conclusion</h3><div>This study introduces a novel approach for identifying distributed FC subnetworks patterns relevant to PD and PD-MCI. While predictive performance was modest, the detected subnetworks nonetheless contained measurable predictive signals related to both diagnostic status and clinical severity, highlighting the potential utility of whole-brain multivariate FC analyses for future mechanistic research and therapeutic interventions in PD.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"235 ","pages":"Article 111723"},"PeriodicalIF":3.7,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145948024","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 role of optic flow on reactive brain processing in cognitive tasks during locomotion","authors":"BiancaMaria Di Bello ,&nbsp;Natalie Ferrulli ,&nbsp;Camilla Panacci ,&nbsp;Margherita Filosa ,&nbsp;Sabrina Pitzalis ,&nbsp;Francesco Di Russo","doi":"10.1016/j.brainresbull.2026.111722","DOIUrl":"10.1016/j.brainresbull.2026.111722","url":null,"abstract":"<div><div>Perception and action share neural resources that must be flexibly allocated across simultaneous tasks. In this context, the optic flow provides key visual input during locomotion and may interact with concurrent cognitive processing. This study aimed to: 1) examine how walking modulates event-related potential (ERP) components linked to visual, attentional, and sensorimotor processes evoked by a concomitant cognitive task; 2) relate neural changes to behavior; 3) test whether optic flow modifies these locomotion effects; and 4) extend previous findings on anticipatory brain processing to post-stimulus activity. To these aims, forty participants performed a visual discrimination task under four conditions that manipulated locomotion (walking vs. standing) and visual stimulation (with vs. without optic flow). Behavioral measures (response time (RT), accuracy, RT variability) and ERP components indexing distinct brain processing stages were recorded. Behaviorally, walking improved performance by increasing accuracy and reducing RT variability, while optic flow reduced accuracy without affecting RT. At the brain level, walking decreased the prefrontal N1 (pN1), indicating lower visual awareness, but increased the N1 (enhanced visual attention). Walking with the optic flow also increased the prefrontal P1 (pP1), indicating greater sensorimotor awareness. The presence of the optic flow independently reduced P1 (associated with early visual processing) and increased the pN1 and the N1. The P3 varied only with stimulus type, indicating no walking or optic flow effects on post-perceptual evaluation. Overall, walking facilitated early cognitive processing, whereas the optic flow added sensory-attentional load, reducing accuracy via competition for visual resources. These results support multiple-resource allocation dual-task theories, highlighting how ecological multisensory environments may dynamically reallocate cognitive resources and shape neural processing during action. In addition, present data can be used to design immersive environments, motor-cognitive dual-task training, and real-world cognition studies.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"235 ","pages":"Article 111722"},"PeriodicalIF":3.7,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145948648","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}