Frontiers in Neuroscience最新文献

{"title":"BTP2, a store-operated calcium channel inhibitor, attenuates morphine antinociceptive tolerance in rats.","authors":"Weibo Xiao, Feng Xiao, Yingying Zhang, Lei Zeng","doi":"10.3389/fnins.2026.1758352","DOIUrl":"https://doi.org/10.3389/fnins.2026.1758352","url":null,"abstract":"<p><strong>Introduction: </strong>Morphine antinociceptive tolerance remains a critical problem in the clinical management of pain. Spinal cord glial cell activation and neuroinflammation appear to play a crucial role in the development and maintenance of this tolerance. BTP2, a potent store-operated calcium channel inhibitor, has anti-inflammatory properties in the central nervous system. This study aimed to investigate the effect of BTP2 on the development of morphine antinociceptive tolerance and glial cell-derived pro-inflammatory cytokines production by chronic morphine treatment.</p><p><strong>Methods: </strong>A rat model of morphine antinociceptive tolerance was made by intrathecal injection of morphine (15 μg/d). Two separate studies were conducted: Firstly, to investigate whether BTP2 could attenuate the development of tolerance, BTP2 (2 and 10 nmol) was given intrathecally 30 min before each intrathecal delivery of morphine for consecutive 7 days. Secondly, to investigate whether BTP2 could reverse the established tolerance, BTP2 administration was initiated on day 8 after 7 days of morphine treatment and continued for 4 days.</p><p><strong>Results: </strong>The results showed that BTP2 not only attenuated the development of morphine tolerance but also partially reversed the established tolerance. Immunohistochemistry revealed that chronic morphine-induced activation of astrocytes in the spinal cord, while BTP2 was shown to suppress the activation of astrocytes. Moreover, the administration of BTP2 alleviated the activation of astrocytic ERK and the production of proinflammatory cytokines (e.g., TNF-α and Il-1β) in the spinal cord.</p><p><strong>Discussion: </strong>These findings suggest that BTP2 can be a potential therapeutic drug for morphine antinociceptive tolerance, and the store-operated calcium channel may play an important role in morphine antinociceptive tolerance.</p>","PeriodicalId":12639,"journal":{"name":"Frontiers in Neuroscience","volume":"20 ","pages":"1758352"},"PeriodicalIF":3.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13079626/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147698387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Short-term amblyopic eye deprivation boosts the binocular intermodulation in anisometropic amblyopia.","authors":"Siyuan Deng, Fang Li, Wenbin Huang","doi":"10.3389/fnins.2026.1780127","DOIUrl":"https://doi.org/10.3389/fnins.2026.1780127","url":null,"abstract":"<p><strong>Purpose: </strong>We tested whether short-term monocular deprivation (STMD) of the amblyopic eye enhances binocular intermodulation steady-state visual evoked potentials (SSVEPs), reflecting reduced suppression from the fellow eye.</p><p><strong>Methods: </strong>Fifteen anisometropic amblyopes (15.6 ± 5.8 years) underwent 2-h STMD of their fellow eye on the first day, followed by a similar session on their amblyopic eye on the second day. We recorded SSVEPs from 21 occipital electrodes pre/post STMD during binocular rivalry (6/7.5 Hz flicker).</p><p><strong>Results: </strong>Similar to the previous study, the monocular SSVEP amplitude of the deprived eye increased after STMD, whereas that of the non-deprived eye remained unchanged. Critically, STMD of the amblyopic eye significantly increased f<i>1</i>+f<i>2</i> intermodulation amplitude (<i>t</i> = 2.42, pFDR = 0.030), while STMD of the fellow eye showed no such effect (<i>p</i> > 0.05). Baseline f<i>1</i>+f<i>2</i> amplitude was strongly correlated with the magnitude of SSVEP change following STMD (<i>r</i> = 0.789, <i>p</i> < 0.001).</p><p><strong>Conclusion: </strong>STMD of the amblyopic eye, but not the fellow eye, significantly enhanced binocular SSVEP intermodulation. Baseline f1+f2 amplitude predicted the magnitude of plasticity, suggesting its potential as an electrophysiological biomarker for reverse deprivation therapy.</p>","PeriodicalId":12639,"journal":{"name":"Frontiers in Neuroscience","volume":"20 ","pages":"1780127"},"PeriodicalIF":3.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13081743/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147698370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic potential of neuroprotective plant extracts in Parkinson's disease.","authors":"Shifang Luo, Linao Zhang, Xue Wu, Jiying Wang, Qing Li, Wentao Chen, Rongyu Li, Lingli Zhou, Na Zhou, Rong Chen, Yuhuan Xie, Peixin Guo","doi":"10.3389/fnins.2026.1813133","DOIUrl":"https://doi.org/10.3389/fnins.2026.1813133","url":null,"abstract":"<p><strong>Objective: </strong>This review aims to summarize the application and mechanisms of plant extracts with neuroprotective effects in Parkinson's disease (PD), emphasizing their therapeutic potential in PD management.</p><p><strong>Background: </strong>Parkinson's disease is a widespread neurodegenerative disorder, predominantly affecting middle-aged and elderly populations. Characterized by varied etiologies, clinical presentations, and complex pathogenesis, its hallmark symptoms include tremor and bradykinesia. Despite the availability of limited pharmacological treatments, current approaches primarily focus on symptom management rather than modifying disease progression. Recent research have increasingly investigates the use of neuroprotective plant extracts, which have shown demonstrating promising therapeutic effects, garnering significant attention in the field.</p><p><strong>Methods: </strong>A systematic review was conducted on preclinical and clinical studies published from 2000 to 2025, sourced from PubMed, ScienceDirect, Google Scholar, and China National Knowledge Infrastructure (CNKI), to evaluate the effects of neuroprotective plant extracts in PD treatment.</p><p><strong>Results: </strong>The review reveals that plant extracts with neuroprotective properties exert anti-PD effects through mechanisms including antioxidant and anti-inflammatory actions, inhibition of α-synuclein (α-syn) aggregation, enhancement of dopaminergic neuron survival, and restoration of synaptic function.</p><p><strong>Conclusion: </strong>This review outlines research directions for the development of neuroprotective plant extracts as novel PD therapies, suggesting their potential as complementary treatments alongside conventional pharmacological interventions.</p>","PeriodicalId":12639,"journal":{"name":"Frontiers in Neuroscience","volume":"20 ","pages":"1813133"},"PeriodicalIF":3.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13079682/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147698417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Moxa-combustion byproducts improve cognitive function via olfactory-mediated modulation of the GSK-3β/CREB pathway.","authors":"Jia-Wei Wu, Ya-Jie Liu, Jing He, Yu-Qing Shi, Bai-Xiao Zhao","doi":"10.3389/fnins.2026.1759500","DOIUrl":"https://doi.org/10.3389/fnins.2026.1759500","url":null,"abstract":"<p><strong>Objective: </strong>Olfactory dysfunction in early-stage Alzheimer's disease (AD) is associated with GSK-3β abnormalities localized in the olfactory bulb. These pathological changes not only compromise hippocampus-dependent learning and memory via synaptic impairments but also contribute to emotional disturbances such as anxiety and depression. Given that moxa-combustion byproducts (MCB), a key therapeutic component of moxibustion, enhance synaptic plasticity and improve cognition, this study aimed to investigate whether MCB ameliorates cognitive deficits by olfactory-mediated modulation of the GSK-3β/CREB pathway.</p><p><strong>Methods: </strong>Four-month-old APP/PS1 mice received 12-week MCB interventions. Behavioral assessments (Morris water maze, buried food pellet test and open field test) evaluated olfactory and cognitive functions. Pathological changes and synaptic structure in olfactory bulbs and hippocampus were analyzed via hematoxylin-eosin (HE) staining and transmission electron microscopy (TEM). Protein levels of GSK3β, CREB, and c-Fos were quantified by Western blot (WB).</p><p><strong>Results: </strong>MCB significantly improved spatial learning, memory, and olfactory performance in AD mice. HE staining showed that MCB increased the number of olfactory mitral cells and hippocampal CA1 neurons, and could regulate synaptic plasticity. MCB downregulated GSK-3β while upregulating CREB and c-Fos in both olfactory bulb and hippocampal tissues. The effect of MCB disappeared after olfactory blockade using 3-methylindole, suggesting olfactory-mediated action.</p><p><strong>Conclusion: </strong>MCB enhances cognitive-olfactory functions and mitigates anxiety- and depression-like behaviors in AD mice, potentially via modulation of GSK-3β/CREB pathway-related proteins in the olfactory system.</p>","PeriodicalId":12639,"journal":{"name":"Frontiers in Neuroscience","volume":"20 ","pages":"1759500"},"PeriodicalIF":3.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13079272/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147698410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Facial micro-movements as a proxy of increasingly erratic heart rate variability while experiencing pressure pain.","authors":"Elizabeth B Torres, Mona Elsayed","doi":"10.3389/fnins.2026.1702124","DOIUrl":"https://doi.org/10.3389/fnins.2026.1702124","url":null,"abstract":"<p><strong>Introduction: </strong>The sensation of pain varies from person to person. These patterns of individual variation are difficult to capture using coarse subjective self-reports. However, they are important when prescribing therapies and tailoring them to each person's own sensations. Pain can be experienced differently by the same person and can fluctuate based on context; yet, most analyses treat the problem with a one-size-fits-all model.</p><p><strong>Methods: </strong>In this work, we introduce a series of assays to assess pressure pain across tasks with different motoric and cognitive demands, in relation to a resting state. In a cohort of healthy individuals, we examine pain-free <i>vs</i>. pain states at rest, during drawing with heavy cognitive demands, during pointing to a visual target, and during a grooved peg task, such as inserting a grooved key into a matching keyhole. We adopt a standardized data type called micro-movement spikes (MMS) to characterize the biorhythmic activities of facial micro-expressions and the micro-fluctuations in the heart's inter-beat interval timings.</p><p><strong>Results: </strong>Using the MMS peaks, we find that the continuous Gamma family of probability distribution functions best fits the frequency histograms of both the facial and heart data. Furthermore, we find that the Gamma shape and scale parameters in both signals span a scaling power law whereby, as the noise-to-signal ratio (Gamma scale parameter) increases, so does the randomness of the stochastic process. We find that as the heart IBI becomes more erratic (noisier and more random), the facial ophthalmic region also increases in noise and randomness, with higher linear correlation for tasks requiring haptic feedback (<i>R</i> ² 0.84) and lower correlation for tasks requiring greater cognitive and memory loads (<i>R</i> ² 0.77).</p><p><strong>Conclusion: </strong>Increases in transfer entropy show that recent past activity (~167 ms back) of the heart IBI and facial data combined lower the uncertainty in predicting the present ophthalmic facial activity, suggesting that this facial region may serve as a proxy for the increasingly dysregulated heart. These results have implications for the detection and monitoring of pressure pain.</p>","PeriodicalId":12639,"journal":{"name":"Frontiers in Neuroscience","volume":"20 ","pages":"1702124"},"PeriodicalIF":3.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13079607/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147698416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Attenuation of mGluR1/5-dependent synaptic plasticity and ERK pathway dysfunction in the hippocampus of diabetic rats.","authors":"Hayuma Otsuka, Sachie Sasaki-Hamada, Hitoshi Ishibashi, Jun-Ichiro Oka","doi":"10.3389/fnins.2026.1814915","DOIUrl":"https://doi.org/10.3389/fnins.2026.1814915","url":null,"abstract":"<p><p>Streptozotocin-induced diabetic rats (STZ rats), an established animal model of type 1 diabetes mellitus, develop cognitive decline, which has been linked to impairments in hippocampal synaptic plasticity. Long-term depression (LTD) in the hippocampus may be induced by the activation of different types of G protein-coupled receptors, particularly metabotropic glutamate receptors (mGluRs) and muscarinic acetylcholine receptors. We previously demonstrated that acetylcholine receptor activation-dependent LTD was impaired in STZ rats, and herein investigated group I mGluR (mGluR1/5)-dependent LTD in the Schaffer collateral-CA1 synapses of STZ rats. Extracellular field recordings revealed that the chemical activation of mGluR1/5 with (S)-3,5-dihydroxyphenylglycine (DHPG, 50 μM, 10 min) induced sustained LTD in both control and STZ rats; however, the magnitude of DHPG-LTD was significantly smaller in STZ rats. Moreover, the paired-pulse ratio between before and 80 min after the application of DHPG increased in both control and STZ rats, and DHPG-LTD was independent of NMDA receptor activation. A Western blot analysis showed that DHPG-induced extracellular signal-regulated kinase (ERK) phosphorylation was reduced in STZ rats, whereas DHPG-induced phosphoinositide-dependent kinase 1 phosphorylation and the expression level of the scaffold protein, Homer1, were unchanged. Collectively, these results suggest that impaired ERK/MAPK signaling affected hippocampal mGluR1/5-dependent LTD in STZ rats, and the dysregulation of ERK may contribute to diabetes-associated cognitive decline because of its crucial role in protein synthesis-dependent synaptic plasticity.</p>","PeriodicalId":12639,"journal":{"name":"Frontiers in Neuroscience","volume":"20 ","pages":"1814915"},"PeriodicalIF":3.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13079662/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147698362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spiking neural networks provide accurate and time-efficient models for whisker stimulus classification of the awake mouse.","authors":"Steffen Albrecht, Jens R Vandevelde, Edoardo Vecchi, Gabriele Berra, Davide Bassetti, Maik C Stüttgen, Heiko J Luhmann, Illia Horenko","doi":"10.3389/fnins.2026.1605209","DOIUrl":"https://doi.org/10.3389/fnins.2026.1605209","url":null,"abstract":"<p><p>Machine learning algorithms have great potential for classifying brain activity, and lightweight classifier algorithms, requiring little computational resources, can be used on low-energy neuromorphic hardware designed for implantable neuroprosthetics. One of these efficient algorithms, the Liquid State Machine, implements the concept of Spiking Neural Networks and has been shown to achieve outstanding results on the task of whisker stimulus detection from the mouse barrel cortex, a widely used model system. While this is promising for neuroprosthetics, it has been unclear how a Spiking Neural Network or other machine learning algorithms perform on data recorded from awake mice and how trained models generalize across individuals, the latter being relevant to transferring trained models to new hardware. Using laminar multi-electrode local field potential recordings obtained from four mice performing a single-whisker detection task, we benchmarked the performance of a collection of lightweight classification algorithms. We found that the Liquid State Machine, a generalized linear model, and the time series classifier ROCKET are the most accurate for stimulus detection. Among those, the Liquid State Machine achieved the fastest model training and inference runtime and provided robust accuracy across individual mice. Additional analyses show that there is no significant improvement in using multiple cortical layers as input for the model and that 40 ms of stimulus recording is sufficient to maintain high detection accuracy.</p>","PeriodicalId":12639,"journal":{"name":"Frontiers in Neuroscience","volume":"20 ","pages":"1605209"},"PeriodicalIF":3.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13079647/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147698399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spatial coupling of enlarged perivascular spaces and white matter lesions across the Alzheimer's disease continuum.","authors":"Serena Tang, Pamela Thropp, Isabella Hausle, Kyan Younes, Duygu Tosun","doi":"10.3389/fnins.2026.1772024","DOIUrl":"https://doi.org/10.3389/fnins.2026.1772024","url":null,"abstract":"<p><strong>Introduction: </strong>Emerging evidence suggests that impaired waste-clearance systems contribute to Alzheimer's disease pathogenesis, yet the etiology of clearance dysfunction markers, such as enlarged perivascular spaces, remains unclear. Because enlarged perivascular spaces and white matter lesions are both consequences of microvascular injury involving neuroinflammation and impaired cerebrovascular function, we hypothesize that these markers may be spatially coupled through local interstitial fluid stagnation, where impaired perivascular clearance associates with white matter injury.</p><p><strong>Methods: </strong>We assessed global perivascular space differences and correlations across diagnostic and biomarker-informed groups in the Alzheimer's Disease Neuroimaging Initiative dataset within whole brain, white matter, and basal ganglia regions, as well as within and outside of white matter lesions. To assess the spatial relationships between enlarged perivascular spaces and white matter lesions, we examined perivascular space distribution at distances away from white matter lesions.</p><p><strong>Results: </strong>Group-wise analyses revealed greater perivascular space counts and volumes within the white matter lesions and the basal ganglia in the mild cognitively impaired versus cognitively unimpaired group. Perivascular space counts and volumes and white matter lesion volumes correlated significantly within basal ganglia and white matter lesion regions across the cohort, with no differences in this relationship across diagnostic groups. Spatial analyses demonstrated greater perivascular space density within 5-15 mm of white matter lesions in mild cognitively impaired-amyloid positive and all amyloid positive groups compared to cognitively unimpaired-amyloid negative groups and all amyloid negative groups respectively, but reduced density ≥30 mm from white matter lesions in the Alzheimer's diagnosed-amyloid positive versus cognitively unimpaired-amyloid negative groups. White matter lesion volume consistently predicted perivascular spaces counts across all distance bins, with associations weakening as distance from white matter lesions increased. These results were all age and sex adjusted, indicating that the observed changes may reflect pathological processes beyond normal aging.</p><p><strong>Discussion: </strong>These findings demonstrate spatial coupling between enlarged perivascular spaces and white matter lesions across the Alzheimer's disease continuum, with coupling changes emerging early in disease stages, supporting the hypothesis that local perivascular clearance dysfunction and white matter injury represent interacting pathological processes that may serve as early biomarkers of Alzheimer's disease.</p>","PeriodicalId":12639,"journal":{"name":"Frontiers in Neuroscience","volume":"20 ","pages":"1772024"},"PeriodicalIF":3.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13079328/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147698408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacological interventions targeting the gut-brain axis in neurological disorders: mechanisms and translational applications.","authors":"Xu Li, Wenke Zhou, Shuran Yang, Xiangkai Huang, Kuihong Zheng","doi":"10.3389/fnins.2026.1806532","DOIUrl":"https://doi.org/10.3389/fnins.2026.1806532","url":null,"abstract":"<p><p>The microbiota-gut-brain axis represents a complex bidirectional communication network linking the gastrointestinal system and the central nervous system and has been increasingly recognized as a key contributor to neurological and psychiatric disorders. Growing evidence indicates that alterations in gut microbiota composition and function can influence brain development and function through neural, immune, endocrine, and metabolic pathways, thereby modulating neuroinflammation, neurotransmission, and blood-brain barrier integrity. Dysregulation of this axis has been implicated in a range of conditions, including Parkinson's disease, Alzheimer's disease, multiple sclerosis, autism spectrum disorder, depression, anxiety, and stroke. Recent pharmacological advances have identified the microbiota-gut-brain axis as a promising therapeutic target. Current strategies focus on modulating shared pathophysiological mechanisms rather than disease-specific endpoints and include microbiota-directed interventions, immune-inflammatory modulators, neurotransmitter-targeting agents, and approaches aimed at restoring intestinal and blood-brain barrier function. In this review, we summarize the core mechanisms underlying microbiota-gut-brain axis dysfunction and organize existing pharmacological strategies according to their primary targets. By integrating evidence across multiple disorders, we provide a mechanism-oriented framework to support future drug development and precision therapeutic approaches for brain disorders.</p>","PeriodicalId":12639,"journal":{"name":"Frontiers in Neuroscience","volume":"20 ","pages":"1806532"},"PeriodicalIF":3.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13079292/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147698413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distinct patterns of cortical activation and functional connectivity in children with high-functioning autism during a verbal fluency task: a comparative fNIRS study.","authors":"Bin Yu, Jian-Min Lv, Ge Lei, Jing-Li Wu, Ding-Xu Li, Xuan-Yue Song, Xi-Ning He, Na Zhao, Qian Shu, Hong-Xia Li","doi":"10.3389/fnins.2026.1736415","DOIUrl":"https://doi.org/10.3389/fnins.2026.1736415","url":null,"abstract":"<p><strong>Objective: </strong>Children with High-Functioning Autism (HFA) often show marked deficits in executive functioning, particularly during verbal fluency tasks (VFTs). These behavioral impairments are believed to stem from neurophysiological abnormalities in the prefrontal cortex (PFC) functioning, characterized by atypical activation patterns and disrupted functional connectivity. This study utilized functional near-infrared spectroscopy (fNIRS) to investigate hemodynamic responses and connectivity metrics during VFT performance. By comparing children with HFA to age-matched typically developing (TD) controls, this study aimed to clarify the neural mechanisms underlying the executive control of language production in HFA.</p><p><strong>Methods: </strong>The sample included 29 children who met diagnostic criteria for HFA and 26 TD controls. All participants had a Full-Scale Intelligence Quotient of 70 or higher and were matched for age and cognitive ability. During a standardized phonemic VFT, cortical hemodynamics were continuously monitored using a 19-channel fNIRS system, with analyses focusing on changes in oxygenated hemoglobin concentration within PFC regions.</p><p><strong>Results: </strong>Compared with TD controls, children with HFA exhibited reduced cortical activation across multiple prefrontal regions, including channels 1 (<i>t</i> = -2.975, <i>p</i> = 0.017), 2 (<i>t</i> = -4.320, <i>p</i> = 0.001), 3 (<i>t</i> = -3.381, <i>p</i> = 0.012), 9 (<i>t</i> = -3.127, <i>p</i> = 0.014), and 19 (<i>t</i> = -3.279, <i>p</i> = 0.012). These regions correspond anatomically to the inferior prefrontal gyrus, frontopolar cortex, and dorsolateral PFC. Functional connectivity analyses demonstrated significantly reduced interregional coupling in the HFA group (<i>p</i> < 0.001), with mean connectivity values of 0.512 (SD = 0.076) compared with 0.566 (SD = 0.069) in TD participants. Furthermore, Oxy-Hb changes in prefrontal channels 1 (<i>r</i> = -0.424, <i>p</i> = 0.022), 2 (<i>r</i> = -0.432, <i>p</i> = 0.019), and 3 (<i>r</i> = -0.394, <i>p</i> = 0.034) were negatively correlated with Social Responsiveness Scale total scores, indicating that weaker prefrontal activation was associated with greater social impairment.</p><p><strong>Conclusion: </strong>The results reveal distinct cortical activation and functional connectivity alterations in children with HFA during VFTs. These findings support the hypothesis that disrupted interregional brain coordination underlies executive difficulties in language production in HFA children, who exhibit reduced PFC activation and weaker interregional functional connectivity during the VFT.</p>","PeriodicalId":12639,"journal":{"name":"Frontiers in Neuroscience","volume":"20 ","pages":"1736415"},"PeriodicalIF":3.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13079335/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147698446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}