Pub Date : 2026-01-23eCollection Date: 2025-01-01DOI: 10.3389/fnins.2025.1735068
Mohammadreza Koolani, Simeon Bamford, Petr Trunin, Simon F Müller-Cleve, Matteo Lo Preti, Fulvio Mastrogiovanni, Lucia Beccai, Chiara Bartolozzi
This paper presents a neuromorphic, event-driven tactile sensing system for soft, large-area skin, based on the Dynamic Vision Sensors (DVS) integrated with a flexible silicone optical waveguide skin. Instead of repetitively scanning embedded photoreceivers, this design uses a stereo vision setup comprising two DVS cameras looking sideways through the skin. Such a design produces events as changes in brightness are detected, and estimates press positions on the 2D skin surface through triangulation, utilizing Density-Based Spatial Clustering of Applications with Noise (DBSCAN) to find the center of mass of contact events resulting from pressing actions. The system is evaluated over a 4,620 mm probed area of the skin using a meander raster scan. Across 95 % of the presses visible to both cameras, the press localization achieved a Root-Mean-Squared Error (RMSE) of 4.66 mm. The results highlight the potential of this approach for wide-area flexible and responsive tactile sensors in soft robotics and interactive environments. Moreover, we examined how the system performs when the amount of event data is strongly reduced. Using stochastic down-sampling, the event stream was reduced to 1/1,024 of its original size. Under this extreme reduction, the average localization error increased only slightly (from 4.66 mm to 9.33 mm), and the system still produced valid press localizations for 85 % of the trials. This reduction in pass rate is expected, as some presses no longer produce enough events to form a reliable cluster for triangulation. These results show that the sensing approach remains functional even with very sparse event data, which is promising for reducing power consumption and computational load in future implementations. The system exhibits a detection latency distribution with a characteristic width of 31 ms.
{"title":"An event-based opto-tactile skin.","authors":"Mohammadreza Koolani, Simeon Bamford, Petr Trunin, Simon F Müller-Cleve, Matteo Lo Preti, Fulvio Mastrogiovanni, Lucia Beccai, Chiara Bartolozzi","doi":"10.3389/fnins.2025.1735068","DOIUrl":"10.3389/fnins.2025.1735068","url":null,"abstract":"<p><p>This paper presents a neuromorphic, event-driven tactile sensing system for soft, large-area skin, based on the Dynamic Vision Sensors (DVS) integrated with a flexible silicone optical waveguide skin. Instead of repetitively scanning embedded photoreceivers, this design uses a stereo vision setup comprising two DVS cameras looking sideways through the skin. Such a design produces events as changes in brightness are detected, and estimates press positions on the 2D skin surface through triangulation, utilizing Density-Based Spatial Clustering of Applications with Noise (DBSCAN) to find the center of mass of contact events resulting from pressing actions. The system is evaluated over a 4,620 mm probed area of the skin using a meander raster scan. Across 95 % of the presses visible to both cameras, the press localization achieved a Root-Mean-Squared Error (RMSE) of 4.66 mm. The results highlight the potential of this approach for wide-area flexible and responsive tactile sensors in soft robotics and interactive environments. Moreover, we examined how the system performs when the amount of event data is strongly reduced. Using stochastic down-sampling, the event stream was reduced to 1/1,024 of its original size. Under this extreme reduction, the average localization error increased only slightly (from 4.66 mm to 9.33 mm), and the system still produced valid press localizations for 85 % of the trials. This reduction in pass rate is expected, as some presses no longer produce enough events to form a reliable cluster for triangulation. These results show that the sensing approach remains functional even with very sparse event data, which is promising for reducing power consumption and computational load in future implementations. The system exhibits a detection latency distribution with a characteristic width of 31 ms.</p>","PeriodicalId":12639,"journal":{"name":"Frontiers in Neuroscience","volume":"19 ","pages":"1735068"},"PeriodicalIF":3.2,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12878655/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146142175","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}
Introduction: Functional near-infrared spectroscopy (fNIRS) has emerged as a promising neuroimaging modality for investigating cortical activity in auditory and vestibular domains. Its portability, device compatibility, and motion tolerance make it particularly suited for use in populations that are challenging to study with conventional neuroimaging techniques, such as infants and cochlear implant (CI) users. The present study aims to explore the potential and limitations of this neuroimaging technique in the audiological and vestibular fields, offering an integrated perspective across pediatric, adult and elderly populations.
Methods: A narrative review of studies using fNIRS in hearing loss, tinnitus, and vestibular disorders was conducted through searches in PubMed and Scopus up to March 2025. Studies were included if they employed fNIRS to investigate cortical responses in individuals with diagnosed hearing loss, chronic tinnitus or to investigate vestibular function.
Results: A total of 60 studies were reviewed: 36 on hearing loss, 11 on tinnitus, and 13 on vestibular disorders. In hearing research, fNIRS successfully identified cortical activation patterns related to auditory perception, speech processing, and cross-modal plasticity in CI users across development, adulthood and aging. The technique showed prognostic potential in predicting CI outcomes and monitoring listening effort and cognitive load. In tinnitus research, fNIRS consistently demonstrate hyper-activation in the auditory cortex and altered functional connectivity with frontal-limbic networks, reflecting sensory, cognitive, and emotional involvement. The technique was sensitive to treatment effects following interventions such as transcranial stimulation, acupuncture, and cochlear implantation. In vestibular research, fNIRS enabled the mapping of cortical networks involved in balance control and multisensory integration during various stimulation paradigms, including caloric testing, motion platforms, and optic flow in virtual environments. Although current applications are mostly exploratory, findings suggest fNIRS can capture vestibular-related cortical activity in real-world conditions.
Conclusion: fNIRS offers a valuable, non-invasive, and ecologically valid method for investigating auditory and vestibular function across the lifespan. In hearing and tinnitus research, it shows strong potential for clinical translation, especially if methodological standardization is achieved. Applications in vestibular research remain preliminary but promising.
{"title":"A narrative review of functional near-infrared spectroscopy (fNIRS) applications in hearing loss, tinnitus and vestibular disorders.","authors":"Davide Brotto, Gaia Lucarini, Valeria Del Vecchio, Nicole Galoforo, Elisa Lovato, Benedetta Colavolpe, Giusy Melcarne, Gino Marioni, Judit Gervain, Anna Rita Fetoni, Patrizia Trevisi","doi":"10.3389/fnins.2025.1703917","DOIUrl":"10.3389/fnins.2025.1703917","url":null,"abstract":"<p><strong>Introduction: </strong>Functional near-infrared spectroscopy (fNIRS) has emerged as a promising neuroimaging modality for investigating cortical activity in auditory and vestibular domains. Its portability, device compatibility, and motion tolerance make it particularly suited for use in populations that are challenging to study with conventional neuroimaging techniques, such as infants and cochlear implant (CI) users. The present study aims to explore the potential and limitations of this neuroimaging technique in the audiological and vestibular fields, offering an integrated perspective across pediatric, adult and elderly populations.</p><p><strong>Methods: </strong>A narrative review of studies using fNIRS in hearing loss, tinnitus, and vestibular disorders was conducted through searches in PubMed and Scopus up to March 2025. Studies were included if they employed fNIRS to investigate cortical responses in individuals with diagnosed hearing loss, chronic tinnitus or to investigate vestibular function.</p><p><strong>Results: </strong>A total of 60 studies were reviewed: 36 on hearing loss, 11 on tinnitus, and 13 on vestibular disorders. In hearing research, fNIRS successfully identified cortical activation patterns related to auditory perception, speech processing, and cross-modal plasticity in CI users across development, adulthood and aging. The technique showed prognostic potential in predicting CI outcomes and monitoring listening effort and cognitive load. In tinnitus research, fNIRS consistently demonstrate hyper-activation in the auditory cortex and altered functional connectivity with frontal-limbic networks, reflecting sensory, cognitive, and emotional involvement. The technique was sensitive to treatment effects following interventions such as transcranial stimulation, acupuncture, and cochlear implantation. In vestibular research, fNIRS enabled the mapping of cortical networks involved in balance control and multisensory integration during various stimulation paradigms, including caloric testing, motion platforms, and optic flow in virtual environments. Although current applications are mostly exploratory, findings suggest fNIRS can capture vestibular-related cortical activity in real-world conditions.</p><p><strong>Conclusion: </strong>fNIRS offers a valuable, non-invasive, and ecologically valid method for investigating auditory and vestibular function across the lifespan. In hearing and tinnitus research, it shows strong potential for clinical translation, especially if methodological standardization is achieved. Applications in vestibular research remain preliminary but promising.</p>","PeriodicalId":12639,"journal":{"name":"Frontiers in Neuroscience","volume":"19 ","pages":"1703917"},"PeriodicalIF":3.2,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12876175/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146142154","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}
Introduction: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder causing progressive motor neuron death in cortex, brainstem and spinal cord. The most common genetic cause is the G4C2 hexanucleotide repeat expansion in the non-coding region of exon 1 of C9ORF72, accounting for ~40% of familial and ~7% of sporadic ALS. RNA dysregulation is increasingly recognized as a key contributor to ALS pathogenesis. This study aimed to identify specific microRNAs (miRNAs) involved in motor neuron degeneration in C9ORF72-ALS.
Methods: We profiled 754 miRNAs in human post-mortem spinal cord tissue from C9ORF72-ALS patients and healthy donors. Laser capture microdissection isolated ventral horn regions, and in silico target prediction identified potential genes and pathways regulated by differentially expressed miRNAs. Target genes were validated by Real time PCR.
Results: Two subsets of miRNAs were exclusively expressed in ventral horn regions: miR-200b-3p and miR-346 in C9ORF72-ALS patients, and miR-30d-5p, miR-106b-5p and miR-135a-5p in healthy donors. Target prediction and molecular analysis identified putative genes and pathways linked to cell death, inflammation, protein metabolism, DNA modification, excitotoxicity, autophagy and vesicles trafficking.
Discussion: This study identifies specific miRNAs and their target genes as key molecules in motor neuron degeneration in C9ORF72-ALS. Restoring their expression could represent a therapeutic approach for ALS.
简介:肌萎缩性侧索硬化症(ALS)是一种致死性神经退行性疾病,导致皮层、脑干和脊髓的运动神经元进行性死亡。最常见的遗传原因是C9ORF72外显子1非编码区G4C2六核苷酸重复扩增,占家族性ALS的约40%,散发性ALS的约7%。RNA失调越来越被认为是ALS发病的关键因素。本研究旨在鉴定参与C9ORF72-ALS运动神经元退行性变的特异性microRNAs (miRNAs)。方法:我们分析了来自C9ORF72-ALS患者和健康供体的人死后脊髓组织中的754种mirna。激光捕获显微解剖分离腹角区域,并在计算机靶标预测中确定了由差异表达的miRNAs调节的潜在基因和途径。目的基因通过Real - time PCR验证。结果:两个mirna亚群在腹角区独家表达:C9ORF72-ALS患者的miR-200b-3p和miR-346,健康供者的miR-30d-5p, miR-106b-5p和miR-135a-5p。靶标预测和分子分析确定了与细胞死亡、炎症、蛋白质代谢、DNA修饰、兴奋毒性、自噬和囊泡运输相关的假定基因和途径。讨论:本研究确定了C9ORF72-ALS患者运动神经元退行性变的关键分子是特异性mirna及其靶基因。恢复它们的表达可能是治疗ALS的一种方法。
{"title":"MicroRNA profiling in post-mortem spinal cord of C9ORF72-related ALS patients reveals molecular pathways involved in motor neuron degeneration.","authors":"Giorgia Farinazzo, Eleonora Giagnorio, Matteo Marcuzzo, Marco Cattaneo, Claudia Malacarne, Paola Cavalcante, Silvia Bonanno, Emanuela Maderna, Viviana Pensato, Cinzia Gellera, Gianluca Marucci, Samanta Mazzetti, Erika Salvi, Giuseppe Lauria, Stefania Marcuzzo","doi":"10.3389/fnins.2026.1741065","DOIUrl":"10.3389/fnins.2026.1741065","url":null,"abstract":"<p><strong>Introduction: </strong>Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder causing progressive motor neuron death in cortex, brainstem and spinal cord. The most common genetic cause is the G4C2 hexanucleotide repeat expansion in the non-coding region of exon 1 of C9ORF72, accounting for ~40% of familial and ~7% of sporadic ALS. RNA dysregulation is increasingly recognized as a key contributor to ALS pathogenesis. This study aimed to identify specific microRNAs (miRNAs) involved in motor neuron degeneration in C9ORF72-ALS.</p><p><strong>Methods: </strong>We profiled 754 miRNAs in human post-mortem spinal cord tissue from C9ORF72-ALS patients and healthy donors. Laser capture microdissection isolated ventral horn regions, and in silico target prediction identified potential genes and pathways regulated by differentially expressed miRNAs. Target genes were validated by Real time PCR.</p><p><strong>Results: </strong>Two subsets of miRNAs were exclusively expressed in ventral horn regions: miR-200b-3p and miR-346 in C9ORF72-ALS patients, and miR-30d-5p, miR-106b-5p and miR-135a-5p in healthy donors. Target prediction and molecular analysis identified putative genes and pathways linked to cell death, inflammation, protein metabolism, DNA modification, excitotoxicity, autophagy and vesicles trafficking.</p><p><strong>Discussion: </strong>This study identifies specific miRNAs and their target genes as key molecules in motor neuron degeneration in C9ORF72-ALS. Restoring their expression could represent a therapeutic approach for ALS.</p>","PeriodicalId":12639,"journal":{"name":"Frontiers in Neuroscience","volume":"20 ","pages":"1741065"},"PeriodicalIF":3.2,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12876226/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146142095","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}
Pub Date : 2026-01-23eCollection Date: 2026-01-01DOI: 10.3389/fnins.2026.1678894
Xian-Mu Luo, Jun Luo, Qian Zhang, Ling-Yong Zeng, Bin Liu, Chun-Ling Chi
Background: Current clinical research suggests that the ketogenic diet (KD) intervention can alleviate Parkinson's disease (PD) symptoms. However, the underlying mechanisms remain unclear. This pilot study explored the potential link between KD-induced clinical improvements and gut microbiota alterations.
Methods: We engaged 27 PD patients in a 12-week ketogenic dietary trial (16 completed) and employed 16S rRNA sequencing to analyze gut microbiota differences compared to 27 healthy controls.
Results: Baseline analysis revealed distinct dysbiosis in PD patients, characterized by increased abundance of Enterobacteriaceae. Following the 12-week intervention, patients exhibited significant improvements in both motor (MDS-UPDRS Part III, p < 0.001) and non-motor symptoms (NMSS, p < 0.0001). These clinical improvements were accompanied by specific microbial shifts: a significant increase in Enterococcus and Synergistota, and a decrease in Alloprevotella.
Conclusion: These findings suggest that the therapeutic effects of the ketogenic diet in PD are associated with specific remodeling of the gut microbiota, particularly the enrichment of potential beneficial taxa and reduction of pro-inflammatory genera.
背景:目前的临床研究表明,生酮饮食(KD)干预可以缓解帕金森病(PD)的症状。然而,潜在的机制仍不清楚。这项初步研究探讨了kd诱导的临床改善和肠道菌群改变之间的潜在联系。方法:我们对27名PD患者进行了为期12周的生酮饮食试验(16名完成),并采用16S rRNA测序分析了与27名健康对照者相比肠道微生物群的差异。结果:基线分析显示PD患者明显的生态失调,其特征是肠杆菌科的丰度增加。经过12周的干预,患者表现出运动(MDS-UPDRS第三部分,p p 肠球菌和协同菌)的显著改善,Alloprevotella的减少。结论:这些研究结果表明,生酮饮食对PD的治疗作用与肠道微生物群的特异性重塑有关,特别是潜在有益类群的富集和促炎属的减少。临床试验注册:https://www.chictr.org.cn/index.html,唯一标识符:ChiCTR2100045394。
{"title":"Exploring the role of gut microbiota in potential mechanism of ketogenic diet in alleviating Parkinson's disease symptoms.","authors":"Xian-Mu Luo, Jun Luo, Qian Zhang, Ling-Yong Zeng, Bin Liu, Chun-Ling Chi","doi":"10.3389/fnins.2026.1678894","DOIUrl":"10.3389/fnins.2026.1678894","url":null,"abstract":"<p><strong>Background: </strong>Current clinical research suggests that the ketogenic diet (KD) intervention can alleviate Parkinson's disease (PD) symptoms. However, the underlying mechanisms remain unclear. This pilot study explored the potential link between KD-induced clinical improvements and gut microbiota alterations.</p><p><strong>Methods: </strong>We engaged 27 PD patients in a 12-week ketogenic dietary trial (16 completed) and employed 16S rRNA sequencing to analyze gut microbiota differences compared to 27 healthy controls.</p><p><strong>Results: </strong>Baseline analysis revealed distinct dysbiosis in PD patients, characterized by increased abundance of Enterobacteriaceae. Following the 12-week intervention, patients exhibited significant improvements in both motor (MDS-UPDRS Part III, <i>p</i> < 0.001) and non-motor symptoms (NMSS, <i>p</i> < 0.0001). These clinical improvements were accompanied by specific microbial shifts: a significant increase in <i>Enterococcus</i> and Synergistota, and a decrease in <i>Alloprevotella</i>.</p><p><strong>Conclusion: </strong>These findings suggest that the therapeutic effects of the ketogenic diet in PD are associated with specific remodeling of the gut microbiota, particularly the enrichment of potential beneficial taxa and reduction of pro-inflammatory genera.</p><p><strong>Clinical trial registration: </strong>https://www.chictr.org.cn/index.html, Unique Identifier: ChiCTR2100045394.</p>","PeriodicalId":12639,"journal":{"name":"Frontiers in Neuroscience","volume":"20 ","pages":"1678894"},"PeriodicalIF":3.2,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12876210/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146142168","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}
Introduction: Perception operates as rhythmically structured sampling in which temporal predictions determine when incoming signals are weighted. Fixational eye movements carry opposing consequences, enhancing acuity yet inducing brief peri-saccadic suppression, suggesting that their timing is paced by expected, salient rhythms. Auditory scenes can be parsed into competing streams that unfold over time. If fixation dynamics are shaped by temporal expectation, and auditory streaming imposes a percept-dependent temporal structure on otherwise identical acoustics, then fixational eye movements might provide a window into how listeners parse sound over time. We asked whether fixational eye movements reflect the perceived rather than the physical temporal organization of an ambiguous ABA- pattern.
Methods: While listeners fixated and either attended High, Low, or All tones (Experiment 1, n = 15) or freely reported their percept (Experiment 2, n = 15), we recorded binocular eye position (500 Hz) and quantified microsaccade (MS) dynamics and eye-velocity spectra.
Results: Across both experiments, eye-velocity spectra showed a percept-dependent redistribution between 2 and 4 Hz, with relative power shifting with the instructed/reported stream. A normalized 4-2 Hz index (ΔPSD) separated Low-tone from High-tone percepts across procedures. Time-resolved analyses further revealed within-trial waxing-and-waning of 2 vs. 4 Hz dominance, consistent with bistable fluctuations in maintaining a stream. Moreover, microsaccade reaction time (msRT), aligned to the onset of the sound sequence, differed significantly depending on the percept.
Discussion: These findings extend oculomotor inhibition beyond discrete events, positioning fixation dynamics as a sensitive, report-free marker of auditory scene organization. We discuss mechanistic links to temporal attention and active sensing, and implications for a multisensory timing framework.
{"title":"Perceptual punctuation: fixational eye movements reveal segmentation of auditory streams.","authors":"Vincenzo Rizzuto, Oren Kadosh, Roberto Montanari, Yoram Bonneh","doi":"10.3389/fnins.2026.1731980","DOIUrl":"10.3389/fnins.2026.1731980","url":null,"abstract":"<p><strong>Introduction: </strong>Perception operates as rhythmically structured sampling in which temporal predictions determine when incoming signals are weighted. Fixational eye movements carry opposing consequences, enhancing acuity yet inducing brief peri-saccadic suppression, suggesting that their timing is paced by expected, salient rhythms. Auditory scenes can be parsed into competing streams that unfold over time. If fixation dynamics are shaped by temporal expectation, and auditory streaming imposes a percept-dependent temporal structure on otherwise identical acoustics, then fixational eye movements might provide a window into how listeners parse sound over time. We asked whether fixational eye movements reflect the perceived rather than the physical temporal organization of an ambiguous ABA- pattern.</p><p><strong>Methods: </strong>While listeners fixated and either attended High, Low, or All tones (Experiment 1, <i>n</i> = 15) or freely reported their percept (Experiment 2, <i>n</i> = 15), we recorded binocular eye position (500 Hz) and quantified microsaccade (MS) dynamics and eye-velocity spectra.</p><p><strong>Results: </strong>Across both experiments, eye-velocity spectra showed a percept-dependent redistribution between 2 and 4 Hz, with relative power shifting with the instructed/reported stream. A normalized 4-2 Hz index (ΔPSD) separated Low-tone from High-tone percepts across procedures. Time-resolved analyses further revealed within-trial waxing-and-waning of 2 vs. 4 Hz dominance, consistent with bistable fluctuations in maintaining a stream. Moreover, microsaccade reaction time (msRT), aligned to the onset of the sound sequence, differed significantly depending on the percept.</p><p><strong>Discussion: </strong>These findings extend oculomotor inhibition beyond discrete events, positioning fixation dynamics as a sensitive, report-free marker of auditory scene organization. We discuss mechanistic links to temporal attention and active sensing, and implications for a multisensory timing framework.</p>","PeriodicalId":12639,"journal":{"name":"Frontiers in Neuroscience","volume":"20 ","pages":"1731980"},"PeriodicalIF":3.2,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12876199/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146142135","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}
Bainbridge-Ropers syndrome (BRPS, OMIM #615485) is a rare, heterogeneous autosomal dominant genetic disease that is mainly characterized by intellectual disability (ID) of varying degrees, developmental delay (DD), language impairments, failure to thrive, behavioral issues, hypotonia, feeding difficulties, and distinctive craniofacial features. It is caused by heterozygous pathogenic variants in the additional sex combs-like 3 (ASXL3, OMIM #615115) gene. In this study, four Chinese patients were diagnosed with BRPS caused by ASXL3 variants through whole exome sequencing. We detected two novel and two previously reported variants of the ASXL3 gene (NM_030632.3) in these 4 unrelated Chinese patients: two novel variants, namely, c.1276del (p.Val426*) and c.3750del (p.Glu1251Asnfs*5), and two recurrent variants, namely, c.4330C>T (p.Arg1444*) and c.4336_4337delAG (p.Arg1446fs*2). All four patients had a clinical profile similar to that associated with BRPS. Compared with previously reported cases of BRPS, these patients exhibited novel complications, including long eyelashes, congenital laryngeal cartilage hypoplasia and dextrocardia. These findings broaden our understanding of the mutational and clinical spectrum of BRPS, emphasizing the importance of long-term monitoring and vigilance regarding potential complications, such as cardiac abnormalities, in BRPS patients.
{"title":"ASXL3 gene variants causing Bainbridge-Ropers syndrome: clinical and genetic analysis of four Chinese patients.","authors":"Qi Yang, Qiang Zhang, Xunzhao Zhou, Shang Yi, Zailong Qin, Sheng Yi, Sheng He, Jingsi Luo","doi":"10.3389/fnins.2025.1739877","DOIUrl":"10.3389/fnins.2025.1739877","url":null,"abstract":"<p><p>Bainbridge-Ropers syndrome (BRPS, OMIM #615485) is a rare, heterogeneous autosomal dominant genetic disease that is mainly characterized by intellectual disability (ID) of varying degrees, developmental delay (DD), language impairments, failure to thrive, behavioral issues, hypotonia, feeding difficulties, and distinctive craniofacial features. It is caused by heterozygous pathogenic variants in the additional sex combs-like 3 (<i>ASXL3</i>, OMIM #615115) gene. In this study, four Chinese patients were diagnosed with BRPS caused by <i>ASXL3</i> variants through whole exome sequencing. We detected two novel and two previously reported variants of the <i>ASXL3</i> gene (NM_030632.3) in these 4 unrelated Chinese patients: two novel variants, namely, c.1276del (<i>p</i>.Val426<sup>*</sup>) and c.3750del (<i>p</i>.Glu1251Asnfs<sup>*</sup>5), and two recurrent variants, namely, c.4330C>T (<i>p</i>.Arg1444<sup>*</sup>) and c.4336_4337delAG (<i>p</i>.Arg1446fs<sup>*</sup>2). All four patients had a clinical profile similar to that associated with BRPS. Compared with previously reported cases of BRPS, these patients exhibited novel complications, including long eyelashes, congenital laryngeal cartilage hypoplasia and dextrocardia. These findings broaden our understanding of the mutational and clinical spectrum of BRPS, emphasizing the importance of long-term monitoring and vigilance regarding potential complications, such as cardiac abnormalities, in BRPS patients.</p>","PeriodicalId":12639,"journal":{"name":"Frontiers in Neuroscience","volume":"19 ","pages":"1739877"},"PeriodicalIF":3.2,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12872894/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146141714","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}
Background: Maternal immune activation (MIA) is a risk factor for neurodevelopmental disorders (NDDs) in offspring. While MIA-induced changes in the gut bacterial communities of offspring and their metabolites have been linked to behavioral abnormalities, the effects of MIA on the gut fungal communities and their mycotoxin-associated metabolites in offspring remain poorly characterized.
Methods: In this study, MIA was modeled in pregnant rats through intraperitoneal injection of 5 mg/kg Poly I:C on gestational day 15. The model's efficacy was validated using behavioral assessments, including the open-field test, elevated plus maze, and Morris water maze. Internal transcribed spacer (ITS) sequencing and untargeted metabolomics analysis were employed to detect the alterations of gut fungal microbiota and mycotoxin levels.
Results: Poly I:C-exposed offspring exhibited increased anxiety and cognitive deficits. Meanwhile, Poly I:C induces sex-related differences in gut fungal communities and mycotoxin levels in juvenile offspring rats. Several fungal genera and mycotoxins were significantly correlated with variations in anxiety-like behaviors and spatial learning performance.
Discussion: Our findings suggest that MIA-induced behavioral deficits in offspring are accompanied by sex-specific disruptions in gut fungal composition and mycotoxin metabolism, which highlights the need for further intervention studies to establish causality and elucidate the underlying mechanisms of gut fungi and mycotoxins in NDDs.
{"title":"Altered gut fungal microbiota and associated mycotoxins in juvenile rat offspring induced by maternal immune activation with Poly I:C.","authors":"Fuchun Zhong, Menglu Zeng, Huiyu Chen, Yanfang Lu, Zhenju Cao, Fei Xue, Shuangyan Yang, Lirong Yang, Xinyu Yang, Wei Lin, Anying Shen, Yueqing Su","doi":"10.3389/fnins.2026.1702092","DOIUrl":"10.3389/fnins.2026.1702092","url":null,"abstract":"<p><strong>Background: </strong>Maternal immune activation (MIA) is a risk factor for neurodevelopmental disorders (NDDs) in offspring. While MIA-induced changes in the gut bacterial communities of offspring and their metabolites have been linked to behavioral abnormalities, the effects of MIA on the gut fungal communities and their mycotoxin-associated metabolites in offspring remain poorly characterized.</p><p><strong>Methods: </strong>In this study, MIA was modeled in pregnant rats through intraperitoneal injection of 5 mg/kg Poly I:C on gestational day 15. The model's efficacy was validated using behavioral assessments, including the open-field test, elevated plus maze, and Morris water maze. Internal transcribed spacer (ITS) sequencing and untargeted metabolomics analysis were employed to detect the alterations of gut fungal microbiota and mycotoxin levels.</p><p><strong>Results: </strong>Poly I:C-exposed offspring exhibited increased anxiety and cognitive deficits. Meanwhile, Poly I:C induces sex-related differences in gut fungal communities and mycotoxin levels in juvenile offspring rats. Several fungal genera and mycotoxins were significantly correlated with variations in anxiety-like behaviors and spatial learning performance.</p><p><strong>Discussion: </strong>Our findings suggest that MIA-induced behavioral deficits in offspring are accompanied by sex-specific disruptions in gut fungal composition and mycotoxin metabolism, which highlights the need for further intervention studies to establish causality and elucidate the underlying mechanisms of gut fungi and mycotoxins in NDDs.</p>","PeriodicalId":12639,"journal":{"name":"Frontiers in Neuroscience","volume":"20 ","pages":"1702092"},"PeriodicalIF":3.2,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12872866/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146142092","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}
Pub Date : 2026-01-22eCollection Date: 2026-01-01DOI: 10.3389/fnins.2026.1761550
Marika Alborghetti, Camilla Moliterni, Edoardo Bianchini, Domiziana Rinaldi, Daniela Caissutti, Antonella Capozzi, Fabiana Giada Radicati, Antonella Moschillo, Martina Marino, Isabella Berardelli, Marco Salvetti, Ferdinando Nicoletti, Roberta Misasi, Francesco Ernesto Pontieri
Background: Preclinical and clinical studies suggest that the multimodal antidepressant vortioxetine may offer a valuable therapeutic option in the treatment of depression associated with neurological disorders, including Parkinson's disease (PD).
Objectives: To compare the effect of vortioxetine and the SSRI sertraline in the treatment of PD and comorbid depression, placing emphasis on peripheral inflammation markers.
Methods: This is an observational longitudinal study. We have recruited 33 patients affected by PD with comorbid depression, evaluated for motor and non-motor symptoms, depression, and peripheral and soluble markers of inflammation at baseline and at the end of antidepressant treatment. Patients were divided into two groups treated with either vortioxetine (10-20 mg/day) or sertraline (50 mg/day) for 4 months. A group of 12 healthy controls was also used for comparative purposes.
Results: At baseline PD patients showed a higher number of "classical" monocytes and a lower number of "non-classical" monocytes and myeloid dendritic cells (mDCs). The number and activity of DCs generated from isolated monocytes were also lower in PD patients. While both sertraline and vortioxetine treatment further reduced the number of mDCs, only vortioxetine had a restorative effect on CD40- and CD54-expressing DCs and their function. Both drugs display an antidepressant activity, but vortioxetine was superior to sertraline in improving cognitive function, anxiety, anhedonia, and apathy.
Conclusion: These data evaluate for the first time the immunomodulatory effects of two different treatments in PD patients with comorbid depression, highlighting the greater immunomodulatory capacity of vortioxetine.
{"title":"Comparative effect of vortioxetine and sertraline on clinical and inflammatory profile in Parkinson's disease with comorbid depression.","authors":"Marika Alborghetti, Camilla Moliterni, Edoardo Bianchini, Domiziana Rinaldi, Daniela Caissutti, Antonella Capozzi, Fabiana Giada Radicati, Antonella Moschillo, Martina Marino, Isabella Berardelli, Marco Salvetti, Ferdinando Nicoletti, Roberta Misasi, Francesco Ernesto Pontieri","doi":"10.3389/fnins.2026.1761550","DOIUrl":"10.3389/fnins.2026.1761550","url":null,"abstract":"<p><strong>Background: </strong>Preclinical and clinical studies suggest that the multimodal antidepressant vortioxetine may offer a valuable therapeutic option in the treatment of depression associated with neurological disorders, including Parkinson's disease (PD).</p><p><strong>Objectives: </strong>To compare the effect of vortioxetine and the SSRI sertraline in the treatment of PD and comorbid depression, placing emphasis on peripheral inflammation markers.</p><p><strong>Methods: </strong>This is an observational longitudinal study. We have recruited 33 patients affected by PD with comorbid depression, evaluated for motor and non-motor symptoms, depression, and peripheral and soluble markers of inflammation at baseline and at the end of antidepressant treatment. Patients were divided into two groups treated with either vortioxetine (10-20 mg/day) or sertraline (50 mg/day) for 4 months. A group of 12 healthy controls was also used for comparative purposes.</p><p><strong>Results: </strong>At baseline PD patients showed a higher number of \"classical\" monocytes and a lower number of \"non-classical\" monocytes and myeloid dendritic cells (mDCs). The number and activity of DCs generated from isolated monocytes were also lower in PD patients. While both sertraline and vortioxetine treatment further reduced the number of mDCs, only vortioxetine had a restorative effect on CD40- and CD54-expressing DCs and their function. Both drugs display an antidepressant activity, but vortioxetine was superior to sertraline in improving cognitive function, anxiety, anhedonia, and apathy.</p><p><strong>Conclusion: </strong>These data evaluate for the first time the immunomodulatory effects of two different treatments in PD patients with comorbid depression, highlighting the greater immunomodulatory capacity of vortioxetine.</p>","PeriodicalId":12639,"journal":{"name":"Frontiers in Neuroscience","volume":"20 ","pages":"1761550"},"PeriodicalIF":3.2,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12874709/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146142158","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}
Pub Date : 2026-01-22eCollection Date: 2025-01-01DOI: 10.3389/fnins.2025.1736601
Jiali Luo, Qi Chen
Background: Insomnia significantly impairs well-being, cognitive function, and social functioning, yet subjective psychological assessments often yield equivocal results regarding the extent of this impairment. Neural function may underlie this discrepancy and offer a more precise foundation for guiding treatment. This study therefore employed non-invasive transcranial magnetic stimulation (TMS) and functional near-infrared spectroscopy (fNIRS) to investigate cortical excitability and brain activity patterns in patients with short-term insomnia disorder (SID) and chronic insomnia disorder (CID), aiming to identify associated neural function changes.
Methods: We recruited 30 patients with SID and 30 with CID. For all participants, cortical excitability was assessed by measuring the resting motor threshold (RMT) via single-pulse TMS. fNIRS was utilized to measure the concentrations of oxy-hemoglobin (Oxy-Hb) and functional connectivity in the cerebral cortex during a verbal fluency task (VFT).
Results: Our study revealed that patients with SID had significantly lower RMT and higher cortical activation in the hemodynamic responses of Oxy-Hb in the bilateral dorsolateral prefrontal cortex (DLPFC), the left medial prefrontal cortex (mPFC), and the right temporal lobe (TL) than CID patients during the 60 s task period. The CID group showed significantly lower average inter-channel connectivity strength compared to the SID group. Moreover, the CID group exhibited significantly lower connectivity from the right DLPFC to the left DLPFC and the left mPFC compared to the SID group. For the SID patient group, we found that the RMT was negatively correlated with mean Oxy-Hb changes in the left mPFC. Conversely, functional connectivity between the left DLPFC and TL showed a positive correlation with RMT. Furthermore, diminished connectivity between the left TL and mPFC was associated with elevated cortical excitability.
Conclusion: Patients with CID demonstrated lower cortical excitability, decreased brain activity, and reduced task-related functional connectivity relative to the SID group. This finding indicates distinct neurological profiles between short-term and chronic insomnia, a distinction that will be critical for tailoring effective neuromodulatory interventions.
{"title":"Cortical excitability and brain function in patients with insomnia: a pilot transcranial magnetic stimulation and functional near-infrared spectroscopy study.","authors":"Jiali Luo, Qi Chen","doi":"10.3389/fnins.2025.1736601","DOIUrl":"10.3389/fnins.2025.1736601","url":null,"abstract":"<p><strong>Background: </strong>Insomnia significantly impairs well-being, cognitive function, and social functioning, yet subjective psychological assessments often yield equivocal results regarding the extent of this impairment. Neural function may underlie this discrepancy and offer a more precise foundation for guiding treatment. This study therefore employed non-invasive transcranial magnetic stimulation (TMS) and functional near-infrared spectroscopy (fNIRS) to investigate cortical excitability and brain activity patterns in patients with short-term insomnia disorder (SID) and chronic insomnia disorder (CID), aiming to identify associated neural function changes.</p><p><strong>Methods: </strong>We recruited 30 patients with SID and 30 with CID. For all participants, cortical excitability was assessed by measuring the resting motor threshold (RMT) via single-pulse TMS. fNIRS was utilized to measure the concentrations of oxy-hemoglobin (Oxy-Hb) and functional connectivity in the cerebral cortex during a verbal fluency task (VFT).</p><p><strong>Results: </strong>Our study revealed that patients with SID had significantly lower RMT and higher cortical activation in the hemodynamic responses of Oxy-Hb in the bilateral dorsolateral prefrontal cortex (DLPFC), the left medial prefrontal cortex (mPFC), and the right temporal lobe (TL) than CID patients during the 60 s task period. The CID group showed significantly lower average inter-channel connectivity strength compared to the SID group. Moreover, the CID group exhibited significantly lower connectivity from the right DLPFC to the left DLPFC and the left mPFC compared to the SID group. For the SID patient group, we found that the RMT was negatively correlated with mean Oxy-Hb changes in the left mPFC. Conversely, functional connectivity between the left DLPFC and TL showed a positive correlation with RMT. Furthermore, diminished connectivity between the left TL and mPFC was associated with elevated cortical excitability.</p><p><strong>Conclusion: </strong>Patients with CID demonstrated lower cortical excitability, decreased brain activity, and reduced task-related functional connectivity relative to the SID group. This finding indicates distinct neurological profiles between short-term and chronic insomnia, a distinction that will be critical for tailoring effective neuromodulatory interventions.</p>","PeriodicalId":12639,"journal":{"name":"Frontiers in Neuroscience","volume":"19 ","pages":"1736601"},"PeriodicalIF":3.2,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12872878/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146141877","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}
Pub Date : 2026-01-22eCollection Date: 2026-01-01DOI: 10.3389/fnins.2026.1745862
Yingsheng Zhang, Changlin Wang, Wei Gui, Xiaojun Feng, Yu Wang
Background: Migraine is a prevalent neurological disorder that is frequently observed in clinical practice and is commonly comorbid with insomnia. Insomnia can exacerbate and precipitate migraine attacks, with both conditions exerting a reciprocal influence on one another. The cerebellar crus is significantly associated with the pathophysiology of migraine and insomnia. The relationship between cerebellar crus functional alterations and migraine-associated insomnia remains unclear. This study utilizes resting-state functional magnetic resonance imaging (rs-fMRI) to examine functional alterations in the cerebellar crus of patients with migraine and concurrent insomnia.
Methods: Participants underwent resting-state functional magnetic resonance imaging. Subsequently, the disparity in amplitude of low-frequency fluctuations (ALFF) values among groups was analyzed, followed by functional connectivity (FC) investigations employing the cerebellum crus as seed regions.
Results: Migraine patients frequently experience neuropsychological disorders and insomnia, which are interconnected. Both migraine with insomnia (MwI) and migraine without insomnia (MwoI) groups demonstrated elevated amplitude of low-frequency fluctuations (ALFF) in the left Crus I and II compared to the healthy controls (HC) group, with the MwI group exhibiting more pronounced alterations. Additionally, both patient groups showed decreased FC between the left Crus I and the right middle temporal gyrus (MTG) and inferior temporal gyrus (ITG) relative to the HC group. The MwoI group showed significantly lower FC compared to both the HC and MwI groups. A significant negative correlation was observed between ALFF in the left Crus I/II and Pittsburgh Sleep Quality Index (PSQI) scores in the MwoI group. Conversely, in the combined migraine cohort, FC between the left Crus I and the right MTG/ITG showed a positive correlation with PSQI scores.
Conclusion: This study identified a correlation between aberrant functional activity in the left Crus I/II and migraine comorbidity with insomnia. These findings provide fresh perspectives on the neural mechanisms underlying the migraine-insomnia relationship, thereby facilitating the identification of potential neuroimaging biomarkers and the exploration of targeted interventions for this patient subgroup.
{"title":"Abnormal functional activity in the cerebellar crus can distinguish patients with migraine with comorbid insomnia.","authors":"Yingsheng Zhang, Changlin Wang, Wei Gui, Xiaojun Feng, Yu Wang","doi":"10.3389/fnins.2026.1745862","DOIUrl":"10.3389/fnins.2026.1745862","url":null,"abstract":"<p><strong>Background: </strong>Migraine is a prevalent neurological disorder that is frequently observed in clinical practice and is commonly comorbid with insomnia. Insomnia can exacerbate and precipitate migraine attacks, with both conditions exerting a reciprocal influence on one another. The cerebellar crus is significantly associated with the pathophysiology of migraine and insomnia. The relationship between cerebellar crus functional alterations and migraine-associated insomnia remains unclear. This study utilizes resting-state functional magnetic resonance imaging (rs-fMRI) to examine functional alterations in the cerebellar crus of patients with migraine and concurrent insomnia.</p><p><strong>Methods: </strong>Participants underwent resting-state functional magnetic resonance imaging. Subsequently, the disparity in amplitude of low-frequency fluctuations (ALFF) values among groups was analyzed, followed by functional connectivity (FC) investigations employing the cerebellum crus as seed regions.</p><p><strong>Results: </strong>Migraine patients frequently experience neuropsychological disorders and insomnia, which are interconnected. Both migraine with insomnia (MwI) and migraine without insomnia (MwoI) groups demonstrated elevated amplitude of low-frequency fluctuations (ALFF) in the left Crus I and II compared to the healthy controls (HC) group, with the MwI group exhibiting more pronounced alterations. Additionally, both patient groups showed decreased FC between the left Crus I and the right middle temporal gyrus (MTG) and inferior temporal gyrus (ITG) relative to the HC group. The MwoI group showed significantly lower FC compared to both the HC and MwI groups. A significant negative correlation was observed between ALFF in the left Crus I/II and Pittsburgh Sleep Quality Index (PSQI) scores in the MwoI group. Conversely, in the combined migraine cohort, FC between the left Crus I and the right MTG/ITG showed a positive correlation with PSQI scores.</p><p><strong>Conclusion: </strong>This study identified a correlation between aberrant functional activity in the left Crus I/II and migraine comorbidity with insomnia. These findings provide fresh perspectives on the neural mechanisms underlying the migraine-insomnia relationship, thereby facilitating the identification of potential neuroimaging biomarkers and the exploration of targeted interventions for this patient subgroup.</p>","PeriodicalId":12639,"journal":{"name":"Frontiers in Neuroscience","volume":"20 ","pages":"1745862"},"PeriodicalIF":3.2,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12872798/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146141947","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}