CNS Neuroscience & Therapeutics最新文献

{"title":"Prefrontal Neurovascular Coupling Abnormalities Associated With Cognitive Performance in Multiple Sclerosis.","authors":"Ruisi Gong, Hao Zhang, Jinlin Jiao, Lei Liu, Xiaohan Xu, Huiwen Song, Yuexin Zhou, Yuanjie Duan, Hefei Fu, Jibin Cao, Lingling Cui","doi":"10.1002/cns.71124","DOIUrl":"10.1002/cns.71124","url":null,"abstract":"<p><strong>Background: </strong>Cognitive impairment is a prevalent and debilitating feature in multiple sclerosis (MS), yet its pathophysiology remains incompletely understood. Dysfunction of the neurovascular unit (NVU) and impaired neurovascular coupling (NVC) may be related to cognitive performance in MS, but this pathway remains insufficiently studied. This study investigated whether NVC abnormalities are associated with cognitive performance in MS.</p><p><strong>Methods: </strong>Ninety-seven MS patients and 83 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging (rs-fMRI) and arterial spin labeling (ASL) perfusion MRI acquisition. The amplitude of low-frequency fluctuations (ALFF) was used as an index of regional spontaneous neuronal activity, and cerebral blood flow (CBF) was quantified. NVC was quantified globally (CBF-ALFF correlation) and regionally (CBF/ALFF ratio). We analyzed the correlations between regional NVC metrics and cognitive performance and Expanded Disability Status Scale (EDSS) scores. Sensitivity analyses tested robustness across alternative functional metrics, gray matter volume (GMV), T2 lesion volume, disability severity, treatment status, and the relapsing-remitting multiple sclerosis (RRMS) subgroup.</p><p><strong>Results: </strong>Compared with HCs, MS patients demonstrated (1) reduced CBF-ALFF coupling in the ALFF-based analysis, and (2) increased CBF/ALFF ratios in the bilateral medial prefrontal cortex (mPFC). The regional mPFC finding, particularly on the left, remained robust across sensitivity analyses and was associated with worse cognitive performance and higher EDSS scores.</p><p><strong>Conclusion: </strong>These findings suggest altered NVC in MS, with regional prefrontal abnormalities representing the most robust and clinically relevant finding. Regional prefrontal NVC abnormalities may provide a potential imaging correlate of cognitive performance in MS.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 9","pages":"e71124"},"PeriodicalIF":6.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13530862/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148862777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PPARγ-Dependent Pioglitazone Treatment Suppresses Neuroinflammation and Improves Cognition in Sepsis-Associated Encephalopathy in Mice.","authors":"Jing Zhang, Peng Wang, Nan Li, Yan Gao","doi":"10.1002/cns.71103","DOIUrl":"10.1002/cns.71103","url":null,"abstract":"<p><strong>Objective: </strong>To assess whether pioglitazone (Pio) protects against sepsis-associated encephalopathy (SAE) and to probe underlying mechanisms.</p><p><strong>Methods: </strong>Sepsis was induced in male C57BL/6 mice by caecal ligation and puncture (CLP). At 24 h post-CLP, mice received Pio and/or the PPAR-γ antagonist GW9662 and were followed for 14-day survival. Cognitive and affective behaviors were evaluated using a behavioral battery. Blood-brain barrier (BBB) permeability was assessed by Evans blue extravasation, and hippocampal inflammatory and apoptotic readouts were examined by ELISA, immunoblotting, and TUNEL staining.</p><p><strong>Results: </strong>CLP reduced 14-day survival to 21.82%, whereas Pio increased survival to 46.15%; GW9662 abolished this benefit (19.36%). Pio improved behavior consistent with reduced anxiety-like behavior and better learning/memory. Mechanistically, Pio decreased Evans blue leakage and increased Claudin-5, suppressed TLR4/NF-κB-associated inflammation (lower TNF-α, IL-1β, and IL-6; higher IL-10), and reduced neuronal apoptosis; these effects were largely reversed by GW9662.</p><p><strong>Conclusion: </strong>Pioglitazone alleviates sepsis-induced brain dysfunction and improves survival in mice in a PPAR-γ-dependent manner.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 9","pages":"e71103"},"PeriodicalIF":6.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13527159/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148862855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Whole-Brain Monosynaptic Inputs to and Axonal Projections From Posterior Insular Cortex GABAergic Neurons in Mice.","authors":"Wan-Qiao Qi, Xin-Yue Zhang, Wei-Xiang Ma, Wei-Min Qu, Jia-Qi Shi, Zhi-Li Huang, Yu-Lan Zhu","doi":"10.1002/cns.71102","DOIUrl":"https://doi.org/10.1002/cns.71102","url":null,"abstract":"<p><strong>Background: </strong>The posterior insular cortex (PIC) is a multimodal sensory integration center, and the GABAergic neurons are associated with functions such as pain perception, emotional regulation, and fear memories encoding. However, the whole-brain connectivity to PIC GABAergic neurons remains unclear.</p><p><strong>Objective: </strong>To map the whole-brain input-output connectivity of PIC GABAergic neurons.</p><p><strong>Methods: </strong>This study combined cell-type-specific retrograde/anterograde viral tracing systems with Cre/loxP genetic technology to perform a comparative analysis of the localization and quantification of monosynaptic inputs and axonal projections of PIC GABAergic neurons.</p><p><strong>Results: </strong>Retrograde tracing identified 45 input nuclei, with densest inputs from the piriform cortex (Pir) and secondary somatosensory cortex (S2) of the isocortex, thalamic nuclei including the posterior thalamic nuclear group (PO) and parafascicular thalamic (PAF), exhibiting ipsilateral preference. Anterograde tracing revealed 18 output targets, with densest projections to the caudate putamen (CPu), external globus pallidus (GPe), and ventral pallidum (VP) of the basal ganglia and multiple subnuclei of the amygdala.</p><p><strong>Conclusions: </strong>PIC GABAergic neurons receive dense inputs from the isocortex and thalamus and send prominent projections to the basal ganglia and amygdala, with these brain regions constituting key hubs of the whole-brain connectivity network. This connectivity pattern provides a novel anatomical perspective for elucidating their roles in physiological behavior regulation.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 9","pages":"e71102"},"PeriodicalIF":6.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148890580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Whole-Brain Monosynaptic Inputs and Outputs of Corticotropin-Releasing Hormone Neurons of the Paraventricular Nucleus of the Hypothalamus in Male Mice.","authors":"Ziteng Yue, Danyang Zhao, Xinxin Chen, Yousheng Zhang, Heng Zhang, Yinchang Wang, Yuhang Liu, Yuxin Yang, Can Geng, Yimeng Song, Xiaoyi Wang, Sheng Wang","doi":"10.1002/cns.71127","DOIUrl":"10.1002/cns.71127","url":null,"abstract":"<p><strong>Objective: </strong>The paraventricular nucleus of the hypothalamus (PVN) is a central hub integrating neuroendocrine, autonomic, and behavioral responses. Corticotropin-releasing hormone (CRH) neurons in the PVN (PVN^CRH) play a pivotal role in stress responses, anxiety, and motivation. However, the brain-wide monosynaptic input-output architecture of PVN^CRH neurons remains incompletely defined, limiting circuit-based functional dissection.</p><p><strong>Methods: </strong>Using Cre-dependent modified rabies virus for retrograde monosynaptic tracing and adeno-associated viruses for anterograde tracing in CRH-Cre mice, we systematically mapped the whole-brain inputs and outputs of PVN^CRH neurons.</p><p><strong>Results: </strong>PVN^CRH neurons received direct inputs from 55 brain regions, with a predominant contribution from diencephalon areas and an overall ipsilateral bias (61.4%). Notably, highly specific inputs originated from the ventral hippocampal CA1 and nucleus accumbens core. PVN^CRH neurons also sent widespread axonal projections throughout the brain. These outputs converge onto multiple circuit modules, with dense projections to emotion-related nuclei and autonomic regulatory centers.</p><p><strong>Conclusion: </strong>This study establishes a comprehensive whole-brain monosynaptic input-output atlas of PVN^CRH neurons. The resultant neuroanatomical framework delineates their extensive connectivity with stress-, emotion-, autonomic-, and respiration-related circuits, providing a structural basis for future circuit-level investigations into stress-related psychiatric disorders and systemic autonomic dysregulation.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 9","pages":"e71127"},"PeriodicalIF":6.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13527161/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148862824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"P7C3 Compounds as Targeted Mitochondrial Therapeutics for Brain Disorders.","authors":"Yajing Chen, Xiaohuan Du, Fang Li, Shuwei Yuan, Wenjing Wang, Zengyan Zhu, Mei Wang, Chao Gu","doi":"10.1002/cns.71139","DOIUrl":"10.1002/cns.71139","url":null,"abstract":"<p><strong>Background: </strong>P7C3 compounds are aminopropyl carbazole derivatives identified through phenotypic screening for proneurogenic activity. They directly activate nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in the NAD⁺ salvage pathway. However, a comprehensive synthesis of their mechanisms and therapeutic potential across neurological disorders is currently lacking.</p><p><strong>Methods: </strong>A systematic literature review was conducted in PubMed, Web of Science, and Scopus to synthesize the discovery trajectory, structure-activity relationships, molecular mechanisms, and preclinical efficacy of P7C3 compounds. The following keyword combinations were used: (\"P7C3\" OR \"P7C3 compound\") AND (\"NAMPT\" OR \"NAD+\" OR \"sirtuin\" OR \"mitochondria\") AND (\"neuroprotection\" OR \"neurodegenerative\").</p><p><strong>Results: </strong>P7C3 elevates intracellular NAD⁺ levels, engages SIRT1 and SIRT3 deacetylase cascades, enhances mitochondrial quality control and attenuates oxidative stress. This review discusses the discovery, structure-activity relationships, and molecular mechanisms of P7C3, with a particular emphasis on mitochondrial dynamics and redox homeostasis. The efficacy of P7C3 in preclinical studies was evaluated across Alzheimer's disease (AD), Parkinson's disease (PD), traumatic brain injury (TBI), ischemic stroke, depression, and chemotherapy-induced neuropathy. These neuroprotective effects occur independently of disease-specific aggregates. Challenges hindering clinical application include the on-target safety of NAMPT activation given the concurrent development of NAMPT inhibitors for tumorigenesis, the absence of validated predictive biomarkers, and the failure of prior NAMPT-targeting trials.</p><p><strong>Conclusions: </strong>P7C3 illustrates how phenotypic screening coupled with target deconvolution can yield therapeutic candidates with potential applications across a broad spectrum of neurological disorders.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 9","pages":"e71139"},"PeriodicalIF":6.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148890573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Melatonin Improves Cognitive Function and Suppresses Excessive Mitophagy in Rats With Vascular Dementia.","authors":"Si-Jia Hou, Xing-Yi Guo, Zhi-Gang Wang, Ting-Yan Chen, Yang Li, Sui-Yi Xu","doi":"10.1002/cns.71141","DOIUrl":"10.1002/cns.71141","url":null,"abstract":"<p><strong>Aims: </strong>Melatonin has shown neuroprotective potential in various models of cerebrovascular diseases, but its effects on mitophagy in vascular dementia (VaD) induced by chronic cerebral hypoperfusion (CCH) remain unclear.</p><p><strong>Methods: </strong>Eighteen adult male Sprague-Dawley rats underwent bilateral common carotid artery occlusion (BCCAO) to induce CCH. Animals were randomly assigned to three groups (n = 6 per group): sham-operated controls, BCCAO model animals receiving vehicle injection, and BCCAO animals treated with daily melatonin (10 mg/kg, intraperitoneally for 14 days). Cognitive performance was evaluated using the Morris water maze. Regional cerebral blood flow (rCBF) was measured with high-resolution laser Doppler imaging. Mitophagy was assessed via Western blot analysis of LC3BII/I, TOMM20, COX IV, caspase-3, and immunofluorescence colocalization of LC3B with TOMM20 in the hippocampal CA1 subfield.</p><p><strong>Results: </strong>BCCAO rats exhibited significant cognitive deficits in the Morris water maze, along with persistently reduced rCBF. BCCAO also induced a significant upregulation of hippocampal mitophagy, as indicated by an elevated LC3BII/I, decreased TOMM20 and COX IV levels, and increased colocalization of TOMM20 and LC3B immunofluorescence signals. Caspase-3 expression was markedly higher in the BCCAO group. Melatonin treatment improved rCBF recovery at day 14, mitigated the spatial learning and memory impairments, decreased the LC3BII/I, increased mitochondrial protein markers (TOMM20, COX IV), reduced the colocalization of TOMM20 and LC3B puncta, and attenuated caspase-3 levels.</p><p><strong>Conclusion: </strong>These findings indicate that CCH in the VaD model induces excessive hippocampal mitophagy and cognitive impairment. The cognitive improvement observed with melatonin treatment is closely correlated with restored cerebral perfusion and attenuated mitophagic activity.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 9","pages":"e71141"},"PeriodicalIF":6.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13540647/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148885812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Awake Craniotomy for Eloquent Region Glioblastoma Classified by Tumor Location-A Retrospective and Prospective Cohort Study.","authors":"Yuzhe Li, Shimeng Weng, Jiahan Dong, Jiangwei Wang, Zhong Zhang, Xing Fan, Yinyan Wang, Wenbin Ma, Tao Jiang, Shengyu Fang","doi":"10.1002/cns.71126","DOIUrl":"10.1002/cns.71126","url":null,"abstract":"<p><strong>Introduction: </strong>The efficacy of awake craniotomy (AC) with intraoperative mapping for glioblastoma (GBM) in eloquent regions remains debated. This study aims to evaluate functional and survival outcomes of GBM patients undergoing AC stratified by tumor locations.</p><p><strong>Methods: </strong>A combined retrospective (2015-2023, n = 114: 43 AC vs. 71 standard craniotomy) and prospective cohort (2023-2025, n = 28: 13 AC vs. 15 standard craniotomy) of GBM patients with motor/language-eloquent tumors was analyzed. Tumors were classified into motor subtypes (I: precentral gyrus; II: premotor/supplementary motor; III: internal capsule posterior limb; IV: other) and language subtypes (I: Broca's/precentral; II: postcentral/supramarginal gyrus; III: Wernicke's; IV: insular; V: other). Outcomes included extent of resection (EOR), postoperative motor/language recovery, overall survival (OS), and progression-free survival (PFS).</p><p><strong>Results: </strong>The retrospective cohort demonstrated that AC has advantages in functional preservation across various motor/language subtypes. However, AC was associated with significantly deteriorated survival outcomes specifically in precentral gyrus GBMs. A prospective cohort study, enrolling only precentral gyrus GBMs for validation, yielded results consistent with the retrospective findings: worsened OS and PFS (OS: HR = 3.223, p = 0.0450; PFS: HR = 2.374, p = 0.0476); reduced EOR (AC: 74.3% ± 5.3%; standard craniotomy: 86.9% ± 12.3%, p = 0.0470); and better motor recovery.</p><p><strong>Conclusions: </strong>Functional preservation and survival outcomes of AC in GBM exhibited subtype-specific correlations with tumor locations. AC with intraoperative mapping effectively preserves neurological function in GBM patients. However, for tumors involving the precentral gyrus, the AC approach carries greater risks than benefits and should be considered with caution.</p><p><strong>Trial registration: </strong>Strategic Intervention on Preserving Motor Function During Awake Craniotomy: NCT05143788. Strategic Intervention on Preserving Language Function During Awake Craniotomy: NCT05143775.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 9","pages":"e71126"},"PeriodicalIF":6.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13538451/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148878766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurodevelopmental Alterations in Inhibitory Interneurons of Cortex, Hippocampus, and Striatum of Genetic Absence Epilepsy Rats.","authors":"Nihan Çarçak, Elif Tuğçe Erdeve, Courtney J Wright, Elif Keskinöz, My Andersson, Filiz Onat, Deniz Kırık","doi":"10.1002/cns.71110","DOIUrl":"10.1002/cns.71110","url":null,"abstract":"<p><strong>Aims: </strong>Absence seizures, characterized by spike-and-wave discharges (SWDs), are mediated by reciprocal thalamocortical interactions; however, the contribution of developing inhibitory networks to SWDs remains unclear. We investigated the developmental trajectory of inhibitory interneurons in Genetic Absence Epilepsy Rats from Strasbourg (GAERS) by analyzing their distribution across postnatal development in the somatosensory (S1) and motor (M1) cortices, the hippocampus, and striatum.</p><p><strong>Methods: </strong>The neurodevelopmental trajectory of parvalbumin-positive (PV+) and somatostatin-positive (SST+) interneurons was quantified at three critical stages: postnatal day 14 (P14), when SWDs were not yet observed, P21 when immature SWDs appear, and adulthood (P90), when mature SWDs are established. Wistar rats served as controls. Brain sections were processed immunohistochemically to quantify interneuron density.</p><p><strong>Results: </strong>PV+ interneuron density across S1 and M1 was significantly higher in GAERS at P14 than control. However, this difference was not maintained at P21 and adults. Conversely, SST+ interneurons exhibited a delayed increase in M1. GAERS displayed higher PV+ interneuron density in the dentate gyrus and CA1 at P14, whereas SST+ interneuron density remained unchanged across hippocampal subfields. Striatal PV+ and SST+ interneurons increased at later developmental stages, suggesting altered inhibition in basal ganglia.</p><p><strong>Conclusion: </strong>These findings demonstrate a temporally dynamic and region-specific reorganization of interneurons in GAERS that may underlie absence epileptogenesis.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 9","pages":"e71110"},"PeriodicalIF":6.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13540994/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148885955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pragmatic Phenotype-Electrophysiology-Genomics Integration in Pediatric Congenital Myasthenic Syndromes: Insights From 36 Patients in a Single-Center Study in China.","authors":"Liya Cui, Kaiyue Ma, Xiaona Fu, Lin Ge, Bingbing Jia, Wenna Ma, Lei Yang, Zhimei Liu, Junlan Lv, Wenmiao Xu, Lijuan Wang, Guangyuan Zhao, Jiuwei Li, Jie Wu, Quan Wang, Changhong Ding, Xiaotun Ren, Xinming Shen, Hui Xiong","doi":"10.1002/cns.71123","DOIUrl":"https://doi.org/10.1002/cns.71123","url":null,"abstract":"<p><strong>Aims: </strong>To characterize the clinical, electrophysiological, and genetic spectrum of pediatric CMS and evaluate genotype-informed outcomes using an integrated phenotype-electrophysiology-genomics approach.</p><p><strong>Methods: </strong>We retrospectively reviewed 36 pediatric CMS patients evaluated at a single center between 2015 and 2025. Clinical features, RNS, targeted NGS/WES variants, ventilator use, treatments, ACMG/AMP classifications, and MG-ADL outcomes were analyzed.</p><p><strong>Results: </strong>Of 36 patients, 28 (77.8%) developed symptoms in the neonatal period or infancy. Biallelic variants involved 17 CMS genes; postsynaptic CMS was most common (55.6%, 20/36). COLQ and CHRNE were the most frequent genes (13.9%, 5/36 each), followed by CHAT (11.1%, 4/36). VUS were detected in 19 patients (52.8%, 19/36), including 8 with biallelic VUS supported by phenotype, neuromuscular transmission findings, treatment response, and follow-up. RNS showed a ≥ 10% decrement in 16/21 tested patients (76.2%). CHAT-CMS was associated with higher ventilator use (3/4 vs. 6/32; p = 0.041) and early mortality (3/4 vs. 1/32; p = 0.002). Median MG-ADL improved from 5 to 3 after genotype-informed therapy.</p><p><strong>Conclusion: </strong>Pediatric CMS shows marked genetic heterogeneity and frequent VUS-related uncertainty. Integrating phenotype, electrophysiology, and genomics supports diagnosis and mechanism-guided therapy. CHAT-CMS is high risk for early respiratory failure and mortality.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 9","pages":"e71123"},"PeriodicalIF":6.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148896214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disrupted Functional Network Organization in Crohn's Disease: Interoceptive Alterations Linked to Anxiety.","authors":"Shuai Xu, Chunhui Bao, Xinyi Zhu, Qianfeng Wang, Boyu Zhang, Luyi Wu, Hongwei Li, Xuchen Yu, Zhou Hao, Zhensen Chen, He Wang, Huangan Wu","doi":"10.1002/cns.71113","DOIUrl":"10.1002/cns.71113","url":null,"abstract":"<p><strong>Background and aims: </strong>How Crohn's disease alters large-scale brain network organization and interacts with affective symptoms remains poorly understood. We aimed to characterize disease-related disruptions in functional topology, rich-club organization, and hierarchical gradients, and to determine their associations with disease activity and anxiety.</p><p><strong>Methods: </strong>Ninety-seven Crohn's disease patients and 64 healthy controls underwent resting-state fMRI. Graph-theoretical metrics, rich-club analysis, functional gradients, and spectral dynamic causal modeling were applied to assess network properties, hierarchical architecture, and effective connectivity. Associations with the Crohn's Disease Activity Index and anxiety were examined via linear regression.</p><p><strong>Results: </strong>Crohn's disease patients showed widespread network disruptions modestly linked to disease activity, including reduced global and local efficiency, impaired rich-club connectivity, and compressed sensorimotor gradients. Decreased degree centrality in the insula, thalamus, and postcentral gyrus was accompanied by altered hierarchical organization and effective connectivity. Spectral dynamic causal modeling revealed anxiety-related modulation of insular excitation and thalamo-putaminal pathways.</p><p><strong>Conclusions: </strong>Crohn's disease involves widespread functional network disruption and reorganization, particularly in interoceptive regions supporting sensory and emotional processing. Anxiety modulates core limbic circuitry, highlighting the interplay between disease activity and affective symptoms in shaping brain network.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 9","pages":"e71113"},"PeriodicalIF":6.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13526404/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148860443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}