Disentangling the Switching Behavior in Functional Connectivity Dynamics in Autism Spectrum Disorder: Insights from Developmental Cohort Analysis and Molecular‐Cellular Associations
Abstract Characterizing the transition or switching behavior between multistable brain states in functional connectivity dynamics (FCD) holds promise for uncovering the underlying neuropathology of Autism Spectrum Disorder (ASD). However, whether and how switching behaviors in FCD change in patients...
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| Format: | Article |
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Wiley
2025-05-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202403801 |
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| author | Wei Li Xia Qiu Jin Chen Kexuan Chen Meiling Chen Yinyan Wang Wenjie Sun Jing Su Yongchang Chen Xiaobao Liu Congying Chu Jiaojian Wang |
| author_facet | Wei Li Xia Qiu Jin Chen Kexuan Chen Meiling Chen Yinyan Wang Wenjie Sun Jing Su Yongchang Chen Xiaobao Liu Congying Chu Jiaojian Wang |
| author_sort | Wei Li |
| collection | DOAJ |
| description | Abstract Characterizing the transition or switching behavior between multistable brain states in functional connectivity dynamics (FCD) holds promise for uncovering the underlying neuropathology of Autism Spectrum Disorder (ASD). However, whether and how switching behaviors in FCD change in patients with developmental ASD, as well as their cellular and molecular basis, remains unexplored. This study develops a region‐wise FCD switching index (RFSI) to investigate the drivers of FCD. This work finds that brain regions within the salience, default mode, and frontoparietal networks serve as abnormal drivers of FCD in ASD across different developmental stages. Additionally, changes in RFSI at different developmental stages of ASD correlated with transcriptomic profiles and neurotransmitter density maps. Importantly, the abnormal RFSI identifies in humans has also been observed in genetically edited ASD monkeys. Finally, single‐nucleus RNA sequencing data from patients with developmental ASD are analyzed and aberrant switching behaviors in FCD may be mediated by somatostatin‐expressing interneurons and altered differentiation patterns in astrocyte State2. In conclusion, this study provides the first evidence of abnormal drivers of FCD across different stages of ASD and their associated cellular and molecular mechanisms. These findings deepen the understanding of ASD neuropathology and offer valuable insights into treatment strategies. |
| format | Article |
| id | doaj-art-da631891384b43caba4853673ea10045 |
| institution | OA Journals |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-da631891384b43caba4853673ea100452025-08-20T02:02:16ZengWileyAdvanced Science2198-38442025-05-011220n/an/a10.1002/advs.202403801Disentangling the Switching Behavior in Functional Connectivity Dynamics in Autism Spectrum Disorder: Insights from Developmental Cohort Analysis and Molecular‐Cellular AssociationsWei Li0Xia Qiu1Jin Chen2Kexuan Chen3Meiling Chen4Yinyan Wang5Wenjie Sun6Jing Su7Yongchang Chen8Xiaobao Liu9Congying Chu10Jiaojian Wang11State Key Laboratory of Primate Biomedical Research Institute of Primate Translational Medicine Kunming University of Science and Technology Kunming 650500 ChinaState Key Laboratory of Primate Biomedical Research Institute of Primate Translational Medicine Kunming University of Science and Technology Kunming 650500 ChinaState Key Laboratory of Primate Biomedical Research Institute of Primate Translational Medicine Kunming University of Science and Technology Kunming 650500 ChinaMedical School Kunming University of Science and Technology Kunming 650500 ChinaDepartment of Clinical Psychology the First People's Hospital of Yunnan Province The Affiliated Hospital of Kunming University of Science and Technology Kunming 650500 ChinaDepartment of Neurosurgery Beijing Tiantan Hospital Capital Medical University Beijing 100070 ChinaState Key Laboratory of Primate Biomedical Research Institute of Primate Translational Medicine Kunming University of Science and Technology Kunming 650500 ChinaState Key Laboratory of Primate Biomedical Research Institute of Primate Translational Medicine Kunming University of Science and Technology Kunming 650500 ChinaState Key Laboratory of Primate Biomedical Research Institute of Primate Translational Medicine Kunming University of Science and Technology Kunming 650500 ChinaFaculty of Mechanical and Electrical Engineering Kunming University of Science and Technology Kunming 650500 ChinaBrainnetome Center & National Laboratory of Pattern Recognition Institute of Automation Chinese Academy of Sciences Beijing 100190 ChinaState Key Laboratory of Primate Biomedical Research Institute of Primate Translational Medicine Kunming University of Science and Technology Kunming 650500 ChinaAbstract Characterizing the transition or switching behavior between multistable brain states in functional connectivity dynamics (FCD) holds promise for uncovering the underlying neuropathology of Autism Spectrum Disorder (ASD). However, whether and how switching behaviors in FCD change in patients with developmental ASD, as well as their cellular and molecular basis, remains unexplored. This study develops a region‐wise FCD switching index (RFSI) to investigate the drivers of FCD. This work finds that brain regions within the salience, default mode, and frontoparietal networks serve as abnormal drivers of FCD in ASD across different developmental stages. Additionally, changes in RFSI at different developmental stages of ASD correlated with transcriptomic profiles and neurotransmitter density maps. Importantly, the abnormal RFSI identifies in humans has also been observed in genetically edited ASD monkeys. Finally, single‐nucleus RNA sequencing data from patients with developmental ASD are analyzed and aberrant switching behaviors in FCD may be mediated by somatostatin‐expressing interneurons and altered differentiation patterns in astrocyte State2. In conclusion, this study provides the first evidence of abnormal drivers of FCD across different stages of ASD and their associated cellular and molecular mechanisms. These findings deepen the understanding of ASD neuropathology and offer valuable insights into treatment strategies.https://doi.org/10.1002/advs.202403801autism spectrum disorderbrain dynamicsdevelopmentmolecular mechanismsresting‐state fMRI |
| spellingShingle | Wei Li Xia Qiu Jin Chen Kexuan Chen Meiling Chen Yinyan Wang Wenjie Sun Jing Su Yongchang Chen Xiaobao Liu Congying Chu Jiaojian Wang Disentangling the Switching Behavior in Functional Connectivity Dynamics in Autism Spectrum Disorder: Insights from Developmental Cohort Analysis and Molecular‐Cellular Associations Advanced Science autism spectrum disorder brain dynamics development molecular mechanisms resting‐state fMRI |
| title | Disentangling the Switching Behavior in Functional Connectivity Dynamics in Autism Spectrum Disorder: Insights from Developmental Cohort Analysis and Molecular‐Cellular Associations |
| title_full | Disentangling the Switching Behavior in Functional Connectivity Dynamics in Autism Spectrum Disorder: Insights from Developmental Cohort Analysis and Molecular‐Cellular Associations |
| title_fullStr | Disentangling the Switching Behavior in Functional Connectivity Dynamics in Autism Spectrum Disorder: Insights from Developmental Cohort Analysis and Molecular‐Cellular Associations |
| title_full_unstemmed | Disentangling the Switching Behavior in Functional Connectivity Dynamics in Autism Spectrum Disorder: Insights from Developmental Cohort Analysis and Molecular‐Cellular Associations |
| title_short | Disentangling the Switching Behavior in Functional Connectivity Dynamics in Autism Spectrum Disorder: Insights from Developmental Cohort Analysis and Molecular‐Cellular Associations |
| title_sort | disentangling the switching behavior in functional connectivity dynamics in autism spectrum disorder insights from developmental cohort analysis and molecular cellular associations |
| topic | autism spectrum disorder brain dynamics development molecular mechanisms resting‐state fMRI |
| url | https://doi.org/10.1002/advs.202403801 |
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