Disentangling the Switching Behavior in Functional Connectivity Dynamics in Autism Spectrum Disorder: Insights from Developmental Cohort Analysis and Molecular-Cellular Associations
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.
基金:
the Yunnan Fundamental Research Projects (202501AV070005,202201BE070001-004), Kunming University of Science and Technology,and First People’s Hospital of Yunnan Province Joint Special Project on Medical Research (KUST-KH2022024Y).
第一作者机构:[1]Kunming Univ Sci & Technol, Inst Primate Translat Med, State Key Lab Primate Biomed Res, Kunming 650500, Peoples R China[2]Kunming Univ Sci & Technol, Fac Mech & Elect Engn, Kunming 650500, Peoples R China
共同第一作者:
通讯作者:
通讯机构:[1]Kunming Univ Sci & Technol, Inst Primate Translat Med, State Key Lab Primate Biomed Res, Kunming 650500, Peoples R China[6]Chinese Acad Sci, Brainnetome Ctr, Inst Automat, Beijing 100190, Peoples R China[7]Chinese Acad Sci, Inst Automat, Natl Lab Pattern Recognit, Beijing 100190, Peoples R China[8]Yunnan Key Lab Primate Biomed Res, Kunming 650500, Peoples R China
推荐引用方式(GB/T 7714):
Li Wei,Qiu Xia,Chen Jin,et al.Disentangling the Switching Behavior in Functional Connectivity Dynamics in Autism Spectrum Disorder: Insights from Developmental Cohort Analysis and Molecular-Cellular Associations[J].ADVANCED SCIENCE.2025,doi:10.1002/advs.202403801.
APA:
Li, Wei,Qiu, Xia,Chen, Jin,Chen, Kexuan,Chen, Meiling...&Wang, Jiaojian.(2025).Disentangling the Switching Behavior in Functional Connectivity Dynamics in Autism Spectrum Disorder: Insights from Developmental Cohort Analysis and Molecular-Cellular Associations.ADVANCED SCIENCE,,
MLA:
Li, Wei,et al."Disentangling the Switching Behavior in Functional Connectivity Dynamics in Autism Spectrum Disorder: Insights from Developmental Cohort Analysis and Molecular-Cellular Associations".ADVANCED SCIENCE .(2025)