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Disentangling the Switching Behavior in Functional Connectivity Dynamics in Autism Spectrum Disorder: Insights from Developmental Cohort Analysis and Molecular-Cellular Associations

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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 [3]Kunming Univ Sci & Technol, Med Sch, Kunming 650500, Peoples R China [4]Kunming Univ Sci & Technol, Affiliated Hosp, Peoples Hosp Yunnan Prov 1, Dept Clin Psychol, Kunming 650500, Peoples R China [5]Capital Med Univ, Beijing Tiantan Hosp, Dept Neurosurg, Beijing 100070, 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
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关键词: autism spectrum disorder brain dynamics development molecular mechanisms resting-state fMRI

摘要:
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.

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大类 | 1 区 综合性期刊
小类 | 1 区 化学:综合 1 区 材料科学:综合 1 区 纳米科技
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Q1 CHEMISTRY, MULTIDISCIPLINARY Q1 MATERIALS SCIENCE, MULTIDISCIPLINARY Q1 NANOSCIENCE & NANOTECHNOLOGY

影响因子: 最新[2023版] 最新五年平均 出版当年[2024版] 出版当年五年平均 出版前一年[2023版]

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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
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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
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