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Background <p>Patients with schizophrenia exhibit widespread disruptions in large-scale brain network communication, particularly within the default mode network (DMN), central executive network (CEN), and salience network (SN) — collectively termed the triple networks. While existing research has established the association between functional abnormalities in these networks and the pathophysiological mechanisms of schizophrenia, investigations into white matter’s functional role remain limited. Specifically, the involvement of white matter in dynamic interactions among the triple networks remains unclear. Dynamic functional connectivity (DFC), capable of capturing time-varying characteristics of brain activity, may offer novel insights into both triple network dysfunction and white matter abnormalities in schizophrenia.</p> Methods <p>This study enrolled 93 schizophrenia patients and 92 healthy controls. To assess white matter function, we extracted 48 white matter networks based on the Johns Hopkins University (JHU) white matter atlas and employed sliding window analysis to examine DFC patterns and global coupling properties within both triple networks and white matter networks. Additionally, a longitudinal observational follow-up study (approximately 5 months) was conducted with 39 patients to evaluate treatment-related changes in DFC and coupling dynamics.</p> Results <p>Compared with healthy controls, schizophrenia patients exhibited significant alterations in both intra-network DFC and global coupling across the triple networks and white matter networks. Longitudinal observations revealed DFC changes and temporal characteristics, particularly within white matter networks. Patients exhibited higher baseline scores for fractional window and mean dwell time than healthy individuals, which decreased during treatment follow-up. Additionally, the PANSS scores of the patients were significantly lower compared to before treatment. Brain regions showing significant global coupling changes included anterior/posterior DMN, corpus callosum, and the left crus of cerebellum.</p> Conclusion <p>Our findings highlight the pathophysiological significance of functional and coupling abnormalities between triple networks and white matter networks in schizophrenia. These&#xa0;results provide novel insights into dynamic alterations within brain networks of schizophrenia patients and may suggest potential neuroimaging biomarkers for future therapeutic strategies.</p>

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Dynamic functional connectivity and coupling analysis of triple networks and white matter functional networks in first-episode schizophrenia patients: mechanisms revealed by follow-up studies

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月24日

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  • Xusha Wu,
  • Yan Li,
  • Wenzhong Hu,
  • Yang Zhang,
  • Xuan Li,
  • Xiaowei Kang,
  • Hong Yin,
  • Yibin Xi

摘要

Background

Patients with schizophrenia exhibit widespread disruptions in large-scale brain network communication, particularly within the default mode network (DMN), central executive network (CEN), and salience network (SN) — collectively termed the triple networks. While existing research has established the association between functional abnormalities in these networks and the pathophysiological mechanisms of schizophrenia, investigations into white matter’s functional role remain limited. Specifically, the involvement of white matter in dynamic interactions among the triple networks remains unclear. Dynamic functional connectivity (DFC), capable of capturing time-varying characteristics of brain activity, may offer novel insights into both triple network dysfunction and white matter abnormalities in schizophrenia.

Methods

This study enrolled 93 schizophrenia patients and 92 healthy controls. To assess white matter function, we extracted 48 white matter networks based on the Johns Hopkins University (JHU) white matter atlas and employed sliding window analysis to examine DFC patterns and global coupling properties within both triple networks and white matter networks. Additionally, a longitudinal observational follow-up study (approximately 5 months) was conducted with 39 patients to evaluate treatment-related changes in DFC and coupling dynamics.

Results

Compared with healthy controls, schizophrenia patients exhibited significant alterations in both intra-network DFC and global coupling across the triple networks and white matter networks. Longitudinal observations revealed DFC changes and temporal characteristics, particularly within white matter networks. Patients exhibited higher baseline scores for fractional window and mean dwell time than healthy individuals, which decreased during treatment follow-up. Additionally, the PANSS scores of the patients were significantly lower compared to before treatment. Brain regions showing significant global coupling changes included anterior/posterior DMN, corpus callosum, and the left crus of cerebellum.

Conclusion

Our findings highlight the pathophysiological significance of functional and coupling abnormalities between triple networks and white matter networks in schizophrenia. These results provide novel insights into dynamic alterations within brain networks of schizophrenia patients and may suggest potential neuroimaging biomarkers for future therapeutic strategies.