ORIGINAL RESEARCH article
Front. Psychiatry
Sec. Sleep Disorders
This article is part of the Research TopicThe Advance on Sleep Disorder: Mechanisms and InterventionsView all 20 articles
Alterations in Coupling between Global Brain Activity and Cerebrospinal Fluid Flow in Patients with Insomnia Disorder before and after Transcranial Direct Current Stimulation: A Resting-State Functional MRI Study
Provisionally accepted
- The First Hospital of Jilin University, Changchun, China
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Background: The coupling between global blood-oxygen-level-dependent (gBOLD) signals and cerebrospinal fluid (CSF) flow has been established in humans and is thought to reflect the function of the brain's glymphatic system. This study aimed to investigate glymphatic system dysfunction in insomnia disorder (ID) and its correlation with clinical symptoms, and to evaluate whether transcranial direct current stimulation (tDCS) can modulate glymphatic system and alleviate insomnia. Methods: We totally enrolled 33 IDs (20 females, 42.3±15.0 years) and 27 healthy controls (HCs, 15 females, 53.6±17.7 years). Among them, 19 IDs (9 females, 38.4±16.1 years) received 2-week tDCS treatment. gBOLD-CSF coupling strength was compared between groups and correlated with clinical scale scores (PSQI, PHQ-9, GAD-7). Changes in gBOLD-CSF coupling strength and clinical scores after tDCS were also examined. Results: IDs showed significantly weaker gBOLD–CSF coupling than HCs (p=0.003). Coupling strength was negatively correlated with PSQI score (r=-0.363, p=0.045) and GAD-7 score (r=-0.435, p=0.014), but not with PHQ-9. After tDCS, patients exhibited significantly reducing in PSQI score(p=0.014), GAD-7 score (p=0.0001) and PHQ-9 score (p<0.0001), along with increasing in gBOLD-CSF coupling strength (p=0.002). Conclusion: Our results indicate that IDs exhibit impaired glymphatic system function, as reflected by reduced gBOLD–CSF coupling strength. This reduction was correlated with the severity of both insomnia and anxiety symptoms. Moreover, we demonstrated that tDCS can not only improve symptoms of insomnia, anxiety, and depression but also enhance glymphatic activity in IDs.
Keywords: insomnia, Anxiety, Depression, Cerebrospinal Fluid, global blood-oxygen-level-dependent signal, Glymphatic system, transcranial direct current stimulation
Received: 14 Sep 2025; Accepted: 25 Nov 2025.
Copyright: © 2025 Liu, Chen, Zhang, Peng, Zhou and Lan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Wenjing Lan
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