Efficacy and neural mechanisms of transcutaneous auricular vagus nerve stimulation for chronic insomnia: a study...

Traditional auricular therapy for chronic insomnia (Bu Mei in TCM) is used in clinical practice but is limited by insufficient standardization and poorly understood mechanisms. Transcutaneous auricular vagus nerve stimulation (taVNS) provides a quantifiable and reproducible neuromodulatory approach by stimulating vagally innervated regions of the auricular concha, which overlap with auricular acupoints used in TCM. However, evidence in insomnia remains predominantly based on clinical outcomes, whereas longitudinal neuroimaging evidence is limited. Resting-state functional magnetic resonance imaging (rs-fMRI) may complement clinical assessments by characterizing spontaneous brain activity and treatment-related functional changes, thereby providing objective neuroimaging evidence relevant to the potential mechanisms of taVNS.

This protocol will recruit 60 patients with chronic insomnia disorder (CID) and 30 age- and sex-matched healthy controls (HCs). Patients with CID will be randomized 1:1 to receive 4 weeks of active or sham-taVNS. Resting-state functional magnetic resonance imaging (rs-fMRI) will be performed at baseline in all participants and repeated at Week 4 in patients with CID, within 24 hours after the final intervention session. Fractional amplitude of low-frequency fluctuation (fALFF) will serve as a prespecified exploratory neuroimaging measure, with amplitude of low-frequency fluctuation (ALFF) included as a complementary exploratory measure. The neuroimaging analyses will examine baseline differences between patients with CID and HCs and between-group differences in baseline-to-Week-4 changes between the active and sham-taVNS groups to characterize brain functional alterations associated with CID and changes associated with active taVNS relative to sham-taVNS. The primary clinical outcome will be the change in Pittsburgh Sleep Quality Index (PSQI) score from baseline to Week 4. Secondary and follow-up assessments will evaluate insomnia severity, daytime sleepiness, emotional status, cognitive function, pre-sleep arousal, and quality of life. Exploratory correlations between changes in neuroimaging measures and clinical outcomes will also be examined.

This study will integrate clinical assessments with rs-fMRI to evaluate the clinical effects of taVNS in patients with CID and explore associated changes in spontaneous brain activity. The integration of clinical outcomes and exploratory neuroimaging measures may provide complementary evidence on treatment effects and associated brain functional changes, thereby informing future investigation of the potential neural mechanisms of taVNS in CID.

https://www.chictr.org.cn/hvshowprojectEN.html?id=277442&v=1.0, identifier ChiCTR2500103157.