Brain Functional Mechanisms Determining the Efficacy of Transcutaneous Auricular Vagus Nerve Stimulation in Primary Insomnia.

Transcutaneous auricular vagus nerve stimulation (taVNS) has been reported to be effective in the treatment of primary insomnia (PI); however, its efficacy varies considerably across individuals for reasons that are unclear. In order to clarify the underlying mechanisms, this study investigated the effects of taVNS on spontaneous neuronal activity and autonomic nervous system function by functional magnetic resonance imaging (fMRI) and measurement of heart rate variability (HRV), respectively, in patients with PI. Forty patients with PI were divided into effective (group A) and ineffective (group B) groups based on their response to taVNS as determined by Pittsburgh Sleep Quality Index score reduction rate (group A ≥ 25% and group B 50 ms, and high frequency) of group A were higher than those of group B during continuous taVNS state. In the fMRI scan, the fALFF values of the right cerebellum, right medial superior frontal gyrus, and bilateral supplementary motor area-which belong to the sensorimotor network (SMN)-were lower in group A than in group B during continuous taVNS state. The correlation analysis revealed that the efficacy of continuous taVNS and HRV and fALFF values were interrelated. These findings demonstrate that differential regulation of the SMN by the autonomic nervous system may be responsible for inter-individual variations in the efficacy of taVNS and suggest that HRV and fALFF are potential biomarkers for predicting PI patients' response to taVNS treatment.