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

Xiao Wu; Yue Zhang; Wen-Ting Luo; Run-Ru Mai; Xiao-Yan Hou; Zi-Qiang Xia; Bi-Yun Xu; Bo Liu

doi:10.3389/fnins.2021.609640

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

Front Neurosci. 2021 Mar 12:15:609640. doi: 10.3389/fnins.2021.609640. eCollection 2021.

Authors

Xiao Wu¹, Yue Zhang², Wen-Ting Luo³, Run-Ru Mai⁴, Xiao-Yan Hou², Zi-Qiang Xia³, Bi-Yun Xu⁴, Bo Liu²

Affiliations

¹ Department of Chinese Medicine, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
² Department of Radiology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.
³ The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, China.
⁴ Department of Sleep Disorder, Fangcun Branch, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.

Abstract

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 < 25%). Spontaneous neuronal activity was measured by fractional amplitude of low-frequency fluctuations (fALFF) and HRV values and was compared between the two groups as well as before vs after taVNS. We then analyzed the correlations among efficacy of taVNS for 4 weeks, the fALFF and HRV values during continuous taVNS state. The results showed that the HRV parameter values (i.e., root mean square of successive differences, percentage of adjacent NN intervals differing by >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.

Keywords: bio-markers; efficacy; fractional amplitude of low-frequency fluctuations (fALFF); heart rate variability (HRV); primary insomnia; transcutaneous auricular vagus nerve stimulation (taVNS).