Early Fractional Amplitude of Low Frequency Fluctuation Can Predict the Efficacy of Transcutaneous Auricular Vagus Nerve Stimulation Treatment for Migraine Without Aura.

Menghan Feng,Yongsong Ye,Wenting Luo,Chengwei Fu,Xiaoyan Hou,Zeying Wen,Bo Liu,Yue Zhang

doi:10.3389/fnmol.2022.778139

Abstract

Migraine is a common primary headache disorder. Transcutaneous auricular vagus nerve stimulation (taVNS) has been verified to be effective in patients with migraine without aura (MWoA). However, there are large interindividual differences in patients’ responses to taVNS. This study aimed to explore whether pretreatment fractional amplitude of low frequency fluctuation (fALFF) features could predict clinical outcomes in MWoA patients after 4-week taVNS. Sixty MWoA patients and sixty well-matched healthy controls (HCs) were recruited, and migraineurs received 4-week taVNS treatment. Resting-state functional magnetic resonance imaging (rs-fMRI) data were collected, and the significant differences of fALFF were detected between MWoA patients and HCs using two-sample t-test. A mask of these significant regions was generated and used for subsequent analysis. The abnormal fALFF in the mask was used to predict taVNS efficacy for MWoA using a support vector regression (SVR) model combining with feature select of weight based on the LIBSVM toolbox. We found that (1) compared with HCs, MWoA patients exhibited increased fALFF in the left thalamus, left inferior parietal gyrus (IPG), bilateral precentral gyrus (PreCG), right postcentral gyrus (PoCG), and bilateral supplementary motor areas (SMAs), but decreased in the bilateral precuneus and left superior frontal gyrus (SFG)/medial prefrontal cortex (mPFC); (2) after 4-week taVNS treatment, the fALFF values significantly decreased in these brain regions based on the pretreatment comparison. Importantly, the decreased fALFF in the bilateral precuneus was positively associated with the reduction in the attack times (r = 0.357, p = 0.005, Bonferroni correction, 0.05/5), whereas the reduced fALFF in the right PoCG was negatively associated with reduced visual analog scale (VAS) scores (r = −0.267, p = 0.039, uncorrected); (3) the SVR model exhibited a good performance for prediction (r = 0.411, p < 0.001),which suggests that these extracted fALFF features could be used as reliable biomarkers to predict the treatment response of taVNS for MWoA patients. This study demonstrated that the baseline fALFF features have good potential for predicting individualized treatment response of taVNS in MWoA patients, and those weight brain areas are mainly involved in the thalamocortical (TC) circuits, default mode network (DMN), and descending pain modulation system (DPMS). This will contribute to well understanding the mechanism of taVNS in treating MWoA patients and may help to screen ideal patients who respond well to taVNS treatment.

Highlights

Migraine, a common chronic neurological disorder, is characterized by recurrent headache and typically accompanied by nausea, photophobia, and sensitivities to light–sound–smell (Steiner et al, 2013)
We explored how the Transcutaneous auricular vagus nerve stimulation (taVNS) could modulate those abnormal fractional amplitude of lowfrequency fluctuation (fALFF) in patients with Migraine without aura (MWoA), through comparing the fALFF differences between pre- and posttreatment in the mask. (3)We further supposed that the abnormal fALFF of these regions in the mask at baseline could serve as a reliable biomarker to predict the taVNS treatment outcomes for MWoA patients using a support vector regression (SVR) model combined with feature select of weight based on the LIBSVM toolbox
Our results showed that the SVR model works well at predicting the treatment response of taVNS for MWoA patients at baseline (r = 0.411), and those weight brain areas are located in the left thalamus, bilateral SMA, right postcentral gyrus (PoCG), left inferior parietal gyrus (IPG), the bilateral precuneus, and left superior frontal gyrus (SFG)/medial prefrontal cortex (mPFC), mainly involved in the TC circuits, default mode network (DMN), and descending pain modulation system (DPMS)

Summary

Introduction

A common chronic neurological disorder, is characterized by recurrent headache and typically accompanied by nausea, photophobia, and sensitivities to light–sound–smell (Steiner et al, 2013). Medication therapy for MWoA could provide pain control at 45 min to 48 h and lead to addiction and other adverse effects (Diener et al, 2012; Lanteri-Minet, 2014; Westergaard et al, 2014; Abu Bakar et al, 2016; Buse et al, 2016). Transcutaneous auricular vagus nerve stimulation (taVNS), one kind of noninvasive neuromodulation technique, has been verified to relieve headache intensity and reduce the frequency of migraine attacks for MWoA patients in several clinical trials (Luo W. et al, 2020; Zhang et al, 2021). Despite the effectiveness of taVNS for MWoA, the efficacy varies considerably across different subjects. Identifying a valid and objective biomarker for treatment response will be of great importance as it could help screen ideal migraineurs to improve the clinical efficacy and avoid the waste of medical resources

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