Transcutaneous Auricular Vagus Nerve Stimulation Modulates the Prefrontal Cortex in Chronic Insomnia Patients: fMRI Study in the First Session

Abstract

Objectives: Transcutaneous auricular vagus nerve stimulation (taVNS) has been reported to be effective for chronic insomnia (CI). However, the appropriate population for taVNS to treat insomnia is unclear.

Methods: Total twenty-four patients with CI and eighteen health controls (HC) were recruited. Rest-state functional magnetic resonance imaging (Rs-fMRI) was performed before and after 30 min' taVNS at baseline. The activated and deactivated brain regions were revealed by different voxel-based analyses, then the seed-voxel functional connectivity analysis was calculated. In the CI group, 30 min of taVNS were applied twice daily for 4 weeks. Pittsburgh Sleep Quality Index (PSQI) and Flinders Fatigue Scale (FFS) were also assessed before and after 4 weeks of treatment in the CI group. The HC group did not receive any treatment. The correlations were estimated between the clinical scales' score and the brain changes.

Results: The scores of PSQI (p < 0.01) and FFS (p < 0.05) decreased after 4 weeks in the CI group. Compared to the HC group, the first taVNS session up-regulated left dorsolateral prefrontal cortex (dlPFC) and decreased the functional connectivity (FCs) between dlPFC and bilateral medial prefrontal cortex in the CI group. The CI groups' baseline voxel wised fMRI value in the dlPFC were negatively correlated to the PSQI and the FFS score after 4 weeks treatment.

Conclusions: It manifests that taVNS has a modulatory effect on the prefrontal cortex in patients with CI. The initial state of dlPFC may predict the efficacy for taVNS on CI.

Keywords: biomarkers; chronic insomnia; functional magnetic resonance imaging (fMRI); neuromodulation; prefrontal cortex; transcutaneous auricular vagus nerve stimulation.

Figure 1

(A) The electrodes were attached to the surface of cymba conchae. (B) The stimulating place of taVNS. RS-fMRI, rest-state functional Magnetic Resonance Imaging; taVNS, Transcutaneous Auricular Vagus Nerve Stimulation.

Figure 2

Changes of fMRI induced by instant taVNS were measured before and after the first treatment on the two groups. Clinical scales for patients were assessed before and after the 4 weeks' taVNS treatment.

Figure 3

(A) Different voxel based analyses showed similar up- regulated area in left dorsolateral prefrontal cortex. (B) Changes of different voxel based analyses before and after taVNS. (C) ALFF analysis showed taVNS aroused higher activation in the CI group than in the HC group. (D) The FC between the up- regulated dlPFC and bilateral dorsomedial prefrontal cortex decreased after taVNS. (E) Correlations between the clinical scales' scores and the fMRI values. PSQI, Pittsburgh Sleep Quality Index; FFS, Flinders Fatigue Scale; ALFF, amplitude of low frequency fluctuation; fALFF, Fractional ALFF; ReHo, Regional homogeneity; FC, Functional connectivity; 0w, before taVNS treatment; 4w, after 4 week taVNS treatment; Relief Rate, The remission rate was defined as the difference in scale scores before and after treatment divided by the scale scores before treatment. ^*p < 0.05; ^**p < 0.01.