Predicting treatment response to transcutaneous auricular vagus nerve stimulation in patients with insomnia: resting-state functional connectivity based multivoxel pattern analysis

BACKGROUND: The salience network, with the insula as its central hub, plays a pivotal role in the pathophysiology of primary insomnia (PI). Transcutaneous auricular vagus nerve stimulation (taVNS) shows therapeutic potential, its neural mechanisms and predictive biomarkers remain uncharacterized. METHODS: In a double‐blind trial, 67 PI patients (taVNS = 34, sham = 33) underwent clinical assessments and resting‐state fMRI at baseline and after 4‐week treatment. We analyzed:1)Treatment‐induced changes in bilateral insula‐cortical functional connectivity (FC); 2)Predictive value of baseline FC using support vector regression. RESULTS: TaVNS group showed significantly improved clinical assessment compared with staVNS. Decreased rs‐FCs were found between the left insula and areas involved in DMN(superior parietal gyrus, SPG), Visual/Auditory (superior occipital gyrus, SOG; middle occipital gyrus, MOG; calcarine and middle temporal gyrus, MTG) and cingulo‐opercular network(middle frontal gyrus, MFG and cerebellum).In addition, decreased FC between left insula and left cerebellum correlated negatively with sleep disturbances score improvement (r = ‐0.502, p = 0.006, Bonferroni correction), while decreased FC between left insula and right SOG positively with sleep latency score (r = 0.391, p = 0.040,uncorrection). Baseline left insula‐visual/auditory circuit FC can predicte taVNS treatment response in PI (r = 0.534, p = 0.002, 5000 permutation test). CONCLUSIONS: TaVNS may alleviate PI symptoms by reducing FCs between the salience and task‐positive networks and within the cingulo‐opercular network to reduce visual‐related overactivity and hypervigilance.The baseline functional connectivity in the left insula‐visual/auditory circuit could act as a candidate biomarker for predicting taVNS treatment response, which enable the screen of therapy‐responsive insomnia patients before treatment. CLINICAL TRIALS REGISTRATION: Chinese Clinical Trial Registry (ChiCTR 1900022535, 2019‐04‐16). SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12888‐025‐07484‐x.