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Rs-fMRI reveals that taVNS improves cognitive and emotional function in mild cognitive impairment by reconfiguration of “sensory relay-salience-default” cross-network effective connectivity: a randomized; double-blind; sham-controlled trial
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DOI：10.3389/fneur.2026.1891440.png)
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Abstract
En 中文
BackgroundTranscutaneous auricular vagus nerve stimulation (taVNS) is a promising noninvasive intervention for mild cognitive impairment (MCI); but its clinical efficacy and network-level mechanisms remain unclear.MethodsIn this prospective; randomized; sham-controlled; parallel-group trial; 60 patients with MCI were assigned 1:1 to 12-week taVNS or sham taVNS. The primary outcome was the between-group difference in change from baseline to week 12 on the Montreal Cognitive Assessment-Basic (MoCA-B). Secondary outcomes included AVLT-H; STT-A/B; AFT; BNT; HAMD-17; and HAMA scores. Twenty-eight healthy controls underwent baseline rs-fMRI as a non-randomized reference cohort. Functional connectivity (FC) identified MCI-related abnormal regions; which together with theory-driven regions served as seeds for Granger causality analysis (GCA) to characterize intervention-related effective connectivity changes. Imaging-behavior associations were examined using Pearson correlations. The final per-protocol analysis included 52 randomized patients with complete clinical and imaging data.ResultsAfter 12 weeks; the taVNS group showed significant within-group improvements in global cognition and multiple secondary outcomes; whereas the sham group did not. The between-group difference in MoCA-B change was significant (mean difference = 2.91; 95% CI: 0.79 to 5.03; Cohen’s d = 0.59); indicating a moderate-to-large effect. Baseline FC abnormalities in MCI mainly involved the insula; medial frontal cortex; precuneus; temporal cortex; thalamus; cingulate cortex; and parieto-occipital regions. Following taVNS; effective connectivity was selectively reconfigured within a distributed network centered on the insula; anterior cingulate cortex; temporal cortex; and precuneus. Changes in directed connectivity correlated with changes in MoCA-B; AFT; and HAMA scores. No serious adverse events occurred.Clinical trial registrationhttps://www.chictr.org.cn/showproj.html?proj=131823; identifier (ChiCTR2100049940).
Keywords:
functional connectivity
functional magnetic resonance imaging
mild cognitive impairment
transcutaneous auricular vagus nerve stimulation
brain networks
granger causality analysis
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