Deqi is taken as an indispensable requirement to achieve acupuncture efficacy. This study aimed to explore the central influence of deqi on the efficacy of acupuncture for functional dyspepsia (FD). 70 FD patients were randomized to receive 20 sessions’ acupuncture treatment with (n = 35) and without deqi (n = 35). In each group, 25 FD patients randomly selected underwent functional magnetic resonance imaging (fMRI) scans before and after treatment. After group re-division according to deqi response, changes of amygdala subregions-based resting-state functional connectivity (rsFC) were compared between the acupuncture with and without obvious deqi group. The clinical changes of the Nepean Dyspepsia Symptom Index (NDSI) measuring FD symptoms were also used to further assess the correlation with amygdala subregions rsFC in FD patients. The decrease in the NDSI scores (pre-pos) in the obvious deqi group was significantly greater than that in the acupuncture without obvious deqi group (p < 0.05). Compared to the without obvious deqi group, the obvious deqi group showed significantly decreased the left basolateral amygdala (BLA) rsFC with bilateral insular (INS), putamen and middle/posterior cingulate cortex (MCC/PCC), right pallidum and hippocampus (HIPP) after treatment. The changed NDSI scores(pre-post) of all 41 FD patients was significantly positively correlated with their Fisher's transformed z value of the left BLA rsFC with left INS (r = 0.376, FDR corrected p = 0.015), and rsFC with right HIPP (r = 0.394, FDR corrected p = 0.015). The changed NDSI scores(pre-post) of the obvious deqi group was significantly negatively correlated with their Fisher's transformed z value of the right centromedial amygdala (CMA) rsFC with left medial prefrontal cortex (mPFC) (r = -0.463, p = 0.035). The results tested the hypothesis that the advantage of deqi on efficacy is related to affecting the BLA and CMA rsFC. It suggested that deqi might influence the abnormal rsFC within the salience network (SN), and participate in the adaptive modulation of disrupted relationship between the SN and default mode network (DMN).

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