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Objective: Lifelong premature ejaculation (PE) is regarded as one of the most common male sexual dysfunction. We aimed to detect whether insula-related brain functional networks are altered in lifelong PE patients and whether such alterations are "normalised" after selective serotonin reuptake inhibitors (SSRI) administration., Methods: Twenty-three drug-naive lifelong PE patients and 30 healthy controls (HC) were recruited in current study. All subjects underwent resting-state functional magnetic resonance imaging (fMRI) scan at first. One hour after dapoxetine administration, all patients underwent fMRI scanning again. The degree centrality (DC), amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) analysis, and ROI-based functional connectivity (FC) analysis were applied to calculate the abnormalities in insula-related functions among three groups., Results: Compared to HC group, PE patients at baseline showed significantly altered DC, ALFF, and ReHo value of the bilateral insula, which subsequently showed a "normalised" trend after dapoxetine administration. Additionally, compared to HC group, PE patients at baseline showed significantly decreased FC between insula and precentral gyrus, inferior frontal gyrus, middle/inferior temporal gyrus, and caudate, while patients after dapoxetine administration showed increased insula-related FC in anterior cingulate cortex and decreased FC in thalamus and middle/inferior temporal gyrus. The main effects of dapoxetine were located in precentral gyrus, inferior frontal gyrus, caudate, and limbic system., Conclusions: Our findings report altered brain mechanism of insula in lifelong PE patients and also indicate that dapoxetine can "normalise" the abnormal function of the insula to certain extent in lifelong PE patients., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)