Abstract: Objective To investigate the changes of brain functional activity in resting-state functional magnetic resonance imaging (rs-fMRI) before and after modified electroconvulsive therapy (MECT), so as to clarify the neuroimaging mechanism of MECT in first-episode patients with major depressive disorder (MDD). Methods A total of 28 MDD patients who were admitted to the Affiliated Xuzhou Oriental Hospital of Xuzhou Medical University and scheduled for MECT from January 2021 to February 2022 were selected. Then, rs-fMRI scan was performed, and the 24 Hamilton Depression Scale (HAMD-24) scores were evaluated before and after MECT. Imaging data were processed by the DPABI V6.0 software based on Matlab R2019b platform. The standardized amplitude of low-frequency fluctuation (mALFF) value and functional connectivity (FC) value were obtained from the brain regions with remarkable differences. Then, their associations with the rate of score reduction during clinical treatment were analyzed. Results Compared with those before treatment, the total score of HAMD-24 in MDD patients after MECT significantly decreased (P<0.001). Compared with those before treatment, the mALFF of the postcentral gyrus on both sides of the MDD patients decreased after MECT (P＜0.05), and was negatively associated with the rate of score reduction during clinical treatment (r=-0.558,P=0.002). When the left postcentral gyrus was highlighted as a region of interest (ROI), the FC of the left postcentral gyrus to the right calcarine gyrus and the right lingual gyrus decreased after MECT in MDD patients (P＜0.05), and was negatively associated with the rate of score reduction during clinical treatment (r=-0.425,P=0.024). Conclusions MECT may relieve the depression symptoms of MDD patients through regulating the mALFF of the postcentral gyrus on both sides, and the FC of the left postcentral gyrus to the right calcarine gyrus and the right lingual gyrus. Therefore, fMRI plays an important role in investigating the changes of brain function before and after MECT in depression patients.