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Background: Although electroconvulsive therapy (ECT) is the most potent treatment for severely major depressive disorder (MDD), little is known about the neural mechanism of ECT in MDD patients. The frontal pole (Fp) plays an important role in integrating social, emotional, and cognitive processes. However, the exact role of Fp, especially at the sub-regional level, response for ECT in MDD remains largely unknown.  Methods and Findings: We combined voxel-based morphometry and resting-state functional connectivity (RSFC) to investigate the structural and functional alterations in Fp sub-regions to explore the mechanism of ECT in 23 MDD patients before and after ECT. Structurally, we found increased gray matter volume (GMV) of the left Fp1 and left Fp2 in MDD patients after ECT. Functionally, we found decreased RSFC between the left Fp1 and right cerebellum, left fusiform gyrus, and between right Fp1 and left fusiform gyrus, as well as increased RSFC between right Fp1 and left angular gyrus, left cuneus, and between right Fp2 and left cuneus in MDD patients after ECT. Furthermore, we also found significant associations between the changes of the GMV/RSFC and the therapeutic efficacy or side effects of ECT in MDD patients.  Conclusion: These results showed that the ECT can distinctly modulate GMV and RSFC of Fp at subregional level in MDD patients, which provide a novel view to understand the mechanism of ECT and may help us optimize the ECT procedures for improving therapeutic efficacy and reducing side effects.

Electroconvulsive Therapy Modulates the Structural and Functional Architecture of Frontal Pole in Major Depressive Disorder