Electroconvulsive therapy reduces frontal cortical connectivity in severe depressive disorder

TLDR

ECT is the most potent treatment for severe depression, yet its mechanisms remain unclear after more than 70 years of clinical use. The study employed functional MRI and a data‑driven analysis to compare brain functional connectivity before and after ECT. Results revealed that ECT produces lasting reductions in global connectivity of the left dorsolateral prefrontal cortex, which coincided with significant symptom improvement, supporting the hyperconnectivity hypothesis.

Abstract

To date, electroconvulsive therapy (ECT) is the most potent treatment in severe depression. Although ECT has been successfully applied in clinical practice for over 70 years, the underlying mechanisms of action remain unclear. We used functional MRI and a unique data-driven analysis approach to examine functional connectivity in the brain before and after ECT treatment. Our results show that ECT has lasting effects on the functional architecture of the brain. A comparison of pre- and posttreatment functional connectivity data in a group of nine patients revealed a significant cluster of voxels in and around the left dorsolateral prefrontal cortical region (Brodmann areas 44, 45, and 46), where the average global functional connectivity was considerably decreased after ECT treatment (P < 0.05, family-wise error-corrected). This decrease in functional connectivity was accompanied by a significant improvement (P < 0.001) in depressive symptoms; the patients' mean scores on the Montgomery Asberg Depression Rating Scale pre- and posttreatment were 36.4 (SD = 4.9) and 10.7 (SD = 9.6), respectively. The findings reported here add weight to the emerging "hyperconnectivity hypothesis" in depression and support the proposal that increased connectivity may constitute both a biomarker for mood disorder and a potential therapeutic target.