Electroconvulsive therapy reduces frontal cortical connectivity in severe depressive disorder

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.

Fig. 1.

Significant reduction in the average global functional connectivity after ECT treatment in a group of severely depressed patients (n = 9). A significant decrease (P < 0.05, FWE-corrected) was observed in a cluster of voxels in and around the left DLPFC region (BAs 44, 45, and 46). Results were obtained by means of a nonparametric permutation test comparing post- and pretreatment global connectivity data on a voxel-by-voxel basis.

Fig. 2.

3D orthogonal representation of the left DLPFC cluster of voxels (shown in red) for which a significant reduction in the average global functional connectivity was observed after ECT treatment (Fig. 1). The coordinates (x, y, and z) refer to Montreal Neurological Institute standard space.

Fig. 3.

Functional connectivity in severely depressed patients before ECT (displayed in orange) and persisting connectivity after ECT (displayed in cyan), showing a substantial reduction in cortical connectivity after ECT treatment (P < 0.001, FWE-corrected); z values refer to distance in millimeters from the midline in stereotaxic space [Montreal Neurological Institute standard space]. The observed reduction in functional connectivity following ECT treatment was accompanied by a significant decrease (P < 0.001) in depressive symptoms (bar chart).