Electroconvulsive therapy response in major depressive disorder: a pilot functional network connectivity resting state FMRI investigation

Abstract

Major depressive disorder (MDD) is associated with increased functional connectivity in specific neural networks. Electroconvulsive therapy (ECT), the gold-standard treatment for acute, treatment-resistant MDD, but temporal dependencies between networks associated with ECT response have yet to be investigated. In the present longitudinal, case-control investigation, we used independent component analysis to identify distinct networks of brain regions with temporally coherent hemodynamic signal change and functional network connectivity (FNC) to assess component time course correlations across these networks. MDD subjects completed imaging and clinical assessments immediately prior to the ECT series and a minimum of 5 days after the last ECT treatment. We focused our analysis on four networks affected in MDD: the subcallosal cingulate gyrus, default mode, dorsal lateral prefrontal cortex, and dorsal medial prefrontal cortex (DMPFC). In an older sample of ECT subjects (n = 12) with MDD, remission associated with the ECT series reverses the relationship from negative to positive between the posterior default mode (p_DM) and two other networks: the DMPFC and left dorsal lateral prefrontal cortex (l_DLPFC). Relative to demographically healthy subjects (n = 12), the FNC between the p_DM areas and the DMPFC normalizes with ECT response. The FNC changes following treatment did not correlate with symptom improvement; however, a direct comparison between ECT remitters and non-remitters showed the pattern of increased FNC between the p_DM and l_DLPFC following ECT to be specific to those who responded to the treatment. The differences between ECT remitters and non-remitters suggest that this increased FNC between p_DM areas and the left dorsolateral prefrontal cortex is a neural correlate and potential biomarker of recovery from a depressed episode.

Keywords: electroconvulsive therapy; functional network connectivity; independent component analysis; major depressive disorder; resting state fMRI.

Figure 1

The Hamilton Depression Rating Scale-24 (HDRS-24) is on the y-axis, and the pre- and post-ECT depression ratings are on the x-axis. The dashed red line (HDRS-24) differentiates ECT remitters from non-remitters.

Figure 2

Maps of the networks of interest include the anterior default mode network (a_DM), subcallosal cingulate gyrus (SCC), dorsal medial prefrontal cortex (DMPFC), posterior default mode network (p_DM), and dorsal lateral prefrontal cortex (r_DLPFC, l_DPLFC). Each component map has a lower threshold of t = 10. The images are shown in radiological convention. The arrows represent the significant (FDR-corrected), longitudinal differences in FNC associated with ECT response.

Figure 3

(A) Functional network connectivity (FNC) increased between the p_DM and DMPFC pre- to post-ECT. FNC correlations are represented on the y-axis. The red lines (dashes) are the means (standard errors) of the matched healthy comparison FNC correlations. Relative to healthy comparisons, the pre-ECT FNC was significantly reduced and normalized with ECT response. (B) The p_DM and l_DLPFC had a similar increase in FNC associated with the ECT series. (DMPFC, dorsal medial prefrontal cortex; p_DM, posterior default mode network; l_DLPFC, left dorsal lateral prefrontal cortex.)