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.
Highlights
Electroconvulsive therapy (ECT) remains the gold-standard treatment for severe, treatment-resistant patients with major depressive disorder (MDD) where a rapid response is indicated
We focus our analysis on four regions affected in MDD: the subcallosal cingulate gyrus (SCC), default mode network, dorsal lateral prefrontal cortex, and dorsal medial prefrontal cortex (DMPFC) (Greicius et al, 2007; Sheline et al, 2010)
PARTICIPANTS Prior to initiating this study, ethical approval was obtained from the Human Research Protections Office at the University of New Mexico (UNM), and the study was conducted in accordance with the principles expressed in the Declaration of Helsinki
Summary
Electroconvulsive therapy (ECT) remains the gold-standard treatment for severe, treatment-resistant patients with major depressive disorder (MDD) where a rapid response is indicated. Resting state functional magnetic resonance imaging (fMRI) has recently expanded the scope and generalizability of fMRI investigations to include patients with severe MDD treated with ECT (Beall et al, 2012; Perrin et al, 2012). A cross-sectional seed-based approach of MDD revealed increased temporal coherence within limbic, cortical, and default mode networks (Sheline et al, 2010). These networks overlapped with an area of the dorsal medial prefrontal cortex (DMPFC). Perrin et al (2012) tested this hypothesis with a longitudinal resting state fMRI investigation and found that ECT response was associated with reduced temporal coherence within the left dorsal lateral prefrontal cortex (l_DLPFC; Perrin et al, 2012) The increased temporal coherence of these brain regions may be an important therapeutic target in MDD. Perrin et al (2012) tested this hypothesis with a longitudinal resting state fMRI investigation and found that ECT response was associated with reduced temporal coherence within the left dorsal lateral prefrontal cortex (l_DLPFC; Perrin et al, 2012)
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