Abstract

Electroconvulsive therapy (ECT) is the most effective antidepressant treatment for severe depression. Although recent structural magnetic resonance imaging (MRI) studies have consistently reported ECT-induced hippocampal volume increases, most studies did not find the association of the hippocampal volume changes with clinical improvement. To understand the underlying mechanisms of ECT action, we aimed to identify the longitudinal effects of ECT on hippocampal functional connectivity (FC) and their associations with clinical improvement. Resting-state functional MRI was acquired before and after bilateral ECT in 27 depressed individuals. A priori hippocampal seed-based FC analysis and a data-driven multivoxel pattern analysis (MVPA) were conducted to investigate FC changes associated with clinical improvement. The statistical threshold was set at cluster-level false discovery rate-corrected p < 0.05. Depressive symptom improvement after ECT was positively associated with the change in the right hippocampus-ventromedial prefrontal cortex FC, and negatively associated with the right hippocampus-superior frontal gyrus FC. MVPA confirmed the results of hippocampal seed-based analyses and identified the following additional clusters associated with clinical improvement following ECT: the thalamus, the sensorimotor cortex, and the precuneus. ECT-induced change in the right frontotemporal connectivity and thalamocortical connectivity, and changes in the nodes of the default mode network were associated with clinical improvement. Modulation of these networks may explain the underlying mechanisms by which ECT exert its potent and rapid antidepressant effect.

Highlights

  • Neuroimaging studies have revealed that neuronal network disorganization is related to various depressive symptoms (Northoff, 2016), supporting the notion of depression as a neuronal network disorder (Mayberg, 2009; Price & Drevets, 2010)

  • Abnormal resting-state functional connectivity (FC) among certain brain regions has been reported in depressed individuals: those brain regions include the subcallosal cingulate cortex (SCC), thalamus, medial prefrontal cortex (MPFC), orbitofrontal cortex (OFC), medial temporal lobe (MTL), and precuneus (Cheng et al, 2016; Greicius et al, 2007; Kaiser, Andrews-Hanna, Wager, & Pizzagalli, 2015)

  • Hamilton Depression Rating Scale (HAM-D) changes showed a positive correlation with the following FC changes: (1) right MTL and several other brain regions, including superior frontal gyrus (SFG), MPFC, SCC, and precuneus; (2) bilateral precuneus and left occipital cortex

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Summary

Introduction

Neuroimaging studies have revealed that neuronal network disorganization is related to various depressive symptoms (Northoff, 2016), supporting the notion of depression as a neuronal network disorder (Mayberg, 2009; Price & Drevets, 2010). Recent structural magnetic resonance imaging (MRI) studies have consistently reported ECT-induced hippocampal volume increases, most studies did not find the association of the hippocampal volume changes with clinical improvement. To understand the underlying mechanisms of ECT action, we aimed to identify the longitudinal effects of ECT on hippocampal functional connectivity (FC) and their associations with clinical improvement. MVPA confirmed the results of hippocampal seed-based analyses and identified the following additional clusters associated with clinical improvement following ECT: the thalamus, the sensorimotor cortex, and the precuneus. ECT-induced change in the right frontotemporal connectivity and thalamocortical connectivity, and changes in the nodes of the default mode network were associated with clinical improvement Modulation of these networks may explain the underlying mechanisms by which ECT exert its potent and rapid antidepressant effect

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