Electroconvulsive therapy-induced volumetric brain changes converge on a common causal circuit in depression

Abstract

Neurostimulation is a mainstream treatment option for major depression. Neuromodulation techniques apply repetitive magnetic or electrical stimulation to some neural target but significantly differ in their invasiveness, spatial selectivity, mechanism of action, and efficacy. Despite these differences, recent analyses of transcranial magnetic stimulation (TMS) and deep brain stimulation (DBS)-treated individuals converged on a common neural network that might have a causal role in treatment response. We set out to investigate if the neuronal underpinnings of electroconvulsive therapy (ECT) are similarly associated with this common causal network (CCN). Our aim here is to provide a comprehensive analysis in three cohorts of patients segregated by electrode placement (N = 246 with right unilateral, 79 with bitemporal, and 61 with mixed) who underwent ECT. We conducted a data-driven, unsupervised multivariate neuroimaging analysis (Principal Component Analysis, PCA) of the cortical and subcortical volume changes and electric field (EF) distribution to explore changes within the CCN associated with antidepressant outcomes. Despite the different treatment modalities (ECT vs TMS and DBS) and methodological approaches (structural vs functional networks), we found a highly similar pattern of change within the CCN in the three cohorts of patients (spatial similarity across 85 regions: r = 0.65, 0.58, 0.40, df = 83). Most importantly, the expression of this pattern correlated with clinical outcomes. This evidence further supports that treatment interventions converge on a CCN in depression. Optimizing modulation of this network could serve to improve the outcome of neurostimulation in depression.

Figure 1

Electric field (EF) and volume change (ΔVOL) correlate across 85 regions in RUL (blue), BT (green) and MIX (orange) electrode placements. The upper line shows the average EF (V/m), the lower line shows the effect size of the volume change (Cohen’s d) color coded. The right panel shows the values in the corresponding regions in a scatterplot.

Figure 2

Unsupervised multivariate analysis (principal component analysis - PCA) of the regional volume changes (A) and the EF values (B). The first component (left side) reflected the main effect. The second PC of the volume change was very similar to the Common Causal Network recently reported by Siddiqi et al. (2021) regardless of the electrode placement (C). The second PC of the EF reflected the spatial distribution stemming from the different electrode placements. The second PC of the volume changes not only correlated with the map reported by Siddiqi et al, but also correlated with the clinical outcome (D), the more similar the pattern was to the Common Causal Network the better the clinical outcome was.