White matter changes following electroconvulsive therapy for depression: a multicenter ComBat harmonization approach

Abstract

ECT is proposed to exert a therapeutic effect on WM microstructure, but the limited power of previous studies made it difficult to highlight consistent patterns of change in diffusion metrics. We initiated a multicenter analysis and sought to address whether changes in WM microstructure occur following ECT. Diffusion tensor imaging (DTI) data (n = 58) from 4 different sites were harmonized before pooling them by using ComBat, a batch-effect correction tool that removes inter-site technical variability, preserves inter-site biological variability, and maximizes statistical power. Downstream statistical analyses aimed to quantify changes in Fractional Anisotropy (FA), Mean Diffusivity (MD), Radial Diffusivity (RD) and Axial Diffusivity (AD), by employing whole-brain, tract-based spatial statistics (TBSS). ECT increased FA in the right splenium of the corpus callosum and the left cortico-spinal tract. AD in the left superior longitudinal fasciculus and the right inferior fronto-occipital fasciculus was raised. Increases in MD and RD could be observed in overlapping white matter structures of both hemispheres. At baseline, responders showed significantly smaller FA values in the left forceps major and smaller AD values in the right uncinate fasciculus compared with non-responders. By harmonizing multicenter data, we demonstrate that ECT modulates altered WM microstructure in important brain circuits that are implicated in the pathophysiology of depression. Furthermore, responders appear to present a more decreased WM integrity at baseline which could point towards a specific subtype of patients, characterized by a more altered neuroplasticity, who are especially sensitive to the potent neuroplastic effects of ECT.