Hippocampal microstructural changes following electroconvulsive therapy in severe depression

Abstract Introduction Electroconvulsive therapy (ECT) induces an increase in hippocampal volume presumed to reflect neurogenesis in severely depressed patients. We hypothesized that Neurite Orientation Dispersion and Density Imaging (NODDI) provides in vivo evidence of hippocampal neurogenesis following ECT. Methods This prospective longitudinal study included 43 depressed patients treated by ECT. Three sequential evaluations (V1: baseline, V2: at 2 weeks into ECT, V3: 14 days within completing ECT) included a 3T MR-scan with 3D T1-weighted and multi-shell diffusion (b = 200/1500/2500 s/mm2, 30/45/60 directions) sequences and clinical assessment with depression scales. Q-ball, Diffusion Tensor and NODDI models provided the following metrics: axial (AD), radial (RD) and mean diffusivity (MD), fractional anisotropy (FA) and generalized FA (GFA), neurite density index (NDI), isotropic fraction (Fiso), neurite orientation and dispersion index (ODI). FreeSurfer was used to extract whole hippocampal and subfields volumes from T1-weighted images. A linear mixed-effect model assessed the changes over time in hippocampal volumes and mean diffusion metrics, and their relationship with clinical response was analyzed with ANOVA. Bonferroni corrections were applied. Results 107 MRI were obtained at V1 (n = 43), V2 (n = 34) and V3 (n = 30) from 43 patients. Mean (± SD) interval between V1-V3 was 70 ± 25 days. Diffusion metrics in the hippocampus were: at V2, a decrease in left GFA, right AD, bilateral Fiso, and a bilateral ODI increase. Additionally, at V3, we observed a left MD decrease, bilateral AD decrease, right NDI increase, and bilateral ODI increase. Notably, NDI and Fiso changes were localized to the dentate gyrus but not to the hippocampal tail. ECT-responders showed a significant right hippocampus volume increase at 2 weeks into ECT. Conclusion After ECT, the observed increase in hippocampal volume is accompanied by bilateral changes in NODDI parameters, consistent with hippocampal neuroplasticity.