Temporal trajectory of brain tissue property changes induced by electroconvulsive therapy

Background: After more than eight decades of electroconvulsive therapy (ECT) for pharmaco-resistant depression, the mechanisms governing its anti-depressant effects remain poorly understood. Computational anatomy studies using longitudinal T1-weighted magnetic resonance imaging (MRI) data have demonstrated ECT effects on hippocampus volume and cortical thickness, but they lack the interpretational specificity about underlying neurobiological processes. Methods: We sought to fill in the gap of knowledge by acquiring quantitative MRI indicative for brain's myelin, iron and tissue water content at multiple time-points before, during and after ECT treatment. We adapted established tools for longitudinal spatial registration of MRI data to the relaxometry-based multi-parameter maps aiming to preserve the initial total signal amount and introduced a dedicated multivariate analytical framework. Results: The whole-brain voxel-based analysis based on a multivariate general linear model showed that there is no brain tissue oedema contributing to the predicted ECT-induced hippocampus volume increase neither in the short, nor in the long-term observations. Improvements in depression symptom severity over time were associated with changes in both volume estimates and brain tissue properties expanding beyond mesial temporal lobe structures to anterior cingulate cortex, precuneus and striatum. Conclusion: The obtained results stemming from multi-contrast MRI quantitative data provided a fingerprint of ECT-induced brain tissue changes over time that are contrasted against the background of established morphometry findings. The introduced data processing and statistical testing algorithms provided a reliable analytical framework for longitudinal multi-parameter brain maps. The results, particularly the evidence of lack of ECT impact on brain tissue water, should be considered preliminary considering the small sample size of the study.