Seizure-induced Transient Disruptive Changes in Brain Microstructure
A leading hypothesis for the mechanisms of electroconvulsive therapy (ECT) posits an initial disruptive effect followed by enhanced neuroplasticity. However, direct evidence of the presumed early disruptive changes, potentially driven by seizures, remains limited. This study examined longitudinal changes in multishell diffusion MRI-derived metrics in 25 individuals with depression, with scans acquired two hours before and after their first ECT session. Follow-up scans were collected within 14 days and 6 months after the last ECT session. To control for potential confounding effects of anesthesia and repeated measurements, two additional groups were included: 16 individuals undergoing short-acting anesthesia and 16 healthy controls without interventions. A multicompartment model was applied to explore extracellular free water and microstructures in the intracellular/extracellular compartments. Whole-brain voxel-wise analyses identified a pattern consistent with vasogenic edema (e.g., increased extracellular free water) in widespread bilateral brain regions following a single ECT session. Increases in brain tissue free water were significantly correlated with electrical stimulus charge (r=0.51, p=0.01) but not with post-ictal reorientation time (r=0.11, p=0.92). These changes were not observed in either control group. Follow-up assessments confirmed that the alterations in tissue free water resolved within 14 days. A single ECT-induced seizure induces transient, reversible changes consistent with vasogenic edema, rather than irreversible cellular injury typically associated with cytotoxic edema. These reversible changes may represent an initial disruptive phase that facilitates subsequent adaptive brain responses, including neuroplasticity and network reorganization underlying the therapeutic effects of ECT.