Electric field strength, hippocampal volume change, and cognitive outcomes following electroconvulsive therapy: the role of sex and anatomy

Background: Electroconvulsive therapy (ECT) induces hippocampal volume alterations, but the clinical significance of the volumetric change remains unclear. Greater electric field (EF) strength has been associated with increases in hippocampal volume and decline in cognitive performance following ECT, and this association might be moderated by individual-level variables, such as sex. Methods: In this study, 29 patients with severe or treatment-resistant depression underwent right unilateral ECT. EF strength was simulated using ROAST, and hippocampal volumes were segmented with FreeSurfer. Cognitive performance was assessed pre- and post-ECT using a multidomain neuropsychological battery. Associations between EF strength, hippocampal volume change, and cognitive outcomes were analyzed, with sex as a moderator. Results: At the group level, ECT reduced depressive symptom severity, without cognitive decline. Female patients exhibited higher EF strength in bilateral hippocampi, associated with smaller intracranial volumes and greater changes in the left hippocampal volume following ECT. Exploratory analyses indicated that higher EF strength and greater left hippocampal volume increase were linked to smaller improvement in verbal memory performance; moreover, a sex×volume interaction suggested opposite trends by sex, with volume increase correlating with greater improvement in males but smaller in females. Greater hippocampal volume change was also linked to lower consistency in autobiographical memory; however, post-hoc sensitivity analysis indicated that this association was outlier-driven and should be interpreted with caution. Conclusions: Our findings suggest that individual anatomical variability influences the EF and may contribute to cognitive side effects following ECT. Awareness of anatomy-related EF differences may inform future research strategies for individualized treatment planning and cognitive monitoring.