Effects of electroconvulsive therapy on hippocampal longitudinal axis and its association with cognitive side effects.

BACKGROUND: Electroconvulsive therapy (ECT)-mediated hippocampal volumetric increase is consistently reported, though its clinical relevance remains debated. This study evaluates if ECT-related cognitive side effects are associated with regional volumetric changes along the hippocampal longitudinal axis. METHODS: Longitudinal T1-weighted MRI scans in 435 patients (54.0 ± 15.0 years, 261 female) with major depression from the Global ECT-MRI Research Collaboration (GEMRIC) were used to measure changes in right global and longitudinal axis hippocampal subdivisions (head, body, tail) from baseline to post-treatment. Cognitive side effects were evaluated using pre-to-post treatment changes in two different verbal fluency tests available for 124 patients. Electric field modelling was applied to explore whether the regional hippocampal electric field strength related to individual changes in cognitive performance. RESULTS: Global hippocampal enlargement is observed pre-to-post ECT (pFDR < 0.001), but enlargement of the hippocampal head significantly exceeds the volumetric change in the hippocampal body and tail (pFDR < 0.001). Volumetric expansion of the hippocampal body and tail significantly associates with reduced verbal fluency scores (pFDR< 0.05). Moreover, volumetric reduction of the hippocampal tail at 6 months post-ECT associates with improved cognitive performance (pFDR < 0.05, N = 24). Finally, patients performing worse on verbal fluency tests following treatment have greater electric field during ECT in the right hippocampal body (puncorrected < 0.05). CONCLUSIONS: The findings support that cognitive performance following ECT relates to macrostructural changes in the posterior cognitive hippocampus. Thus, there may be a threshold of ECT induced posterior hippocampal volumetric change, beyond which cognitive side effects occur.