Electroconvulsive therapy (ECT) is an effective treatment for depression but is often associated with cognitive side effects. In patients, ECT-induced electric field (E-field) strength across brain regions varies significantly due to anatomical differences, which may explain individual differences in cognitive side effects. We examined the relationship between regional E-field strength and change in verbal fluency score (i.e., category fluency animals score from pre- to 1 week post-ECT; as key proxy of cognitive side effects) across different electrode placements in depressed patients. Secondary, we examined the relationship between regional E-field strength and depression outcome. Using T1 magnetic resonance imaging, we performed E-field modeling in a total of 109 patients. Linear mixed models were executed to analyze the relationship between E-field strength across all 118 brain regions and both cognitive and depression outcomes, while correcting for nuisance variables (e.g., age, total number of ECT sessions, and study cohort). We found that a higher E-field strength was significantly associated with a higher decline in verbal fluency (n = 71, false discovery rate [FDR] corrected p < 0.01) in several brain regions in the left hemisphere (e.g., temporal gyrus and operculum cortex). Moreover, numerous significant associations were found only in the 24 patients treated with right unilateral ECT. No significant relationships were found between regional E-field strength and depression outcome. In conclusion, significant associations between verbal fluency and E-field strength were found in areas crucial for linguistic processing and semantic memory. Our findings underscore the importance of considering individualized dosing strategies to optimize cognitive outcome in ECT, while maintaining its antidepressant efficacy.
© 2025. The Author(s), under exclusive licence to American College of Neuropsychopharmacology.