Olga Therese Ousdal, Miklos Argyelan, Maarten Laroy, Amit Anand, Filip Bouckaert, Joan A Camprodon, Marta Cano, Narcis Cardoner, Udo Dannlowski, Annemiek Dols, Louise Emsell, Randall Espinoza, Kaat Hebbrecht, René Hurlemann, Martin Jorgensen, Maximillian Kiebs, Taishiro Kishimoto, Katherine L Narr, Pia Nordanskog, Nils Opel, Ronny Redlich, Didi Rhebergen, Alexander Sartorius, Didier Schrijvers, Pascal Sienaert, Carles Soriano-Mas, Akihiro Takamiya, Freek Ten Doesschate, Indira Tendolkar, Mikel Urretavizcaya, Linda van Diermen, Philip van Eijndhoven, Guido van Wingen, Jeroen van Waarde, Mathieu Vandenbulcke, Joey Verdijk, Benjamin S C Wade, Yrondi Antoine, Njål Brekke, Joan Prudic, Shawn McClintock, Ute Kessler, Hauke Bartsch, Ketil Odegaard, Jan Haavik, Åsa Hammar, Christopher Abbott, Leif Oltedal
{"title":"Effects of electroconvulsive therapy on hippocampal longitudinal axis and its association with cognitive side effects.","authors":"Olga Therese Ousdal, Miklos Argyelan, Maarten Laroy, Amit Anand, Filip Bouckaert, Joan A Camprodon, Marta Cano, Narcis Cardoner, Udo Dannlowski, Annemiek Dols, Louise Emsell, Randall Espinoza, Kaat Hebbrecht, René Hurlemann, Martin Jorgensen, Maximillian Kiebs, Taishiro Kishimoto, Katherine L Narr, Pia Nordanskog, Nils Opel, Ronny Redlich, Didi Rhebergen, Alexander Sartorius, Didier Schrijvers, Pascal Sienaert, Carles Soriano-Mas, Akihiro Takamiya, Freek Ten Doesschate, Indira Tendolkar, Mikel Urretavizcaya, Linda van Diermen, Philip van Eijndhoven, Guido van Wingen, Jeroen van Waarde, Mathieu Vandenbulcke, Joey Verdijk, Benjamin S C Wade, Yrondi Antoine, Njål Brekke, Joan Prudic, Shawn McClintock, Ute Kessler, Hauke Bartsch, Ketil Odegaard, Jan Haavik, Åsa Hammar, Christopher Abbott, Leif Oltedal","doi":"10.1038/s43856-025-01120-1","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>Global hippocampal enlargement is observed pre-to-post ECT (p<sub>FDR</sub> < 0.001), but enlargement of the hippocampal head significantly exceeds the volumetric change in the hippocampal body and tail (p<sub>FDR</sub> < 0.001). Volumetric expansion of the hippocampal body and tail significantly associates with reduced verbal fluency scores (p<sub>FDR</sub>< 0.05). Moreover, volumetric reduction of the hippocampal tail at 6 months post-ECT associates with improved cognitive performance (p<sub>FDR</sub> < 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 (p<sub>uncorrected</sub> < 0.05).</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":72646,"journal":{"name":"Communications medicine","volume":"5 1","pages":"409"},"PeriodicalIF":5.4000,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12489027/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Communications medicine","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1038/s43856-025-01120-1","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
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Abstract
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.
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