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

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

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

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 OpelRonny 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

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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 (p_FDR < 0.001), but enlargement of the hippocampal head significantly exceeds the volumetric change in the hippocampal body and tail (p_FDR < 0.001). Volumetric expansion of the hippocampal body and tail significantly associates with reduced verbal fluency scores (p_FDR< 0.05). Moreover, volumetric reduction of the hippocampal tail at 6 months post-ECT associates with improved cognitive performance (p_FDR < 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_uncorrected < 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.

Original language	English
Article number	409
Pages (from-to)	1-9
Number of pages	9
Journal	Communications medicine
Volume	5
Issue number	1
DOIs	https://doi.org/10.1038/s43856-025-01120-1
Publication status	Published - 1 Oct 2025

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Ousdal, O. T., Argyelan, M., Laroy, M., Anand, A., Bouckaert, F., Camprodon, J. A., Cano, M., Cardoner, N., Dannlowski, U., Dols, A., Emsell, L., Espinoza, R., Hebbrecht, K., Hurlemann, R., Jorgensen, M., Kiebs, M., Kishimoto, T., Narr, K. L., Nordanskog, P., ... Oltedal, L. (2025). Effects of electroconvulsive therapy on hippocampal longitudinal axis and its association with cognitive side effects. Communications medicine, 5(1), 1-9. Article 409. https://doi.org/10.1038/s43856-025-01120-1

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title = "Effects of electroconvulsive therapy on hippocampal longitudinal axis and its association with cognitive side effects",

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.",

author = "Ousdal, \{Olga Therese\} and Miklos Argyelan and Maarten Laroy and Amit Anand and Filip Bouckaert and Camprodon, \{Joan A\} and Marta Cano and Narcis Cardoner and Udo Dannlowski and Annemiek Dols and Louise Emsell and Randall Espinoza and Kaat Hebbrecht and Ren{\'e} Hurlemann and Martin Jorgensen and Maximillian Kiebs and Taishiro Kishimoto and Narr, \{Katherine L\} and Pia Nordanskog and Nils Opel and Ronny Redlich and Didi Rhebergen and Alexander Sartorius and Didier Schrijvers and Pascal Sienaert and Carles Soriano-Mas and Akihiro Takamiya and \{Ten Doesschate\}, Freek and Indira Tendolkar and Mikel Urretavizcaya and \{van Diermen\}, Linda and \{van Eijndhoven\}, Philip and \{van Wingen\}, Guido and \{van Waarde\}, Jeroen and Mathieu Vandenbulcke and Joey Verdijk and Wade, \{Benjamin S C\} and Yrondi Antoine and Nj{\aa}l Brekke and Joan Prudic and Shawn McClintock and Ute Kessler and Hauke Bartsch and Ketil Odegaard and Jan Haavik and {\AA}sa Hammar and Christopher Abbott and Leif Oltedal",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2025.",

year = "2025",

month = oct,

day = "1",

doi = "10.1038/s43856-025-01120-1",

language = "English",

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Ousdal, OT, Argyelan, M, Laroy, M, Anand, A, Bouckaert, F, Camprodon, JA, Cano, M, Cardoner, N, Dannlowski, U, Dols, A, Emsell, L, Espinoza, R, Hebbrecht, K, Hurlemann, R, Jorgensen, M, Kiebs, M, Kishimoto, T, Narr, KL, Nordanskog, P, Opel, N, Redlich, R, Rhebergen, D, Sartorius, A, Schrijvers, D, Sienaert, P, Soriano-Mas, C, Takamiya, A, Ten Doesschate, F, Tendolkar, I, Urretavizcaya, M, van Diermen, L, van Eijndhoven, P, van Wingen, G, van Waarde, J, Vandenbulcke, M, Verdijk, J, Wade, BSC, Antoine, Y, Brekke, N, Prudic, J, McClintock, S, Kessler, U, Bartsch, H, Odegaard, K, Haavik, J, Hammar, Å, Abbott, C & Oltedal, L 2025, 'Effects of electroconvulsive therapy on hippocampal longitudinal axis and its association with cognitive side effects', Communications medicine, vol. 5, no. 1, 409, pp. 1-9. https://doi.org/10.1038/s43856-025-01120-1

TY - JOUR

T1 - Effects of electroconvulsive therapy on hippocampal longitudinal axis and its association with cognitive side effects

AU - Ousdal, Olga Therese

AU - Argyelan, Miklos

AU - Laroy, Maarten

AU - Anand, Amit

AU - Bouckaert, Filip

AU - Camprodon, Joan A

AU - Cano, Marta

AU - Cardoner, Narcis

AU - Dannlowski, Udo

AU - Dols, Annemiek

AU - Emsell, Louise

AU - Espinoza, Randall

AU - Hebbrecht, Kaat

AU - Hurlemann, René

AU - Jorgensen, Martin

AU - Kiebs, Maximillian

AU - Kishimoto, Taishiro

AU - Narr, Katherine L

AU - Nordanskog, Pia

AU - Opel, Nils

AU - Redlich, Ronny

AU - Rhebergen, Didi

AU - Sartorius, Alexander

AU - Schrijvers, Didier

AU - Sienaert, Pascal

AU - Soriano-Mas, Carles

AU - Takamiya, Akihiro

AU - Ten Doesschate, Freek

AU - Tendolkar, Indira

AU - Urretavizcaya, Mikel

AU - van Diermen, Linda

AU - van Eijndhoven, Philip

AU - van Wingen, Guido

AU - van Waarde, Jeroen

AU - Vandenbulcke, Mathieu

AU - Verdijk, Joey

AU - Wade, Benjamin S C

AU - Antoine, Yrondi

AU - Brekke, Njål

AU - Prudic, Joan

AU - McClintock, Shawn

AU - Kessler, Ute

AU - Bartsch, Hauke

AU - Odegaard, Ketil

AU - Haavik, Jan

AU - Hammar, Åsa

AU - Abbott, Christopher

AU - Oltedal, Leif

PY - 2025/10/1

Y1 - 2025/10/1

N2 - 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.

AB - 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.

U2 - 10.1038/s43856-025-01120-1

DO - 10.1038/s43856-025-01120-1

M3 - Article

C2 - 41034627

SN - 2730-664X

VL - 5

SP - 1

EP - 9

JO - Communications medicine

JF - Communications medicine

IS - 1

M1 - 409

ER -

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

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