Negative Valence in Obsessive-Compulsive Disorder: A Worldwide Mega-Analysis of Task-Based Functional Neuroimaging Data of the ENIGMA-OCD Consortium

Nadza Dzinalija; Chris Vriend; Lea Waller; H. Blair Simpson; Iliyan Ivanov; Sri Mahavir Agarwal; Pino Alonso; Lea L. Backhausen; Srinivas Balachander; Aniek Broekhuizen; Miguel Castelo-Branco; Ana Daniela Costa; Hailun Cui; Damiaan Denys; Isabel Catarina Duarte; Goi Khia Eng; Susanne Erk; Sophie M. D. D. Fitzsimmons; Jonathan Ipser; Fern Jaspers-Fayer; Niels T. de Joode; Minah Kim; Kathrin Koch; Jun Soo Kwon; Wieke van Leeuwen; Christine Lochner; Hein J. F. van Marle; Ignacio Martinez-Zalacain; Jose M. Menchon; Pedro Morgado; Janardhanan C. Narayanaswamy; Ian S. Olivier; Maria Picó-Pérez; Tjardo S. Postma; Daniela Rodriguez-Manrique; Veit Roessner; Oana Georgiana Rus-Oswald; Venkataram Shivakumar; Carles Soriano-Mas; Emily R. Stern; S. Evelyn Stewart; Anouk L. van der Straten; Bomin Sun; Sophia I. Thomopoulos; Dick J. Veltman; Nora C. Vetter; Henny Visser; Valerie Voon; Henrik Walter; Ysbrand D. van der Werf; Guido van Wingen; Sara Bertolin; Nicole Beyer; Joao Castelhano; Sunah Choi; Beatriz Couto; Eva Real; Cinto Segalas; Nuno Sousa; Anne Uhlmann; Yijie Zhao; Dan J. Stein; Paul M. Thompson; Ilya M. Veer; Odile A. van den Heuvel

doi:10.1016/j.biopsych.2024.12.011

Negative Valence in Obsessive-Compulsive Disorder: A Worldwide Mega-Analysis of Task-Based Functional Neuroimaging Data of the ENIGMA-OCD Consortium

Nadza Dzinalija^*, Chris Vriend, Lea Waller, H. Blair Simpson, Iliyan Ivanov, Sri Mahavir Agarwal, Pino Alonso, Lea L. Backhausen, Srinivas Balachander, Aniek Broekhuizen, Miguel Castelo-Branco, Ana Daniela Costa, Hailun Cui, Damiaan Denys, Isabel Catarina Duarte, Goi Khia Eng, Susanne Erk, Sophie M. D. D. Fitzsimmons, Jonathan Ipser, Fern Jaspers-FayerNiels T. de Joode, Minah Kim, Kathrin Koch, Jun Soo Kwon, Wieke van Leeuwen, Christine Lochner, Hein J. F. van Marle, Ignacio Martinez-Zalacain, Jose M. Menchon, Pedro Morgado, Janardhanan C. Narayanaswamy, Ian S. Olivier, Maria Picó-Pérez, Tjardo S. Postma, Daniela Rodriguez-Manrique, Veit Roessner, Oana Georgiana Rus-Oswald, Venkataram Shivakumar, Carles Soriano-Mas, Emily R. Stern, S. Evelyn Stewart, Anouk L. van der Straten, Bomin Sun, Sophia I. Thomopoulos, Dick J. Veltman, Nora C. Vetter, Henny Visser, Valerie Voon, Henrik Walter, Ysbrand D. van der Werf, Guido van Wingen, Sara Bertolin, Nicole Beyer, Joao Castelhano, Sunah Choi, Beatriz Couto, Eva Real, Cinto Segalas, Nuno Sousa, Anne Uhlmann, Yijie Zhao, Dan J. Stein, Paul M. Thompson, Ilya M. Veer, Odile A. van den Heuvel

^*Corresponding author for this work

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

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Abstract

Objective: Obsessive-compulsive disorder (OCD) is associated with altered brain function related to processing of negative emotions. To investigate neural correlates of negative valence in OCD, we pooled functional magnetic resonance imaging data of 633 individuals with OCD and 453 healthy control participants from 16 studies using different negatively valenced tasks across the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Consortium's OCD Working Group. Methods: Participant data were processed uniformly using HALFpipe, to extract voxelwise participant-level statistical images of one common first-level contrast: negative versus neutral stimuli. In preregistered analyses, parameter estimates were entered into Bayesian multilevel models to examine whole-brain and regional effects of OCD and its clinically relevant features—symptom severity, age of onset, and medication status. Results: We provided a proof of concept that participant-level data can be combined across several task paradigms and observed one common task activation pattern across individuals with OCD and control participants that encompasses frontolimbic and visual areas implicated in negative valence. Compared with control participants, individuals with OCD showed very strong evidence of weaker activation of the bilateral occipital cortex (P+ < 0.001) and adjacent visual processing regions during negative valence processing that was related to greater OCD severity, late onset of the disorder, and an unmedicated status. Individuals with OCD also showed stronger activation in the orbitofrontal, subgenual anterior cingulate, and ventromedial prefrontal cortex (all P+ < 0.1) that was related to greater OCD severity and late onset. Conclusions: In the first mega-analysis of this kind, we replicated previous findings of stronger ventral prefrontal activation in OCD during negative valence processing and highlight the lateral occipital cortex as an important region implicated in altered negative valence processing.

Original language	English
Pages (from-to)	219-229
Number of pages	11
Journal	Biological psychiatry
Volume	98
Issue number	3
Early online date	2025
DOIs	https://doi.org/10.1016/j.biopsych.2024.12.011
Publication status	Published - 1 Aug 2025

Keywords

Clinical features
Disorder effects
Mega-analysis
Negative valence
Obsessive-compulsive disorder
Task-based fMRI

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Dzinalija, N., Vriend, C., Waller, L., Simpson, H. B., Ivanov, I., Agarwal, S. M., Alonso, P., Backhausen, L. L., Balachander, S., Broekhuizen, A., Castelo-Branco, M., Costa, A. D., Cui, H., Denys, D., Duarte, I. C., Eng, G. K., Erk, S., Fitzsimmons, S. M. D. D., Ipser, J., ... van den Heuvel, O. A. (2025). Negative Valence in Obsessive-Compulsive Disorder: A Worldwide Mega-Analysis of Task-Based Functional Neuroimaging Data of the ENIGMA-OCD Consortium. Biological psychiatry, 98(3), 219-229. https://doi.org/10.1016/j.biopsych.2024.12.011

@article{7f96fa31bd4d45d68740e2b648813f1f,

title = "Negative Valence in Obsessive-Compulsive Disorder: A Worldwide Mega-Analysis of Task-Based Functional Neuroimaging Data of the ENIGMA-OCD Consortium",

abstract = "Objective: Obsessive-compulsive disorder (OCD) is associated with altered brain function related to processing of negative emotions. To investigate neural correlates of negative valence in OCD, we pooled functional magnetic resonance imaging data of 633 individuals with OCD and 453 healthy control participants from 16 studies using different negatively valenced tasks across the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Consortium's OCD Working Group. Methods: Participant data were processed uniformly using HALFpipe, to extract voxelwise participant-level statistical images of one common first-level contrast: negative versus neutral stimuli. In preregistered analyses, parameter estimates were entered into Bayesian multilevel models to examine whole-brain and regional effects of OCD and its clinically relevant features—symptom severity, age of onset, and medication status. Results: We provided a proof of concept that participant-level data can be combined across several task paradigms and observed one common task activation pattern across individuals with OCD and control participants that encompasses frontolimbic and visual areas implicated in negative valence. Compared with control participants, individuals with OCD showed very strong evidence of weaker activation of the bilateral occipital cortex (P+ < 0.001) and adjacent visual processing regions during negative valence processing that was related to greater OCD severity, late onset of the disorder, and an unmedicated status. Individuals with OCD also showed stronger activation in the orbitofrontal, subgenual anterior cingulate, and ventromedial prefrontal cortex (all P+ < 0.1) that was related to greater OCD severity and late onset. Conclusions: In the first mega-analysis of this kind, we replicated previous findings of stronger ventral prefrontal activation in OCD during negative valence processing and highlight the lateral occipital cortex as an important region implicated in altered negative valence processing.",

keywords = "Clinical features, Disorder effects, Mega-analysis, Negative valence, Obsessive-compulsive disorder, Task-based fMRI",

author = "Nadza Dzinalija and Chris Vriend and Lea Waller and Simpson, \{H. Blair\} and Iliyan Ivanov and Agarwal, \{Sri Mahavir\} and Pino Alonso and Backhausen, \{Lea L.\} and Srinivas Balachander and Aniek Broekhuizen and Miguel Castelo-Branco and Costa, \{Ana Daniela\} and Hailun Cui and Damiaan Denys and Duarte, \{Isabel Catarina\} and Eng, \{Goi Khia\} and Susanne Erk and Fitzsimmons, \{Sophie M. D. D.\} and Jonathan Ipser and Fern Jaspers-Fayer and \{de Joode\}, \{Niels T.\} and Minah Kim and Kathrin Koch and Kwon, \{Jun Soo\} and \{van Leeuwen\}, Wieke and Christine Lochner and \{van Marle\}, \{Hein J. F.\} and Ignacio Martinez-Zalacain and Menchon, \{Jose M.\} and Pedro Morgado and Narayanaswamy, \{Janardhanan C.\} and Olivier, \{Ian S.\} and Maria Pic{\'o}-P{\'e}rez and Postma, \{Tjardo S.\} and Daniela Rodriguez-Manrique and Veit Roessner and Rus-Oswald, \{Oana Georgiana\} and Venkataram Shivakumar and Carles Soriano-Mas and Stern, \{Emily R.\} and Stewart, \{S. Evelyn\} and \{van der Straten\}, \{Anouk L.\} and Bomin Sun and Thomopoulos, \{Sophia I.\} and Veltman, \{Dick J.\} and Vetter, \{Nora C.\} and Henny Visser and Valerie Voon and Henrik Walter and \{van der Werf\}, \{Ysbrand D.\} and \{van Wingen\}, Guido and Sara Bertolin and Nicole Beyer and Joao Castelhano and Sunah Choi and Beatriz Couto and Eva Real and Cinto Segalas and Nuno Sousa and Anne Uhlmann and Yijie Zhao and Stein, \{Dan J.\} and Thompson, \{Paul M.\} and Veer, \{Ilya M.\} and \{van den Heuvel\}, \{Odile A.\}",

note = "Publisher Copyright: {\textcopyright} 2024 Society of Biological Psychiatry",

year = "2025",

month = aug,

day = "1",

doi = "10.1016/j.biopsych.2024.12.011",

language = "English",

volume = "98",

pages = "219--229",

journal = "Biological psychiatry",

issn = "0006-3223",

publisher = "Elsevier USA",

number = "3",

}

Dzinalija, N , Vriend, C, Waller, L, Simpson, HB, Ivanov, I, Agarwal, SM, Alonso, P, Backhausen, LL, Balachander, S, Broekhuizen, A, Castelo-Branco, M, Costa, AD, Cui, H, Denys, D, Duarte, IC, Eng, GK, Erk, S, Fitzsimmons, SMDD, Ipser, J, Jaspers-Fayer, F, de Joode, NT, Kim, M, Koch, K, Kwon, JS, van Leeuwen, W, Lochner, C, van Marle, HJF, Martinez-Zalacain, I, Menchon, JM, Morgado, P, Narayanaswamy, JC, Olivier, IS, Picó-Pérez, M, Postma, TS, Rodriguez-Manrique, D, Roessner, V, Rus-Oswald, OG, Shivakumar, V, Soriano-Mas, C, Stern, ER, Stewart, SE, van der Straten, AL, Sun, B, Thomopoulos, SI, Veltman, DJ, Vetter, NC, Visser, H, Voon, V, Walter, H, van der Werf, YD , van Wingen, G, Bertolin, S, Beyer, N, Castelhano, J, Choi, S, Couto, B, Real, E, Segalas, C, Sousa, N, Uhlmann, A, Zhao, Y, Stein, DJ, Thompson, PM, Veer, IM & van den Heuvel, OA 2025, 'Negative Valence in Obsessive-Compulsive Disorder: A Worldwide Mega-Analysis of Task-Based Functional Neuroimaging Data of the ENIGMA-OCD Consortium', Biological psychiatry, vol. 98, no. 3, pp. 219-229. https://doi.org/10.1016/j.biopsych.2024.12.011

TY - JOUR

T1 - Negative Valence in Obsessive-Compulsive Disorder

T2 - A Worldwide Mega-Analysis of Task-Based Functional Neuroimaging Data of the ENIGMA-OCD Consortium

AU - Dzinalija, Nadza

AU - Vriend, Chris

AU - Waller, Lea

AU - Simpson, H. Blair

AU - Ivanov, Iliyan

AU - Agarwal, Sri Mahavir

AU - Alonso, Pino

AU - Backhausen, Lea L.

AU - Balachander, Srinivas

AU - Broekhuizen, Aniek

AU - Castelo-Branco, Miguel

AU - Costa, Ana Daniela

AU - Cui, Hailun

AU - Denys, Damiaan

AU - Duarte, Isabel Catarina

AU - Eng, Goi Khia

AU - Erk, Susanne

AU - Fitzsimmons, Sophie M. D. D.

AU - Ipser, Jonathan

AU - Jaspers-Fayer, Fern

AU - de Joode, Niels T.

AU - Kim, Minah

AU - Koch, Kathrin

AU - Kwon, Jun Soo

AU - van Leeuwen, Wieke

AU - Lochner, Christine

AU - van Marle, Hein J. F.

AU - Martinez-Zalacain, Ignacio

AU - Menchon, Jose M.

AU - Morgado, Pedro

AU - Narayanaswamy, Janardhanan C.

AU - Olivier, Ian S.

AU - Picó-Pérez, Maria

AU - Postma, Tjardo S.

AU - Rodriguez-Manrique, Daniela

AU - Roessner, Veit

AU - Rus-Oswald, Oana Georgiana

AU - Shivakumar, Venkataram

AU - Soriano-Mas, Carles

AU - Stern, Emily R.

AU - Stewart, S. Evelyn

AU - van der Straten, Anouk L.

AU - Sun, Bomin

AU - Thomopoulos, Sophia I.

AU - Veltman, Dick J.

AU - Vetter, Nora C.

AU - Visser, Henny

AU - Voon, Valerie

AU - Walter, Henrik

AU - van der Werf, Ysbrand D.

AU - van Wingen, Guido

AU - Bertolin, Sara

AU - Beyer, Nicole

AU - Castelhano, Joao

AU - Choi, Sunah

AU - Couto, Beatriz

AU - Real, Eva

AU - Segalas, Cinto

AU - Sousa, Nuno

AU - Uhlmann, Anne

AU - Zhao, Yijie

AU - Stein, Dan J.

AU - Thompson, Paul M.

AU - Veer, Ilya M.

AU - van den Heuvel, Odile A.

PY - 2025/8/1

Y1 - 2025/8/1

N2 - Objective: Obsessive-compulsive disorder (OCD) is associated with altered brain function related to processing of negative emotions. To investigate neural correlates of negative valence in OCD, we pooled functional magnetic resonance imaging data of 633 individuals with OCD and 453 healthy control participants from 16 studies using different negatively valenced tasks across the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Consortium's OCD Working Group. Methods: Participant data were processed uniformly using HALFpipe, to extract voxelwise participant-level statistical images of one common first-level contrast: negative versus neutral stimuli. In preregistered analyses, parameter estimates were entered into Bayesian multilevel models to examine whole-brain and regional effects of OCD and its clinically relevant features—symptom severity, age of onset, and medication status. Results: We provided a proof of concept that participant-level data can be combined across several task paradigms and observed one common task activation pattern across individuals with OCD and control participants that encompasses frontolimbic and visual areas implicated in negative valence. Compared with control participants, individuals with OCD showed very strong evidence of weaker activation of the bilateral occipital cortex (P+ < 0.001) and adjacent visual processing regions during negative valence processing that was related to greater OCD severity, late onset of the disorder, and an unmedicated status. Individuals with OCD also showed stronger activation in the orbitofrontal, subgenual anterior cingulate, and ventromedial prefrontal cortex (all P+ < 0.1) that was related to greater OCD severity and late onset. Conclusions: In the first mega-analysis of this kind, we replicated previous findings of stronger ventral prefrontal activation in OCD during negative valence processing and highlight the lateral occipital cortex as an important region implicated in altered negative valence processing.

AB - Objective: Obsessive-compulsive disorder (OCD) is associated with altered brain function related to processing of negative emotions. To investigate neural correlates of negative valence in OCD, we pooled functional magnetic resonance imaging data of 633 individuals with OCD and 453 healthy control participants from 16 studies using different negatively valenced tasks across the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Consortium's OCD Working Group. Methods: Participant data were processed uniformly using HALFpipe, to extract voxelwise participant-level statistical images of one common first-level contrast: negative versus neutral stimuli. In preregistered analyses, parameter estimates were entered into Bayesian multilevel models to examine whole-brain and regional effects of OCD and its clinically relevant features—symptom severity, age of onset, and medication status. Results: We provided a proof of concept that participant-level data can be combined across several task paradigms and observed one common task activation pattern across individuals with OCD and control participants that encompasses frontolimbic and visual areas implicated in negative valence. Compared with control participants, individuals with OCD showed very strong evidence of weaker activation of the bilateral occipital cortex (P+ < 0.001) and adjacent visual processing regions during negative valence processing that was related to greater OCD severity, late onset of the disorder, and an unmedicated status. Individuals with OCD also showed stronger activation in the orbitofrontal, subgenual anterior cingulate, and ventromedial prefrontal cortex (all P+ < 0.1) that was related to greater OCD severity and late onset. Conclusions: In the first mega-analysis of this kind, we replicated previous findings of stronger ventral prefrontal activation in OCD during negative valence processing and highlight the lateral occipital cortex as an important region implicated in altered negative valence processing.

KW - Clinical features

KW - Disorder effects

KW - Mega-analysis

KW - Negative valence

KW - Obsessive-compulsive disorder

KW - Task-based fMRI

UR - https://www.scopus.com/pages/publications/85218686060

U2 - 10.1016/j.biopsych.2024.12.011

DO - 10.1016/j.biopsych.2024.12.011

M3 - Article

C2 - 39725297

SN - 0006-3223

VL - 98

SP - 219

EP - 229

JO - Biological psychiatry

JF - Biological psychiatry

IS - 3

ER -

Negative Valence in Obsessive-Compulsive Disorder: A Worldwide Mega-Analysis of Task-Based Functional Neuroimaging Data of the ENIGMA-OCD Consortium

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