Nature Communications (Aug 2025)
Neural correlates of human fear conditioning and sources of variability in 2199 individuals
- Joaquim Radua,
- Hannah S. Savage,
- Enric Vilajosana,
- Alec Jamieson,
- Birgit Abler,
- Fredrik Åhs,
- Tom Beckers,
- Narcís Cardoner,
- Josh M. Cisler,
- Juliana B. Diniz,
- Dominik R. Bach,
- Sigrid Elsenbruch,
- Steven G. Greening,
- Daphne J. Holt,
- Antonia N. Kaczkurkin,
- Andreas Keil,
- Merel Kindt,
- Kathrin Koch,
- Kevin S. LaBar,
- Charlene L. Lam,
- Christine L. Larson,
- Tina B. Lonsdorf,
- Christian J. Merz,
- Katie A. McLaughlin,
- Yuval Neria,
- Daniel S. Pine,
- Carien M. van Reekum,
- Alexander J. Shackman,
- Carles Soriano-Mas,
- Victor I. Spoormaker,
- Daniel M. Stout,
- Benjamin Straube,
- Thomas Straube,
- Lauri Tuominen,
- Renée M. Visser,
- Laura Ahumada,
- Volker Arolt,
- Marcelo C. Batistuzzo,
- Paulo R. Bazán,
- Emma E. Biggs,
- Marta Cano,
- Pamela Chavarría-Elizondo,
- Samuel E. Cooper,
- Udo Dannlowski,
- Víctor de la Peña-Arteaga,
- Stephanie N. DeCross,
- Katharina Domschke,
- Mana R. Ehlers,
- John L. Graner,
- Alfons O. Hamm,
- Martin J. Herrmann,
- Ashley A. Huggins,
- Adriane Icenhour,
- Asier Juaneda-Seguí,
- Markus Junghoefer,
- Tilo Kircher,
- Katja Koelkebeck,
- Manuel Kuhn,
- Franziska Labrenz,
- Shmuel M. Lissek,
- Martin Lotze,
- Ulrike Lueken,
- Jürgen Margraf,
- Ignacio Martínez-Zalacaín,
- Robert Moeck,
- Jayne Morriss,
- María Ortuño,
- Andre Pittig,
- Daniel Porta-Casteras,
- Jan Richter,
- Isabelle C. Ridderbusch,
- Winfried Rief,
- Kati Roesmann,
- Jörgen Rosén,
- Alena N. Rußmann,
- Rachel Sjouwerman,
- Jennifer Spohrs,
- Andreas Ströhle,
- Benjamin Suarez-Jimenez,
- Martin Ulrich,
- Hans-Ulrich Wittchen,
- Xi Zhu,
- Lea Waller,
- Henrik Walter,
- Paul M. Thompson,
- Janna Marie Bas-Hoogendam,
- Nynke A. Groenewold,
- Dan J. Stein,
- Nic J. Van der Wee,
- Joseph E. Dunsmoor,
- Andre F. Marquand,
- Ben J. Harrison,
- Miquel A. Fullana
Affiliations
- Joaquim Radua
- Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)
- Hannah S. Savage
- Donders Institute of Brain, Cognition and Behaviour, Radboud University
- Enric Vilajosana
- Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)
- Alec Jamieson
- Department of Psychiatry, The University of Melbourne
- Birgit Abler
- Department of Psychiatry and Psychotherapy III, Ulm University Clinic
- Fredrik Åhs
- Department of Psychology and Social Work, Mid Sweden University
- Tom Beckers
- Faculty of Psychology and Educational Sciences
- Narcís Cardoner
- Sant Pau Mental Health Group, Institut d’Investigació Biomèdica Sant Pau (IBB-Sant Pau)
- Josh M. Cisler
- Department of Psychiatry and Behavioral Sciences, Dell Medical School, University of Texas at Austin
- Juliana B. Diniz
- Department of Psychiatry, Faculdade de Medicina, Universidade de São Paulo
- Dominik R. Bach
- University of Bonn, Transdisciplinary Research Area “Life and Health”, Hertz Chair for Artificial Intelligence and Neuroscience, Institute of Computer Science, Medical Faculty, Institute of Experimental Epileptology and Cognition Research
- Sigrid Elsenbruch
- Department of Medical Psychology and Medical Sociology, Medical Faculty, Ruhr University
- Steven G. Greening
- Brain & Cognitive Sciences, Department of Psychology, University of Manitoba
- Daphne J. Holt
- Department of Psychiatry, Massachusetts General Hospital
- Antonia N. Kaczkurkin
- Department of Psychology, Vanderbilt University
- Andreas Keil
- Department of Psychology, University of Florida
- Merel Kindt
- Department of Psychology, University of Amsterdam
- Kathrin Koch
- School of Medicine and Health, Technical University of Munich
- Kevin S. LaBar
- Center for Cognitive Neuroscience, Duke University
- Charlene L. Lam
- Laboratory of Clinical Psychology & Affective Neuroscience, Department of Psychology, University of Hong Kong
- Christine L. Larson
- University of Wisconsin-Milwaukee, Department of Psychology
- Tina B. Lonsdorf
- Biological Psychology and Cognitive Neuroscience, Bielefeld University
- Christian J. Merz
- Department of Cognitive Psychology, Institute of Cognitive Neuroscience, Ruhr University Bochum
- Katie A. McLaughlin
- Department of Psychology, Harvard University
- Yuval Neria
- Department of Psychiatry, Columbia University Irving Medical Center
- Daniel S. Pine
- Section on Development and Affective Neuroscience, National Institute of Mental Health
- Carien M. van Reekum
- School of Psychology and Clinical Language Sciences, University of Reading
- Alexander J. Shackman
- Department of Psychology, Neuroscience and Cognitive Science Program, University of Maryland
- Carles Soriano-Mas
- Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III (ISCIII)
- Victor I. Spoormaker
- Max Planck Institute of Psychiatry
- Daniel M. Stout
- University of California
- Benjamin Straube
- Department of Psychiatry and Psychotherapy, University of Marburg
- Thomas Straube
- Institute of Medical Psychology and Systems Neuroscience, University of Muenster
- Lauri Tuominen
- University of Ottawa Institute of Mental Health Research at the Royal
- Renée M. Visser
- Department of Psychology, University of Amsterdam
- Laura Ahumada
- Department of Psychology, University of Florida
- Volker Arolt
- Institute for Translational Psychiatry, University of Münster
- Marcelo C. Batistuzzo
- Department of Psychiatry, Faculdade de Medicina, Universidade de São Paulo
- Paulo R. Bazán
- Radiology Institute, Faculdade de Medicina, Universidade de São Paulo
- Emma E. Biggs
- Faculty of Psychology and Educational Sciences
- Marta Cano
- Sant Pau Mental Health Group, Institut d’Investigació Biomèdica Sant Pau (IBB-Sant Pau)
- Pamela Chavarría-Elizondo
- Psychiatry and Mental Health Group, Neuroscience Program, Institut d’Investigació Biomèdica de Bellvitge - IDIBELL
- Samuel E. Cooper
- Department of Psychiatry and Behavioral Sciences, University of Texas at Austin
- Udo Dannlowski
- Institute for Translational Psychiatry, University of Münster
- Víctor de la Peña-Arteaga
- Sant Pau Mental Health Group, Institut d’Investigació Biomèdica Sant Pau (IBB-Sant Pau)
- Stephanie N. DeCross
- Department of Psychology, Harvard University
- Katharina Domschke
- Department of Psychiatry and Psychotherapy, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg
- Mana R. Ehlers
- Biological Psychology and Cognitive Neuroscience, Bielefeld University
- John L. Graner
- Center for Cognitive Neuroscience, Duke University
- Alfons O. Hamm
- Department of Psychology, University of Greifswald
- Martin J. Herrmann
- Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg
- Ashley A. Huggins
- Department of Psychology, University of Arizona
- Adriane Icenhour
- Department of Medical Psychology and Medical Sociology, Medical Faculty, Ruhr University
- Asier Juaneda-Seguí
- Psychiatry and Mental Health Group, Neuroscience Program, Institut d’Investigació Biomèdica de Bellvitge - IDIBELL
- Markus Junghoefer
- Otto-Creutzfeld-Center of Cognitive Neuroscience, University of Münster
- Tilo Kircher
- Department of Psychiatry and Psychotherapy, University of Marburg
- Katja Koelkebeck
- Bielefeld University, Medical School and University Medical Center OWL, Protestant Hospital of the Bethel Foundation, Department of Psychiatry and Psychotherapy
- Manuel Kuhn
- Institute for Systems Neuroscience, University Medical Center Hamburg Eppendorf
- Franziska Labrenz
- Department of Medical Psychology and Medical Sociology, Medical Faculty, Ruhr University
- Shmuel M. Lissek
- Department of Psychology, University of Minnesota
- Martin Lotze
- Diagnostic Radiology, University Medicine Greifswald
- Ulrike Lueken
- German Center of Mental Health (DZPG), partner site Berlin/Potsdam
- Jürgen Margraf
- Mental Health Research and Treatment Center, Ruhr-University Bochum (FBZ) and German Center for Mental Health (DZPG), partner site Bochum/Marburg
- Ignacio Martínez-Zalacaín
- Psychiatry and Mental Health Group, Neuroscience Program, Institut d’Investigació Biomèdica de Bellvitge - IDIBELL
- Robert Moeck
- Institute of Medical Psychology and Systems Neuroscience, University of Muenster
- Jayne Morriss
- School of Psychology, Faculty of Environmental and Life Sciences, University of Southampton
- María Ortuño
- Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)
- Andre Pittig
- Translational Psychotherapy, Institute for Psychology, University of Göttingen
- Daniel Porta-Casteras
- Sant Pau Mental Health Group, Institut d’Investigació Biomèdica Sant Pau (IBB-Sant Pau)
- Jan Richter
- Department of Experimental Psychopathology, University of Hildesheim
- Isabelle C. Ridderbusch
- Department of Psychiatry and Psychotherapy, University of Marburg
- Winfried Rief
- Division of Clinical Psychology and Psychotherapy, University of Marburg
- Kati Roesmann
- Institute for Biomagnetism and Biosignal analysis, University of Münster
- Jörgen Rosén
- Department of Clinical Neuroscience, Karolinska Institutet
- Alena N. Rußmann
- Institute for Systems Neuroscience, University Medical Center Hamburg Eppendorf
- Rachel Sjouwerman
- Institute for Systems Neuroscience, University Medical Center Hamburg Eppendorf
- Jennifer Spohrs
- Department of Child and Adolescent Psychiatry and Psychotherapy, Ulm University Medical Centre
- Andreas Ströhle
- Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin
- Benjamin Suarez-Jimenez
- Department of Neuroscience, University of Rochester Medical Center
- Martin Ulrich
- Department of Psychiatry and Psychotherapy III, Ulm University Clinic
- Hans-Ulrich Wittchen
- Psychiatric University Hospital, Ludwig-Maximilians-University München
- Xi Zhu
- Department of Psychiatry, Columbia University Irving Medical Center
- Lea Waller
- Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin
- Henrik Walter
- German Center of Mental Health (DZPG), partner site Berlin/Potsdam
- Paul M. Thompson
- Imaging Genetics Center, Stevens Neuroimaging & Informatics Institute, Keck School of Medicine, University of Southern California
- Janna Marie Bas-Hoogendam
- Developmental and Educational Psychology, Institute of Psychology, Leiden University
- Nynke A. Groenewold
- Department of Psychiatry and Mental Health, Neuroscience Institute, University of Cape Town
- Dan J. Stein
- SAMRC Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry and Mental Health, Neuroscience Institute, University of Cape Town
- Nic J. Van der Wee
- Leiden Institute for Brain and Cognition, Leiden University Medical Center
- Joseph E. Dunsmoor
- Department of Neuroscience, University of Texas at Austin
- Andre F. Marquand
- Donders Institute of Brain, Cognition and Behaviour, Radboud University
- Ben J. Harrison
- Department of Psychiatry, The University of Melbourne
- Miquel A. Fullana
- Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)
- DOI
- https://doi.org/10.1038/s41467-025-63078-x
- Journal volume & issue
-
Vol. 16,
no. 1
pp. 1 – 18
Abstract
Abstract Pavlovian fear conditioning is a fundamental process in both health and disease. We investigate its neural correlates and sources of variability using harmonized functional magnetic resonance imaging data from 2199 individuals across nine countries, including 1888 healthy individuals and 311 with anxiety-related or depressive disorders. Using mega-analysis and normative modeling, we show that fear conditioning consistently engages brain regions within the “central autonomic–interoceptive” or “salience” network. Several task variables strongly modulate activity in these regions, contributing to variability in neural responses. Additionally, brain activation patterns differ between healthy individuals and those with anxiety-related or depressive disorders, with distinct profiles characterizing specific disorders such as post-traumatic stress disorder and obsessive-compulsive disorder. While the neural correlates of fear conditioning are highly generalizable at the population level, variability arises from differences in task design and clinical status, highlighting the importance of methodological diversity in capturing fear learning mechanisms.
