Neural correlates of human fear conditioning and sources of variability in 2199 individuals
Por:
Radua, J, Savage, HS, Vilajosana, E, Jamieson, A, Abler, B, Åhs, F, Beckers, T, Cardoner, N, Cisler, JM, Diniz, JB, Bach, DR, Elsenbruch, S, Greening, SG, Holt, DJ, Kaczkurkin, AN, Keil, A, Kindt, M, Koch, K, LaBar, KS, Lam, CL, Larson, CL, Lonsdorf, TB, Merz, CJ, McLaughlin, KA, Neria, Y, Pine, DS, van Reekum, CM, Shackman, AJ, Soriano-Mas, C, Spoormaker, VI, Stout, DM, Straube, B, Straube, T, Tuominen, L, Visser, RM, Ahumada, L, Arolt, V, Batistuzzo, MC, Bazán, PR, Biggs, EE, Cano, M, Chavarría-Elizondo, P, Cooper, SE, Dannlowski, U, de la Peña-arteaga, V, Decross, SN, Domschke, K, Ehlers, MR, Graner, JL, Hamm, AO, Herrmann, MJ, Huggins, AA, Icenhour, A, Juaneda-Seguí, A, Junghoefer, M, Kircher, T, Koelkebeck, K, Kuhn, M, Labrenz, F, Lissek, SM, Lotze, M, Lueken, U, Margraf, J, Martínez-Zalacaín, I, Moeck, R, Morriss, J, Ortuño, M, Pittig, A, Porta-Casteras, D, Richter, J, Ridderbusch, IC, Rief, W, Roesmann, K, Rosén, J, Russmann, AN, Sjouwerman, R, Spohrs, J, Ströhle, A, Suarez-Jimenez, B, Ulrich, M, Wittchen, HU, Zhu, X, Waller, L, Walter, H, Thompson, PM, Bas-Hoogendam, JM, Groenewold, NA, Stein, DJ, van der Wee, NJ, Dunsmoor, JE, Marquand, AF, Harrison, BJ, Fullana, MA
Publicada:
23 ago 2025
Resumen:
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.
Filiaciones:
Radua, J:
Inst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona, Spain
Univ Barcelona, Barcelona, Spain
Inst Salud Carlos III ISCIII, Ctr Invest Biomed Red Salud Mental CIBERSAM, Madrid, Spain
Savage, HS:
Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Nijmegen, Netherlands
Radboud Univ Nijmegen, Med Ctr, Dept Cognit Neurosci, Nijmegen, Netherlands
UCL, Inst Cognit Neurosci, London, England
Vilajosana, E:
Inst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona, Spain
Univ Barcelona, Barcelona, Spain
Jamieson, A:
Univ Melbourne, Dept Psychiat, Parkville, Vic, Australia
Abler, B:
Ulm Univ Clin, Dept Psychiat & Psychotherapy 3, Ulm, Germany
Åhs, F:
Mid Sweden Univ, Dept Psychol & Social Work, Ostersund, Sweden
Beckers, T:
Katholieke Univ Leuven, Fac Psychol & Educ Sci, Leuven, Belgium
Katholieke Univ Leuven, Leuven Brain Inst, Leuven, Belgium
Cardoner, N:
Inst Invest Biomed St Pau IBB St Pau, St Pau Mental Hlth Grp, Barcelona, Spain
Hosp Santa Creu & Sant Pau, Barcelona, Spain
Univ Autonoma Barcelona, Barcelona, Spain
Cisler, JM:
Univ Texas Austin, Dell Med Sch, Dept Psychiat & Behav Sci, Austin, TX USA
Diniz, JB:
Univ Sao Paulo, Fac Med, Dept Psychiat, Sao Paulo, Brazil
Bach, DR:
Univ Bonn, Inst Comp Sci,Transdisciplinary Res Area Life & H, Inst Expt Epileptol & Cognit Res,Med Fac, Hertz Chair Artificial Intelligence & Neurosci, Bonn, Germany
Univ Hosp Bonn, Dept Psychiat & Psychotherapy, Bonn, Germany
UCL, UCL Queen Sq Inst Neurol, Dept Imaging Neurosci, London, England
Elsenbruch, S:
Ruhr Univ Bochum, Med Fac, Dept Med Psychol & Med Sociol, Bochum, Germany
Greening, SG:
Univ Manitoba, Dept Psychol, Brain & Cognit Sci, Winnipeg, MB, Canada
Holt, DJ:
Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA
Harvard Med Sch, Boston, MA USA
Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA USA
Kaczkurkin, AN:
Vanderbilt Univ, Dept Psychol, Nashville, TN USA
Keil, A:
Univ Florida, Dept Psychol, Gainesville, FL USA
Kindt, M:
Univ Amsterdam, Dept Psychol, Amsterdam, Netherlands
Koch, K:
Tech Univ Munich, Sch Med & Hlth, Munich, Germany
Lam, CL:
Univ Hong Kong, Dept Psychol, Lab Clin Psychol & Affect Neurosci, Hong Kong, Peoples R China
State Key Lab Brain & Cognit Sci, Hong Kong, Peoples R China
Larson, CL:
Univ Wisconsin, Dept Psychol, Milwaukee, WI USA
Lonsdorf, TB:
Bielefeld Univ, Biol Psychol & Cognit Neurosci, Bielefeld, Germany
Univ Med Ctr Hamburg Eppendorf, Inst Syst Neurosci, Hamburg, Germany
Merz, CJ:
Ruhr Univ Bochum, Inst Cognit Neurosci, Dept Cognit Psychol, Bochum, Germany
McLaughlin, KA:
Harvard Univ, Dept Psychol, Cambridge, MA USA
Univ Oregon, Ballmer Inst Childrens Behav Hlth, Eugene, OR USA
Neria, Y:
Columbia Univ, Irving Med Ctr, Dept Psychiat, New York, NY USA
Pine, DS:
NIMH, Sect Dev & Affect Neurosci, Bethesda, MD USA
van Reekum, CM:
Univ Reading, Sch Psychol & Clin Language Sci, Reading, England
Shackman, AJ:
Univ Maryland, Dept Psychol, Neurosci & Cognit Sci Program, College Pk, MD USA
Univ Maryland, Maryland Neuroimaging Ctr, College Pk, MD USA
Soriano-Mas, C:
Inst Salud Carlos III ISCIII, Ctr Invest Biomed Red Salud Mental CIBERSAM, Madrid, Spain
Univ Barcelona, Inst Neurosci, Dept Social Psychol & Quantitat Psychol, Barcelona, Spain
Inst Invest Biomed Bellvitge IDIBELL, Neurosci Program, Psychiat & Mental Hlth Grp, Lhospitalet De Llobregat, Spain
Spoormaker, VI:
Max Planck Inst Psychiat, Munich, Germany
Stout, DM:
Univ Calif San Diego, San Diego, CA USA
VA San Diego Healthcare Syst, San Diego, CA USA
Ctr Excellence Stress & Mental Hlth, San Diego, CA USA
Straube, B:
Univ Marburg, Dept Psychiat & Psychotherapy, Marburg, Germany
Univ Marburg, Ctr Mind Brain & Behav, Marburg, Germany
Straube, T:
Univ Munster, Inst Med Psychol & Syst Neurosci, Munster, Germany
Tuominen, L:
Univ Ottawa, Inst Mental Hlth Res Royal, Ottawa, ON, Canada
Visser, RM:
Univ Amsterdam, Dept Psychol, Amsterdam, Netherlands
Ahumada, L:
Univ Florida, Dept Psychol, Gainesville, FL USA
Arolt, V:
Univ Munster, Inst Translat Psychiat, Munster, Germany
Univ Munster, Otto Creutzfeld Ctr Cognit & Behav Neurosci, Munster, Germany
Batistuzzo, MC:
Univ Sao Paulo, Fac Med, Dept Psychiat, Sao Paulo, Brazil
Pontifical Catholic Univ, Dept Methods & Tech Psychol, Sao Paulo, Brazil
Bazán, PR:
Univ Sao Paulo, Fac Med, Radiol Inst, Sao Paulo, Brazil
Biggs, EE:
Katholieke Univ Leuven, Fac Psychol & Educ Sci, Leuven, Belgium
Cano, M:
Inst Invest Biomed St Pau IBB St Pau, St Pau Mental Hlth Grp, Barcelona, Spain
Hosp Santa Creu & Sant Pau, Barcelona, Spain
Chavarría-Elizondo, P:
Inst Invest Biomed Bellvitge IDIBELL, Neurosci Program, Psychiat & Mental Hlth Grp, Lhospitalet De Llobregat, Spain
Univ Barcelona, Sch Med, Dept Clin Sci, LHospitalet De Llobregat, Barcelona, Spain
Cooper, SE:
Univ Texas Austin, Dept Psychiat & Behav Sci, Austin, TX USA
Dannlowski, U:
Univ Munster, Inst Translat Psychiat, Munster, Germany
de la Peña-arteaga, V:
Inst Invest Biomed St Pau IBB St Pau, St Pau Mental Hlth Grp, Barcelona, Spain
Hosp Santa Creu & Sant Pau, Barcelona, Spain
Univ Barcelona, Inst Neurosci, Dept Social Psychol & Quantitat Psychol, Barcelona, Spain
Decross, SN:
Harvard Univ, Dept Psychol, Cambridge, MA USA
Domschke, K:
Univ Freiburg, Med Ctr, Fac Med, Dept Psychiat & Psychotherapy, Freiburg, Germany
German Ctr Mental Hlth DZPG, Partner Site Berlin Potsdam, Berlin, Germany
Ehlers, MR:
Bielefeld Univ, Biol Psychol & Cognit Neurosci, Bielefeld, Germany
Univ Med Ctr Hamburg Eppendorf, Inst Syst Neurosci, Hamburg, Germany
Graner, JL:
Duke Univ, Ctr Cognit Neurosci, Durham, NC USA
Hamm, AO:
Univ Greifswald, Dept Psychol, Greifswald, Germany
Herrmann, MJ:
Univ Wurzburg, Dept Psychiat Psychosomat & Psychotherapy, Wurzburg, Germany
Huggins, AA:
Univ Arizona, Dept Psychol, Tucson, AZ USA
Icenhour, A:
Ruhr Univ Bochum, Med Fac, Dept Med Psychol & Med Sociol, Bochum, Germany
Juaneda-Seguí, A:
Inst Invest Biomed Bellvitge IDIBELL, Neurosci Program, Psychiat & Mental Hlth Grp, Lhospitalet De Llobregat, Spain
Junghoefer, M:
Univ Munster, Otto Creutzfeld Ctr Cognit & Behav Neurosci, Munster, Germany
Univ Munster, Inst Biomagnetism & Biosignal Anal, Munster, Germany
Kircher, T:
Univ Marburg, Dept Psychiat & Psychotherapy, Marburg, Germany
Univ Marburg, Ctr Mind Brain & Behav, Marburg, Germany
Koelkebeck, K:
Bielefeld Univ, Med Sch, Bielefeld, Germany
Univ Med Ctr OWL, Protestant Hosp, Bethel Fdn, Dept Psychiat & Psychotherapy, Bielefeld, Germany
Kuhn, M:
Univ Med Ctr Hamburg Eppendorf, Inst Syst Neurosci, Hamburg, Germany
McLean Hosp, Ctr Depress Anxiety & Stress Res, Belmont, MA USA
Harvard Med Sch, Dept Psychiat, Cambridge, MA USA
Labrenz, F:
Ruhr Univ Bochum, Med Fac, Dept Med Psychol & Med Sociol, Bochum, Germany
Lissek, SM:
Univ Minnesota, Dept Psychol, Minneapolis, MN USA
Lotze, M:
Univ Med Greifswald, Diagnost Radiol, Greifswald, Germany
Lueken, U:
German Ctr Mental Hlth DZPG, Partner Site Berlin Potsdam, Berlin, Germany
Humboldt Univ, Dept Psychol, Berlin, Germany
Margraf, J:
Ruhr Univ Bochum FBZ, Mental Hlth Res & Treatment Ctr FBZ, Bochum, Germany
German Ctr Mental Hlth DZPG, Partner site Bochum Marburg, Bochum, Germany
Martínez-Zalacaín, I:
Inst Invest Biomed Bellvitge IDIBELL, Neurosci Program, Psychiat & Mental Hlth Grp, Lhospitalet De Llobregat, Spain
Hosp Univ Bellvitge, Radiol Dept, Lhospitalet De Llobregat, Barcelona, Spain
Moeck, R:
Univ Munster, Inst Med Psychol & Syst Neurosci, Munster, Germany
Morriss, J:
Univ Southampton, Fac Environm & Life Sci, Sch Psychol, Southampton, England
Ortuño, M:
Inst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona, Spain
Pittig, A:
Univ Gottingen, Inst Psychol, Translat Psychotherapy, Gottingen, Germany
Porta-Casteras, D:
Inst Invest Biomed St Pau IBB St Pau, St Pau Mental Hlth Grp, Barcelona, Spain
Richter, J:
Univ Hildesheim, Dept Expt Psychopathol, Hildesheim, Germany
Ridderbusch, IC:
Univ Marburg, Dept Psychiat & Psychotherapy, Marburg, Germany
Univ Marburg, Ctr Mind Brain & Behav, Marburg, Germany
Rief, W:
Univ Marburg, Div Clin Psychol & Psychotherapy, Marburg, Germany
Roesmann, K:
Univ Munster, Inst Biomagnetism & Biosignal Anal, Munster, Germany
Univ Osnabruck, Inst Psychol Clin Psychol Childhood & Adolescence, Osnabruck, Germany
Rosén, J:
Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden
Russmann, AN:
Univ Med Ctr Hamburg Eppendorf, Inst Syst Neurosci, Hamburg, Germany
Univ Hamburg, Dept Psychol Clin Psychol & Neurosci, Hamburg, Germany
Sjouwerman, R:
Univ Med Ctr Hamburg Eppendorf, Inst Syst Neurosci, Hamburg, Germany
Maastricht Univ, Expt Hlth Psychol, Maastricht, Netherlands
Spohrs, J:
Ulm Univ, Dept Child & Adolescent Psychiat & Psychotherapy, Med Ctr, Ulm, Germany
Mil Med Ctr, Dept Psychiat Psychotherapy & Psychotraumatol, Ulm, Germany
Ströhle, A:
Charite Univ Med Berlin, Dept Psychiat & Psychotherapy, Berlin, Germany
Suarez-Jimenez, B:
Univ Rochester, Med Ctr, Dept Neurosci, Rochester, NY USA
Univ Rochester, Ctr Visual Sci, Rochester, NY USA
Ulrich, M:
Ulm Univ Clin, Dept Psychiat & Psychotherapy 3, Ulm, Germany
Wittchen, HU:
Ludwig Maximilians Univ Munchen, Psychiat Univ Hosp, Munich, Germany
Zhu, X:
Columbia Univ, Irving Med Ctr, Dept Psychiat, New York, NY USA
New York State Psychiat Inst & Hosp, New York, NY USA
Waller, L:
Charite Univ Med Berlin, Dept Psychiat & Psychotherapy, Berlin, Germany
Walter, H:
German Ctr Mental Hlth DZPG, Partner Site Berlin Potsdam, Berlin, Germany
Charite Univ Med Berlin, Dept Psychiat & Psychotherapy, Berlin, Germany
Thompson, PM:
Univ Southern Calif, Imaging Genet Ctr, Stevens Neuroimaging & Informat Inst, Keck Sch Med, Los Angeles, CA USA
Bas-Hoogendam, JM:
Leiden Univ, Inst Psychol, Dev & Educ Psychol, Leiden, Netherlands
Leiden Univ, Med Ctr, Leiden Inst Brain & Cognit, Leiden, Netherlands
Leiden Univ, Dept Psychiat, Med Ctr, Leiden, Netherlands
Groenewold, NA:
Univ Cape Town, Neurosci Inst, Dept Psychiat & Mental Hlth, Cape Town, South Africa
Stein, DJ:
Univ Cape Town, Dept Psychiat & Mental Hlth, SAMRC Unit Risk & Resilience Mental Disorders, Cape Town, South Africa
van der Wee, NJ:
Leiden Univ, Med Ctr, Leiden Inst Brain & Cognit, Leiden, Netherlands
Leiden Univ, Dept Psychiat, Med Ctr, Leiden, Netherlands
Dunsmoor, JE:
Univ Texas Austin, Dept Neurosci, Austin, TX USA
Marquand, AF:
Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Nijmegen, Netherlands
Radboud Univ Nijmegen, Med Ctr, Dept Cognit Neurosci, Nijmegen, Netherlands
Fullana, MA:
Inst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona, Spain
Hosp Clin Barcelona, Inst Neurosci, Adult Psychiat & Psychol Dept, Barcelona, Spain
Green Submitted, gold
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