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Neural correlates of human fear conditioning and sources of variability in 2199 individuals.

Publication ,  Journal Article
Radua, J; Savage, HS; Vilajosana, E; Jamieson, A; Abler, B; Åhs, F; Beckers, T; Cardoner, N; Cisler, JM; Diniz, JB; Bach, DR; Elsenbruch, S ...
Published in: Nature communications
August 2025

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.

Duke Scholars

Published In

Nature communications

DOI

EISSN

2041-1723

ISSN

2041-1723

Publication Date

August 2025

Volume

16

Issue

1

Start / End Page

7869

Related Subject Headings

  • Young Adult
  • Stress Disorders, Post-Traumatic
  • Obsessive-Compulsive Disorder
  • Middle Aged
  • Male
  • Magnetic Resonance Imaging
  • Humans
  • Female
  • Fear
  • Conditioning, Classical
 

Citation

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Radua, J., Savage, H. S., Vilajosana, E., Jamieson, A., Abler, B., Åhs, F., … Fullana, M. A. (2025). Neural correlates of human fear conditioning and sources of variability in 2199 individuals. Nature Communications, 16(1), 7869. https://doi.org/10.1038/s41467-025-63078-x
Radua, Joaquim, Hannah S. Savage, Enric Vilajosana, Alec Jamieson, Birgit Abler, Fredrik Åhs, Tom Beckers, et al. “Neural correlates of human fear conditioning and sources of variability in 2199 individuals.Nature Communications 16, no. 1 (August 2025): 7869. https://doi.org/10.1038/s41467-025-63078-x.
Radua J, Savage HS, Vilajosana E, Jamieson A, Abler B, Åhs F, et al. Neural correlates of human fear conditioning and sources of variability in 2199 individuals. Nature communications. 2025 Aug;16(1):7869.
Radua, Joaquim, et al. “Neural correlates of human fear conditioning and sources of variability in 2199 individuals.Nature Communications, vol. 16, no. 1, Aug. 2025, p. 7869. Epmc, doi:10.1038/s41467-025-63078-x.
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 H-U, Zhu X, Waller L, Walter H, Thompson PM, Bas-Hoogendam JM, Groenewold NA, J Stein D, Van der Wee NJ, Dunsmoor JE, Marquand AF, J Harrison B, Fullana MA. Neural correlates of human fear conditioning and sources of variability in 2199 individuals. Nature communications. 2025 Aug;16(1):7869.

Published In

Nature communications

DOI

EISSN

2041-1723

ISSN

2041-1723

Publication Date

August 2025

Volume

16

Issue

1

Start / End Page

7869

Related Subject Headings

  • Young Adult
  • Stress Disorders, Post-Traumatic
  • Obsessive-Compulsive Disorder
  • Middle Aged
  • Male
  • Magnetic Resonance Imaging
  • Humans
  • Female
  • Fear
  • Conditioning, Classical