Radua Joaquim, Savage Hannah S, Vilajosana Enric, Jamieson Alec, Abler Birgit, Åhs Fredrik, Beckers Tom, Cardoner Narcís, Cisler Josh M, Diniz Juliana B, Bach Dominik R, Elsenbruch Sigrid, Greening Steven G, Holt Daphne J, Kaczkurkin Antonia N, Keil Andreas, Kindt Merel, Koch Kathrin, LaBar Kevin S, Lam Charlene L, Larson Christine L, Lonsdorf Tina B, Merz Christian J, McLaughlin Katie A, Neria Yuval, Pine Daniel S, van Reekum Carien M, Shackman Alexander J, Soriano-Mas Carles, Spoormaker Victor I, Stout Daniel M, Straube Benjamin, Straube Thomas, Tuominen Lauri, Visser Renée M, Ahumada Laura, Arolt Volker, Batistuzzo Marcelo C, Bazán Paulo R, Biggs Emma E, Cano Marta, Chavarría-Elizondo Pamela, Cooper Samuel E, Dannlowski Udo, de la Peña-Arteaga Víctor, DeCross Stephanie N, Domschke Katharina, Ehlers Mana R, Graner John L, Hamm Alfons O, Herrmann Martin J, Huggins Ashley A, Icenhour Adriane, Juaneda-Seguí Asier, Junghoefer Markus, Kircher Tilo, Koelkebeck Katja, Kuhn Manuel, Labrenz Franziska, Lissek Shmuel M, Lotze Martin, Lueken Ulrike, Margraf Jürgen, Martínez-Zalacaín Ignacio, Moeck Robert, Morriss Jayne, Ortuño María, Pittig Andre, Porta-Casteras Daniel, Richter Jan, Ridderbusch Isabelle C, Rief Winfried, Roesmann Kati, Rosén Jörgen, Rußmann Alena N, Sjouwerman Rachel, Spohrs Jennifer, Ströhle Andreas, Suarez-Jimenez Benjamin, Ulrich Martin, Wittchen Hans-Ulrich, Zhu Xi, Waller Lea, Walter Henrik, Thompson Paul M, Bas-Hoogendam Janna Marie, Groenewold Nynke A, J Stein Dan, Van der Wee Nic J, Dunsmoor Joseph E, Marquand Andre F, J Harrison Ben, Fullana Miquel A
Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
University of Barcelona, Barcelona, Spain.
Nat Commun. 2025 Aug 23;16(1):7869. doi: 10.1038/s41467-025-63078-x.
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.
巴甫洛夫式恐惧条件反射是健康和疾病中的一个基本过程。我们使用来自九个国家2199名个体的协调功能磁共振成像数据来研究其神经关联和变异性来源，其中包括1888名健康个体和311名患有焦虑相关或抑郁障碍的个体。通过元分析和规范建模，我们表明恐惧条件反射始终会激活“中枢自主-内感受”或“显著性”网络内的脑区。几个任务变量强烈调节这些区域的活动，导致神经反应的变异性。此外，健康个体与患有焦虑相关或抑郁障碍的个体之间的脑激活模式不同，特定障碍（如创伤后应激障碍和强迫症）具有独特的特征。虽然恐惧条件反射的神经关联在人群水平上具有高度普遍性，但变异性源于任务设计和临床状态的差异，这突出了方法多样性在捕捉恐惧学习机制中的重要性。
