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Salience and central executive networks track overgeneralization of conditioned-fear in post-traumatic stress disorder

Published online by Cambridge University Press:  05 May 2020

Hannah Berg
Department of Psychology, University of Minnesota, Minneapolis, MN, USA
Yizhou Ma
Department of Psychology, University of Minnesota, Minneapolis, MN, USA
Amanda Rueter
Department of Psychology, University of Minnesota, Minneapolis, MN, USA
Antonia Kaczkurkin
Department of Psychological Sciences, Vanderbilt University, Nashville, TN, USA
Philip C. Burton
Office of the CLA Associate Dean for Research, University of Minnesota, Minneapolis, MN, USA
Colin G. DeYoung
Department of Psychology, University of Minnesota, Minneapolis, MN, USA
Angus W. MacDonald III
Department of Psychology, University of Minnesota, Minneapolis, MN, USA
Scott R. Sponheim
Minneapolis Veterans Affairs Health Care System, Minneapolis, MN, USA Department of Psychiatry, University of Minnesota, Minneapolis, MN, USA
Shmuel M. Lissek*
Department of Psychology, University of Minnesota, Minneapolis, MN, USA
Author for correspondence: Shmuel M. Lissek, E-mail:



Generalization of conditioned-fear, a core feature of post-traumatic stress disorder (PTSD), has been the focus of several recent neuroimaging studies. A striking outcome of these studies is the frequency with which neural correlates of generalization fall within hubs of well-established functional networks including salience (SN), central executive (CEN), and default networks (DN). Neural substrates of generalization found to date may thus reflect traces of large-scale brain networks that form more expansive neural representations of generalization. The present study includes the first network-based analysis of generalization and PTSD-related abnormalities therein.


fMRI responses in established intrinsic connectivity networks (ICNs) representing SN, CEN, and DN were assessed during a generalized conditioned-fear task in male combat veterans (N = 58) with wide-ranging PTSD symptom severity. The task included five rings of graded size. Extreme sizes served as conditioned danger-cues (CS+: paired with shock) and safety-cues (CS−), and the three intermediate sizes served as generalization stimuli (GSs) forming a continuum-of-size between CS+ and CS–. Generalization-gradients were assessed as behavioral and ICN response slopes from CS+, through GSs, to CS–. Increasing PTSD symptomatology was predicted to relate to less-steep slopes indicative of stronger generalization.


SN, CEN, and DN responses fell along generalization-gradients with levels of generalization within and between SN and CEN scaling with PTSD symptom severity.


Neural substrates of generalized conditioned-fear include large-scale networks that adhere to the functional organization of the brain. Current findings implicate levels of generalization in SN and CEN as promising neural markers of PTSD.

Original Article
Copyright © The Author(s), 2020. Published by Cambridge University Press

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