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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 Open the ORCID record for Hannah Berg [Opens in a new window] ,
Yizhou Ma Open the ORCID record for Yizhou Ma [Opens in a new window] ,
Amanda Rueter Open the ORCID record for Amanda Rueter [Opens in a new window] ,
Antonia Kaczkurkin Open the ORCID record for Antonia Kaczkurkin [Opens in a new window] ,
Philip C. Burton ,
Colin G. DeYoung Open the ORCID record for Colin G. DeYoung [Opens in a new window] ,
Angus W. MacDonald III Open the ORCID record for Angus W. MacDonald III [Opens in a new window] ,
Scott R. Sponheim  and
Shmuel M. Lissek Open the ORCID record for Shmuel M. Lissek [Opens in a new window]
Hannah Berg
Affiliation:
Department of Psychology, University of Minnesota, Minneapolis, MN, USA
Yizhou Ma
Affiliation:
Department of Psychology, University of Minnesota, Minneapolis, MN, USA
Amanda Rueter
Affiliation:
Department of Psychology, University of Minnesota, Minneapolis, MN, USA
Antonia Kaczkurkin
Affiliation:
Department of Psychological Sciences, Vanderbilt University, Nashville, TN, USA
Philip C. Burton
Affiliation:
Office of the CLA Associate Dean for Research, University of Minnesota, Minneapolis, MN, USA
Colin G. DeYoung
Affiliation:
Department of Psychology, University of Minnesota, Minneapolis, MN, USA
Angus W. MacDonald III
Affiliation:
Department of Psychology, University of Minnesota, Minneapolis, MN, USA
Scott R. Sponheim
Affiliation:
Minneapolis Veterans Affairs Health Care System, Minneapolis, MN, USA Department of Psychiatry, University of Minnesota, Minneapolis, MN, USA
Shmuel M. Lissek*
Affiliation:
Department of Psychology, University of Minnesota, Minneapolis, MN, USA
*
Author for correspondence: Shmuel M. Lissek, E-mail: smlissek@umn.edu
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Abstract

Background

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.

Methods

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.

Results

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

Conclusions

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.

Keywords

Central executive networkconditioned-feardefault networkgeneralizationpost-traumatic stress disordersalience network
Type
Original Article
Information
Psychological Medicine , Volume 51 , Issue 15 , November 2021 , pp. 2610 - 2619
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Copyright
Copyright © The Author(s), 2020. Published by Cambridge University Press

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