Neural Processing During Fear Extinction Predicts Intrusive Memories

Stephan F Miedl; Julina A Rattel; Laila K Franke; Jens Blechert; Martin Kronbichler; Victor I Spoormaker; Frank H Wilhelm

doi:10.1016/j.bpsc.2019.12.017

Neural Processing During Fear Extinction Predicts Intrusive Memories

Biol Psychiatry Cogn Neurosci Neuroimaging. 2020 Apr;5(4):403-411. doi: 10.1016/j.bpsc.2019.12.017. Epub 2020 Jan 13.

Authors

Stephan F Miedl¹, Julina A Rattel², Laila K Franke², Jens Blechert³, Martin Kronbichler⁴, Victor I Spoormaker⁵, Frank H Wilhelm²

Affiliations

¹ Clinical Stress and Emotion Laboratory, Division of Clinical Psychology, Psychotherapy, and Health Psychology, Department of Psychology, University of Salzburg, Salzburg, Austria. Electronic address: stephan.miedl@sbg.ac.at.
² Clinical Stress and Emotion Laboratory, Division of Clinical Psychology, Psychotherapy, and Health Psychology, Department of Psychology, University of Salzburg, Salzburg, Austria.
³ Clinical Stress and Emotion Laboratory, Division of Clinical Psychology, Psychotherapy, and Health Psychology, Department of Psychology, University of Salzburg, Salzburg, Austria; Centre for Cognitive Neuroscience, University of Salzburg, Salzburg, Austria.
⁴ Centre for Cognitive Neuroscience, University of Salzburg, Salzburg, Austria; Neuroscience Institute, Christian Doppler Clinic, Paracelsus Medical University Salzburg, Salzburg, Austria.
⁵ Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany.

PMID: 32111578
DOI: 10.1016/j.bpsc.2019.12.017

Abstract

Background: Deficient extinction learning has been suggested as an important mechanism involved in the etiology of posttraumatic stress disorder. A key feature of posttraumatic stress disorder, reexperiencing the trauma in form of intrusions, may be linked to deficient extinction learning. This link is investigated in a novel, functional magnetic resonance imaging-compatible fear conditioning procedure that uses trauma films. Based on previous results, we expected deficient fear extinction indexed by exaggerated responding in the anterior insula and dorsal anterior cingulate cortex to predict subsequent intrusions.

Methods: A total of 58 healthy participants underwent acquisition and extinction learning with faces as conditioned stimuli (CS) and highly aversive 16-second films depicting interpersonal violence as unconditioned stimuli. During the subsequent 3 days, participants reported intrusive memories on their smartphone.

Results: Successful fear acquisition was evidenced by differential (CS+ > CS-) activity (threat cues associated with trauma films > cues paired only with neutral films) of a widespread network, including the anterior insula and dorsal anterior cingulate cortex, whereas extinction was characterized exclusively by differential anterior insula activity. Differential conditioned responding during late extinction in the anterior insula and dorsal anterior cingulate cortex was positively related to intrusive memory frequency independent of unconditioned stimuli responding. Exploratory analysis also revealed intrusion sensitivity of the hippocampus, rostral anterior cingulate cortex, and ventromedial prefrontal cortex, among others.

Conclusions: Results support the role of extinction learning in intrusive memory formation; a failure to uncouple conditioned emotional responding from external threat cues was associated with subsequent intrusive memories, representing a potential risk marker for developing posttraumatic stress disorder symptomatology after trauma.

Keywords: Extinction memory; Fear conditioning; Intrusions; Posttraumatic stress disorder; Trauma film; fMRI.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Conditioning, Classical
Extinction, Psychological*
Fear*
Hippocampus
Humans
Magnetic Resonance Imaging

Grants and funding

W 1233/FWF_/Austrian Science Fund FWF/Austria