Neural Processing During Fear Extinction Predicts Intrusive Memories

• Published in: Biological psychiatry : cognitive neuroscience and neuroimaging 2020-04, Vol.5 (4), p.403-411
• Main Authors: Miedl, Stephan F., Rattel, Julina A., Franke, Laila K., Blechert, Jens, Kronbichler, Martin, Spoormaker, Victor I., Wilhelm, Frank H.
• Format: Article
• Language: English
• Subjects: Conditioning, Classical; Extinction memory; Extinction, Psychological; Fear; Fear conditioning; fMRI; Hippocampus; Humans; Intrusions; Magnetic Resonance Imaging; Posttraumatic stress disorder; Trauma film
• ISSN: 2451-9022; 2451-9030
• DOI: 10.1016/j.bpsc.2019.12.017

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. 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. 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. 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.