Neural adaptation of cingulate and insular activity during delayed fear extinction: A replicable pattern across assessment sites and repeated measurements
Isabelle C. Ridderbusch,
Adrian Wroblewski,
Yunbo Yang,
Jan Richter,
Maike Hollandt,
Alfons O. Hamm,
Hans-Ulrich Wittchen,
Andreas Ströhle,
Volker Arolt,
Jürgen Margraf,
Ulrike Lueken,
Martin J. Herrmann,
Tilo Kircher,
Benjamin Straube
Affiliations
Isabelle C. Ridderbusch
Department of Psychiatry and Psychotherapy and Center for Mind, Brain and Behavior - CMBB, Philipps-Universität Marburg, Germany; Corresponding author.
Adrian Wroblewski
Department of Psychiatry and Psychotherapy and Center for Mind, Brain and Behavior - CMBB, Philipps-Universität Marburg, Germany
Yunbo Yang
Department of Psychiatry and Psychotherapy and Center for Mind, Brain and Behavior - CMBB, Philipps-Universität Marburg, Germany
Jan Richter
Institute for Psychology, University of Greifswald, Germany
Maike Hollandt
Institute for Psychology, University of Greifswald, Germany
Alfons O. Hamm
Institute for Psychology, University of Greifswald, Germany
Hans-Ulrich Wittchen
Institute for Clinical Psychology and Psychotherapie, Technichal University of Dresden, Germany; Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University (LMU) Muenchen, Germany
Andreas Ströhle
Klinik für Psychiatrie und Psychotherapie, Campus Charité Mitte, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berliner Institut für Gesundheitsforschung, Germany
Volker Arolt
Department of Psychiatry and Psychotherapy, University Hospital Muenster, Germany
Jürgen Margraf
Chair in Psychiatry and Psychotherapy, Ruhr University Bochum (RUB), Germany
Ulrike Lueken
Center for Mental Health, Department of Psychiatry, Psychosomatics, and Psychotherapy, University Hospital Wuerzburg, Germany; Department of Psychology, Humboldt-Universität zu Berlin, Germany
Martin J. Herrmann
Center for Mental Health, Department of Psychiatry, Psychosomatics, and Psychotherapy, University Hospital Wuerzburg, Germany
Tilo Kircher
Department of Psychiatry and Psychotherapy and Center for Mind, Brain and Behavior - CMBB, Philipps-Universität Marburg, Germany
Benjamin Straube
Department of Psychiatry and Psychotherapy and Center for Mind, Brain and Behavior - CMBB, Philipps-Universität Marburg, Germany
Adapting threat-related memories towards changing environments is a fundamental ability of organisms. One central process of fear reduction is suggested to be extinction learning, experimentally modeled by extinction training that is repeated exposure to a previously conditioned stimulus (CS) without providing the expected negative consequence (unconditioned stimulus, US). Although extinction training is well investigated, evidence regarding process-related changes in neural activation over time is still missing. Using optimized delayed extinction training in a multicentric trial we tested whether: 1) extinction training elicited decreasing CS-specific neural activation and subjective ratings, 2) extinguished conditioned fear would return after presentation of the US (reinstatement), and 3) results are comparable across different assessment sites and repeated measures. We included 100 healthy subjects (measured twice, 13-week-interval) from six sites. 24 h after fear acquisition training, extinction training, including a reinstatement test, was applied during fMRI. Alongside, participants had to rate subjective US-expectancy, arousal and valence. In the course of the extinction training, we found decreasing neural activation in the insula and cingulate cortex as well as decreasing US-expectancy, arousal and negative valence towards CS+. Re-exposure to the US after extinction training was associated with a temporary increase in neural activation in the anterior cingulate cortex (exploratory analysis) and changes in US-expectancy and arousal ratings. While ICCs-values were low, findings from small groups suggest highly consistent effects across time-points and sites. Therefore, this delayed extinction fMRI-paradigm provides a solid basis for the investigation of differences in neural fear-related mechanisms as a function of anxiety-pathology and exposure-based treatment.
