Timing matters: Providing Contingency Instructions to modify Fear Extinction Memories in Anxiety Disorders

Background: Cognitive processes play a significant role in fear extinction. Contingency instructions (CI), about the non-occurrence of the unconditioned stimulus (UCS), can be used to promote fear extinction learning and extinction retrieval. However, previous research has been mainly performed in healthy individuals, and a systematic study on the effects of CI administered during different phases of the extinction memory acquisition in patients with anxiety disorders (ADs) is lacking.Methods: We investigated the effects of CI administered before and/or after fear extinction training on extinction learning and retrieval processes in 240 participants (120 patients with ADs, 120 healthy controls) using a three-day fear conditioning paradigm. Skin conductance responses (SCRs), CS (conditioned stimulus) valence, and UCS expectancy ratings served as readout measures.Results: CI before extinction training enhanced extinction learning for both patients with ADs and healthy controls on the level of SCRs and affective measures. Similarly, post-extinction CI administration led to reduced CS differentiation in SCRs and UCS expectancy during extinction retrieval in healthy controls and patients. After reinstatement, post-extinction CI administration also diminished fear relapse in the original acquisition and novel context. Here, time-dependent effects of CI seem to further depend on contextual cues established during the initial fear acquisition and extinction.Conclusions: Our findings contribute to the existing knowledge on the role of time-dependent administration of CI in fear extinction and offer novel insights into how cognitive interventions can be integrated to augment existing therapeutic approaches for ADs.This study was registered at ClinicalTrials.gov (Identifier: NCT05718271).