State-of-the-art and future directions for extinction as a translational model for fear and anxiety.

Through advances in both basic and clinical scientific research, Pavlovian fear conditioning and extinction have become an exemplary translational model for understanding and treating anxiety disorders. Discoveries in associative and neurobiological mechanisms underlying extinction have informed techniques for optimizing exposure therapy that enhance the formation of inhibitory associations and their consolidation and retrieval over time and context. Strategies that enhance formation include maximizing prediction-error correction by violating expectancies, deepened extinction, occasional reinforced extinction, attentional control and removal of safety signals/behaviours. Strategies that enhance consolidation include pharmacological agonists of NMDA (i.e. d-cycloserine) and mental rehearsal. Strategies that enhance retrieval include multiple contexts, retrieval cues, and pharmacological blockade of contextual encoding. Stimulus variability and positive affect are posited to influence the formation and the retrieval of inhibitory associations. Inhibitory regulation through affect labelling is considered a complement to extinction. The translational value of extinction will be increased by more investigation of elements central to extinction itself, such as extinction generalization, and interactions with other learning processes, such as instrumental avoidance reward learning, and with other clinically relevant cognitive-emotional processes, such as self-efficacy, threat appraisal and emotion regulation, will add translational value. Moreover, framing fear extinction and related processes within a developmental context will increase their clinical relevance.This article is part of a discussion meeting issue 'Of mice and mental health: facilitating dialogue between basic and clinical neuroscientists'.