Abstract

Background Experimental extinction serves as a model for psychiatric treatments based on associative learning. However, the effects of extinction are often transient, as evidenced by post-extinction return of defensive behaviors. From a therapeutic perspective, an inherent problem with extinction may be that mere omission of threat is not sufficient to reduce future threat uncertainty. The current study tested an augmented form of extinction that replaced- rather than merely omitted- expected threat outcomes with novel non-threat outcomes, with the goal of reducing post-extinction return of defensive behaviors. Methods Thirty-two healthy male Sprague-Dawley rats and 47 human adults underwent threat conditioning to a conditioned stimulus paired with an electrical shock. Subjects then underwent a standard extinction protocol with shock omitted, or an augmented extinction protocol wherein the shock was replaced by a surprising tone. Tests of post-extinction recovery occurred 24 hours later in the absence of the tone. Results Replacing the shock with a novel non-threat outcome, as compared to shock omission, reduced post-extinction recovery (freezing in rats and anticipatory skin conductance responses in humans) when tested 24 hours later. Self-reported intolerance of uncertainty was positively correlated with recovery following standard extinction in humans, providing new evidence that post-extinction recovery is related to sensitivity to future threat uncertainty. Conclusions These findings provide cross-species evidence of a novel strategy to enhance extinction that may have broad implications for how to override associative learning that has become maladaptive, and offer a simple technique that could be straightforwardly adapted and implemented in clinical situations.