Effects of prediction error and acute stress on retrieval-extinction of fear memories of different strengths

Abstract

(1) to test the effect of memory strength in a human on (2) examine the of during on destabilizing different strength memories and (3) to test the possible of post-reactivation exogenous stress to the of retrieval-extinction study. We manipulated memory strength through two kinds of acquisition procedures on the day, varied the predictability of the unconditioned stimulus (US) occurrence after the conditioned Twenty-four hours later, a reminder containing a single PE was used to reactivate memories, which was followed by a stress task (Social Evaluate Cold Pressor test, SECPT) or not before extinction. After 24 hours, a test of spontaneous recovery and reinstatement was utilized to measure the return of fear in each condition. All participants were divided into three conditions: CS-Predictable US_no Stress Group, CS-Unpredictable US_no Stress Group and the CS-Unpredictable US_Stress Group. Skin conductance response (SCR) and fear-potentiated startle response (FPS) were used as measurements of conditioned fear. The results showed that there was a relatively stronger increase in fear response (SCR) from Day 1 to Day 2 in the CS-Unpredictable US condition than the CS-Predictable US condition, which may suggest a difference in memory strength between conditions. And for the weak fear memory (CS-predictable US), the reactivation that involved a single PE and was followed by extinction training prevented the spontaneous recovery, especially on the SCR measurement. On the other hand, in the enhanced memory condition (CS-unpredictable US), the extinguished memory returned in the memory test on the third day, which suggests a failure of memory destabilization. Furthermore, when the post-reactivation acute stress task was adopted in the enhanced memory condition, the return of fear further increased, compared with the no stress manipulation conditions. These results indicate that PE used to destabilize weak memories is insufficient to destabilize strong memories; and that post-reactivation acute stress cannot nullify this deficit which is due to boundary conditions (e.g., strength). We discuss possible interpretations of these results and the implications for the translation of retrieval-extinction to clinical practice.