Unravelling the neurocognitive mechanisms underlying counterconditioning in humans.

Counterconditioning (CC) aims to enhance extinction of threat memories by establishing new associations of opposite valence. While its underlying neurocognitive mechanisms remain largely unexplored, previous studies suggest qualitatively different mechanisms from regular extinction. In this functional MRI study, participants underwent categorical threat conditioning (CS+/CS-: images of animals/tools), followed by either CC (CS + images reinforced with monetary rewards, n=24) or regular extinction (n=24). The following day, we assessed spontaneous recovery of threat responses and episodic memory for CS + and CS- category exemplars. While the ventromedial prefrontal cortex (vmPFC) was activated during regular extinction, participants undergoing CC showed persistent CS+-specific deactivation of the vmPFC and hippocampus, and CS+-specific activation of the nucleus accumbens (NAcc). The following day, physiological threat responses returned in the regular extinction group, but not in the CC group. Counterconditioning furthermore strengthened episodic memory for CS + exemplars presented during CC, and retroactively also for CS + exemplars presented during the threat conditioning phase. Our findings confirm that CC leads to more persistent extinction of threat memories, as well as altered consolidation of the threat conditioning episode. Crucially, we show a qualitatively different activation pattern during CC versus regular extinction, with a shift away from the vmPFC and towards the NAcc.