Cortisol decreases activation in extinction related brain areas resulting in an impaired recall of context-dependent extinction memory

Conditioned responding gradually stops during successful extinction learning. The renewal effect is defined as the recovery of a extinguished conditioned response when the context of extinction is different from acquisition. The stress hormone cortisol is known to have an influence on extinction memory and associative learning. Different effects of cortisol on behaviour and brain activity have been observed with respect to stress timing, duration, and intensity. However, the influence of cortisol prior to the initial encoding of stimulus-outcome associations on extinction learning, renewal and its behavioural and neurobiological correlates is still largely unknown. In our study, 60 human participants received 20 mg cortisol or placebo and then learned, extinguished, and recalled the associations between food stimuli presented in distinct contexts and different outcomes in three subsequent task phases. Learning performance during acquisition and extinction phases was equally good for both treatment groups. In the cortisol group, significantly more participants showed renewal compared to placebo. In the subgroup of participants with renewal, cortisol treated participants showed significantly better extinction learning performance compared to placebo. Participants showing renewal had in general difficulties with recalling extinction memory, but in contrast to placebo, the cortisol group exhibited a context-dependent impairment of extinction memory recall. Imaging analyses revealed that cortisol decreased activation in the hippocampus during acquisition. The cortisol group also showed reduced dorsolateral prefrontal cortex activation when extinction learning took place in a different context, but enhanced activation in inferior frontal gyrus during extinction learning without context change. During recall, cortisol decreased ventromedial prefrontal cortex activation. Taken together, our findings illustrate cortisol as a potent modulator of extinction learning and recall of extinction memory which also promotes renewal.