The renewal effect of extinction demonstrates the context-dependency of extinction learning. It is defined as the recovery of an extinguished response occurring when the contexts of extinction and recall differ. Behavioral studies showed that modulating context relevance can strengthen context-specific responses. In our fMRI study, we investigated to what extent a modulation of context salience can alter renewal levels and provide additional information about the neural basis for renewal. In a withinsubjects design, participants completed two sessions of an associative learning task in randomized order. In the salient condition (SAL), a context was presented alone at the start of each trial, before being presented together with the stimulus. The regular condition (REG) contained no context-alone phase. In about one-third of participants (SWITCH), the context salience modulation significantly increased renewal rates in the SAL compared to the REG condition. The other participants showed either renewal (REN) or no renewal (NoREN) in both conditions. The modulation did not significantly affect learning performance during the initial forming of associations or extinction learning. In the SWITCH group, activation in left opercular inferior frontal gyrus (iFG) during the recall phase was associated with a renewal effect, together with activity in the bilateral posterior hippocampus and ventromedial prefrontal cortex (vmPFC). Also during the extinction phase, left opercular iFG activation was higher in groups exhibiting renewal in recall, irrespective of the context salience modulation. Besides confirming the participation of vmPFC in extinction recall, our findings provide novel insights regarding an as yet undetected, potentially important role for renewal-supporting processes in left iFG during extinction learning and recall, which are presumably based on the region's proposed function of evaluating competing response options under conditions of ambiguity.
Renewal is defined as the recovery of an extinguished response when the contexts of extinction and recall differ. Prominent hippocampal activity during context-related extinction can predict renewal. Dopaminergic antagonism during extinction learning impaired extinction and reduced hippocampal activation, without affecting renewal. However, to what extent dopaminergic stimulation during extinction influences hippocampal processing and renewal is as yet unknown. In this fMRI study, we investigated the effects of the dopamine D2-like agonist bromocriptine upon renewal in an associative learning task, in hippocampus and ventromedial PFC. We observed significant differences between bromocriptine (BROMO) and placebo (PLAC) treatments in the subgroups showing (REN) and lacking (NoREN) renewal: the renewal level of BROMO REN was significantly higher, and associated with more prominent hippocampal activation during extinction and recall, compared to PLAC REN and BROMO NoREN. Results suggest that an interaction between D2like-agonist-induced enhancement of hippocampal activity and a pre-existing tendency favoring context processing contributed to the higher renewal levels. In contrast, ventromedial prefrontal activation was unchanged, indicating that increased hippocampal context processing and not prefrontal response selection constituted the central driving force behind the high renewal levels. The findings demonstrate that hippocampal dopamine is important for encoding and providing of context information, and thus crucially involved in the renewal effect.
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