Abstract
Renewal describes the recovery of an extinguished response if recall is tested in a context different from the extinction context. Behavioral studies demonstrated that attention to relevant context strengthens renewal. Neurotransmitters mediating attention and learning such as the dopaminergic (DA) system presumably modulate extinction learning and renewal. However, the role of DA for non-fear-based extinction learning and renewal in humans has not yet been investigated. This fMRI study investigated effects of DA-antagonism upon context-related extinction in a predictive learning task in which extinction occurred either in a novel (ABA) or an unchanged (AAA) context. The tiapride-treated group (TIA) showed significantly impaired ABA extinction learning and a significant within-group difference between ABA and AAA extinction, compared to placebo (PLAC). Groups did not differ in their level of ABA renewal. In ABA extinction, TIA showed reduced activation in dlPFC and OFC, hippocampus, and temporal regions. Across groups, activation in PFC and hippocampus correlated negatively with ABA extinction errors. Results suggest that in context-related extinction learning DA in PFC and hippocampus is involved in readjusting the cue-outcome relationship in the presence of a novel context. However, relating context to the appropriate association during recall does not appear to rely exclusively on DA signaling.
Highlights
The renewal effect of extinction describes the recovery of an extinguished response when extinction learning has been performed in a context different from that present during extinction recall (Bouton and Bolles, 1979)
When considering only extinction learning in a novel context (ABA condition), the TIA group was significantly impaired compared to PLAC [t(38) = 1.989 p = 0.027; TIA 24.00% ± 3.81; PLAC 15.00% ± 2.43], while there was no significant difference in a familiar context-cue compound (AAA) extinction learning between groups [t(38) = 0.673 p = 0.252; TIA 18.25% ± 2.93; PLAC 16.00% ± 1.59—all t-tests one-tailed]. (See Figure 2A) within the TIA group, we found a significant difference between extinction learning performance in the ABA and the AAA conditions [t(19) = 2.498 p = 0.022], which is absent in the PLAC group [t(19) = 0.462 p = 0.649]
The difference in dlPFC activation is prominent for the ABA condition, where the PLAC group activates a number of clusters in bilateral BA 8, 9, and 46, while there is no dlPFC activation in TIA
Summary
The renewal effect of extinction describes the recovery of an extinguished response when extinction learning has been performed in a context different from that present during extinction recall (Bouton and Bolles, 1979). Hippocampal activation is more pronounced in participants who later exhibit renewal than in those who do not, suggesting that their encoding of context is more effective (Lissek et al, 2013) These results are in line with previous findings in human fear extinction that associated hippocampus and vmPFC with context processing (Kalisch et al, 2006; Milad et al, 2007).
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