title: Hippocampal activation during extinction learning predicts occurrence of the renewal effect in extinction recall.
abstract: The renewal effect describes the reoccurrence of a previously extinguished response in situations where the context of extinction differs from that of acquisition, thus illustrating the context-dependency of extinction learning. A number of studies on contextual fear extinction have implicated hippocampus and vmPFC in processing and retrieval of context both during extinction learning and recall of extinction. In this functional magnetic resonance imaging (fMRI) study we explored the neural correlates of the renewal effect in associative learning, using a predictive learning task that required participants to learn relations between cues and outcomes presented in particular contexts. During extinction in a novel context, compared to extinction in a context identical to the acquisition context, participants who exhibited the renewal effect (REN) showed increased activation in brain regions including bilateral posterior hippocampus and left parahippocampal gyrus. This activation pattern was absent in participants that did not show the renewal effect (NOREN). In direct comparisons between the groups, the REN group exhibited higher activation in bilateral hippocampus, while the NOREN group showed higher activation in left dlPFC (BA 46) and right anterior cingulate (BA 32). During extinction recall, stimuli that had been extinguished in a different context were again presented in the context of acquisition. Here both groups exhibited predominantly prefrontal activation, with the REN group's focus upon bilateral OFC (BA 47) and bilateral vmPFC (BA 10), while the NOREN group showed generally more widespread activation, predominantly in large clusters of dlPFC (BA 8,9,45). In a direct comparison, the REN group showed higher activation than the NOREN group in left vmPFC (BA 10), while NOREN participants exhibited more activation in dlPFC (BA 9, 46). Activation in left vmPFC during extinction recall correlated with the number of renewal effect responses, while the dlPFC activation showed a negative correlation with renewal effect responses. These results highlight the differential activation patterns of processes that will eventually produce or not produce a renewal effect, indicating that during extinction learning hippocampus encodes the relation between context and cue-outcome, while in extinction recall vmPFC is active to retrieve this association.
authors.affiliation: Department of Neurology, BG University Hospital Bergmannsheil, Ruhr-Universitaet Bochum, Bochum, Germany. Electronic address: silke.lissek@ruhr-uni-bochum.de.
authors.forename: Silke
authors.initials: S
authors.lastname: Lissek
authors.affiliation: Department of Neurology, BG University Hospital Bergmannsheil, Ruhr-Universitaet Bochum, Bochum, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Glaubitz
authors.affiliation: Faculty of Psychology, Philipps-Universitaet Marburg, Marburg, Germany.
authors.forename: Metin
authors.initials: M
authors.lastname: Uengoer
authors.affiliation: Department of Neurology, BG University Hospital Bergmannsheil, Ruhr-Universitaet Bochum, Bochum, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Tegenthoff
mesh_terms: D000328:Adult; D001245:Association Learning / Q000502:physiology*; D001931:Brain Mapping; D003214:Conditioning, Classical / Q000502:physiology; D003463:Cues; D005108:Extinction, Psychological / Q000502:physiology*; D005260:Female; D006624:Hippocampus / Q000502:physiology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D011939:Mental Recall / Q000502:physiology*; D011930:Reaction Time / Q000502:physiology; D055815:Young Adult
keywords: Extinction; Hippocampus; Learning; Renewal effect; fMRI; vmPFC