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The Journal of Neuroscience, September 13, 2006, 26(37):9503-9511; doi:10.1523/JNEUROSCI.2021-06.2006
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Behavioral/Systems/Cognitive
Context-Dependent Human Extinction Memory Is Mediated by a Ventromedial Prefrontal and Hippocampal Network
Raffael Kalisch, Elian Korenfeld, Klaas E. Stephan, Nikolaus Weiskopf, Ben Seymour, andRaymond J. Dolan Wellcome Department of Imaging Neuroscience, Functional Imaging Laboratory, Institute of Neurology, University College London, London, WC1N 3BG, United Kingdom
Correspondence should be addressed to Dr. Raffael Kalisch at his present address: Institut für Systemische Neurowissenschaften, Universitätsklinikum Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany. Email: rkalisch{at}uke.uni-hamburg.de
In fear extinction, an animal learns that a conditioned stimulus (CS) no longer predicts a noxious stimulus [unconditioned stimulus (UCS)] to which it had previously been associated, leading to inhibition of the conditioned response (CR). Extinction creates a new CS–noUCS memory trace, competing with the initial fear (CS–UCS) memory. Recall of extinction memory and, hence, CR inhibition at later CS encounters is facilitated by contextual stimuli present during extinction training. In line with theoretical predictions derived from animal studies, we show that, after extinction, a CS-evoked engagement of human ventromedial prefrontal cortex (VMPFC) and hippocampus is context dependent, being expressed in an extinction, but not a conditioning, context. Likewise, a positive correlation between VMPFC and hippocampal activity is extinction context dependent. Thus, a VMPFC–hippocampal network provides for context-dependent recall of human extinction memory, consistent with a view that hippocampus confers context dependence on VMPFC.
Key words: fear conditioning; extinction; context; hippocampus; ventromedial prefrontal cortex; extinction memory
Received March 10, 2006; revised July 3, 2006; accepted Aug. 8, 2006.
Correspondence should be addressed to Dr. Raffael Kalisch at his present address: Institut für Systemische Neurowissenschaften, Universitätsklinikum Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany. Email: rkalisch{at}uke.uni-hamburg.de
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