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Nat Neurosci. 2004 Oct;7(10):1144-52. Epub 2004 Sep 12.

Human orbitofrontal cortex mediates extinction learning while accessing conditioned representations of value.

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Wellcome Department of Imaging Neuroscience, Functional Imaging Laboratory, 12 Queen Square, London, WC1N 3BG, UK. <>


In extinction, an animal learns that a previously conditioned stimulus (CS+) no longer predicts delivery of a salient reinforcer (unconditioned stimulus, UCS). Rodent studies indicate that extinction relies on amygdala-prefrontal interactions and involves formation of memories that inhibit, without actually erasing, the original conditioning trace. Whether extinction learning in humans follows similar neurobiological principles is unknown. We used functional magnetic resonance imaging to measure human brain activity evoked during olfactory aversive conditioning and extinction learning. Neural responses in orbitofrontal cortex and amygdala were preferentially enhanced during extinction, suggesting potential cross-species preservation of learning mechanisms that oppose conditioning. Moreover, by manipulating UCS aversiveness via reinforcer inflation, we showed that a CS+ retains access to representations of UCS value in distinct regions of ventral prefrontal cortex, even as extinction proceeds.

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