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

Abstract

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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Figure 1: Experimental design.
Figure 2: Behavioral and neural substrates of conditioning and extinction.
Figure 3: Functional overlaps and dissociations in amygdala and OFC during extinction and conditioning.
Figure 4: Behavioral impact of UCS inflation on CS+ processing.
Figure 5: A representation of (aversive) UCS value in lateral OFC during extinction.
Figure 6: A representation of (less aversive) UCS value in ventromedial PFC during extinction.

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Acknowledgements

This work was supported by a Howard Hughes Physician-Scientist Fellowship Grant (J.A.G.) and a Wellcome Trust Programme Grant (R.J.D.). We thank J.S. Winston and J.M. Kilner for helpful discussions.

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Correspondence to Jay A Gottfried.

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Gottfried, J., Dolan, R. Human orbitofrontal cortex mediates extinction learning while accessing conditioned representations of value. Nat Neurosci 7, 1144–1152 (2004). https://doi.org/10.1038/nn1314

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