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The Journal of Neuroscience, March 9, 2005, 25(10):2733-2740; doi:10.1523/JNEUROSCI.3360-04.2005

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Behavioral/Systems/Cognitive
Learning to Like: A Role for Human Orbitofrontal Cortex in Conditioned Reward

Sylvia M. L. Cox,^1,2,3 Alexandre Andrade,^1,4 and Ingrid S. Johnsrude^1,5

¹Medical Research Council Cognition and Brain Sciences Unit, Cambridge CB2 2EF, United Kingdom, ²Experimental Psychopharmacology Unit, Brain and Behavior Institute, University of Maastricht, 6200 MD Maastricht, The Netherlands, ³Department of Psychiatry, McGill University, Montreal, Quebec, Canada H3A 1A1, ⁴Institute of Biophysics and Biomedical Engineering, University of Lisbon, 1700 Lisbon, Portugal, and ⁵Department of Psychology, Queen's University, Kingston, Ontario, Canada K7L 3N6

A great deal of human behavior and motivation is based on the intrinsic emotional significance of rewarding or aversive events, as well as on the associations formed between such emotional events and concurrent environmental stimuli. Recent functional neuroimaging studies have implicated the ventral striatum, orbitofrontal cortex (OFC), and amygdala in the representation of reward values and/or in the anticipation of rewarding events. Here, we use functional magnetic resonance imaging to compare brain activation during the presentation of reward with that during presentation of (conditioned) stimuli that have been paired previously with reward. Specifically, we aimed to investigate conditioned reward in the absence of explicit reward anticipation. Twenty-two healthy volunteers were scanned while monochrome visual patterns were incidentally associated with reward or negative feedback in the context of a simple card game. In the subsequent session, visual patterns, including the conditioned stimuli, were presented without reward or negative feedback, and the affective valence of these stimuli was assessed behaviorally. The presentation of reward compared with negative feedback activated the ventral striatum and OFC. Activation in the same OFC region was observed when, in the subsequent session, subjects passively viewed the stimuli that had been paired with reward, without the administration of reward and with subjects being essentially unaware of the conditioning manipulation. These findings suggest that the OFC in humans plays an important role in the representation of both rewarding stimuli and conditioned stimuli that have acquired reward value.

Key words: appetitive conditioning; nucleus accumbens; prefrontal cortex; amygdala; preference judgments; financial reward

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Received Aug 16, 2004; revised January 3, 2005; accepted January 30, 2005.

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