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J Neurosci. 2005 May 4;25(18):4641-8.

Double dissociation of exteroceptive and interoceptive feedback systems in the orbital and ventromedial prefrontal cortex of humans.

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  • 1Cognitive Neuroimaging Unit, Veterans Affairs Medical Center, Minneapolis, Minnesota 55417, USA.


The primate ventral prefrontal cortex contains two densely interconnected subregions: a lateral/orbital cortex processing primarily sensory/exteroceptive information, and a ventromedial cortex processing primarily visceroappetitive/interoceptive information. These regions have major afferents from and efferents to other associative cortices. The organization of these structures leads to an hypothesized role in feedback processing. We use neuroimaging to test this model, defined so far mostly through anatomical studies. Healthy volunteers were trained operantly on a transitive inference task (A>B, B>C ==> A>C) requiring flexible manipulation of feedback to solve. Two groups of subjects learned an arbitrary face hierarchy, one adjacent face pair at a time; each group received either visual/exteroceptive ("XXXX") or visceroappetitive/interoceptive (fruit juice) feedback for correct responses to adjacent face pairs. After task acquisition, the subjects were tested on novel stimulus pairs (i.e., nonadjacent, TEST) derived from the acquired hierarchy. The TEST condition required transitive inference. No feedback was provided during TEST. Brain activity during TEST in the group trained with visual/exteroceptive feedback increased in the orbital prefrontal cortex and decreased in the ventromedial prefrontal cortex. In contrast, brain activity during TEST in the group trained with visceroappetitive/interoceptive feedback decreased in the orbital prefrontal cortex and increased in the ventromedial prefrontal cortex. These results provide functional evidence, consistent with previous anatomical studies, for two major feedback systems in human ventral prefrontal cortex: a lateral system specialized for exteroceptive information and a medial system specialized for interoceptive information. Although highly interconnected, there is a double dissociation of function between these networks in healthy humans.

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