How do you (estimate you will) like them apples? Integration as a defining trait of orbitofrontal function

Abstract

The past 15 years have seen a rapid increase in our understanding of orbitofrontal function. Today this region is the focus of an enormous amount of research, including work on such complex phenomena as regret, ambiguity, and willingness to pay. The orbitofrontal cortex is also credited as a major player in a host of neuropsychiatric diseases. This transformation arguably began with the application of concepts derived from animal learning theory. We will review data from studies emphasizing these approaches to argue that the orbitofrontal cortex forms a crucial part of a network of structures that signals information about expected outcomes. Further we will suggest that, within this network, the orbitofrontal cortex provides the critical ability to integrate information in real-time to make what amounts to actionable predictions or estimates about future outcomes. As we will show, the influence of these estimates can be demonstrated experimentally in appropriate behavioral settings, and their operation can also readily explain the role of orbitofrontal cortex in much more complex phenomena such as those cited above.

Figure 1

The role of orbitofrontal cortex in changing conditioned responding as a result of reinforcer devaluation. A. Changes in Pavlovian conditioned responding in sham and orbitofrontal-lesioned rats after reinforcer devaluation. Rats were trained to associate a light cue with food. Subsequently the food was devalued by pairing it with illness, then responding to the cue was assessed in a final probe session. Orbitofrontal-lesioned rats showed normal conditioning to the cues and stopped eating the food when it was paired with illness but, as shown in the figure, failed to change conditioned responding as a result of devaluation in the final probe test. B. Changes in discriminative responding in sham and orbitofrontal lesioned monkeys after reinforcer devaluation. Monkeys were trained to associate different objects with different food rewards. Subsequently one food was devalued by over-feeding, then discrimination performance was assessed in a probe test. As illustrated in the figure by a difference score comparing pre- and post-satiation bias, orbitofrontal-lesioned monkeys failed to bias their choices away from objects associated with the satiated food. C. Changes in BOLD signal in human orbitofrontal cortex after reinforcer devaluation. Subjects were scanned during presentation of odors of different foods. Subsequently one food was devalued by over-feeding, then subjects were re-scanned. As illustrated in the figure, appetive ratings of the odor and BOLD response in orbitofrontal cortex declined to odors of satiated (Tgt CS/US) but not non-satiated (nTgt CS/US) foods. Adapted from Gallagher et al., Journal of Neuroscience, 1999, Izquierdo et al, Journal of Neuroscience, 2004, and Gottfried et al, Science, 2003.

Figure 2

Effect of inactivation of bilateral inactivation of ventral tegmental area or contralateral inactivation orbitofrontal cortex + ventral tegmental area on changes in behavior after over-expectation. Rats in all groups conditioned normally and maintained responding during compound training (though only controls showed summation to the compound cue). Shown is food cup responding to the auditory cues during the critical probe test. As in Figure 13, controls (A) exhibited weaker responding in this probe test to the cue that had been compounded. This decline in responding was not observed if ventral tegmental area had been inactivated bilaterally (B) during prior compound training or if ventral tegmental area and orbitofrontal cortex were disconnected via contralateral inactivation (C). Adapted from Takahashi et al, Neuron, 2009.