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Prefrontal mechanisms of behavioral flexibility, emotion regulation and value updating

Nature Neuroscience volume 16, pages 1140–1145 (2013)Cite this article

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Abstract

Two ideas have dominated neuropsychology concerning the orbitofrontal cortex (OFC). One holds that OFC regulates emotion and enhances behavioral flexibility through inhibitory control. The other ascribes to OFC a role in updating valuations on the basis of current motivational states. Neuroimaging, neurophysiological and clinical observations are consistent with either or both hypotheses. Although these hypotheses are compatible in principle, we present results supporting the latter view of OFC function and arguing against the former. We found that excitotoxic, fiber-sparing lesions confined to OFC in monkeys did not alter either behavioral flexibility, as measured by object reversal learning, or emotion regulation, as assessed by fear of snakes. A follow-up experiment indicated that a previously reported loss of inhibitory control resulted from damage to nearby fiber tracts and not from OFC dysfunction. Thus, OFC has a more specialized role in reward-guided behavior and emotion than has been thought, a function that includes value updating.

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Figure 1: Excitotoxic lesions of OFC.
Figure 2: Excitotoxic lesions of OFC did not disrupt object reversal learning.
Figure 3: Excitotoxic lesions of OFC did not alter emotional responses, but disrupted monkeys' ability to link objects with food value.
Figure 4: Strip lesions in posterior OFC.
Figure 5: Monkeys with aspiration lesions of a narrow strip of posterior OFC, like monkeys with complete aspiration lesions of OFC, were impaired on object reversal learning and showed reduced emotional responsiveness.

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Acknowledgements

We thank D. Lundgren and E. Howland for assistance with data collection and R. Reoli for help performing surgery. We also thank S. Wise and M. Walton for comments on an earlier version of the manuscript. This work was supported by the Intramural Research Program of the US National Institute of Mental Health.

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  1. Section on the Neurobiology of Learning and Memory, Laboratory of Neuropsychology, National Institute of Mental Health, US National Institutes of Health, Bethesda, Maryland, USA

    Peter H Rudebeck, Richard C Saunders, Anna T Prescott, Lily S Chau & Elisabeth A Murray

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  1. Peter H Rudebeck
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Contributions

P.H.R. designed the experiment, assisted in surgery, analyzed the data and wrote the manuscript. R.C.S. performed the surgeries and edited the manuscript. A.T.P. and L.S.C. collected and analyzed the data. E.A.M. designed the experiment, performed the surgeries, supervised the project and wrote the manuscript.

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Correspondence to Peter H Rudebeck.

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Rudebeck, P., Saunders, R., Prescott, A. et al. Prefrontal mechanisms of behavioral flexibility, emotion regulation and value updating. Nat Neurosci 16, 1140–1145 (2013). https://doi.org/10.1038/nn.3440

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