Prefrontal mechanisms of behavioral flexibility, emotion regulation and value updating

Nat Neurosci. 2013 Aug;16(8):1140-5. doi: 10.1038/nn.3440. Epub 2013 Jun 23.


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.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Adaptation, Psychological / physiology*
  • Animals
  • Axotomy / adverse effects
  • Discrimination Learning / drug effects
  • Discrimination Learning / physiology
  • Emotions / physiology*
  • Fear / physiology
  • Feedback, Physiological
  • Feeding Behavior / physiology
  • Feeding Behavior / psychology
  • Female
  • Inhibition, Psychological
  • Macaca mulatta
  • Male
  • Models, Psychological*
  • Motivation / physiology*
  • Neural Pathways / injuries
  • Neurotoxins / toxicity
  • Prefrontal Cortex / drug effects
  • Prefrontal Cortex / injuries
  • Prefrontal Cortex / physiology*
  • Prefrontal Cortex / physiopathology
  • Prefrontal Cortex / surgery
  • Reinforcement, Psychology
  • Reward
  • Social Values*


  • Neurotoxins