• The Orbitofrontal Cortex and Inferred Value: Neural Correlates and the Effects of Cocaine

      Wied, Heather Marie; Schoenbaum, Geoffrey (2014)
      The orbitofrontal cortex (OFC) is important for guiding behavior and making decisions based on predicted outcomes. Recently, the Schoenbaum lab, using a sensory preconditioning task, demonstrated that the OFC is critical for the ability to make decisions in novel situations based on predicted outcomes, and that it is not essential for decisions based off of previous experiences. This study also demonstrated that the OFC was important for learning when expectations about predicted outcomes were not met. This study laid the foundation for this investigation which seeks to understand the neurophysiological mechanism of how the OFC might signal this inferred value, and if cocaine exposure disrupts OFC's ability to use inferred value to adequately guide behavior and new learning. To test the hypothesis that the OFC is signaling inferred value in the sensory preconditioning task, electrodes were implanted into the OFC in rats. During the preconditioning phase the mean firing rate of neurons to the stimulus-stimulus cues were strongly correlated. This correlation was still significant at the time of testing, suggesting the conditioned cues firing rate predicted the preconditioned cues firing rate. Cocaine addiction is characterized by impaired decision-making. Evidence suggests that cocaine-induced changes in the OFC may lead to difficulty with flexible and adaptive model-based behavior. The second part of this study tests the hypothesis that exposure to cocaine through self-administration would disrupt the ability of animals to use inferred value to adequately guide behavior and new learning. Rats self-administered cocaine for 14 days, and after a four-week withdrawal period, were tested using sensory preconditioning and blocking. The previous exposure to cocaine disrupted both the expression of behavior and learning that is contingent upon inferred values, but it did not affect behavior or learning when normal behavior could be supported by cached values. These results are similar to the effects observed when the OFC is inactivated during the critical sensory preconditioning probe test and during blocking. Moreover, they are likewise consistent with the idea that dysfunction in decision making that arises in drug addiction is potentially mediated through neural deficits within the OFC.