1. ¹Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA, USA
2. ²Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA
3. ³Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA

Correspondence: Dr B Moghaddam, Department of Neuroscience, University of Pittsburgh, A210 Langley Hall, Pittsburgh, PA 15260, USA. Tel: +1 412 624 4880; Fax: +1 412 624 9198; E-mail: bita@pitt.edu

Received 23 June 2007; Revised 29 July 2007; Accepted 30 July 2007; Published online 3 October 2007.

Abstract

The 'executive' regions of the prefrontal cortex (PFC) such as the dorsolateral PFC (dlPFC) and its rodent equivalent medial PFC (mPFC) are thought to respond in concert with the 'limbic' regions of the PFC such as the orbitofrontal (OFC) cortex to orchestrate behavior that is consistent with context and expected outcome. Both groups of regions have been implicated in behavioral abnormalities associated with addiction and psychiatric disorders, in particular, schizophrenia and mood disorders. Theories about the pathophysiology of these disorders, however, incorporate abnormalities in discrete PFC regions independently of each other or assume they are one and the same and, thus, bunch them under umbrella of 'PFC dysfunction.' Emerging data from animal studies suggest that mPFC and OFC neurons display opposing patterns of plasticity during associative learning and in response to repeated exposure to psychostimulants. These data corroborate clinical studies reporting different patterns of activation in OFC versus dlPFC in individuals with schizophrenia or addictive disorders. These suggest that concomitant but divergent engagement of discrete PFC regions is critical for learning stimulus-outcome associations, and the execution of goal-directed behavior that is based on these associations. An atypical interplay between these regions may lead to abnormally high or low salience assigned to stimuli, resulting in symptoms that are fundamental to many psychiatric and addictive disorders, including attentional deficits, improper affective response to stimuli, and inflexible or impulsive behavior.