Reversal learning in fronto-striatal circuits: A functional, autonomic, and neurochemical analysis

Abstract:

The orbitofrontal cortex (OFC) is intimately associated with the processes underlying behavioural flexibility that allow us to interact successfully with our ever-changing environment. Dysfunction within the OFC and its associated circuitry, including the striatum and amygdala, is an important feature of many psychiatric disorders in which behavioural inflexibility is a prominent symptom. The discrimination reversal learning task is a commonly used test of behavioural flexibility, and impaired performance on this test is not only associated with damage to the OFC in rats, monkeys, and humans, but has also been described in patients suffering from a variety of neuropsychiatric disorders, including schizophrenia and psychopathy. In addition, reversal learning-related hypofunction within the OFC may act as a vulnerability marker for obsessive-compulsive disorder. This chapter discusses the role of the OFC in reversal learning from an anatomical, motivational, and neurochemical perspective. It reviews the effect of OFC lesions on discrimination reversal learning in monkeys and rats, along with the anatomical and psychological issues arising from these studies. It provides evidence that supports a role for the OFC in adapting the autonomic, as well as the behavioural, responses in reversal learning, with consideration of the relevance of these results to the emotional uncoupling reported in a number of psychiatric disorders. The monoaminergic modulation of the OFC, and, in particular, the dissociable roles of dopamine and serotonin in behavioural flexibility, are discussed in the context of their relationship to current psychiatric treatments. Finally, the roles of the striatum and amygdala are evaluated in the light of recent findings highlighting the role of serotonin and dopamine in modulating the effectiveness of prefrontal top-down control of these structures.