Affect regulation: a systems neuroscience perspective

OBJECTIVE: To integrate: (1) the neuroanatomical model of affect regulation; (2) a functional model of affect regulation; and (3) the evolving picture of affect dysregulation as exemplified by bipolar disorder. METHODOLOGY: A computerized search for articles on related topics was augmented by additional selected studies. RESULTS: Subdivision between the orbitofrontal cortex (OFC) and dorsolateral prefrontal cortex (DLPFC) is defined by distinct cytoarchitecture, corticocortical and subcortical connectivity, and function. The hierarchical relationship between OFC and amygdala is not resolved. Positive and negative emotions appear to have differential effect on cognitive ability. It is possible that cognitive and affective stimuli activate DLPFC and OFC respectively in a see-saw like manner. This complementary activation may be out of sync in disease models. CONCLUSION: It is critical to account for: (1) differential anatomy and corresponding functions of various parts of the prefrontal cortex as opposed to treating it as a single entity; (2) complexity of clinical presentation of bipolar disorder that involves affect dysregulation, cognitive erosion, and motoric disinhibition in functional imaging studies; and (3) the mutual influence of affect and cognition. Future studies focusing on pharmacological effects using functional magnetic neuroimaging techniques will inform us if the affective circuitry dysfunction is reversible, and if so, what are the predictors of response.