Neural Substrates of Reinforcement Learning and Its Training in Major Depression

Major depressive disorder ranks among the most significant causes of mortality and disability in the world. Recent data from the investigators and others highlight that impairments in reward and loss learning are central to depression, have distinct neural substrates, and improve with successful treatment. Together, these findings suggest an urgent need to delineate the relationships among neural and behavioral learning impairments and depression. Equally important, these insights suggest new targets for treatment such that manipulating the neural and behavioral substrates of learning may facilitate symptom change in depression.

To address these issues, the investigators use functional neuroimaging and a computational psychiatry framework to i) systematically characterize the neural and behavioral substrates that attend reward- and loss- learning in depression and ii) assess the degree to which learning in depression responds to two behavioral methods that target learning in different ways. The investigators test the broad hypotheses that i) that depression may be characterized by distinct neural and behavioral disruptions of learning, and ii) these disruptions and associated symptoms may be ameliorated through different methods of guiding learning. Recent advances in computational psychiatry provide a mechanism-based framework within which to understand the nature and trajectory of potential learning impairments in depression and suggest new ways that disrupted learning and associated symptoms may be improved in depression