Frontal Striatal Systems and Dopamine in Normal and Pathological Behavior

National Institute Of Mental Health

Investigators

Linked publications, trials & patents

Abstract

Our lab uses a combination of computational modeling, neurophysiology, pharmacology and imaging to understand how a set of brain areas composed of the amygdala, striatum, pallidum, thalamus, prefrontal cortex and dopamine underlie learning from emotional events. These areas are connected in highly organized networks, and we base our studies on this organization. We have conceptualized this circuitry as broadly organized into ventral and dorsal systems. The ventral system, also referred to as the limbic system, is phylogenetically older, present in all vertebrates, and important for motivational processes including setting goals. The dorsal system on the other hand, is phylogenetically more recent, highly expanded in humans and other primates, and important for the interplay between cognition and action in the pursuit of goals. Behaviorally, we study the process of learning to predict whether choices will lead to good or bad outcomes. We work closely with clinical collaborators, implementing tasks in animals that have shown differences between patients and controls, and taking findings from the animal work to help understand clinical populations. As we develop a better understanding of how these brain systems support learning, we can develop a better understanding of how pathology in these systems can underlie various psychiatric disorders including anxiety, depression and addiction. Our recent work has focused on broadening our understanding of the network of areas important for these learning processes. Current conceptions of the circuitry that underlies this learning focuses on dopamine and the ventral-striatum, whereas our recent work also points to an important role for the broader set of areas with which the ventral and dorsal striatum are connected. Ongoing work examines whether different neural systems underlie learning from positive vs. negative outcomes (rewards vs. punishments), and whether overlapping or distinct neural systems underlie learning actions that are beneficial vs. learning the values of goal objects. We are also studying how these circuits and the behaviors that they support change during adolescence, as adolescence is an important developmental period during which many psychiatric disorders first emerge. Therefore, understanding the changes that take place in the brain during this period is important for understanding why, in some cases, this developmental period leads to the emergence of psychiatric disorders. Much of the work on these systems, especially in animal models, focuses on learning to make choices to earn primary rewards like food or fluid. We have recently focused on understanding how we learn from symbolic reinforcers. Symbolic reinforcers include money or other tokens that can later be exchanged for a primary reinforcer like food. We have found that, while subcortical structures including the striatum are critical for learning from primary reinforcers, the orbitofrontal cortex plays a more important role when learning from symbolic reinforcers.