Investigation of Neural Mechanisms in the Basal Ganglia and Prefrontal Cortex underlying the Acquisition of Behavior Guiding Rules

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Pasupathy, Anitha, PhD

In everyday situations, e.g. driving down a busy street or ordering food at a restaurant, it is our goals that direct human behavior. To achieve these goals, we need to rely on guiding rules and principles from our past experience. The basal ganglia, in concert with the prefrontal cortex, are thought to play a crucial role in the learning of behavior rules. Dysfunction of the basal ganglia (as in Parkinson’s disease, Huntington’s disease and Tourette’s syndrome) impairs the ability to learn and execute appropriate behavior-guiding rules. In fact, some researchers speculate that the involuntary motor and vocal tics associated with TS may be due to excessive execution of inappropriate rules. The broad aim of this project is to discover the role played by neurons in the basal ganglia in facilitating mechanisms involved in rule-learning. This knowledge will further our understanding of cognitive functions performed by the basal ganglia. Hopefully, this information will also facilitate the design of new drug therapies in the future. With previous TSA funding (2002-2003) we investigated the neural mechanisms of rule representation in the basal ganglia and prefrontal cortex in a rhesus monkey. The animal was seated in front of a computer monitor and learned the association between two visual images (A and B) and two responses (rightward and leftward eye movements). For example, to get a juice reward the animal made a rightward eye-movement if object A appeared on the screen and a leftward eye-movement if B appeared. Once this behavior was mastered, the reward association was reversed, i.e. “A look left” and “B look right” and the animal relearned the new association. We found that the neurons in the basal ganglia encoded more information about the association i.e. the rule in effect, whereas the neurons in the prefrontal cortex encoded more information about the object identity and the independently executed visual response. These findings suggest parallel, complementary roles for these two areas in rule learning. With this year’s TSA support we plan to confirm our previous findings as well as perform experiments to investigate how basal ganglia dysfunction impairs rule learning. To achieve this, neurons in the basal ganglia will be temporarily inactivated and any associated behavioral deficits in the animal will be quantified. Does the behavior appear normal when basal ganglia are inactivated? Does the animal have trouble learning a new rule? Does the animal persist in using a previously learned rule? Answers to these questions will provide insight into basal ganglia dysfunction. The results from these two years of experiments, together, will enhance our understanding about the function of healthy basal ganglia and the behavioral effects induced by their impairment. Anitha Pasupathy, Ph.D., Dept of Brain & Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA Award: $40,000 Tourette Association of America Inc. – Research Grant Award 2003-2004