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

Grant Type
Grant Year
Institution Location
Institution Organization Name
Investigators Name
Pasupathy, Anitha, PhD

In everyday situations, such as driving down a busy street or ordering food at a restaurant, goals direct human behavior. Achieving these goals requires that we call upon some guiding rules and principles (the “rules of the game”) from past experience. The Basal Ganglia, in concert with the Prefrontal Cortex, is thought to play a crucial role in the learning of behavioral rules. Dysfunction of the basal ganglia (as in Parkinson’s Disease, Huntington’s Disease and Tourette Syndrome) impairs the ability to learn and potentiate appropriate behavior-guiding rules. In fact, some researchers speculate that the involuntary motor and vocal tics associated with TS may be due to excessive potentiation of inappropriate rules. The broad aim of my postdoctoral project is to discover the role played by neurons in the basal ganglia that facilitates the learning and potentiation of behavioral rules. Identification of the physiological mechanisms important for rule-learning and following will further our understanding about cognitive functions performed by the basal ganglia. This improved understanding will also open a path to drug therapies designed to alleviate their dysfunction. Evidence suggests that individuals with prefrontal and/or basal ganglia dysfunction have difficulty overcoming previously established behaviors in order to learn new ones. A classic test of this impairment is the Wisconsin Card Sorting Test (WCST). In this task, subjects sort cards according to the shape, color or the number of symbols that appear. The sorting criterion is not explained, and the subject arrives at it by trial and error. Further, the sorting rule changes periodically without an explicit cue. Those with prefrontal or basal ganglia damage learn the first sorting rule, which is relatively straightforward. But when the criterion changes, they stick to the previous sorting rule, and are unable to break away from it and learn the new sorting rule. To decipher the neural basis of rule learning, we will train monkeys to learn simple rules (analogous to the WCST) and while they learn, we will study neural changes in the prefrontal cortex and basal ganglia. Results from this study will help us understand the functions of healthy basal ganglia and prefrontal cortex and will provide insights about what goes wrong that causes dysfunction. This understanding will bring us one step closer to finding the basic causes of TS, as well as other diseases associated with basal ganglia dysfunction. Anitha Pasupathy, Ph.D., Center for Learning and Memory, Department of Brain and Cognitive Sciences, MIT, Cambridge, MA Award: $35,000 This study is funded through the generosity of the William F. Harnisch Foundation Tourette Association of America Inc. – Research Grant Award 2002-2003