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theses

How are aversive associations formed in the brain, and how do they subsequently influence behavior? Imagine an individual who experienced a harrowing flight, and subsequently acquired an intense fear of flying. The sight of airports or planes in flight – previously innocuous stimuli – may now trigger an aversive response within the individual. If the individual continues to fly without facing additional negative experiences, the aversive response may be updated, or extinguished. However, this individual may choose to avoid air travel in order to relieve anxiety, even though future flights would likely not be coupled with negative events. Here, the temporary relief of anxiety renders the avoidance behavior adaptive. However, avoidance can also be maladaptive. For instance, continually avoiding air travel limits the ability to visit family and friends that live afar. While avoidance behaviors are often performed without consequence in everyday life, they also play a role in the persistence of many clinical disorders. The avoidance of an anxiety-provoking stimulus is a defining behavior in anxiety disorders. Similarly, negative reinforcement-based models of addiction posit that avoidance of withdrawal symptoms is a major factor in sustained drug-seeking and relapse. In both of these cases, aversive Pavlovian conditioned stimuli (CS) modulate instrumental avoidance behaviors and vice versa. This dissertation sought to better understand the flexibility of aversive CS-US relationships and how these relationships can motivate avoidance behaviors. A combination of behavioral, neuroimaging and physiological measures were used. The first goal of this dissertation was to understand how aversive Pavlovian CS-US associations are formed and updated in the brain. The second goal was to examine the behavioral and neural correlates of aversive Pavlovian control over instrumental avoidance behavior using the Pavlovian-to-instrumental Transfer (PIT) task, which tests the ability of Pavlovian CS to motivate instrumental behavior. The third goal of this dissertation was to understand how stress, a real-world variable that is often comorbid with anxiety and addiction, affects the ability of aversive CS to motivate instrumental avoidance behavior. Overall, these studies shed light on clinical disorders involving extinction failure and excessive avoidance responses, such as drug addiction, anxiety and post-traumatic stress disorder (PTSD).

ETD_7367

Ph.D.

Includes bibliographical references

by Andrea Houghtling Lewis

doi:10.7282/T3FN18DR

ETD doctoral

The author owns the copyright to this work.