This is a proposal for a K23 Mentored Patient-Oriented Research Career Development Award for Gregory A. Fonzo, Ph.D. entitled: Computational neuroimaging of reward in post-trauma psychopathology. The K23 award would allow Dr. Fonzo to gain proficiency in: 1) reward processing and reinforcement learning theory, paradigms, and analysis; 2) computational approaches to modeling behavior and brain function; 3) basic and systems neuroscience; 4) mechanisms of treatment; and 5) manuscript/grant writing, professional development, and responsible conduct of research. All of the training and research will be conducted at Stanford University and its close affiliate, the Veteran's Affairs Medical Center in Palo Alto, which provides access to abundant intellectual and physical resources. The goal of this project is to better understand diminished positive affect in post-trauma psychopathology (PTP) through characterizing reward processing in a computational framework. Diminished positive affect in PTP is an important area for study, as these symptoms confer worse treatment outcomes, poorer quality of life, and greater levels of disability. Positive affect refers to the frequency and intensity with which an individual subjectively experiences positive valence emotions. The study of reward processing has been utilized for decades in animals and humans to elicit positive emotion and appetitive behavior, and reward processing reliably recruits neural substrates implicated in positive affect. Thus, this experimental framework is the ideal entrance point to begin study of diminished positive affect in PTP. Little work is being done in this area, and the need for a better understanding of the behavioral and neural bases of these symptoms is profound. The central hypothesis to be tested is the development of PTP perturbs reward circuit function, information flow, and subsequent behavioral processing of rewarding stimuli, which promotes diminished positive affect and impairs functioning through disrupting the reinforcement learning that guides and optimizes behavior. The current study aims to: 1) Identify reward circuit abnormalities in PTP during reward processing and at rest; 2) Understand how information is processed differently in PTP during reinforcement learning and how this is instantiated in neural circuits; and 3) Identify how reward processing abnormalities relate to symptoms of diminished positive affect. The PI plans to gain proficiency in proposal domains through: 1) tutorials and meetings with mentors; 2) intensive workshops on modeling information flow within neural circuits and building computational models of reward behavior; 3) formal coursework; 4) attendance of professional meetings; 5) practical application of skills to research data; and 6) planned submission of grant applications and manuscripts. Insights from the proposed work will improve our understanding of the brain processes underlying diminished positive affect in PTP, which will contribute important mechanistic insight to an understudied area of trauma research in humans.
Up to 80% of individuals will experience a traumatic event at some point in their life, and a subset will go on to develop post-trauma psychopathology (PTP). One manifestation of PTP is a reduced capacity for experiencing positive emotions, and greater reductions in this capacity are associated with a worse course of illness, greater disability, and poorer response to treatments. As the brain and behavioral processes underlying this aspect of PTP symptoms are largely unknown and highly pertinent to treatment development and the reduction of PTP public health burden, the overarching goal of this project is to understand how the brain processes underlying the pursuit, processing, and obtainment of rewards are altered in PTP and how these alterations relate to the capacity to experience positive emotion, quality of life, and functional impairment.
