This K23 proposal from Dr. Patricia Gruner, a clinical psychologist at Yale University, examines causal reasoning abnormalities in individuals with obsessive-compulsive disorder (OCD) ? a critical step towards the long-term goal of developing therapeutic remediation precisely targeting cognitive and neural system dysfunction in patients with clinically significant obsessions and compulsions. Concurrently, the accompanying training and mentorship plan will support the PI?s progression towards independence, with a focus on neuroscience-based therapeutic development. Individuals with OCD engage in maladaptive repetitive behaviors reflecting erroneous causal beliefs about the environment. Large knowledge gaps remain regarding causal reasoning deficits in OCD, and the neurobiology of this core clinical abnormality remains unclear. Causal reasoning is a complex construct relying on several distinct underlying computations, including the ability to learn contingencies and to represent abstract outcomes. These computations are difficult to dissociate in real-world situations using existing neurocognitive assessments. To close this knowledge gap, we have developed a neurobiologically-informed behavioral paradigm designed to disambiguate these specific elements of causal reasoning. The paradigm is optimized in conjunction with state-of-the-art neuroimaging to test the hypothesis that behavioral and neural signals of specific contingency learning versus outcome representation differ in OCD relative to matched controls. In turn, we will quantify relationships between symptoms (dimensionally assessed through a battery of well-validated clinical measures), neural signals, and behavioral measure of specific contingency learning and outcome representation. Thus, this project advances our understanding of OCD neurobiology and provides the foundation for treatment development around precise neurobiologically-grounded computations ? a longer-term career objective of the PI. In turn, the outlined training support facilitates the PI?s transition towards independence. Dr. Gruner has extensive clinical and cognitive assessment expertise working with OCD patients. She received postdoctoral training in neuroimaging and cognitive remediation at Yale. This proposal is designed to develop deep expertise in neuroimaging acquisition and analysis techniques with a focus on state-of-the-art protocols developed by the Human Connectome Project, increase knowledge of OCD neurobiology, and advanced skills in task-based imaging using model-based analyses. The PI has assembled an exceptional mentoring team. The primary mentor, Dr. Christopher Pittenger, Director of the Yale OCD Research Clinic, is world-renowned for translational research on OCD and related disorders. Dr. Bruce Wexler, an expert in neuroplasticity and development of neurocognitive interventions, will provide co-mentorship regarding neurocognitive function in OCD. The PI will receive training from Dr. Alan Anticevic, a leading clinical neuroimager, and Dr. Daeyeol Lee, an expert in the mathematical modeling of complex behavioral data. Dr. Rajita Sinha, Chief of the Psychology Section in the Department of Psychiatry at Yale, will provide additional professional mentorship. This proposal supports the PI?s transition to independence via complementary neuroimaging and theoretical skills, facilitating pursuit of R01 funding focused on neuroscience-based therapeutics in OCD.
This career development award will support an early-career clinical psychologist focused on deepening our understanding of obsessive-compulsive disorder (OCD) and using that knowledge to develop new, targeted treatments. Patients with OCD form inaccurate representations of causal relationships between actions and outcomes (e.g. fear that if I don?t continue to wash my hands, I will get ill from germs and die; fear that if I do not flush the toilet in multiples of three, disaster will strike); the neurobiology of this core abnormality remains unknown, which represents a major knowledge gap and impedes the development of targeted therapeutics. To close this knowledge gap, this proposal aims to use a novel neurobiologically-informed behavioral paradigm together with state-of-the-art functional brain imaging to elucidate the underpinnings of abnormal causal thinking in OCD and thereby to provide the foundation for the future development of novel, targeted therapeutic strategies.
