DESCRIPTION (provided by applicant): Pathological uncertainty is a key feature of obsessive compulsive disorder (OCD), impairing everyday decision-making in addition to driving specific obsessions and compulsions. As a potential core process in OCD, increased uncertainty may be a trait characteristic that occurs independently of symptom provocation and could be the focus of research into treatment and prevention of the disorder. Although previous research has shown that OCD patients acquire more information in order to reach a decision than healthy controls, little work has focused on elucidating the cognitive and neural mechanisms associated with abnormal decision-making in OCD. In our preliminary study, sequential pieces of evidence were requested in order to reduce uncertainty and reach a decision. Results revealed that the cost of acquiring new information and the ambiguity of the context in which information was presented were important factors influencing subjective uncertainty and evidence accumulation among control subjects. In three studies, we will test a series of hypotheses predicting that prolonged information acquisition in OCD is driven by a relative insensitivity to these factors. In the first behavioral study, we predict that increasing OC symptom severity will be associated with greater uncertainty and increased evidence accumulation, regardless of the context and cost of information search. In the second and third studies, neural activity will be examined in healthy controls and OCD patients using functional magnetic resonance imagining (fMRI), with the aim of identifying the neural mechanisms underlying the abnormal cognitive experience or emotional appraisal of uncertainty. In particular, hyperactivity in frontal regions implicated in the pathology of OCD, such as dorsomedial prefrontal cortex/anterior cingulate cortex and orbitofrontal cortex, may underlie increases in distinct cognitive and affective aspects of uncertainty processing, respectively. Results from these studies will provide a thorough characterization of OC-related decision-making behavior, enabling clinicians to refine therapeutic techniques for treatment-resistant patients. Moreover, investigation into the neural substrates of these processes may lead to the identification of biological endophenotypes of OCD and further research on genetic susceptibilities of the disorder. The significant disability and emotional distress resulting from pathological indecisiveness in OCD constitutes an important concern for the patient as well as the health care community. The investigation of uncertainty as a core process in OCD is a promising step toward advancing treatment strategies and identifying genetic factors influencing the development of the disorder.