Obsessive-compulsive disorder is a relatively common and debilitating disorder associated with hyperactivity in the orbitofrontal cortex. Current treatments are ineffective for many individuals and the development of new (preferably low-risk) clinical interventions are needed. Furthermore, the neurobiological basis of hyperactivity in orbitofrontal cortex associated with obsessive-compulsive symptoms is not well understood. The proposed research project addresses these issues by developing a protocol to train subjects to control activity in a region of their orbitofrontal cortex associated with contamination-related anxiety using biofeedback of real-time functional magnetic resonance imaging (rt-fMRI) data. Biofeedback of rt-fMRI data is a new technique in which the temporal pattern of activity in a specific region of a subject's brain is provided as a feedback signal to the subject. The subject can experiment with different cognitive strategies to identify those that are effective in influencing brain activity in the region of interest, thereby gaining greater control over the target brain region. The proposed research project examines whether biofeedback of rt-fMRI data can enable healthy subjects to develop greater control over the area of their orbitofrontal cortex associated with contamination-related anxiety. If so, this new technique may yield a low- risk, non-invasive clinical intervention for patients with obsessive-compulsive disorder. In addition, patterns of functional connectivity between the orbitofrontal cortex and other regions of the brain will be examined before and after biofeedback to identify those brain areas whose interactions with the orbitofrontal cortex are related to the ability of subjects to control activity in this area. This will inform our understanding of the network dynamics underlying biofeedback-related changes in orbitofrontal activity patterns. Although this research project is focused on developing a protocol specifically for treating and studying obsessive-compulsive disorder, the methodology has great promise as both a treatment intervention and as a research tool for a broad range of neuropsychiatric disorders. Biofeedback of rt-fMRI data is, however, a highly novel technique, and developmental studies such as the proposed project are needed to realize its full potential. PUBLIC HEALTH RELEVANCE: Real-time brain imaging can provide information regarding activity in specific brain areas almost as it is occurring (with only several seconds delay). By providing people with this information as a feedback signal, we aim to train them to control neural activity in particular regions of their brains and to examine how interactions between brain areas change as a result of such training. The proposed research develops this method as a tool for treating and studying obsessive-compulsive disorder in particular, although it has potential therapeutic and investigative utility for a wide range of mental disorders.