Irritable bowel syndrome (IBS) is a prevalent, often disabling gastrointestinal (GI) disorder without adequate pharmacologic treatment options. Non pharmacological treatment, most notably Cognitive Behavioral Therapy (CBT) may be an effective treatment for many IBS patients. The NIH funded IBS Outcome Study (IBSOS) is the most comprehensive CBT efficacy study to date, including standard and minimal contact versions of CBT and an active control (AC) condition. There is general agreement a) that altered brain-gut interactions, the primary target of CBT, play an important role in IBS symptoms, and b) that IBS as currently defined is likely to represent a heterogeneous disorder, implying any treatment will be most effective for only a subset of patients. In order to develop effective disease management programs for IBS, it is therefore critically important to understand mechanisms of action and factors predictive of treatment response. The proposed study, a synergistic interaction between two NIDDK funded programs, provides a unique opportunity to address this challenge: The recruitment, assessment and treatment components of the IBSOS parent grant combined with the brain imaging infrastructure at UCLA (PAIN@loni.org) will enable this project to efficiently test specific hypotheses regarding both the neurobiological mechanisms underlying CBT treatment for IBS, and to develop predictive markers for which patients may benefit from these treatments. Using multimodal functional and structural MRI imaging of IBSOS participants before and after treatment in combination with psychosocial and symptom measures, this ancillary proposal will test a) the general hypothesis that the anterior insula functions as a hub for emotional arousal, cognitive as well as reward networks involved in IBS symptoms; b) that CBT will result in significant changes in these networks pre to post treatment with greater changes associated with better outcomes; c) that changes in activity, connectivity and structural integrity of these networks following treatment play an important role in mediating long term CBT outcomes; and d) that pre-treatment integrity of these networks will predict CBT response.