Self-regulation of real-time fMRI brain activity in chronic pain: A potential neurobiological mechanism of cognitive behavioral therapy - Project Summary/Abstract Self-regulation is the ability to manage one’s thoughts, emotions, and behaviors to achieve desired goals through a variety of cognitive and emotional processes. It is an important aspect of self-management, which plays a primary role in the efficacious treatment mechanisms of chronic pain, such as fibromyalgia. Fibromyalgia is a chronic pain disorder characterized by widespread pain, impaired sleep, fatigue, and depression. While non-pharmacologic treatment, such as Cognitive-Behavioral Therapy (CBT), has shown efficacy in improving fibromyalgia-related symptoms via self-management skills, little is known about the underlying neurobiological mechanisms of these benefits. Reduction of negative cognitive and emotional processes, such as pain catastrophizing—which involves helplessness, rumination, and magnification of pain complaints—via self-regulation, has been suggested as one of the central mechanistic pathways supporting the benefits following CBT. In fact, many studies have shown that pain catastrophizing is the most consistent psychosocial factor predicting treatment prognosis in chronic musculoskeletal pain, such as fibromyalgia. Thus, we propose investigating the neural correlates of self-regulation, their association with catastrophizing, and the role of changes in self-regulatory capacity in contributing to CBT’s benefits. Neural mechanisms during self- regulation can be investigated and assessed using real-time functional magnetic resonance imaging (fMRI) neurofeedback, which allows observing and regulating one’s brain activity. The neural target in our study is defined from our published study demonstrating that the ventral posterior cingulate cortex (vPCC) and retrosplenial cortex (RSC)—key nodes of the brain’s default mode network—encode pain catastrophizing. Thus, our study will apply fMRI neurofeedback as a probe to elucidate the neurobiological mechanisms underlying the self-regulation of pain catastrophizing. Specifically, our Aims will: (1) Evaluate the effect of CBT on neural mechanisms of catastrophizing self-regulation, assessed with real-time fMRI neurofeedback and (2) Predict clinical improvement following CBT with baseline brain response during pain catastrophizing self- regulation. Furthering our understanding of the neural mechanisms underlying self-regulation of pain catastrophizing in chronic pain will enable clinicians to boost the efficacy of CBT and facilitate the development of multimodal treatment packages, while patients gain control over their cognitive and emotional processes.