PROJECT SUMMARY/ABSTRACT Migraine is a neurological disorder characterized by debilitating headaches. It affects 6% of men and 18% of women and costs $36B annually in direct and indirect costs in the US alone. Many of the commonly-occurring symptoms of migraine point to some form of autonomic dysfunction, supported by brain imaging studies. However, it remains unclear specifically how migraine influences autonomic dysfunction. Previous studies that have aimed to quantify autonomic dysfunction have had conflicting results, likely due to varying methodology and limited monitoring time period. Additional support for the role of autonomic dysfunction in migraine comes from the fact that over 90% of migraineurs experience problems with gut motility that can be linked to gastroparesis, or delayed gastric emptying. Recent advances in wearable technologies, technology miniaturization, and high-resolution multimodal recording have opened new doors to detailed studies of the interactions between the brain, gastric motility, and pain using at-home monitoring. This project seeks to build a unified model of brain-gut dysfunction in migraineurs using at-home multimodal monitoring. By applying sophisticated signal processing and statistical modeling methods to perform causal inference, the proposed work will characterize patterns of dysfunction between the brain, autonomic nervous system, and gut motility in migraineurs compared to healthy controls. Aim 1 of the project will first characterize in detail the relationship between autonomics and gut motility in healthy controls and patients with gastroparesis not linked to migraine using an existing dataset. Then in Aim 2, new data will be collected from healthy controls and migraineurs both in the clinic and at home, and dynamics and patterns of brain-gut information flow will be characterized. Subject-provided descriptions of migraine from the electronic health record will be compared to objective physiological readouts. The results of this project have the potential to transform the understanding of migraine pathophysiology, pave a path towards personalized therapeutic strategies for migraine, and lay the foundation for advance prediction of migraine, which can drastically reduce its economic burden. Furthermore, this project will provide objective physiologic insight into a patient experience of pain that is often ignored or mischaracterized because it cannot be tied to an identifiable pathology. The proposed project will take place at Stanford University, between the Department of Bioengineering, Wu Tsai Neuroscience Institute, School of Medicine, and Stanford Pain Management Center. The project will be co- mentored by Dr. Todd Coleman, a bioengineer and statistician specializing in neuroscience and gut motility, and Dr. Sean Mackey, a world-renowned chronic pain specialist. Dr. Meredith Barad and Dr. Linda Nguyen will be consultants. The training plan includes participation in the T32 Training Program in Int...