Cortical Modulation of Gut Motility

Patients with inflammatory bowel disease (IBD) have dysfunctions in gut motility (the movement of muscles in the gastrointestinal tract). Currently, most available therapeutics developed to directly target the gut fail to stabilize symptoms, suggesting that dysfunctions in gut motility could arise from pathological changes occurring outside the gut. Intriguingly, gut motility problems also occur at high frequencies in patients with neurological disorders, including neurodegenerative, neurodevelopmental and neuropsychiatric diseases, associated with dysregulated neural activity in a specific region of the brain—the cerebral cortex. We propose that dysregulated neural activity in the cortex contributes to the emergence of gut dysfunction. We will test this hypothesis by first identifying specific regions in the cortex that are anatomically connected to the gut and then determining if modulating neural activity within these regions alters gut function. Additionally, we will use established mouse models of various neurological disorders and IBD to ask whether restoring homeostatic levels of neural activity to the cortex improves gut phenotypes. Our study will provide anatomical and functional evidence to support the concept that cortical modulations regulate gut motility. Furthermore, the insight gained from the study can lead to novel therapeutics for ameliorating gut motility symptoms in IBD patients.