The Impact of Inflammation on Brain White and Gray Matter Structure and Function in Pediatric Crohn's Disease

The goal of the current project is to study the association between intestinal and systemic inflammation andbrain structures as well as neurobehavioral outcomes in children with Crohn’s disease (CD) based on recentliterature and our own preliminary data suggesting brain alterations in inflammatory bowel disease (IBD), achronic remitting disease of the gastrointestinal system. Adults with CD show a higher incidence of whitematter abnormalities compared to healthy controls, and structural brain changes have been recently alsodocumented for gray matter, particularly in fronto-limbic and subcortical regions - areas mediating bothcognitive and emotional functions. Several factors including corticosteroid therapy and underlying disease andinflammation have the potential to affect the brain’s white and gray matter. We hypothesize that inflammationdisrupts white and gray matter structure and function, putting children with Crohn’s disease, especially thosewith poorly controlled disease, at developmental risk, acutely and potentially more long term. To test thehypothesis, we use structural and functional imaging of the brain (MRI, rs-fMRI), Diffusion Tensor Imaging(DTI) and testing of neurobehavioral function in children with CD age 10-15 years with active disease (20),disease in remission (20), and 20 healthy controls (HC). We will establish correlations of white mattermicrostructure as well as gray matter volume and cortical thickness with mRNA expression of pro-inflammatorycytokines in blood cells (i.e.IL-1β, IL-2, IL-6, TNF-α), derived from multiplex array. We also assess cognitivefunction and emotion regulation in patients with active and inactive CD and evaluate associations betweenthese behavioral outcomes, inflammation and brain connectivity. Positive findings will inform treatment plans toprevent inflammation-induced brain and behavior changes or mitigate them by more aggressive medical andpsychological intervention.