Disrupted Functional Network Organization in Crohn's Disease: Interoceptive Alterations Linked to Anxiety
ABSTRACT Background and Aims How Crohn's disease alters large‐scale brain network organization and interacts with affective symptoms remains poorly understood. We aimed to characterize disease‐related disruptions in functional topology, rich‐club organization, and hierarchical gradients, and to determine their associations with disease activity and anxiety. Methods Ninety‐seven Crohn's disease patients and 64 healthy controls underwent resting‐state fMRI. Graph‐theoretical metrics, rich‐club analysis, functional gradients, and spectral dynamic causal modeling were applied to assess network properties, hierarchical architecture, and effective connectivity. Associations with the Crohn's Disease Activity Index and anxiety were examined via linear regression. Results Crohn's disease patients showed widespread network disruptions modestly linked to disease activity, including reduced global and local efficiency, impaired rich‐club connectivity, and compressed sensorimotor gradients. Decreased degree centrality in the insula, thalamus, and postcentral gyrus was accompanied by altered hierarchical organization and effective connectivity. Spectral dynamic causal modeling revealed anxiety‐related modulation of insular excitation and thalamo‐putaminal pathways. Conclusions Crohn's disease involves widespread functional network disruption and reorganization, particularly in interoceptive regions supporting sensory and emotional processing. Anxiety modulates core limbic circuitry, highlighting the interplay between disease activity and affective symptoms in shaping brain network.