Disrupted Higher-Order Topology in OCD Brain Networks Revealed by Hodge Laplacian – an ENIGMA Study

Obsessive-compulsive disorder (OCD) is a disabling condition that is characterized by disruptions in distributed brain circuit dynamics. However, current network studies predominantly evaluate these circuits by measuring functional synchrony (connectivity) between pairs of regions of interest, potentially overlooking complex higher-order interactions. In this study, we applied a Hodge Laplacian topological framework to investigate these higher-order interactions in OCD. Using a large-scale resting-state fMRI dataset from the ENIGMA-OCD consortium (1,024 OCD patients and 1,028 healthy controls across 28 sites worldwide), we identified significant disruptions in topological loops spanning frontoparietal, default mode, and sensorimotor networks. Crucially, the edges constituting these abnormal loops largely lacked significant pairwise differences, highlighting higher-order multi-nodal disturbances. Subgroup analyses revealed that these disruptions were most pronounced in adult, medicated, and high-severity OCD patients. Our findings suggest that OCD pathology involves abnormal recurrent higher-order multi-region interactions, providing new insights into the brain's functional organization and offering potential biomarkers for clinical application.