Predictive spread of obsessive-compulsive disorder pathology using the network diffusion model

An increasing body of studies propose that structural abnormalities begin with focal brain regions then propagate to other regions following the architecture of healthy brain network in neuropsychiatric disorders. However, these findings are untested in obsessive-compulsive disorder (OCD), also showing widespread structural brain abnormalities. In this study, we aimed to investigate whether healthy functional brain network contributed to structural brain abnormalities in OCD. The gray matter morphological abnormalities were obtained in 98 patients with OCD in relative to matched healthy controls (n = 130, HCs). The network diffusion model (NDM) was conducted to identify putative seed regions and patterns of disease propagation from seed regions to other brain regions along the functional network in OCD. The NDM has been proved to succeeded in capturing the trans-neuronal propagation of pathology and even in predicting future longitudinal progression of pathology in neurodegenerative diseases. In this study, when seeding at the right anterior cingulate cortex, the NDM best recapitulated the patterns of gray matter morphological abnormalities, suggesting this region was the most likely seed region. Further analyses revealed that pathology preferentially propagated to higher order brain systems from seed region. For non-seed regions, the arrival time of pathology was negatively correlated with their shortest functional paths to the seed (r = -0.46, p < 0.001). These results suggest that gray matter morphological abnormalities are constrained by healthy brain network and reveal temporal sequencing of pathology progression in OCD.