Characterizing insula functional connectivity alterations in obsessive-compulsive disorder: from parcellation and...

The insula serves as an integrative hub across sensory, affective, and cognitive domains, yet its heterogeneous connectivity architecture has been largely overlooked in obsessive-compulsive disorder (OCD). Using both discrete parcellation and continuous gradient approaches, we comprehensively characterized insula functional connectivity (FC) alterations in 92 medication-free, noncomorbid OCD patients and 90 healthy controls. Data-driven clustering divided the insula into anterior and posterior subregions, followed by a diagnosis-by-subregion factorial analysis of variance (ANOVA) to assess group differences. OCD patients showed unbalanced subregional FC alterations with the supplementary motor area, precentral gyrus, and dorsolateral prefrontal cortex, exhibiting increased anterior and decreased posterior insula FC, with a significant effect in the anterior subregion. Within OCD patients, anterior insula-dorsolateral prefrontal FC was negatively correlated with obsession severity. Gradient analysis further revealed reduced explanation ratio, gradient range, and variation in the left insula, but these effects did not survive correction for multiple comparisons. Together, these results indicate that insula FC alterations in OCD are more localized to specific subregions rather than reflecting a large-scale gradient shift, with anterior insula dysconnectivity emerging as a key feature linked to obsessive symptoms.