Altered seed-to-whole-brain functional connectivity of goal-directed/habitual systems in obsessive-compulsive disorder: associated genes and preliminary classification potential

OBJECTIVE: This study aimed to investigate the whole-brain functional connectivity (FC) patterns of goal-directed/habitual systems in patients with obsessive-compulsive disorder (OCD), and to explore their exploratory classification potential and spatial associations with gene expression profiles. METHODS: Resting-state functional magnetic resonance imaging (fMRI) data and clinical variables were collected from 60 patients with OCD and 60 matched healthy controls (HCs). Seed-to-whole-brain FC analyses were conducted using the regions of interest (ROIs) implicated in goal-directed/habitual systems. Pearson correlation analyses were conducted to assess the associations between altered FCs and clinical characteristics. An exploratory support vector machine (SVM) analysis was utilized to evaluate whether altered FC patterns could distinguish patients with OCD from HCs, and neuroimaging-transcriptomic analysis was performed to investigate the spatial association between aberrant FCs and gene expression profiles. RESULTS: Compared to HCs, patients with OCD exhibited decreased FCs between goal-directed system and the default mode network (DMN) and central executive network (CEN), as well as between habitual system and salience network (SN). Conversely, increased FCs were observed between habitual system and DMN. No significant correlations were observed between altered FCs and clinical characteristics after multiple-comparison correction. Exploratory SVM analysis indicated that altered FC patterns of goal-directed system showed higher classification performance (accuracy = 90.83%, AUC = 0.951) than those of the habitual system (accuracy = 79.17%, AUC = 0.867). Imaging-transcriptomic analysis revealed that regional FC alterations were spatially associated with gene (i.e., PPARD and SLC25A12), which were enriched in transmembrane ion transport and metal ion homeostasis. CONCLUSION: OCD exhibited altered FCs patterns between goal-directed/habitual systems and the triple networks at rest. These findings may provide more information to understand the pathology of OCD.