Neural correlates of distance-related functional reorganization in obsessive compulsive disorder

Background: While analyzing distance-dependent functional connectivity strength (FCS) yields valuable information about brain activity, whether the FCS alterations found in obsessive-compulsive disorder (OCD) are linked to inter-regional anatomical distance is still unknown. This study investigated distance-associated functional reorganization in OCD and its associations with clinical assessment data and neurotransmitter receptor/transporter densities. Methods: To quantify FCS across global, long-range, and short-range scales, we analyzed resting-state functional MRI data from 99 OCD patients and 104 matched healthy controls (HCs), followed by a post hoc exploratory seed-based FC analysis to further characterize the key brain contributing to the observed FCS abnormalities. Group differences and correlations with clinical measures (symptom severity, illness duration, and age of onset) and PET-derived neurotransmitter receptor/transporter densities were examined. Results: Compared to HCs, OCD patients exhibited reduced long-range FCS in the bilateral fusiform and parahippocampal gyri, primarily driven by weakened connections with frontal, superior/middle temporal, precuneus, and cingulate regions. Short-range FCS was increased in the right dorsolateral prefrontal cortex but decreased in the precentral gyrus and middle cingulate cortex, mainly due to altered local connections involving the middle frontal gyrus, precentral gyrus, precuneus, and cerebellum. These alterations were robust in cross-validation. No significant correlations were found with clinical measures. However, both long- and short-range FCS changes correlated significantly with neurotransmitter receptors/transporter densities, particularly the excitatory-inhibitory ratio profile. Limitations: Neurotransmitter receptor/transporter maps were derived from publicly available datasets, which may not capture individual variation in receptor density. Conclusion: This study highlights distance-dependent functional connectivity reorganization in OCD and its neurochemical underpinnings, providing new insights into the disorder’s pathophysiology.