Heterogeneous neuroimaging findings in obsessive-compulsive disorder converge to a common brain network using...

Neuroimaging studies in obsessive-compulsive disorder (OCD) have yielded heterogeneous findings, limiting efforts to localize OCD to specific brain regions or networks. This study applied coordinate network mapping (CNM) to test whether these distributed abnormalities converge onto a common brain network and to explore the biological substrates of this network through associations with neurotransmitter systems. We systematically reviewed and extracted coordinates of significant clusters from 66 Gy matter volume (GMV) and resting-state activity studies involving 3123 patients with OCD and 3116 healthy controls. Using CNM and functional connectome data from 1000 healthy individuals, we identified brain networks functionally connected to these abnormalities. Spatial correlations were examined between identified networks and 19 types of neurotransmitter maps acquired from over 1000 healthy subjects. The GMV and resting-state activity findings in OCD both converged to a common, functionally connected brain network involving the striatum, thalamus, cingulate, supplementary motor area, insula, and inferior frontal and superior temporal gyri. The identified networks derived from the two neuroimaging modalities were significantly correlated with the N-Methyl-D-Aspartate (NMDA) receptor distribution (r = 0.551 and r = 0.541, respectively; p < 0.001). Findings were robust across different methodological parameters and demonstrated good test-retest reliability. This study identifies a robust and reproducible brain network underlying the heterogeneous neuroimaging abnormalities in OCD, helping to interpret previous inconsistencies. Furthermore, the alignment of this network with the cortico-striato-thalamo-cortical circuitry and NMDA receptor distribution underscores its biological and clinical relevance, thereby illuminating potential targets for future neuromodulation and pharmacological interventions.