Altered functional network architecture in orbitofronto-striato-thalamic circuit of unmedicated patients with...

Dysfunction of corticostriatal loops has been proposed to underlie certain cognitive and behavioral problems associated with various neuropsychiatric disorders, such as obsessive-compulsive disorder (OCD) characterized by repetitive, unwanted thoughts, and behaviors. Although functional abnormalities in the loops involving the orbitofronto-striato-thalamic (OFST) circuitry in patients with OCD have been reported, our understanding of a link between disruptions in the architecture of the intrinsic functional network of the OFST circuit and their symptoms remain incomplete. Using resting-state functional MRI in conjunction with unsupervised clustering and multilevel functional connectivity (FC) techniques, FC of the OFST network and its topological organization in 61 OCD patients versus 61 matched controls were characterized. Patients exhibited disruptions in small-world properties of the OFST circuit, which indicates an imbalance between functional integration and segregation. Patients also showed decreased FC between the central orbitofrontal cortex and dorsomedial striatum but increased FC between the medial thalamus and striatal areas. Using one of the largest samples of unmedicated OCD patients to date, our findings provide evidence supporting the OFST dysconnection hypothesis in OCD as a basic pathophysiological mechanism underlying the disorder, showing the disruption of FC between specific cortical, striatal, and thalamic clusters and aberrant topological patterns of the OFST circuit. Hum Brain Mapp 38:109-119, 2017. © 2016 Wiley Periodicals, Inc.