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Fig. 1

Cortico-striato-thalamo-cortical (CSTC) circuit dysfunction in OCD. (A) OCD is associated with dysfunction in multiple CSTC loops, spanning both cortical and subcortical regions including the orbitofrontal cortex (OFC), dorsolateral prefrontal cortex (dlPFC), dorsal anterior cingulate cortex (dACC), ventromedial prefrontal cortex (vmPFC), striatum, globus pallidus internus (GPi), globus pallidus externus (GPe), substantia nigra pars reticulata (SNr), and thalamus. (B) Coordinated activity from these structures provides feedback to the thalamus both directly and indirectly. During normal functioning, the direct and indirect pathways provide excitatory and inhibitory cortical feedback in a balanced manner. In OCD, the direct pathway is overactivated relative to the indirect pathway, leading to pathological excitation of cortex.

Obsessive-compulsive disorder is a neuropsychiatric illness associated with significant disability. The neurobiology of the disease is thought to be related to dysregulation of cortico-striato-thalamo-cortical loops that leads to overexcitation of the orbitofrontal cortex. Standard evidence-based therapies include exposure and response prevention and serotonin reuptake inhibitors, but 10% to 15% of patients fail to achieve response to these treatments. Treatment resistance has been defined by a lack of meaningful improvement in time spent on obsessions and compulsions and the distress associated with them. This article discusses intensive cognitive-behavioral therapy, alternative psychotherapy programs, and neurosurgery as therapeutic options for refractory cases.

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