Obsessive-compulsive disorder: beyond segregated cortico-striatal pathways

Abstract

Obsessive-compulsive disorder (OCD) affects approximately 2-3% of the population and is characterized by recurrent intrusive thoughts (obsessions) and repetitive behaviors or mental acts (compulsions), typically performed in response to obsessions or related anxiety. In the past few decades, the prevailing models of OCD pathophysiology have focused on cortico-striatal circuitry. More recent neuroimaging evidence, however, points to critical involvement of the lateral and medial orbitofrontal cortices, the dorsal anterior cingulate cortex and amygdalo-cortical circuitry, in addition to cortico-striatal circuitry, in the pathophysiology of the disorder. In this review, we elaborate proposed features of OCD pathophysiology beyond the classic parallel cortico-striatal pathways and argue that this evidence suggests that fear extinction, in addition to behavioral inhibition, is impaired in OCD.

Figure 1

Schematic illustration of the different components of the cortico-striatl-thalamo-cortical (CSTC) pathways commonly implicated in the psychopathology of obsessive-complusive disorder (OCD). ACC: anterior cingulate cortex, vmPFC: ventromedial prefrontal cortex.

Figure 2

Schematic diagram illustrating the so-called cortico-striatl loops as commonly defined. dlPFC: dorsolateral prefrontal cortex, NAC: nucleus accumbance, OFC: orbitofrontal cortex

Figure 3

Brain regions involved in fear conditioning, extinction learning, and recall appear to overlap with brain regions implicated in the psychopathology of OCD. A. Anatomical illustration of brain regions commonly implicated in OCD. Hipp: hippocampus, Amyg: amygdala, Thal: thalamus, dACC: dorsal anterior cingulate cortex, vmPFC: ventromedial prefrontal cortex. Striatal regions are not illustrated in blue shapes for simplicity, but are clearly visible. Panels in B and C represent results from a meta-analysis focusing on functional neuroimaging studies of fear conditioning (B), extinction learning and recall (C). Crosses displayed on the anatomical images represent change in functional activation during fear conditioning (red) and extinction (green) regardless of the direction of activation (increased or decreased) and includes studies that examined patients with disorders. Structural imaging studies were not included in this meta-analysis. For additional details, see supplemental materials.