Rewiring the OCD brain: Insights beyond cortico-striatal networks

Obsessive-compulsive disorder (OCD) is a debilitating neuropsychiatric condition marked by recurrent obsessions and compulsions. Over the years, research has primarily focused on the cortico-striato-thalamo-cortical (CSTC) circuit and its neurochemical disruptions as an ideal circuit system for the development of treatment strategies. However, recent findings from neuroimaging studies and rodent research have highlighted the involvement of additional brain regions and network-level dysfunctions that are functionally linked to the CSTC loop. These findings suggest that the sole emphasis on the CSTC circuit is insufficient to address the clinical heterogeneity of the disorder. A broader perspective would therefore better capture the disorder's clinical heterogeneity and diverse cognitive and emotional deficits. Here, we review growing evidence for the role of extra-CSTC brain regions and associated neurotransmitter interactions in OCD, outlining potential pathways for novel therapeutic strategies.