Neural mechanisms underlying cognitive inflexibility in obsessive-compulsive disorder: a review

Cognitive inflexibility, a reduced capacity to shift mental set or update behavior when circumstances change, is a significant feature of obsessive-compulsive disorder (OCD). However, while cognitive inflexibility is superficially a coherent entity, it appears to engage a range of distinct cognitive processes. This raises the question of how far deficits in different tasks involve the same core dysfunction and how far the dysfunctions are unique but superficially have similar results. Here we detail the neural basis of OCD deficits across eight tasks that challenge different aspects of cognitive flexibility: set-shifting (Wisconsin Card Sorting Task, Intra/Extra-Dimensional Set Shift), feedback adaptation (Reversal Learning), interference control (Stroop Color and Word Test), response inhibition (Go/No-Go Task and Stop Signal Task), working memory updating (n-back Task), and value-based flexibility (Delay Discounting Task). Cognitive inflexibility in OCD appears linked to functional abnormalities in a largely shared set of core structures (anterior cingulate cortex, caudate nucleus, orbital frontal cortex, and prefrontal cortex) and less shared 'peripheral' structures (putamen, thalamus, parietal cortex), based on cross-task convergence of OCD-specific abnormalities. Even the shared core appears to engage multiple interconnected neural networks. The cortico-striato-thalamo-cortical network appears central, and the salience network and the default mode network also contribute with indirect, task-varying effects on peripheral parts of each. Peripheral areas are less consistently involved but appear to contribute to OCD nonetheless. Cognitive inflexibility in OCD appears to involve failure of interaction between multiple networks rather than dysfunction in any single system.