“Actor-critic” dichotomous hyperactivation and hypoconnectivity in obsessive–compulsive disorder

Dysfunctional response inhibition, mediated by the striatum and its connections, is thought to underly the clinical manifestations of obsessive–compulsive disorder (OCD). However, the exact neural mechanisms remain controversial. In this study, we undertook a novel approach by positing that a) inhibition is a dynamic construct inherently susceptible to numerous failures, which require error-processing, and b) the actor-critic framework of reinforcement learning can integrate neural patterns of inhibition and error-processing in OCD with their behavioural correlates. We invited nineteen adults with OCD and 21 age-matched healthy controls to perform an fMRI-adjusted stop-signal task. Then, we extracted brain activation and connectivity values regarding distinct task phases in the “actor” and “critic” regions, here corresponding to the caudate’s head and dorsal putamen, and midbrain’s nuclei (ventral tegmental area and substantia nigra). During response preparation phases of the inhibitory process, individuals with OCD exhibited decreased functional connectivity between the “critic” structures and frontal regions involved in cognitive and executive control. Activity analysis revealed task-related hyperactivation in the midbrain alongside error-processing-specific hyperactivation in the striatum, which was correlated with excessive behavioural slowness, also found in the clinical group. Finally, we identified a remarkable opponency between activity in the ventral tegmental area and caudate leading to direct increases and indirect decreases in symptom severity. We propose a unique “actor-critic”-based domain- and timing-dependent neural profile in OCD, reflecting “harm-avoidant” styles for response suppression, and influencing symptom severity. The dichotomy of hypoconnectivity and hyperactivation in the “critic” along with the opponent relationship between the “actor” and the “critic” in determining symptom severity suggests the implication of neural adaptation mechanisms in OCD with potential relevance for neurobiologically-driven therapies.