“Continuous Neural Correlates of Imbalanced Reinforcement Learning in Obsessive-Compulsive Disorder and Healthy Individuals”

Abstract Aim Obsessive-compulsive disorder (OCD) is characterized by imbalanced reinforcement learning. This study investigated neural correlates of this imbalance by examining resting-state functional connectivity (rs-fMRI) in non-medicated OCD patients and healthy controls (HCs) exhibiting varying degrees of memory trace imbalance. Methods We employed network-based statistics (NBS), suitable for identifying network-level alterations of rs-fMRI data from 49 OCD patients and 53 HCs (Core Discovery Dataset: Core-DS) to identify a significant network. We validated this network in an independent dataset of 10 OCD patients and 18 HCs (Independent Validation Dataset: IndV-DS). Additionally, we compared functional connectivity in the identified network between subgroups of HCs with imbalanced (OCD-like) and balanced learning profiles (Extension Dataset: Ext-DS; n=10 each). Results NBS identified an ‘OCD network’ with increased connectivity in OCD patients (p adjusted = 0.022), comprising regions in the dorsolateral prefrontal cortex (DLPFC), parietal cortex, retrosplenial cortex, and hippocampal formation. This network’s increased connectivity in OCD patients was replicated in IndV-DS (p = 0.0027). Importantly, imbalanced HCs showed a significant increase in functional connectivity, particularly between the DLPFC and presubiculum, in the identified ‘OCD network’, compared to balanced HCs (p = 0.0051, p adjusted = 0.066). Conclusion Increased functional connectivity in the ‘OCD network,’ especially between the DLPFC and presubiculum, is present in both OCD patients and a subgroup of HCs with learning imbalances. These findings provide evidence for a continuous neural basis of imbalanced reinforcement learning, suggesting a continuum of traits associated with OCD between patients and “healthy” individuals.