Stronger connectivity among reward, cognitive, and attention networks in people with severe Opioid Use Disorder compared with healthy controls.

Abstract One approach to addressing the immense unmet need for treatments of severe Opioid Use Disorder (sOUD) is to understand more about associated changes in the brain’s reward circuitry. It has been shown that during reward anticipation in the Monetary Incentive Delay (MID) task, people with severe substance use disorder (SUD) show blunted responses in reward neural circuitry compared with healthy controls (HC). Conversely, drug-related cues result in heightened responses in the same neural reward circuitry in those with SUD compared with HC. However, it is unclear how such dysfunctional reward processing is related to neural correlates of other processes commonly dysregulated in addiction, such as attention and cognition. The aim of this work was to evaluate whether people with sOUD show different spatiotemporal relationships between reward networks to cognitive and attentional networks. We collected fMRI data while people with sOUD receiving methadone (MD; n = 22) and HC (n = 22) completed the MID and Cue Reactivity tasks. We evaluated differences in functional connectivity (FC) and measures of brain state dynamics. We explored the relationship between FC to µ-Opioid receptor (MOR) and Dopamine D2 Receptor (DRD2) availability due to their involvement in reward processing. During both the MID and Cue Reactivity tasks, MD participants showed significantly higher mutual information FC between regions in the reward network to those in attention and cognitive networks. We found significant, positive relationships between the higher FC in MD vs HC participants and the sum of MOR and D2 receptor availability during the Cue Reactivity task. In summary, the higher integration among reward, attentional, and cognitive networks in MD participants during both non-drug and drug-related tasks suggests that the relationship between these networks is dysregulated in addiction. These mechanistic insights provide alternative targets for treatment to improve sOUD outcomes.