The neural vulnerabilities in reward processing in gambling disorder

Background and aims: Clinical diagnosis of gambling disorder (GD) remains challenging due to the heterogeneity in symptoms and a lack of consistency in the proposed neural mechanisms. Effective classification of GD may depend on neural representations of either risky decision-making or reward processing. Methods: To address these challenges, we recruited more than 100 individuals with GD and matched healthy controls, utilizing event-related fMRI during a novel risky decision-making task to elicit neural representations of risky decision-making and reward processing. Results: During the decision phase, there was no significant difference observed between the two groups even when a very liberal threshold was used. During reward processing, the GD group exhibited significantly increased activation in the right inferior frontal gyrus, right anterior insula, and bilateral posterior cingulate cortex in the risky reward condition compared with the healthy controls. A notable neural activation characteristic was the distinct response between risk-win and risk-loss conditions in reward processing, particularly in the right inferior frontal gyrus in the GD group. The classification for GD using the neural representation of reward yielded an area under the curve of 0.75 (+/- 0.11 SD). Discussion and conclusion: These findings integrate biological and behavioral perspectives to provide new insights into the reward processes underlying GD. These findings highlight specific neural representations associated with GD and suggest potential biomarkers for diagnostic evaluation in GD.