Altered Functional Connectivity in the Reward Circuit in Betel Quid-Dependent Chewers

Betel quid (BQ) is classified as a Group 1 carcinogen, underscoring a significant public health challenge. Neuroimaging evidence demonstrated that betel quid dependence (BQD) was linked to alterations in reward-related brain regions. However, resting-state functional connectivity (FC) in the reward circuit and their neural correlates with pathophysiological characteristics of BQD remain largely unexplored. We recruited 53 male BQD chewers and 53 male healthy controls (HCs) to participate in this study. Eleven reward circuit seeds, such as ventral striatum (VS), ventromedial prefrontal cortex (VMPFC), anterior cingulate cortex (ACC), posterior cingulate cortex (PCC) and others, were selected. Resting-state functional magnetic resonance imaging (rs-fMRI) data were analysed to evaluate FC between predefined seed regions and the whole brain. Association between aberrant FC and clinical features was further investigated. Relative to HCs, individuals with BQD exhibited altered FC in the reward circuit, mainly in VS, VMPFC, ACC, PCC and thalamus (Th). Correlation analysis indicated that FC between right Th and PCC was negatively correlated with BQD scales and dosage of BQ use in BQD subjects. Our findings provided the first empirical evidence that individuals with BQD showed aberrant resting-state FC in the reward circuit. Additionally, decreased connectivity between right Th and PCC was negatively associated with dependence degree and dosage of BQ use. These results highlighted the importance of the reward circuit in the pathophysiology of BQD and suggested that reward circuit dysfunction could serve as a potential circuit-level biomarker.