Abnormal functional connectivity within the reward network: a potential neuroimaging endophenotype of bipolar disorder

Background: Reward circuit dysfunction underlies the pathogenesis of bipolar disorder (BD). This study aims to investigate whether nucleus accumbens (NAcc) and ventromedial prefrontal cortex (vmPFC), two key reward regions for BD, have resting-state dysfunctional connectivity with other brain regions in depressed and euthymic BD. Methods: 40 bipolar depressive (DE), 20 euthymic patients (EU) and 20 healthy controls (HC) were recruited to undergo resting-state functional MRI (rs-fMRI) scanning. Seed-based functional connectivity (FC) was calculated between NAcc/vmPFC and the whole brain. Group differences were calculated and their correlations with clinical characteristics were analyzed. Support vector machine was applied to classify BD patients and HC based on the FC between the cluster of group difference and NAcc/vmPFC. Results: Whole brain networks of FC identified right anterior insular cortex (AIC) as a significant region with bilateral NAcc when compared among three groups. The right AIC-NAcc FC elevated in both patient groups and was highest in the EU group. Interestingly, vmPFC-based networks also identified the right AIC as a significant cluster. The right AIC-vmPFC FC elevated in both patient groups. However, FC between NAcc and vmPFC did not significantly differ BD patients from HC. Furthermore, the strength of FC between bilateral NAcc and the right AIC was positively associated with the illness course of BD. Notably, the NAcc/vmPFC-right AIC classifier acquired an accuracy of 68.75% and AUC-ROC of 78.17%. Limitations: Our sample size is modest. Conclusions: Our findings indicated that elevated NAcc/vmPFC-right AIC connectivity within the reward circuit could be a neuroimaging endophenotype of BD.