Background: The nucleus accumbens (Nac) is a crucial brain region in the pathophysiology of MDD patients with anhedonia. However, the relationship between functional imaging characteristics of Nac subregions and anhedonia remains unclear. Thus, this study aimed to investigate the role of functional connectivity of the Nac subregions between MDD and anhedonia. Methods: We conducted resting-state functional magnetic resonance imaging (fMRI) to measure the resting-state functional connectivity (rsFC) of Nac subregions in 55 MDD patients and 30 healthy controls (HC). A two-sample t-test was performed to obtain the different brain regions with Nac subregions between groups respectively. Then correlation analyses were carried out to investigate the relationships between the aberrant rsFC of Nac subregions and the severity of anhedonia. Furthermore, we constructed a mediation model to explain the role of the aberrant rsFC of Nac subregions between MDD and the severity of anhedonia. Results: The results show that decreased rsFC of Nac subregions with regions of the prefrontal cortex, insula, lingual, and visual association cortex in MDD patients compared with the HC group. In the MDD group, the rsFC of the right Nac shell-like subregions with middle frontal gyrus (MFG)/superior frontal gyrus (SFG) was correlated with consummatory anhedonia; and the rsFC of the Nac core-like subdivisions with inferior frontal gyrus/insula and lingual/visual association cortex was correlated with anticipatory anhedonia. More importantly, the functional alterations of the Nac subregions mediated the association between anhedonia and depression. Conclusions: The present findings suggest the functional alteration of the Nac subregions mediates the association between MDD and anhedonia, which provides evidence for the hypothesis that MDD has different neurobiological underpinnings of reward systems from HC.

Background The nucleus accumbens (Nac) is a crucial brain region in the pathophysiology of major depressive disorder (MDD) patients with anhedonia. However, the relationship between the functional imaging characteristics of Nac subregions and anhedonia remains unclear. Thus, this study aimed to investigate the role of resting-state functional connectivity (rsFC) of the Nac subregions between MDD and anhedonia. Methods We performed resting-state functional magnetic resonance imaging (fMRI) to measure the rsFC of Nac subregions in 55 MDD patients and 30 healthy controls (HCs). A two-sample t test was performed to determine the brain regions with varying rsFC among Nac subregions between groups. Then, correlation analyses were carried out to investigate the relationships between the aberrant rsFC of Nac subregions and the severity of anhedonia. Furthermore, we constructed a mediation model to explain the role of the aberrant rsFC of Nac subregions between MDD and the severity of anhedonia. Results Compared with the HC group, decreased rsFC of Nac subregions with regions of the prefrontal cortex, insula, lingual gyrus, and visual association cortex was observed in MDD patients. In the MDD group, the rsFC of the right Nac shell-like subregions with the middle frontal gyrus (MFG)/superior frontal gyrus (SFG) was correlated with consummatory anhedonia, and the rsFC of the Nac core-like subdivisions with the inferior frontal gyrus (IFG)/insula and lingual gyrus/visual association cortex was correlated with anticipatory anhedonia. More importantly, the functional alterations in the Nac subregions mediated the association between anhedonia and depression. Conclusions The present findings suggest that the functional alteration of the Nac subregions mediates the association between MDD and anhedonia, which provides evidence for the hypothesis that MDD patients have neurobiological underpinnings of reward systems that differ from those of HCs.