Abnormal functional connectivity of the nucleus accumbens subregions mediates the association between anhedonia and major depressive disorder

Abstract

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.

Keywords: Anhedonia; Functional connectivity; Major depressive disorder; Nucleus accumbens subregions.

Fig. 1

The four Nac subregions characterized by Cartmell et al. [44]

Fig. 2

Spatial distributions of the rsFC of the four Nac subregions between the HC group and the MDD group. rsFC data were projected onto the images of the brain using BrainNet Viewer (https://www.nitrc.org/projects/bnv/). The colour bar scale represents t values

Fig. 3

Regions showing significant differences in rsFC with the Nac core-like

Fig. 4

Regions showing significant differences in rsFC with the Nac subregions between the MDD group and HC group. Warm colours represent the regions showing stronger rsFC of Nac subregions in the MDD group than in the HC group. Cool colours represent the regions showing weaker rsFC of Nac subregions in the MDD group than in the HC group. The images were created using BrainNet Viewer (https://www.nitrc.org/projects/bnv/). The colour bar scale represents t values

Fig. 5

Scatter plots of the correlation between significantly different rsFC and the anhedonia scale in both groups. (a) Positive correlation between rsFC of the right Nac shell-like subdivision and TEPS_C score. (b) Positive correlation between rsFC of the left Nac core-like subdivision and TEPS_A score. (c) Positive correlation between rsFC of the right Nac core-like subdivision and TEPS_A score. (MD, major depressive disorder; HC, healthy control; TEPS_C, consummatory pleasure dimension of the Temporal Experience of Pleasure Scale; TEPS_A, anticipatory pleasure dimension of the Temporal Experience of Pleasure Scale; IFG, inferior frontal gyrus; SFG_R, right superior frontal gyrus; MFG_R, right middle frontal gyrus)

Fig. 6

Mediation models for the effect of rsFC on the relationship between group and anhedonia. (a) Mediation model with regression path coefficients of the rsFC of bilateral core-like subdivisions as mediators of the relationship between group and anticipatory anhedonia. (b) Mediation model with regression path coefficients of the rsFC of the right shell-like subdivision as a mediator of the relationship between group and consummatory anhedonia. (core_L, rsFC value of the left Nac core-like subdivision with the right lingual gyrus/visual cortex; core_R, rsFC value of the right Nac core-like subdivision with the IFG/insula; TEPS_A, anticipatory pleasure dimension of the Temporal Experience of Pleasure Scale; shell_R, rsFC value of the right Nac shell-like subdivision with the right MFG/SFG; TEPS_C, consummatory pleasure dimension of the Temporal Experience of Pleasure Scale)