Increased functional connectivity between prefrontal cortex and reward system in pathological gambling

Abstract

Pathological gambling (PG) shares clinical characteristics with substance-use disorders and is thus discussed as a behavioral addiction. Recent neuroimaging studies on PG report functional changes in prefrontal structures and the mesolimbic reward system. While an imbalance between these structures has been related to addictive behavior, whether their dysfunction in PG is reflected in the interaction between them remains unclear. We addressed this question using functional connectivity resting-state fMRI in male subjects with PG and controls. Seed-based functional connectivity was computed using two regions-of-interest, based on the results of a previous voxel-based morphometry study, located in the prefrontal cortex and the mesolimbic reward system (right middle frontal gyrus and right ventral striatum). PG patients demonstrated increased connectivity from the right middle frontal gyrus to the right striatum as compared to controls, which was also positively correlated with nonplanning aspect of impulsiveness, smoking and craving scores in the PG group. Moreover, PG patients demonstrated decreased connectivity from the right middle frontal gyrus to other prefrontal areas as compared to controls. The right ventral striatum demonstrated increased connectivity to the right superior and middle frontal gyrus and left cerebellum in PG patients as compared to controls. The increased connectivity to the cerebellum was positively correlated with smoking in the PG group. Our results provide further evidence for alterations in functional connectivity in PG with increased connectivity between prefrontal regions and the reward system, similar to connectivity changes reported in substance use disorder.

Figure 1. Location of seed regions for functional connectivity analysis

Right middle frontal gyrus: x = 44, y = 48, z = 7, radius of 6 mm. Right ventral striatal seed: x = 5, y = 6, z = -12, radius of 4 mm.

Figure 2. Functional connectivity of right middle frontal seed

Patterns of significantly positive (red spectrum) and negative (blue spectrum) correlations with the right middle frontal gyrus (seed depicted in green) within all subjects and within the groups. Group comparison for significant correlations: PG patients < controls and PG patients > controls (violet spectrum). All maps are thresholded at a z-score > |2.3| (cluster-wise corrected using Gaussian random field theory and Bonferroni corrected for the number of seeds). N_controls = 19, N_PGpatients = 19.

Figure 3. Group differences in functional connectivity of the seeds

Plots show z-values for the significant clusters of difference (encircled in yellow). Number of subjects for right middle frontal gyrus seed region A): N_controls = 19, N_PGpatients = 19, and for right ventral striatal seed region B): N_controls = 18, N_PGpatients = 14.

Figure 4. Functional connectivity of right ventral striatal seed

Patterns of significantly positive (red spectrum) and negative (blue spectrum) correlations with the right ventral striatum (seed depicted in green) within all subjects and within the groups. Group comparison for significant correlations: PG patients > controls (violet spectrum). Please note that the contrast controls > PG patients was not significant. All maps are thresholded at a z-score > |2.3| (cluster-wise corrected using Gaussian random field theory and Bonferroni corrected for the number of seeds). N_controls = 18, N_PGpatients = 14.

Figure 5. Significant positive correlations for connectivity patterns

Scatter plots show significant correlations between the mean z-values of the thresholded clusters of the group contrasts PG patients > controls and smoking habits (number of cigarettes per day [cig/d]), the nonplanning BIS subscale and the VAS for craving. Number of PG patients for right middle frontal gyrus seed region A): N_PGpatients = 19, and for right ventral striatal seed region B): N_PGpatients= 14.