Sex Difference in Brain Responses During Short Abstinence in People With Internet Gaming Disorder

Withdrawal or the adverse response to abstinence is a significant marker of addiction; however, the neural features of internet gaming disorder (IGD), especially the effects of sex under abstinence, have rarely been examined. This study aimed to examine brain reactions in IGD patients after short-term abstinence and the differences between the sexes. Thirty males and 30 females with IGDs and 30 males and 30 females recreational game users (RGUs) were recruited. Resting-state fMRI data were collected after 1.5 h without gaming. In the IGD and RGU groups, we found atypical brain areas with concurrent degree centrality (DC) and regional homogeneity (ReHo) changes. We then performed functional connectivity (FC) analysis and two-factor ANOVA on these regions to compare IGD and RGU and test for sex differences. Compared with RGUs, IGD subjects presented abnormal cerebral areas with concurrent DC and ReHo abnormalities. After short-term abstinence, IGD and RGU patients presented abnormal prefrontal lobe and insula FC values. Subsequent sex difference analyses focused on the superior frontal gyrus (SFG), middle frontal gyrus (MFG), inferior frontal gyrus (IFG) and insula. ANOVA followed by FDR-corrected post hoc comparisons revealed that IGD males exhibited significantly greater prefrontal and insula FC than females after short-term abstinence. Specifically, males showed markedly enhanced FC in multiple prefrontal regions and the insula, with effect sizes (Cohen's d) ranging from medium to large, confirming both the efficacy and reliability of the observed differences. Compared with RGUs, IGD patients presented FC changes in executive control and reward processing brain regions. With respect to sex differences, short-term abstinence may have altered cognitive control functions more in males than in females and increased internet gaming severity in males. These findings suggest that males are more susceptible to IGD.