Internet gaming disorder (IGD) is a concerning issue that requires further research. Here, we seek to examine its neural etiology with an emphasis on the role of the insula. To do so, we relied on the tripartite neurocognitive model of addictive behaviors as applied to IGD. We hypothesized that (a) video game cues will elicit stronger reward system activation and weaker prefrontal activation in gamers vs controls, (b) the IGD scores of gamers will be positively associated with activation of the reward system and negatively with activation of prefrontal regions, (c) deprivation from video gaming will result in increased activation of the insula, when gamers are exposed to video game cues vs to neutral cues, and (d) in deprivation conditions, there will be positive and negative coupling, respectively, between activation of the insula and the reward and prefrontal regions in gamers. We tested these hypotheses with a design with one between-subjects factor (gamers vs controls) and two within-subjects factors: stimuli (gaming vs neutral; for all participants) and session (deprivation vs satiety; only for gamers). Findings based on functional magnetic resonance imaging (fMRI; applied to all 52 subjects, 26 gamers, and 26 controls) and psychophysiological interaction (PPI; applied to the 26 gamers) engaged in a video reactivity task supported our assertions. The IGD score positively correlated with activity in the right ventral striatum and negatively with activity in the right dorsolateral prefrontal cortex (DLPFC). Left insular cortex activity was the highest when observing video gaming cues under deprivation. Lastly, there was an increased coupling between the left insula and left ventral striatum and a decreased coupling with left DLPFC when observing video gaming cues compared with when watching control videos in the deprivation condition.