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More males than females play video games and develop problems with gaming. However, little is known regarding how males and females who game on the Internet may differ with respect to neural responses to gaming cues.Behavioral and functional magnetic resonance imaging (fMRI) data were recorded from 40 female and 68 male Internet gamers. This study included three components including participation in a pre-gaming cue-craving task, 30 min of online gaming and a post-gaming cue-elicited-craving task. Group differences were examined at pre-gaming, post-gaming and post- vs pre-gaming times. Correlations between brain responses and behavioral performance were calculated.Gaming-related cues elicited higher cravings in male vs female subjects. Prior to gaming, males demonstrated greater activations in the striatum, orbitofrontal cortex (OFC), inferior frontal cortex and bilateral declive. Following gaming, male subjects demonstrated greater activations in the medial frontal gyrus and bilateral middle temporal gyri. In a post-pre comparison, male subjects demonstrated greater thalamic activation than did female subjects.Short-term gaming elicited in males vs females more craving-related activations to gaming cues. These results suggest neural mechanisms for why males may be more vulnerable than females in developing Internet gaming disorder.