Abstract
Problematic smartphone use has been associated with altered reward and executive control network activity, yet potential sex differences in the underlying neural mechanisms remain insufficiently understood. We investigated sex-specific neural correlates of smartphone cue reactivity (CR) in 69 healthy young adult smartphone users (age range 18-30 years, female/male n = 45/24). Participants completed the Smartphone Addiction Inventory (SPAI) and underwent functional MRI during a smartphone CR paradigm. In addition, resting-state data were acquired to ensure that neural differences between female and male participants could be attributed to the CR paradigm rather than to sex differences in intrinsic neural activity. Whole-brain analyses revealed stronger activation in males compared to females in response to the presentation of smartphone cues within the right middle frontal gyrus (MFG), thalamus, cortical sensorimotor, parietal and occipital regions, whereas females showed no suprathreshold clusters compared to males. No overlap with resting-state amplitude of low-frequency fluctuation maps was observed with CR results, confirming task specificity. In males, right MFG correlated positively with SPAI-I total score, craving, and sleep interference scores, while in females, right parietal cortex activity correlated negatively with SPAI-I total score, daily life interference, and craving. Complementary cross-modal analyses showed that CR-related activation patterns were associated with several cortical excitatory and inhibitory neuronal and cellular markers, revealing subtle sex differences. These findings suggest sex-specific frontoparietal mechanisms underlying smartphone CR and highlight neurochemical pathways potentially linking excessive smartphone use to differential motivational and cognitive control processes in males compared to females.