Behavioral and anatomical sex-related differences have been traditionally found in decision-making processes assessed by Iowa Gambling Task (IGT). So far, the administration of transcranial direct current stimulation (tDCS) over orbitofrontal regions has shown an enhancing effect over decision-making. However, it is unknown whether there is a sex-dependent effect of stimulation in decision-making, a key question considering previous differences between men and women in IGT and the influence of individual differences in tDCS. The present study examines, at first time, the interaction between sex and tDCS in decision-making. For that aim, in a first experimental phase, ninety-two healthy participants performed the IGT. In a second phase, sixty-one participants received 20 min of anodal or sham tDCS over the right orbitofrontal cortex (rOFC) in a single-session pre-post sham-controlled study. To support the focality of the montage, a Stop Signal Task (SST) was used as a control task and also a numerical simulation of current flow distribution was performed. According to literature, in the first phase, results showed that men outperformed women in the IGT. In the second phase, the stimulation varied the IGT performance according to a sex specific manner: anodal tDCS increased the IGT performance in women, while in men; the stimulation did not produce any effect. Results were mediated by sex-specific morphological differences. These results highlight the necessity to consider the interaction of sex with the effect of the stimulation in future tDCS protocols, specifically in future clinical studies.

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