Investigating the sex-dependent effects of prefrontal cortex stimulation on response execution and inhibition

Context-dependent execution or inhibition of a response is an important aspect of executive control, which is impaired in neuropsychological and addiction disorders. Transcranial direct current stimulation (tDCS) of the dorsolateral prefrontal cortex (DLPFC) has been considered a remedial approach to address deficits in response control; however, considerable variability has been observed in tDCS effects. These variabilities might be related to contextual differences such as background visual-auditory stimuli or subjects' sex. In this study, we examined the interaction of two contextual factors, participants' sex and background acoustic stimuli, in modulating the effects of tDCS on response inhibition and execution. In a sham-controlled and cross-over (repeated-measure) design, 73 participants (37 females) performed a Stop-Signal Task in different background acoustic conditions before and after tDCS (anodal or sham) was applied over the DLPFC. Participants had to execute a speeded response in Go trials but inhibit their response in Stop trials. Participants' sex was fully counterbalanced across all experimental conditions (acoustic and tDCS). We found significant practice-related learning that appeared as changes in indices of response inhibition (stop-signal reaction time and percentage of successful inhibition) and action execution (response time and percentage correct). The tDCS and acoustic stimuli interactively influenced practice-related changes in response inhibition and these effects were uniformly seen in both males and females. However, the effects of tDCS on response execution (percentage of correct responses) were sex-dependent in that practice-related changes diminished in females but heightened in males. Our findings indicate that participants' sex influenced the effects of tDCS on the execution, but not inhibition, of responses. Highlights 1. In a fully counterbalanced (for sex and all experimental conditions), sham-controlled cross-over study, we examined the effects of tDCS over the left DLPFC in the context of Stop-Signal task. 2. The effects of tDCS on response inhibition was uniform across both males and females. 3. The effects of tDCS on response execution differed in males and females. 4. The tDCS mainly modulated the practice-related (learning-related) changes in participants' performance, but these effects of tDCS were different between males and females. 5. These findings highlight the need to adequately control for participants' sex and the need to develop sex-specific tDCS protocols in clinical settings.