Sex matters for the enhancement of cognitive training with transcranial direct current stimulation (tDCS)

Transcranial direct current stimulation (tDCS) can influence brain network activity and associated cognitive and behavioural functions. In addition to the extensive variety in stimulation parameters, numerous biological factors drive these effects, however these are yet poorly understood. Here, we investigate one of the major biological factors by focusing on sex-dependent effects of tDCS on a challenging cognitive control task (adaptive paced auditory serial addition task [PASAT]) in healthy humans.

This sex-specific re-analysis was performed on data of 163 subjects who underwent a 2-week cognitive control training (6 sessions in total). Subjects received either verum (anodal/cathodal) or sham tDCS. Electrodes were placed over the left or right dorsolateral prefrontal cortex and the respective contralateral deltoid muscle. Cognitive control was measured as performance in the PASAT and was analysed in respect to stimulation conditions (sham, anodal, cathodal) and sex.

Regardless of stimulation condition, performance gains between the sexes were higher in females compared to males (p = 0.0038). Female's performance during anodal tDCS exceeded male's (p = 0.0070), yet no effects were found for cathodal or sham tDCS. Moreover, in females we found a superior effect for anodal tDCS over sham stimulation (f_anodal: p = 0.0354; f_cathodal: p = 0.6181), but no such effect in males (m_anodal: p = 0.6882; m_cathodal: p = 0.4822).

This study highlights the relevance of biological sex for the effects of tDCS on cognitive training. Thus, an increased attention to biological sex is advisable in future brain stimulation research to highlight and in consequence better understand potentially underlying sex-specific mechanisms. Considering biological sex will further advance customisation and individualisation of tDCS interventions. Trial registration ClinicalTrials.gov, NCT04108663.