Sex and age differences on how testosterone relates to brain activity during working memory among adolescents and young adults

Working memory is an important cognitive process that develops throughout early life. During adolescence, there is marked improvement in this process that is associated with structural and functional brain changes. These changes have been linked to age; however, endogenous testosterone is thought to regulate structural and functional changes in the brain during puberty, with differential influences across adolescence into early adulthood. Thus, testosterone may have a direct impact on brain activity that is modulated by age. The current study aimed to examine this using a working memory functional magnetic resonance imaging (fMRI) task in adolescents and young adults. Saliva samples collected prior to scanning were assayed for endogenous testosterone levels. One hundred and forty-five typically developing participants (74 female), aged 12-25 yr, completed a working memory fMRI task. Results showed that, for the most difficult versus the 0back conditions, younger female participants (≤19) only had more deactivation in the anterior cingulate cortex with higher level of testosterone. In contrast, male participants showed increased activation in the precentral gyrus with higher testosterone, regardless of age. These findings indicate sex differences in how endogenous testosterone relates to the activity of different brain regions recruited during working memory. Furthermore, these associations vary across typical adolescent development.