Abstract
Motor control is critical to daily functioning and undergoes significant refinement throughout youth. Although the effects of age on the underlying brain circuitry have been well characterized, fewer studies have examined the influence of pubertal factors on this maturation. This distinction is crucial, as an increase in hormones like testosterone may be a better predictor of neural development than age alone and thus more informative in understanding the functional changes observed during youth. To this end, we enrolled 69 typically developing participants (10-17 years old) who performed a motor sequencing task during magnetoencephalography (MEG) and provided saliva samples for testosterone assays. The neural oscillations serving motor control were imaged and examined using whole-brain ANCOVAs with sex and testosterone levels as factors of interest, controlling for age. Our key findings indicated sex-specific effects of testosterone, such that increasing testosterone levels in males, but not females, were associated with weaker beta oscillations in the prefrontal cortex. Increasing testosterone levels were also associated with weaker alpha oscillations across boys and girls in several frontal and inferior parietal regions. Additionally, there were sex-specific effects of testosterone on motor-related gamma oscillations in cerebellar regions, such that increasing testosterone was correlated with stronger activity in males only. Finally, neural responses in several of these regions were significantly coupled with reaction time. These findings suggest that testosterone has important effects on motor-related neurophysiology above and beyond age, and that these changes may serve the functional refinement of motor sequencing during this developmental period. KEY POINTS: The transition from childhood to adolescence is a critical period for brain development and is characterized by improvements in motor performance and increases in levels of pubertal hormone such as testosterone. Previous studies have shown that movement-related neural oscillations in extended motor regions undergo functional refinement during this period, but whether these changes are coupled to developmental increases in testosterone remains unclear. Herein, magnetoencephalography was used to derive whole-brain functional maps of movement-related oscillations during a motor sequencing task in 69 typically-developing youth, who also provided a sample for assaying testosterone. Testosterone levels, controlling for age, were coupled in a sex-specific way to neural oscillatory responses in higher-order brain regions serving motor planning and execution, with activity in several of these regions being correlated with behavioural performance. These findings suggest that testosterone plays a critical role in the maturation of higher-order motor circuitry during the pubertal transition period.