The LC-NE System as a Candidate Mechanism Linking the Acute Benefits of Exercise on Cognitive and Brain Function in Children

Purpose: Physical activity supports cognitive and brain health, however the biological mechanisms underlying these benefits remain unclear. This study investigated changes in salivary alpha-amylase (sAA), a marker of sympathetic nervous system activity, and salivary cortisol (CORT), reflecting hypothalamus-pituitary-adrenal (HPA) axis activity, as candidate mechanisms mediating the effects of acute exercise on brain function, cognition, and academic achievement in children. Methods: In a pre-post randomized crossover design, 104 children (ages 9-10) completed exercise, the Trier Social Stress Test for Children (TSST-C; active control), and seated rest (passive control) conditions, with neuroelectric activity (P3 amplitude and latency), attentional inhibition, and academic achievement as outcomes. Structural equation modeling was performed to examine sAA and CORT as mediators of the relationship between exercise and outcomes. Moderated mediation tested whether the magnitude of the sAA-mediated path varied as a function of pre-intervention baseline CORT. Results: Exercise led to lower sAA than both controls and lower CORT than the TSST-C, controlling for pre-intervention baselines. Post-exercise reductions in sAA mediated reductions in trial-to-trial reaction time variability (SDRT) on incongruent trials, indexing more consistent inhibitory control. Exercise effects on neuroelectric activity (P3 amplitude) varied with baseline CORT. Conclusions: This study is among the first to investigate the biological underpinnings of acute exercise-induced changes in cognition in children using molecular, behavioral, neuroelectric, and academic achievement measures. Findings implicate sAA-indexed sympathetic activity as a candidate mechanism through which acute exercise may support specific aspects of inhibitory control in children, reflected behaviorally as more consistent responding on trials requiring the upregulation of inhibitory control. These findings also suggest that individual differences in baseline HPA axis activity moderate exercise effects on neural markers of attentional inhibition.