Abstract
<jats:p>Introduction: While recent scientific evidence has established a robust link between physical activity and cognitive indicators in children, the specific neurophysiological mechanisms underlying this relationship remain a "black box." Objective: To provide a comprehensive overview of recent evidence regarding the neurophysiological and structural mechanisms mediating the relationship between physical activity practice and cognitive indicators in youths aged 6 to 18. Method: A systematic search of articles published between 2017, and March 2025 was conducted in Scopus, WOS, PubMed, and ERIC databases. Following PRISMA guidelines, and after a blinded peer screening process managed via Rayyan, 26 studies of high methodological quality were included. Results: Findings are categorized into three interconnected pathways: 1) Molecular: Peripheral BDNF exhibits heterogeneous responses, appearing to be dependent on specific exercise intensities and genetic profiles. 2) Functional: Vigorous and coordinative PA enhances prefrontal oxygenation and neural signal efficiency (P300), thereby facilitating inhibitory control. 3) Structural: A restorative effect is notably observed in children with overweight/obesity, where exercise promotes the remodeling of white matter integrity previously compromised by adiposity-related inflammation. Conclusions: The enhancement of cognitive indicators is not driven by a single mechanism, but by a synergistic interplay of neurophysiological adaptations, network efficiency, and morphological changes. These findings suggest a change in thinking towards personalized PA prescription, where cognitive demand and individual variability are key determinants of neurophysiological responses.</jats:p>