Lifetime Physical Activity Moderates the Neural Effects of Childhood Adversity on Resting-State Functional Connectivity

Abstract

Background: Adverse childhood experiences (ACEs) represent a strong influence on the developing brain and profoundly affect corticolimbic circuits, thereby contributing to vulnerability for mental disorders. Individual differences in resilience-related behavior, such as physical activity, may mitigate these effects. Methods: This retrospective study examined whether self-reported lifetime physical activity (LPA) modulates the relationship between ACEs and resting-state functional connectivity (rs-FC) of key limbic regions among 75 adults (mean age = 31.8 years, 82.7% female). Interaction models (ACE × LPA) were constructed for seed-to-voxel analyses, using the amygdala, hippocampus, and anterior cingulate cortex as seeds. Significant clusters were extracted and subjected to moderation analyses, and the Johnson-Neyman technique was used to determine sample-specific LPA ranges where the association between ACEs and connectivity became statistically significant. Results: Significant ACE × LPA interactions were observed across all 3 seed regions, with robust clusters located in subcortical-cerebellar, visual association, and motor networks. Across clusters, greater ACE exposure was associated with reduced connectivity at lower LPA levels but increased connectivity at high levels, indicating a crossover moderation pattern. The Johnson-Neyman technique identified LPA ranges (∼150–390 min/wk) where ACE effects on connectivity were statistically significant. Conclusions: LPA moderated the association between ACEs and rs-FC within emotion- and sensorimotor-related networks. Higher activity levels were linked to connectivity profiles consistent with potential neural resilience to early adversity. These findings highlight physical activity as a modifiable lifestyle factor associated with neurobiological adaptation following early adversity.