Background: Physical activity (PA) is said to be beneficial to many bodily functions. However, the effects of PA in the brain are still inadequately known. The authors aimed to uncover possible brain modulation linked with PA. Here, they combine 4 of their studies with monozygotic twins, who were within-pair discordant in PA for a minimum of 1 year. Methods: The authors performed brain imaging, brain electrophysiology, and cardiovascular and body composition assessments, and collected questionnaire-based data. The present synopsis elucidates the differences associated with differing PA history in conditions without genetic variability. They present new structural and electrophysiological results. Participants, healthy, 45 male monozygotic twins (mean age 34.5 [1.5] y) differed in aerobic capacity and fat percentage (P < .001). Results: More active co-twins showed larger gray matter volumes in striatal, prefrontal, and hippocampal regions, and smaller gray matter volumes in the anterior cingulate area than less active co-twins. Functionally, visual and somatosensory automatic change detection processes differed between more and less active co-twins. Conclusions: In monozygotic twins, who differed in their PA history, differences were observed in identifiable anatomic brain locations involved with motor control and memory functions, as well as in electrophysiological measures detecting brain’s automatic processes. Better aerobic capacity may modify brain morphology and sensory function.