The relations among early cumulative medical risk, cumulative environmental risk, attentional control, and brain activation were assessed in 15-16-year-old adolescents who were born preterm. Functional magnetic resonance imaging found frontal, temporal, and parietal cortex activation during an attention task with greater activation of the left superior-temporal and left supramarginal gyri associated with better performance. Individual differences in early cumulative risk are related to patterns of brain activation such that medical risk is related to left parietal cortex activation and environmental risk is related to temporal lobe activation. The findings suggest that early risk is related to less mature patterns of brain activation, including reduced efficiency of processing and responding to stimuli.