Driving assist systems, which are based on biological information, have been investigated in recent years. In this paper, we measured brain activity during simulated driving using near-infrared spectroscopy. Driving is a complex behavior that requires multiple cognitive elements. Therefore, we conducted two experiments to monitor driving behavior in an unvarying road environment and a road environment including an intersection. In the first experiment, the concentration of oxygenated hemoglobin (oxy-Hb) in the prefrontal cortex changed slightly during driving in an unvarying road environment. However, oxy-Hb in the prefrontal cortex increased significantly in a situation in which the subject was unsettled by unexpected vehicle behavior. In the second experiment, oxy-Hb decreased in the prefrontal cortex during driving that required more in-depth thinking, and this decrease in oxy-Hb was associated with the complexity of thinking. Our results demonstrate that the depth of thinking during driving is responsible for changes in oxy-Hb concentration in the prefrontal cortex.