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Optimal mental workload plays a key role in driving performance. Thus, driver-assisting systems that automatically adapt to a drivers current mental workload via brain–computer interfacing might greatly contribute to traffic safety. To design economic brain computer interfaces that do not compromise driver comfort, it is necessary to identify brain areas that are most sensitive to mental workload changes. In this study, we used functional near-infrared spectroscopy and subjective ratings to measure mental workload in two virtual driving environments with distinct demands. We found that demanding city environments induced both higher subjective workload ratings as well as higher bilateral middle frontal gyrus activation than less demanding country environments. A further analysis with higher spatial resolution revealed a center of activation in the right anterior dorsolateral prefrontal cortex. The area is highly involved in spatial working memory processing. Thus, a main component of drivers’ mental workload in complex surroundings might stem from the fact that large amounts of spatial information about the course of the road as well as other road users has to constantly be upheld, processed and updated. We propose that the right middle frontal gyrus might be a suitable region for the application of powerful small-area brain computer interfaces.