In this paper, we discuss a neuroimaging experiment that employed a mission-based scenario (MBS) design, a new approach for designing experiments in simulated environments for human subjects . This approach aims to enhance the realism of the Soldier-task-environment interaction by eliminating many of the tightly-scripted elements of a typical laboratory experiment; however, the absence of these elements introduces several challenges for both the experimental design and statistical analysis of the experimental data. Here, we describe an MBS experiment using a simulated, closed-hatch crewstation environment. For each experimental session, two Soldiers participated as a Commander-Driver team to perform six simulated low-threat security patrol missions. We discuss challenges faced while designing and implementing the experiment before addressing analysis approaches appropriate for this type of experimentation. We conclude by highlighting three example transition pathways from MBS experiments to enhanced Army capabilities using a class of neurotechnologies called Brain-Computer Interaction Technologies.