Cognitive function, together with good oculomotor control, eye-hand coordination, and spatial orientation perception, is a critical subsystem that is used by the CNS in the control of vehicles and other complex systems in a high-level integrative function. Evidence from space flight research demonstrates that the function of each of these subsystems is altered by the transitions in gravito-inertial force levels. These neuro-vestibular alterations, unfortunately, correspond to mission phases where physical and cognitive performance are particularly critical for crew safety and mission success. To date, there is only limited operational evidence that these alterations cause functional impacts on mission-critical vehicle (or complex system) control capabilities. However, the true operational risks will be estimable only after the investigators have filled the knowledge gaps and when the investigators can accurately assess integrated performance in off-nominal operational settings.