Inattentional deafness is the failure to hear otherwise audible sounds (usually alarms) that may occur under high workload conditions. One potential cause for its occurrence could be an attentional bottleneck that occurs when task demands are high, resulting in lack of resources for processing of additional tasks. In this fMRI experiment, we explore the brain regions active during the occurrence of inattentional deafness using a difficult perceptual-motor task in which the participants fly through a simulated Red Bull air race course and at the same time push a button on the joystick to the presence of audio alarms. Participants were instructed to focus on the difficult piloting task and to press the button on the joystick quickly when they noticed an audio alarm. The fMRI results revealed that audio misses relative to hits had significantly greater activity in the right inferior frontal gyrus IFG and the superior medial frontal cortex. Consistent with an attentional bottleneck, activity in these regions was also present for poor flying performance (contrast of gates missed versus gates passed for the flying task). A psychophysiological interaction analysis from the IFG identified reduced effective connectivity to auditory processing regions in the right superior temporal gyrus for missed audio alarms relative to audio alarms that were heard. This study identifies a neural signature of inattentional deafness in an ecologically valid situation by directly measuring differences in brain activity and effective connectivity between audio alarms that were not heard compared to those that were heard.