The concept of presence is commonly related to whether or not a user feels, acts, and reacts as if he/she were in a real familiar environment when using a virtual reality (VR) application. Understanding the neural correlates of presence may provide a foundation for objective measurements of presence and important constraints for theoretical explanations of presence. Discussions about the neural basis for presence are relatively common, but brain imaging has rarely been applied to investigating this issue. Previous studies have focused on detecting average differences between conditions that correlate with differences in reported presence. In this study we focused on breaks in presence and associated periods of disrupted presence as an important complement to previous work. Specifically, we measured brain activity with functional magnetic resonance imaging (fMRI) during execution of an everyday task in a naturalistic virtual environment (VE). Time periods of disrupted presence were identified by subject reports indicating something strange in the current environment, interpreted as a violation of expectations related to the sense of presence. Disrupted presence was associated with increased activity in the frontopolar cortex (FPC), lateral occipito-temporal cortex (LOTC), the temporal poles (TP), and the posterior superior temporal cortex (pSTC). We relate these areas to integration of key aspects of a presence experience, relating the (changing) situation to management of task and goals (FPC), interpretation of visual input (LOTC), emotional evaluation of the context (TP) and possible interactions (pSTC). Modulation of the activity level in these brain areas is consistent with an interpretation of disrupted presence as a re-evaluation of key aspects of a subjective mental reality, updating the synchronization with the virtual environment as previous predictions fail. Such a subjective mental reality may also be related to a self-centered type of mentalization, providing a link to accounts of presence building on the self.