Predicting the near future is important for survival and plays a central role in theories of perception, language processing, and learning. Prediction failures may be particularly important for initiating the updating of perceptual and memory systems and, thus, for the subjective experience of events. Here, we asked observers to make predictions about what would happen 5 sec later in a movie of an everyday activity. Those points where prediction was more difficult corresponded with subjective boundaries in the stream of experience. At points of unpredictability, midbrain and striatal regions associated with the phasic release of the neurotransmitter dopamine transiently increased in activity. This activity could provide a global updating signal, cuing other brain systems that a significant new event has begun.