Functional magnetic resonance imaging studies of cognition require repeated and consistent engagement of the cognitive process under investigation. Activation is generally averaged across trials that are assumed to tax a specific mental operation or state, whereas intraindividual variability in performance between trials is usually considered error variance. A more recent analysis approach postulates that these fluctuations can reflect variation in the very process taxed by the particular trial type. In the present study, participants responded to targets presented randomly in 1 of 4 peripheral locations. By employing a function of reaction time (RT) of individual trials as a linear regressor, brain regions were identified whose activation varied with RT on a trial-by-trial basis. Whole-brain analysis revealed that the anterior cingulate, posterior cingulate, and left angular/superior temporal gyri were more active in trials with faster RT but only when the target location was unpredictable. No such association was seen in trials where the target location was predicted by a central cue. These results suggest a role for the cingulate and angular gyri in the dynamic regulation of attention to unpredictable events. This is in accordance with the function of a default network that is active in the absence of top-down-focused attention and is thought to continuously provide resources for broad and spontaneous information gathering. Exploiting intertrial performance variability may be particularly suitable for capturing such spontaneous and elusive phenomena as stimulus-driven processes of attention.