Neuroimaging studies have revealed a number of brain regions that show a reduced blood oxygenation level–dependent (BOLD) signal during externally directed tasks compared with a resting baseline. These regions constitute a network whose operation has become known as the default mode. The source of functional magnetic resonance imaging (fMRI) signal reductions in the default mode during task performance has not been resolved, however. It may be attributable to neuronal effects (neuronal firing), physiological effects (e.g., task vs. rest differences in respiration rate), or even increases in neuronal activity with an atypical blood response. To establish the source of signal decreases in the default mode, we used the calibrated fMRI method to quantify changes in the cerebral metabolic rate of oxygen (CMRO2) and cerebral blood flow (CBF) in those regions that typically show reductions in BOLD signal during a demanding cognitive task. CBF:CMRO2 coupling during task-negative responses were linear, with a coupling constant similar to that in task-positive regions, indicating a neuronal source for signal reductions in multiple brain areas. We also identify, for the first time, two modes of neuronal activity in this network; one in which greater deactivation (characterized by metabolic rate reductions) is associated with more effort and one where it is associated with less effort.