Positron emission tomography was used to identify brain regions that showed general increase or decrease in regional cerebral blood flow (rCBF) across time that was task-independent. Twelve male subjects were scanned eight times: the first and last scans were taken while subjects performed a baseline fixation task and the middle six scans were taken while subjects performed a visuomotor activation task. To determine whether there was a consistency across different studies in the regions that showed this time-related change in rCBF two additional datasets were analyzed. There were similarities across all three studies in the regions that showed a monotonic task-independent change in activity. In all three studies there was a general bilateral decrease in rCBF of occipital and temporal areas across scans that might be related to habituation in the visual domain. Increases in rCBF were found in anterior cingulate, postcentral gyrus, and precentral gyrus across studies. It is likely that these changes reflect motor learning and motor program retrieval. This implies that, unless the experimenter controls for time-dependent changes in brain activity, the interpretation of task-related changes in rCBF may be confounded by these monotonic changes in rCBF. We present analytic strategies to identify experimental effects that are independent of nonspecific time effects, which can be used when it is not possible to control these effects through counterbalancing the experimental design. Nonspecific confounds are particularly relevant in functional MRI studies in which the number of scans acquired per study is much larger.