Studies by cognitive psychologists, psychophysicists, neuroscientists, and economists provide ample evidence that humans use prior knowledge to bias decisions adaptively. In this study, we sought to locate and investigate the brain areas mediating this behavior. Participants viewed ambiguous abstract shapes and decided whether a shape was of Category A (smoother) or B (bumpier). The decision was made in the context of one of two prior knowledge cues, 80/20 and 50/50. The 80/20 cue indicated that upcoming shapes had an 80% probability of being of one category, for example, B, and a 20% probability of being of the other. The 50/50 cue indicated that upcoming shapes had an equal probability of being of either category. The shift in bias produced by the 80/20 cue relative to the 50/50 cue was of the predicted sign for every subject but varied in magnitude. We searched for brain regions in which activity changes correlated with the extent of the bias shift; these were dorsolateral pFC (middle frontal gyrus), inferior frontal junction, anterior insula, inferior parietal lobule, intraparietal sulcus, head of the caudate, posterior cingulate cortex, and fusiform gyrus. The findings indicate that an individual's brain activity in these regions reflects the extent to which that individual makes use of prior knowledge to bias decisions. We also created within-ROI tuning curves by binning the shape curvature levels and plotting brain activity levels at each of the nine bins. In the fronto-parietal and anterior insula ROIs, the tuning curves peaked at targets contraindicated by the prior knowledge cue (e.g., Category B targets if the 80/20 cue meant 20% probability B). The increased activity in these regions likely indicates a no-go response when sufficient perceptual evidence favored the alternative contraindicated by the 80/20 cue.