Following damage to specific sectors of the prefrontal cortex, humans develop a defect in real-life decision making, in spite of otherwise normal intellectual performance. The patients so affected may even realize the consequences of their actions but fail to act accordingly, thus appearing oblivious to the future. The neural basis of this defect has resisted explanation. Here we identify a physiological correlate for the defect and discuss its possible significance. We measured the skin conductance responses (SCRs) of 7 patients with prefrontal damage, and 12 normal controls, during the performance of a novel task, a card game that simulates real-life decision making in the way it factors uncertainty, rewards, and penalties. Both patients and controls generated SCRs after selecting cards that were followed by penalties or by reward. However, after a number of trials, controls also began to generate SCRs prior to their selection of a card, while they pondered from which deck to choose, but no patients showed such anticipatory SCRs. The absence of anticipatory SCRs in patients with prefrontal damage is a correlate of their insensitivity to future outcomes. It is compatible with the idea that these patients fail to activate biasing signals that would serve as value markers in the distinction between choices with good or bad future outcomes; that these signals also participate in the enhancement of attention and working memory relative to representations pertinent to the decision process; and that the signals hail from the bioregulatory machinery that sustains somatic homeostasis and can be expressed in emotion and feeling.