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When we make decisions, the benefits of an option often need to be weighed against accompanying costs. Little is known, however, about the neural systems underlying such cost-benefit computations. Using functional magnetic resonance imaging and choice modeling, we show that decision making based on cost-benefit comparison can be explained as a stochastic accumulation of costbenefit difference. Model-driven functional MRI shows that ventromedial and left dorsolateral prefrontal cortex compare costs and benefits by computing the difference between neural signatures of anticipated benefits and costs from the ventral striatum and amygdala, respectively. Moreover, changes in blood oxygen level dependent (BOLD) signal in the bilateral middle intraparietal sulcus reflect the accumulation of the difference signal from ventromedial prefrontal cortex. In sum, we show that a neurophysiological mechanism previously established for perceptual decision making, that is, the difference-based accumulation of evidence, is fundamental also in value-based decisions. The brain, thus, weighs costs against benefits by combining neural benefit and cost signals into a single, differencebased neural representation of net value, which is accumulated over time until the individual decides to accept or reject an option.hen we make decisions, the benefits of a decision option often need to be weighed against accompanying costs. Cost-benefit integration, thus, is an important aspect of decision making. However, value-based decision making is typically investigated in the context of decision uncertainty (1-3), so little is known about the neural mechanisms underlying the integration of costs and benefits as such.Cost-benefit-based decision making involves the binary decision to either accept or reject a choice option based on two competing attributes-the option's expected rewards and losses. Such binary accept-versus-reject decisions bear a strong resemblance to twoalternative choices in perceptual decision making (4, 5). For example, when monkeys performed a direction-of-motion discrimination task in which they had to decide whether a noisy field of dots was moving in one direction or its opposite direction (e.g., leftward or rightward) and indicated their choice with a quick eye movement to the target on the respective side, motion-sensitive neurons in middle temporal visual area MT either respond to leftward motion or to rightward motion. Prefrontal and parietal neurons, in contrast, form a decision by accumulating the difference in the activities of populations of neurons in area MT that code for opposite directions of motion. The monkey's saccade response is faster when more dots are moving in one direction, and this effect is predicted by the strength of the accumulated neuronal difference signal (6). A difference-based decision mechanism has also been identified in the human dorsolateral prefrontal cortex (DLPFC) during perceptual face-house decisions (4, 7). Thus, we hypothesized that cost-benefit decisions involve an analogous decisio...

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Recent studies suggest an association of dopamine D2 receptor (DRD2) availability with flexibility in reward-based learning. We extend these results by demonstrating an association of genetically based differences in DRD2 density with the ability to intentionally switch between nonrewarded tasks: noncarriers of the A1 allele of the DRD2/ANKK1-TaqIa polymorphism, associated with higher DRD2 density, show increased task-switching costs, increased prefrontal switching activity in the inferior frontal junction area, and increased functional connectivity in dorsal frontostriatal circuits, relative to A1 allele carriers. A DRD2 haplotype analysis in the same sample confirmed these results, indicating an association between high D2 density and increased task-switching effort. Our results provide evidence that converges with that from association studies relating increased D2 density to deficits in cognitive flexibility in schizophrenia. We suggest that individual differences in striatal D2 signaling in healthy humans modulate goal-directed gating to prefrontal cortex, thus leading to individual differences in switching intentionally to newly relevant behaviors.