Physiologic studies revealed that neurons in the dopaminergic midbrain of non-human primates encode reward prediction errors. It was furthermore shown that reward prediction errors are adaptively scaled with respect to the range of possible outcomes, enabling sensitive encoding for a large range of reward values. Congruently, neuroimaging studies in humans demonstrated that BOLD-responses in the ventral striatum encode reward prediction errors in similar fashion as dopaminergic midbrain neurons, suggesting that these BOLD-responses may be driven by dopaminergic midbrain activity. However, neuroimaging results are ambiguous with respect to the adaptive scaling of reward prediction errors, leading to the conjecture that under certain circumstances other than dopaminergic midbrain input may drive ventral striatal BOLD-responses. The goal of this study was to substantiate whether BOLD-responses in the ventral striatum rather respond to adaptively scaled reward prediction errors or absolute reward magnitude. In addition, we aimed to identify neuronal structures modulating activity in the ventral striatum. Sixteen healthy participants played a wheel of fortune game, where they could win three differently valued rewards while being scanned. BOLD-responses increased after gaining rewards; this gain was however independent of the absolute reward magnitude. In contrast BOLD-responses upon reward omission decreased with reward magnitude. A psychophysiological interaction analysis identified a cluster in the brainstem in proximity of the dorsal raphe nucleus, a cluster in the lateral orbitofrontal cortex, and a cluster in the rostral cingulate zone. These clusters changed their connectivity with the ventral striatum in relation to the absolute reward magnitude in reward omission trials.

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