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To explore the association of both findings, we investigated 16 unmedicated pathological gamblers using an fMRI paradigm that included two different tasks: the evaluation of personal relevance and a reward task that served as a functional localizer. Pathological gamblers revealed diminished deactivation during monetary loss events in some of our core reward regions, the left nucleus accumbens and the left putamen. Moreover, while pathological gamblers viewed stimuli of high personal relevance, we found decreased neuronal activity in all of our core reward regions, including the bilateral nucleus accumbens and the left ventral putamen cortex as compared to healthy controls. We demonstrated for the first time altered neuronal activity in reward circuitry during personal relevance in pathological gamblers. Our findings may provide new insights into the neurobiological basis of pathological gamblers' preoccupation by gambling. 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