Neuronal basis of persistence

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DESCRIPTION (provided by applicant): Diminished self-control is a major contributor to addiction. In order to develop new treatments, we hope to understand the neural bases of self-control. Here we propose to investigate persistence, a specific type of self-control in which a decision-maker commits to a choice and then has to adhere to it for an extended period of time (here, several seconds, although in theory it could be several years). Persistence mimics the process of abstinence from drug use, and ability to persist has predictive validity for drug addiction and relapse. We will train rhesus monkeys to perform a novel task in which they can reject or accept offers and, if they accept them, must persist in that decision across several seconds to obtain a larger reward. Recent studies suggest that dorsal and ventral portions of the prefrontal cortex contribute to sustaining persistence and succumbing to temptation respectively. We have previously identified a putative control signal in dorsal anterior cingulate (dACC) neurons; these signals are a strong candidate for sustaining persistence. Our more recent studies suggest that ventromedial prefrontal cortex (vmPFC) neurons represent salient offer values, and may thus contribute to temptation processes that lead to persistence failure. Here we propose to record neuronal activity in both dACC and vmPFC to test these ideas directly. In a separate experiment, we will also electrically stimulate the dACC in order to test the hypothesis that stimulation there improves persistence. Successful completion of these studies will yield a basic understanding of the neuroscience of persistence, a critical first step n developing new treatments for addiction and other diseases of self-control.