Neuronal basis of persistence

描述(由申请者提供)：自控力减弱是上瘾的主要原因。为了开发新的治疗方法，我们希望了解自我控制的神经基础。在这里，我们建议研究持久性，这是一种特定类型的自我控制，在这种情况下，决策者承诺做出选择，然后必须在很长一段时间内(这里是几秒钟，尽管理论上可能是几年)坚持下去。坚持模拟戒毒的过程，坚持的能力对药物成瘾和复发具有预测有效性。我们将训练恒河猴执行一项新的任务，在这项任务中，它们可以拒绝或接受提议，如果它们接受了，它们必须在几秒钟内坚持这个决定，以获得更大的奖励。最近的研究表明，前额叶皮质的背侧和腹侧部分分别有助于维持持久性和屈服于诱惑。我们以前已经在背侧前扣带回(DACC)神经元中发现了一个假定的控制信号；这些信号是维持持续性的有力候选者。我们最近的研究表明，腹内侧前额叶皮质(VmPFC)神经元代表着显著的提供值，因此可能参与了导致持续性失败的诱惑过程。在这里，我们建议记录dACC和vmPFC的神经元活动，以直接测试这些想法。在另一个单独的实验中，我们还将对dACC进行电刺激，以测试刺激那里可以提高持久性的假设。这些研究的成功完成将使人们对坚持的神经科学有一个基本的了解，这是开发成瘾和其他自我控制疾病的新疗法的关键第一步。

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.