Self-control and motivation in addictions

有害饮酒是国际上最紧迫的公共卫生问题之一。在联合王国，酒精滥用占疾病和死亡负担的10%，每年造成超过210亿英镑的损失。尽管如此，这些疾病仍然没有得到很好的治疗，迫切需要开发新的治疗方法。这项建议旨在了解冲动和动机之间的相互作用，这是调节行为的基本过程，也是理解成瘾的风险和复发的关键。冲动或自控是指做出快速、考虑不周的决定或无法停止行动的倾向。冲动有多种类型。这里我关注的是一种特定的形式，即等待冲动，或过早采取行动的倾向。在动物研究中，等待冲动有强有力的证据表明与成瘾有关，但在人类中，人们对此了解较少。我认为，人类的等待冲动包括两个过程：自愿停止和动机。自愿停止涉及到内部停止的决定。动机涉及到奖励的作用，以影响行动或激励行为。我使用一项新的任务和多种创新技术来理解自愿停止和动机之间的关系，以及前额叶皮质脑区和基底节之间的关系。然后，我开发了一种基于这些过程的干预措施，以训练酒精使用障碍的自愿自我控制能力，同时刺激潜在的大脑网络。最后，我将这一结论扩展到人群层面，并询问这些过程以及其他因素如何预测酒精滥用。总而言之，这些研究强调了一个可测试的理论驱动的等待冲动模型，并立即对成瘾进行转化治疗。

Harmful alcohol use is one of the most pressing public health issues internationally. In the United Kingdom, alcohol misuse represents 10% of the burden of disease and death costing in excess of £21 billion per year. Despite this, these disorders remain poorly treated emphasizing the urgent need to develop novel therapeutic approaches. This proposal aims to understand the interaction between impulsivity and motivation, processes fundamental to regulating behavior and crucial to understanding the risk for and relapse in addictions. Impulsivity or self-control is the tendency towards rapid poorly considered decisions or the inability to stop actions. There are multiple types of impulsivity. Here I focus on a specific form known as waiting impulsivity, or the tendency to act too early. Waiting impulsivity has robust evidence in animal studies for an association with addictions, and is less well understood in humans. I propose that waiting impulsivity in humans involves two processes: voluntary stopping and motivation. Voluntary stopping involves the internal decision to stop. Motivation involves the role of rewards to influence actions or energize behavior. I use a novel task and multiple innovative techniques to understand this relationship between voluntary stopping and motivation and the relationship between prefrontal cortical brain regions and the basal ganglia. I then develop an intervention based on these processes to train voluntary self-control in alcohol use disorders paired with stimulation of the underlying brain network. Finally I extend this to a population level and ask how these processes along with other factors predict alcohol misuse. Together these studies emphasize a testable theory-driven model of waiting impulsivity with immediate translational treatment for addictions.