Using combined EEG and non-invasive brain stimulation to examine and improve reward functioning in opioid use disorder

项目摘要 认知控制似乎是阿片类药物使用中最一致和最严重的影响功能之一 阿片类药物使用者的治疗中断和药物复发的风险更高。虽然治疗 针对OUD的项目通常侧重于停止物质使用，现在有了坚实的治疗基础 考虑认知控制困难的计划，以提供更多的神经认知针对性支持， 寻求治疗OUD的人。我们的长期目标是改善OUD的认知控制功能， 目标是提高阿片类药物使用者在治疗和维持戒断方面的成功率， 生活改变了主要的科学前提是，认知控制功能可以通过以下方式改善OUD 用一种非侵入性的脑刺激方法来调节前扣带皮层（ACC）的活动， 机器人辅助经颅磁刺激（TMS）。这一前提是建立在强大的 经验和理论支持，以及申请人最近的研究结果。首先，ACC是一个 与认知控制有关的中枢脑区，与多种精神疾病有关，包括 物质使用障碍在人类中，ACC的奖励处理功能可以使用 与事件相关的大脑电位称为奖励积极性，许多奖励积极性研究 研究表明，物质滥用者，无论药物类型，表现出异常的ACC活动的奖励。 重要的是，TMS被传递到左背外侧前额叶皮层已被证明可以增强神经元活动 我们最近证明，经颅磁刺激可以调节戒断者奖励积极性的幅度， 吸烟者，支持TMS作为治疗物质使用障碍的工具的效用。基于这一经验 支持，本申请的总体目标是检查和改善OUD的认知控制功能。 提出这项研究的理由是，将EEG与TMS结合起来提供了前所未有的机会。 系统地研究了OUD中ACC的奖赏功能，以及TMS在调节OUD中的潜在作用。 由ACC分配给OUD中目标导向行为的奖励值水平。这一假设将得到检验 实现两个具体目标。因为奖励积极性还没有在OUD人群中进行过研究， 我们的第一个目标是使用奖励积极性作为评估阿片类药物使用者ACC奖励功能的一种手段。 我们的第二个目标是通过经颅磁刺激调节前扣带回的奖赏功能， OUD中ACC的奖励反应，由奖励积极性评估。这种方法是创新的，因为它 将强调ACC功能障碍在OUD中的重要但未得到充分研究的作用，并调整现有的TMS 为OUD提供一种新的治疗技术。鉴于美国正处于OUD流行之中， 这里获得的实证研究结果将强调继续研究TMS在以下方面的效用的必要性： 对这种疾病的理解和治疗。

Project Summary Cognitive control appears to be one of the most consistently and severely affected functions in opioid use disorder (OUD), putting opioid users at higher risk of treatment dropout and drug relapse. While treatment programs for OUD typically focus on the cessation of substance use, there is now a firm basis for treatment programs to consider cognitive control difficulties in order to provide more neurocognitive targeted support for people seeking treatment for OUD. Our long-term goal is to improve cognitive control functioning in OUD with the aim to increase opioid users' success in treatment and maintaining abstinence, as well as achieving broader life changes. The main scientific premise is that cognitive control functioning may be improved in OUD by modulating the activity of the anterior cingulate cortex (ACC) with a non-invasive brain stimulation method called robot-assisted transcranial magnetic stimulation (TMS). This premise has been formulated on the basis of strong empirical and theoretical support, as well as recent findings produced by the applicant. Foremost, the ACC is a brain area centrally concerned with cognitive control and implicated in a variety of psychiatric disorders, including substance use disorders. In humans, the reward processing function of the ACC can be investigated using an event-related brain potential called the reward positivity, and numerous reward positivity studies have demonstrated that substance abusers, regardless of drug type, exhibit abnormal ACC activity to rewards. Importantly, TMS delivered to the left dorsal lateral prefrontal cortex has been shown to enhance neuronal activity in the ACC. We recently demonstrated that TMS can modulate the amplitude of the reward positivity in abstinent smokers, bolstering the utility of TMS as a tool to treat substance use disorders. Building on this empirical support, the overall objective in this application is to examine and improve cognitive control functioning in OUD. The rationale for the proposed research is that combining EEG with TMS provides an unprecedented opportunity for the systematic examination of the ACC reward function in OUD, and the potential role of TMS in modulating the level of reward value assigned by the ACC to goal-directed behaviors in OUD. This hypothesis will be tested by pursuing two specific aims. Because the reward positivity has not yet been investigated in an OUD population, our first aim is to use the reward positivity as a means to evaluate the reward function of the ACC in opioid users. Our second aim is to modulate the ACC reward function through the frontal-cingulate circuit via TMS to enhance the reward response by ACC in OUD, as evaluated by reward positivity. The approach is innovative because it would highlight an important yet under-investigated role of ACC dysfunction in OUD, and adapt an existing TMS technique to provide a novel treatment for OUD. Given that the US is in the midst of an OUD epidemic, the empirical findings obtained here would underscore such a need for continued research of the utility of TMS in the understanding and treatment of this disorder.