Translational approaches to TMS treatment development for smoking

项目摘要/摘要 在美国，吸烟是每年导致死亡和发病的主要可预防原因 造成约443,000人死亡。吸烟和高复发率可能是由于以下因素造成的 影响大脑的边缘和执行回路，包括对与吸烟有关的显著线索和 认知控制的丧失。越来越多的证据表明，在上瘾时，额叶-纹状体环路涉及 边缘奖赏和冲动行为是相对活跃的，而执行控制电路是 相对不活跃的。因此，干预努力应针对以下两个方面：要么减少 脉冲奖励电路或增加执行控制电路的相对活跃度。经颅 磁刺激(TMS)是FDA批准的一种非侵入性治疗抑郁症的方法，目前 作为一种可能的戒烟治疗方法进行了调查。这个项目的目标是使用小说theta 突发刺激(TBS)方案诱导脉冲和执行力持续下降和上升 分别为控制电路。为此，我们将在前额前腹内侧应用一种衰减形式的TBS 大脑皮质靶向脉冲奖赏回路，TBS增强形式作用于背外侧前额叶皮质 瞄准执行控制电路。然后，我们将研究这些方案在减少 一系列吸烟措施，包括香烟估价、延迟折扣、香烟自我管理和 大脑对吸烟提示的反应。这些调查的结果将为 系统地发展基于神经回路的策略，作为烟草使用和依赖的治疗方法。

PROJECT SUMMARY/ABSTRACT Smoking is the leading preventable cause of mortality and morbidity in the United States, each year contributing to approximately 443,000 deaths. Smoking and high relapse rates are likely due to factors that affect both limbic and executive circuits in the brain, including vulnerability to salient smoking-related cues and loss of cognitive control. Accumulating evidence indicates that in addiction, the frontal-striatal circuits involved in limbic reward and impulsive action are relatively hyperactive, while the executive control circuits are relatively hypoactive. Thus, intervention efforts should be directed at either decreasing the relative activity of the impulsive reward circuit or increasing the relative activity of the executive control circuits. Transcranial magnetic stimulation (TMS) is a non-invasive, FDA-approved treatment for depression which is also being investigated for as a possible treatment for smoking cessation. The goal of this project is to use the novel theta burst stimulation (TBS) protocol to induce sustainable decreases and increases in the impulsive and executive control circuits, respectively. To do so, we will apply an attenuating form of TBS to the ventromedial prefrontal cortex to target the impulsive reward circuit and a potentiating form of TBS to the dorsolateral prefrontal cortex to target the executive control circuit. We will then investigate the efficacy of these protocols for reducing a range of smoking measures, including cigarette valuation, delay discounting, cigarette self-administration, and brain reactivity to smoking cues. The results from these investigations will pave a clear pathway for the systematic development of neural-circuit based strategies as treatments for tobacco use and dependence.