Translational approaches to TMS treatment development for smoking

项目总结/摘要 吸烟是美国每年可预防的死亡和发病的主要原因 导致了大约44.3万人死亡。吸烟和高复发率可能是由于以下因素， 影响大脑的边缘系统和执行回路，包括对与吸烟有关的明显线索的脆弱性， 失去认知控制。越来越多的证据表明，在成瘾中， 在边缘奖励和冲动行动是相对过度活跃，而执行控制电路是 相对活跃。因此，干预工作应针对减少 脉冲奖励电路或增加执行控制电路的相对活动。经颅 磁刺激（TMS）是一种非侵入性的，FDA批准的抑郁症治疗方法， 作为一种可能的戒烟治疗方法进行研究。这个项目的目标是用小说西塔 突发刺激（TBS）协议，以诱导可持续的减少和增加的冲动和执行 控制电路，分别。为此，我们将对腹内侧前额叶应用衰减形式的TBS 皮层以脉冲奖励回路为目标，背外侧前额叶皮层为TBS的增强形式 瞄准执行控制电路然后，我们将研究这些协议的有效性，以减少 一系列吸烟措施，包括香烟估价、延迟折扣、香烟自我管理，以及 大脑对吸烟线索的反应这些调查的结果将为未来的发展铺平一条明确的道路。 系统开发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.