Enhancing relapse prevention for smoking cessation with rTMS

描述(由申请人提供)：烟草使用是当今最重要的癌症控制和公共卫生挑战之一。五分之一的美国人每天吸烟。一半的吸烟者每年都会尝试戒烟；但95%的吸烟者会在12个月内改变这一决定，选择短暂的、立即有回报的吸烟活动，代价是更大的长期回报，如未来的健康和长寿。该项目旨在提高我们对这些决策过程的科学知识，并改进烟草依赖的治疗。背外侧前额叶皮质(DLPFC)通过将抑制机制与来自边缘区域的情感荷电信息相结合来影响决策，从而对诱人的、立即获得回报的长期代价选项(如吸烟)产生抑制影响。延迟贴现是指一个人对延迟结果的价值降低的程度，例如未来的健康和长寿。越来越多的证据表明，选择回报更高的延迟期权与DLPFC中的活动增加有关。我们认为，在做出戒烟决定后选择吸烟，反映了一种情况，即DLPFC没有被充分激活，无法对立即获得回报的吸烟选择施加抑制影响。初步研究表明，用高频重复经颅磁刺激(RTMS)刺激DLPFC可以减少延迟折扣(即导致个人选择延迟的、价值更高的选项)；减少打算戒烟的吸烟者的香烟消费量；改善执行功能、学习、记忆和注意力；是其他疾病认知行为治疗的一种有前途的辅助手段；并可能提高现有烟草依赖认知行为治疗的有效性。我们的目标是根据可行性的衡量标准，就是否应该对这种干预措施的有效性进行测试提出知情建议1、2。我们将使用双盲、随机的受试者间治疗(积极或虚假)设计，其中所有受试者在rTMS刺激期间暴露于相同的复发预防材料。目标1：使用多个可行性指标(需求、可接受性、实用性、可接受性、实用性)，研究高频rTMS与循证、自助、认知-行为预防复发干预相结合的可行性。 有限的药效测试和充分的致盲)。目的2：研究戒烟后2周、4周、8周和12周，活动状态和假状态下延迟折扣的差异。目的3：使用潜伏期复发比较来计算这种干预对禁欲的影响大小的估计。这项探索性研究将推动一种创新科学思想的早期阶段，这一创新科学思想有可能极大地促进对影响烟草使用和治疗的机制以及生物行为癌症控制研究的许多其他方面的理解。如果最终被发现是有效的，这些发现将对许多功能失调的健康行为的治疗产生影响，在这些行为中，个人很难立即拒绝具有诱惑力的选择，这些选择会带来严重的长期健康后果。

DESCRIPTION (provided by applicant): Tobacco use is one of the most significant cancer control and public health challenges today. One in five Americans smoke daily. Half of all smokers will make an attempt to quit each year; but 95% of those who attempt will reverse this decision within 12 months and choose the transient, immediately rewarding activity of smoking at the cost of larger long-term rewards such as future health and long life. This project seeks to improve our scientific knowledge of these decision-making processes and improve tobacco dependence treatments. The dorsolateral prefrontal cortex (DLPFC) influences decision-making by integrating inhibitory mechanisms with emotionally charged information from limbic regions, thereby exerting an inhibitory influence on seductive, immediately rewarding options with long term costs, such as smoking. Delay discounting is the degree to which one de-values delayed outcomes, such as future health and long life. Converging evidence indicates that choosing a delayed option with a larger reward is associated with increased activity in the DLPFC. We propose that choosing to smoke after making a decision to quit reflects a situation where the DLPFC is insufficiently activated to exert an inhibitory influence on the immediately rewarding option of smoking. Preliminary studies indicate that stimulation of the DLPFC with high frequency repetitive Transcranial Magnetic Stimulation (rTMS) reduces delay discounting (i.e., causes individuals to choose delayed, higher value options); reduces cigarette consumption in smokers intending to quit; improves executive function, learning, memory, and attention; is a promising adjunct to cognitive-behavioral treatment of other disorders; and is likely to improve the efficacy of existing cognitive-behavioral treatments for tobacco dependence. Our goal is to make an informed recommendation, based on measures of feasibility,1,2 of whether or not this intervention should be tested for efficacy. We will use a double-blind, randomized between-subjects treatment (active or sham) design in which all subjects are exposed to the same relapse prevention materials during rTMS stimulation. Aim 1: Examine the feasibility of combining high frequency rTMS with an evidence-based, self-help, cognitive-behavioral relapse prevention intervention using multiple feasibility indicators (demand, acceptability, practicality, limited-efficacy testing, and adequate blinding). Aim 2: Examine differences in delay discounting between the active and the sham conditions 2, 4, 8, and 12 weeks after the quit day. Aim 3: Use latency to relapse comparisons to calculate estimates of the effect size of this intervention on abstinence. This exploratory research will promote the early stages of an innovative scientific idea that has the potential to substantially advance the understanding of mechanisms that affect tobacco use and treatment as well as many other aspects of bio-behavioral cancer control research. If ultimately found to be efficacious, the findings will have an impact on the treatment of many dysfunctional health behaviors where individuals have difficulty refusing immediately seductive choices that have serious long-term health consequences.