Developing rTMS as a Potential Treatment for Nicotine Addiction

描述(申请人提供)：在美国，吸烟会导致严重的发病率和死亡率。戒烟很难，吸烟者平均会尝试戒烟五次，才能永久成功。此外，大多数戒烟尝试都会导致复发。大脑刺激戒烟是一个令人兴奋的新领域，它建立在关于成瘾的功能神经回路的神经科学知识的基础上。皮质刺激现在可以通过经颅磁刺激(TMS)进行非侵入性刺激。一些研究表明，TMS可以减少吸烟者对暗示的渴望。我们团队之前的研究表明，与假TMS相比，在左侧背侧前额叶皮质(可能参与抑制渴望的区域)100%运动阈值下进行15分钟高频(10赫兹)重复TMS(RTMS)可以减少线索诱导的渴望。然而，围绕这些初步发现的方法学问题限制了关于TMS在更长一段时间内有效性的明确结论。这一R21方案将整合更严格的实验条件、真正的双盲方法、MRI引导的刺激部位和更长期的随访评估。使用严格的双掩蔽方法和MRI引导的刺激部位，我们建议使用活动的rTMS或假的rTMS，以确定在两周的时间内10次高频rTMS是否可以减少线索诱导的渴望和吸烟者的香烟消费。该项目还将优化合理的rTMS参数，使TMS成为治疗尼古丁依赖的有效药物。在两年的项目中，我们计划招募42名寻求治疗的尼古丁依赖型香烟吸烟者，包括年龄在18岁至60岁之间的所有种族和种族的男性和女性参与这项研究。42名参与者将被随机分配到接受活动的额叶TMS或假的额叶TMS。来自R21的数据将提供所需的信息，以启动对TMS在戒烟方面的潜在临床应用的明确的更大规模的研究。由此产生的结果是 Pilot还可能提供有关皮质刺激对 戒烟。

DESCRIPTION (provided by applicant): Cigarette smoking causes significant morbidity and mortality in the United States. Smoking cessation is difficult, with the average smoker attempting to quit five times before permanent success. Moreover, the majority of smoking quit attempts result in relapse. Brain stimulation for smoke cessation is an exciting new area that builds on advancing neuroscience knowledge concerning the functional neurocircuitry of addiction. Cortical stimulation can now be performed non-invasively by transcranial magnetic stimulation (TMS). A few studies have shown that TMS can reduce cue-elicited craving in smokers. Previous research by our group has shown that a single session of 15 minutes high frequency (10 Hz) repetitive TMS (rTMS) at 100% motor threshold over the left dorsal lateral prefrontal cortex (an area that is likely involved in inhibiting craving) can reduce cue-induced craving compared to sham TMS. However, methodological concerns surrounding these preliminary findings limit definitive conclusions about the effectiveness of TMS over a longer period of time. This R21 proposal will integrate more rigorous experimental conditions, a true double-blind methodology, MRI guided stimulation site and a longer-term follow-up assessment. Using rigorous double-masked methods and MRI guided stimulation site, we propose that using active rTMS or sham rTMS, to determine whether 10 sessions over a two week period consisting of 15 minute high frequency rTMS can reduce cue-induced craving and cigarette consumption for cigarette smokers. The project will also optimize rational rTMS parameters to make TMS to an efficacious treatment for nicotine dependence. In the two years of project, we plan to recruit 42 treatment-seeking nicotine- dependent cigarette smokers, both males and females of all ethnic and racial groups between the ages of 18 and 60 to participate in the study. The 42 participants will be randomly assigned to receive active prefrontal TMS or sham prefrontal TMS. The data from this R21 will provide the information needed for launching a definitive larger-scale investigation into potential clinical applications of TMS in smoke cessation. The results from this pilot will also likely supply substantial information about the utility of cortical stimulation for smoke cessation.