CHANGING THOUGHT AND ACTION IN TOBACCO DEPENDENCE WITH TMS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 了解烟草依赖的大脑机制是降低与当前行为计划和戒烟药物治疗相关的高复发率的重要一步。 该提案旨在确定重复经颅磁刺激（rTMS）治疗烟草依赖的有效性，安全性和耐受性。 烟草依赖是一个严重的公共卫生问题，吸烟者在治疗后表现出大量复发。 这个提议的核心概念是，“戒烟”需要有意识地选择不吸烟（以延迟满足），这种选择受到额顶叶系统和边缘系统之间活动平衡的影响，额顶叶系统处理奖励的价值，边缘系统有利于导致立即满足的驱动状态。目标1将确定不同水平的皮层兴奋，诱导不同的rTMS频率，影响奖励的选择，以及它们如何改变香烟消费。 此外，目标2将确定由于急性尼古丁戒断引起的边缘系统激活如何改变目标1中的这些效应。 20名非吸烟受试者和20名主动吸烟者将接受两种水平的高频rTMS和类似的假刺激（我们使用头皮电刺激开发的方法），在左前额叶皮层上传递。吸烟者还将在尼古丁饱和和戒断条件之间进行交叉，以确定rTMS如何改变与戒断相关的边缘系统激活。 这个项目的初级研究员，克莉丝汀谢弗博士，是烟草依赖循证治疗项目开发和实施各个方面的专家，她在之前的工作中与Warren Bickel一起担任NIH资助的共同研究者，对该提案的认知方面有直接经验。 Sheffer博士代表了与UAMS公共卫生学院的新联系，并将她在流行病学研究方面的经验带到了CTN。 该项目将通过让Sheffer博士建立在成瘾前额叶皮层电生理活动的早期训练基础上，在Sheffer博士的工作中进行转化研究。该项目还有望引发分子核心的平行研究，例如在啮齿动物中检查高强度rTMS后的基因表达，以及在动物电生理学核心中检查rTMS后自发皮层振荡的幅度和频率。 Sheffer博士的总体目标是获得足够的数据，以赢得NIH的第一个R 01。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Understanding the brain mechanisms involved in tobacco dependence is an important step toward reducing the high rate of relapse associated with current behavioral programs and phamacological treatments for smoking cessation. This proposal seeks to define the efficacy, safety and tolerability of repetitive Transcranial Magnetic Stimulation (rTMS) for treating tobacco dependence. Tobacco dependence is a serious public health problem and cigarette smokers exhibit substantial relapse following treatment. A concept central to this proposal is that "quitting" necessitates a conscious choice not to smoke (to delay gratification) and this choice is influenced by the balance of activity between fronto-parietal systems that process the value of rewards and limbic systems that favor drive states leading to immediate gratification. Aim 1 will determine how different levels of cortical excitation, induced by different rTMS frequencies, influence reward choices and how they alter cigarette consumption. Additionally, Aim 2 will determine how limbic activation due to acute nicotine withdrawal modifies these effects in aim 1. Twenty 20 non-smoking subjects and 20 active smokers will receive two levels of high frequency rTMS and comparable sham stimulation (method we developed using electrical scalp stimulation) delivered over left prefrontal cortex. Smokers will also crossover between nicotine satiation and withdrawal conditions to determine how rTMS can modify limbic activation associated with withdrawal. The Junior investigator of this project, Christine Sheffer, Ph.D., is an expert in all aspects of the development and implementation of evidence-based treatment programs for tobacco dependence and she has direct experience with the cognitive aspects of this proposal in prior work as a co-investigator on an NIH grant with Warren Bickel. Dr. Sheffer represents a new link with the UAMS College of Public Health and brings her experience in epidemiological research to the CTN. This project will instigate a translational research effort in Dr. Sheffer's work by allowing her to build on earlier training in the electrophysiological activity of the prefrontal cortex in addiction. This project is also expected to spark parallel investigations in the Molecular Core such as examining gene expression following high intensity rTMS in rodents and work in the Animal Electrophysiology Core examining the amplitude and frequency of spontaneous cortical oscillations following rTMS. The overall goal is for Dr Sheffer to gain data sufficient for winning her first R01 from the NIH.