CHANGING THOUGHT AND ACTION IN TOBACCO DEPENDENCE WITH TMS

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 了解与烟草依赖有关的大脑机制是降低与当前行为程序和戒烟药物治疗相关的高复发率的重要一步。本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，吸烟者在接受治疗后表现出大量复发。这一提议的核心概念是，“戒烟”需要有意识地选择不吸烟(以延迟满足感)，而这一选择受到额顶系统和边缘系统之间活动平衡的影响，额顶系统处理奖励的价值，边缘系统倾向于导致即时满足感的驱动力状态。目标1将确定由不同rTMS频率诱导的不同水平的皮质兴奋如何影响奖励选择，以及它们如何改变香烟消费。此外，目标2将确定急性尼古丁戒断引起的边缘激活如何改变目标1的这些影响。20名不吸烟的受试者和20名活跃的吸烟者将接受两种水平的高频rTMS和类似的假刺激(我们开发的方法使用头皮电刺激)，通过左侧前额皮质传递。吸烟者还将在尼古丁饱和和戒断条件之间交叉，以确定rTMS如何改变与戒断相关的边缘激活。该项目的初级研究员Christine Sheffer博士是烟草依赖循证治疗计划开发和实施的所有方面的专家，她在与Warren Bickel一起担任NIH拨款的联合调查员之前的工作中，对这项建议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。该项目将在谢弗博士的工作中推动一项转化性研究工作，让她能够在上瘾时对前额叶皮质电生理活动的早期训练的基础上再接再厉。该项目还有望引发在分子核心领域的平行研究，例如检查高强度rTMS后啮齿类动物的基因表达，以及在动物电生理学核心研究rTMS后皮质自发振荡的幅度和频率。谢弗博士的总体目标是获得足够的数据，以从NIH获得她的第一个R01。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. 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.