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Transcranial Magnetic Stimulation and Tobacco Use Disorder: A Network-Level Approach with Attention to Sex as a Biological Variable

经颅磁刺激和烟草使用障碍：一种网络级方法，关注性别作为生物变量

基本信息

批准号：
10609996
负责人：
Nicole Petersen
金额：
$ 15.46万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-08-15 至 2024-01-31
项目状态：
已结题

项目摘要

ABSTRACT Smoking remains the leading preventable cause of death in the United States and worldwide, causing nearly one in ten deaths worldwide. The majority (70%) of smokers want to quit, yet most are unsuccessful. Therefore, new approaches to help people quit are urgently needed, and may differ in efficacy between men and women, in whom a number of brain differences have been documented. At the receptor level, smoking induces dopamine release in the ventral striatum in men, but the dorsal striatum in women, and is also linked to decreased striatal dopamine D2-type receptor availability in men, and increased midbrain dopamine D2-type receptor availability in women. At the network level, preliminary data from our laboratory has linked the relief of cigarette craving to the extent of coupling between large-scale networks in women, but not men, in whom smoking instead is linked to changes in insula connectivity. This application builds on these recent findings to test the efficacy of a novel potential smoking cessation aid, repetitive transcranial magnetic stimulation (rTMS), a noninvasive brain stimulation technique, with special attention to sex as a biological variable. This includes two complementary objectives: To test the effect of rTMS on clinical features of smoking separately in men and women, and in so doing, provide additional training that will facilitate the transition to independence as a researcher specializing in brain differences in male and female smokers. This will be achieved through two experiments. In the first experiment (K99 phase) male and female smokers will receive rTMS stimulation targeting the dorsolateral prefrontal cortex (dlPFC), supplementary motor area (SMA), posterior parietal cortex (PPC), or sham, and the effect of rTMS to each region on craving, withdrawal, and affect will be evaluated. The best of these targets (i.e., where stimulation produced the greatest decrease in craving, withdrawal, and negative affect) will be selected for Experiment 2 (R00 phase), in which 13 sessions of rTMS will be performed. Craving, withdrawal, affect, cigarettes per day, and level of dependence will be evaluated seven days before, daily throughout, and daily for six weeks following rTMS. Resting state functional connectivity will be evaluated before and after rTMS to provide mechanistic information regarding the basis of rTMS efficacy in male and female smokers. The K99 phase will take place at UCLA with support and training from the director of the Neuromodulation Division, a collaborator on this project, and two other collaborators with expertise in smoking research. This team of collaborators will provide training with respect to rTMS and smoking research. A separate team will provide professional development feedback and guidance in addition to the faculty mentor through quarterly meetings. Together, this approach will achieve the project's specific aims to: 1. Develop expertise in rTMS as a therapeutic intervention; 2. Measure the effect of rTMS targeting the SMA, PPC, and dlPFC on craving, withdrawal, and affect; 3. Measure the effect of rTMS on RSFC with fMRI; and 4. Measure effects of rTMS on subsequent smoking and dependence.

摘要吸烟仍然是美国和世界范围内可预防的主要死因，全世界每十个死亡病例中就有一个大多数吸烟者（70%）想要戒烟，但大多数都不成功。因此，迫切需要新的方法来帮助人们戒烟，并且在男性之间可能存在疗效差异和女性，其中一些大脑差异已被记录在案。在受体水平，吸烟在男性的腹侧纹状体中诱导多巴胺释放，但在女性的背侧纹状体中，降低男性纹状体多巴胺D2型受体的可用性，增加中脑多巴胺D2型受体的可用性。女性的受体可用性。在网络层面，我们实验室的初步数据已经将香烟渴望的程度耦合之间的大规模网络的妇女，但不是男人，在其中而吸烟则与大脑连接的变化有关。该应用程序基于这些最新发现，测试一种新的潜在戒烟辅助手段，重复经颅磁刺激（rTMS），一种非侵入性的脑刺激技术，特别注意性别作为一个生物变量。这包括两个互补的目标：分别测试rTMS对男性吸烟临床特征的影响，妇女，并在这样做的同时提供额外的培训，以促进过渡到独立，研究人员专门研究男性和女性吸烟者的大脑差异。这将通过两个实验在第一个实验（K99阶段）中，男性和女性吸烟者将接受rTMS刺激针对背外侧前额叶皮层（dlPFC）、辅助运动区（SMA）、后顶叶皮层 (PPC)，或假手术，并将评估rTMS对每个区域对渴望、戒断和影响的影响。的这些目标中最好的（即，在那里，刺激产生了最大的渴望，退缩，负面影响）将被选择用于实验2（R 00阶段），其中将进行13次rTMS。 7天前将评估渴望、戒断、影响、每日吸烟量和依赖程度，在整个过程中每天一次，并且在rTMS之后每天一次，持续六周。将评估静息状态功能连接在rTMS之前和之后，提供关于rTMS在男性中疗效基础的机制信息，女性吸烟者K99阶段将在加州大学洛杉矶分校进行，并得到该中心主任的支持和培训。神经调节部门是该项目的合作者，以及另外两名具有吸烟专业知识的合作者 research.该合作团队将提供rTMS和吸烟研究方面的培训。一除了教师导师外，一个独立的团队将提供专业发展反馈和指导通过季度会议。总之，这种方法将实现该项目的具体目标：1。发展在rTMS作为治疗干预方面的专业知识; 2.测量rTMS靶向SMA、PPC和 dlPFC对渴望，退缩和影响; 3.用fMRI检测rTMS对RSFC的影响; 4.测量 rTMS对随后吸烟和依赖的影响。