Perfusion fMRI of Cue-Induced Nicotine Craving

描述(由申请人提供)： 这个为期五年的培训项目是宾夕法尼亚大学TRC的博士后特蕾莎·R·富兰克林(Teresa R.Franklin)博士将走的道路，她将成为一名拥有脑成像和药物滥用研究专长的独立调查员。这一建议的基础是她的行为神经学背景，在那里她研究了对与药物相关的环境线索的条件反应。该提案概述了她发展和开始完全独立的职业生涯所需的培训和研究经验，使用一种新的成像技术--灌注功能磁共振成像--来表征线索诱导的尼古丁渴求背后的中枢神经系统结构。为了让富兰克林博士做好担任独立调查员的准备，需要一个广泛的培训计划，因为她涉及到几个新的研究领域。富兰克林博士将参与人类伦理学、生物统计学和功能磁共振成像方面的持续结构化教学。她将出席并在国际、国家、大学和中心范围的研讨会、论坛和会议上发言；她将接受在收集和分析灌注功能磁共振数据方面的实践指导培训。候选人将得到一个指导团队和顾问委员会的支持，他们在以下领域具有专业知识：临床药物滥用研究(奇尔德里斯，奥布莱恩)、尼古丁依赖的神经生物学(莱尔曼)、线索诱导的药物渴求(奇尔德里斯，奥布莱恩)、生物统计学、功能磁共振成像和分析技术(Listerud)和灌注功能磁共振(Listerud)。富兰克林博士将使用动脉自旋标记(ASL)灌注功能磁共振技术重点研究训练期间线索诱导的尼古丁渴求现象。这项技术将被用来确定区域大脑激活(研究1，目标1)和可能的性别差异(研究1，目标2)对吸烟线索的反应。ASL灌注功能磁共振成像非常适合于成像在行为状态中观察到的低频变化，如渴望，随着时间的推移而招募。ASL灌注功能磁共振成像将减少大脑区域的易感性伪影，这些区域在药物依赖中很重要，但很难通过BOLD功能磁共振成像来阐明(例如，腹内侧额前皮质)。在第二项研究中，富兰克林博士将评估一种前景看好的止痛药物--GABA B激动剂巴氯芬对尼古丁暗示的主观和大脑反应的影响。烟草的使用是一个巨大的健康问题，因为它是我国可预防的死亡的头号原因。尽管目前采取了干预措施，但复吸率仍然很高：戒烟后一年的复吸率为80%-95%。因此，对其神经学基础的研究对于指导开发与尼古丁成瘾作斗争的行为和药物疗法至关重要。

DESCRIPTION (provided by applicant): This five year training program is the path that Teresa R. Franklin, Ph.D., a Post-doctoral Fellow at the TRC, University of Pennsylvania, will travel to become an independent investigator with expertise in brain imaging and substance abuse research. The foundation underlying this proposal is her behavioral neuroscience background in which she studied conditioned responses to drug-related environmental cues. The proposal outlines the training and research experience necessary for her to develop and launch a fully independent career using a novel imaging technique, perfusion fMRI, to characterize the CNS structures underlying cue-induced nicotine craving. An extensive training program is required to prepare Dr. Franklin to fill the role of an independent investigator, as several research areas new to her are involved. Dr. Franklin will participate in ongoing structured didactics in human ethics, biostatistics and fMRI. She will attend and present at international- national- university- and center-wide seminars, forums and meetings; and will receive hands-on mentored training in collection and analysis of perfusion fMRI data. The candidate will be supported by a Mentoring team and Advisory board with expertise in areas critical to her proposal; clinical substance abuse research (Childress, O'Brien), neurobiology of nicotine dependence (Lerman), cue-induced drug craving (Childress, O'Brien), biostatistics, fMRI imaging and analysis techniques (Listerud) and perfusion fMRI (Listerud). Dr. Franklin will focus on the phenomenon of cue-induced nicotine craving during her training using arterial spin labeled (ASL) perfusion fMRI. This technique will be used to determine regional brain activation (Study 1, Aim 1) and possible sex differences (Study 1, Aim 2) in response to smoking cues. ASL perfusion fMRI is ideally suited for imaging low frequency changes observed in behavioral states, such as craving, that recruit over time. ASL perfusion fMRI will diminish susceptibility artifact in brain regions that are important in drug dependence but difficult to elucidate with BOLD fMRI (e.g., ventromedial prefrontal cortex). In Study 2, Dr. Franklin will assess the impact of a promising anticraving medication, the GABA B agonist, baclofen, on subjective and brain responses to nicotine cues. Tobacco use is a monumental health concern as it is the number one cause of preventable death in our nation. Despite current interventions, smoking relapse rates remain high: 80-95% at one year post cessation. Thus, research into its neurological underpinnings is critical in guiding the development of behavioral and pharmacological therapies to battle nicotine addiction.