Perfusion fMRI of Cue-Induced Nicotine Craving

描述（由申请人提供）： 这个为期五年的培训计划是特雷莎R。富兰克林博士，宾夕法尼亚大学TRC的博士后研究员，将前往成为一名独立的研究员，在脑成像和药物滥用研究方面具有专业知识。这一提议的基础是她的行为神经科学背景，她研究了与药物相关的环境线索的条件反应。该提案概述了必要的培训和研究经验，她开发和启动一个完全独立的职业生涯使用一种新的成像技术，灌注功能磁共振成像，表征中枢神经系统结构的线索诱导尼古丁的渴望。一个广泛的培训计划是需要准备博士富兰克林，以填补一个独立的调查员的作用，因为几个新的研究领域，她参与。富兰克林将参加正在进行的人类伦理学，生物统计学和功能磁共振成像结构教学。她将参加并出席国际-国家-大学-和中心范围的研讨会，论坛和会议;并将接受灌注功能磁共振成像数据收集和分析的实践指导培训。候选人将得到导师团队和顾问委员会的支持，他们在对她的提议至关重要的领域具有专业知识;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（Lerman），线索诱导的药物渴望（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（李斯特）和灌注功能磁共振成像（李斯特）。富兰克林博士将在她的训练过程中使用动脉自旋标记（ASL）灌注功能磁共振成像，重点研究线索诱导的尼古丁渴望现象。这项技术将用于确定区域大脑激活（研究1，目标1）和可能的性别差异（研究1，目标2）在响应吸烟线索。ASL灌注功能磁共振成像是理想的适合成像低频变化观察到的行为状态，如渴望，招募随着时间的推移。ASL灌注fMRI将减少在药物依赖中重要但难以用BOLD fMRI阐明的脑区域中的敏感性伪影（例如，腹内侧前额叶皮质）。在研究2中，富兰克林博士将评估一种有前途的抗癫痫药物--GABA B激动剂巴氯芬--对尼古丁线索的主观和大脑反应的影响。烟草使用是一个巨大的健康问题，因为它是我们国家可预防死亡的头号原因。尽管目前采取了干预措施，但吸烟复吸率仍然很高：戒烟后一年复吸率为80-95%。因此，对其神经基础的研究对于指导行为和药理学疗法的发展以对抗尼古丁成瘾至关重要。

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.