Neural Mechanisms of Cannabinoid-Impaired Decision-Making in Emerging Adults

项目摘要 这个指导职业发展奖（K 01）将使迈克尔·韦斯利博士实现他的长期 目标是成为一名独立的研究者，从事临床神经科学研究项目， 大麻使用障碍（CUD）在新兴的成年人，这是目前的NIDA资助的优先事项。韦斯利博士是一个新的 肯塔基州（英国）大学医学院助理教授。本报告中提出的活动 该奖项建立在韦斯利博士在神经成像和药物滥用研究方面的背景专业知识基础上， 完成以下短期目标：成为（1）临床药理学和（2） 在新出现的成人CUD人群中进行无创脑刺激研究，并增强/发展他的 (3)负责任地进行研究的知识，（4）科学交流和撰写资助文件的技能， （5）有能力管理一个独立的研究项目。 英国有许多专注于药物滥用研究的教师和项目，是一个理想的环境， 博士韦斯利完成这个奖项。韦斯利博士组建了一个由乔什博士 Lile（Mentor）在英国成功开展了NIH资助的临床药理学研究项目， 乔治（共同导师），谁率先使用非侵入性脑刺激治疗抑郁症。在 此外，Dr. Lumy Sawaki（内部指导员）和Dr. Lon Hays（研究医生）将提供当地安全性 监督和医疗监督，Terry Lojanz博士（外部指导员）将提供指导， 神经影像学数据的高级统计分析。韦斯利博士还将参加一系列正式课程， 实验室交流和研究研讨会/会议，以帮助他实现这个奖项的目标。 拟议的研究项目是基于大麻损害决策过程这一前提 并且这些损害作用导致新生儿成人发生CUD的风险增加。这 研究将结合联合收割机的主要精神活性物质--四氢大麻酚（THC）的急性给药， 大麻成分，高清晰度经颅直流电刺激（HD-tDCS）和神经成像， 使用严格的方法，检查前额叶皮层感兴趣的区域在大麻损伤中的作用。 新生儿的决策。目的1将检验提高内源性PFC活性（实验1）的假设。第一章 将减弱，而降低活性（实验2）将增强，THC对测量的损害作用， 决策和相关的神经认知过程在新兴的成年人。目标2将检验假设 基线任务表现期间的大脑活动和连接与随后的 对THC和HD-tDCS的反应。这个高度创新的项目将提高我们对 参与大麻损害决策的机制，这将为CUD管理和解决 日益严重的公共卫生问题。

PROJECT ABSTRACT This mentored career development award (K01) will enable Dr. Michael Wesley to achieve his long-term goal of becoming an independent investigator with a clinical neuroscience research program examining cannabis use disorder (CUD) in emerging adults, which is a current NIDA funding priority. Dr. Wesley is a new Assistant Professor in the University of Kentucky (UK) College of Medicine. The activities proposed in this award build on Dr. Wesley’s background expertise in neuroimaging and drug abuse research and will allow him to accomplish the following short-term objectives: Become an expert in (1) clinical pharmacology and (2) non-invasive brain stimulation research in an emerging adult population with CUD, and enhance/develop his (3) knowledge of the responsible conduct of research, (4) skills for scientific communication and grant writing, and (5) ability to manage an independent research program. UK has numerous faculty and projects focused on drug abuse research and is an ideal environment for Dr. Wesley to complete this award. Dr. Wesley has assembled a stellar mentoring team consisting of Dr. Josh Lile (Mentor), who has a successful NIH-funded clinical pharmacology research program at UK and Dr. Mark George (Co-Mentor), who pioneered the use of non-invasive brain stimulation for treating depression. In addition, Dr. Lumy Sawaki (Internal Preceptor) and Dr. Lon Hays (Study Physician) will provide local safety oversight and medical supervision, and Dr. Terry Lohrenz (External Preceptor) will provide guidance with advanced statistical analysis of neuroimaging data. Dr. Wesley will also engage in a series of formal classes, lab exchanges, and research seminars/meetings to assist him in accomplishing the objectives of this award. The proposed research project is based on the premise that cannabis impairs decision-making processes and these impairing effects contribute to an increased risk of developing CUD in emerging adults. This research will combine the acute administration of ∆9-tetrahydrocannabinol (THC), the main psychoactive ingredient in cannabis, with high-definition transcranial direct current stimulation (HD-tDCS) and neuroimaging, using rigorous methods, to examine the role of prefrontal cortex regions of interest in cannabis-impaired decision-making in emerging adults. Aim 1 will test the hypotheses that raising intrinsic PFC activity (Exp. 1) will attenuate, whereas lowering activity (Exp.2) will enhance, the impairing effects of THC on measures of decision-making and associated neurocognitive processes in emerging adults. Aim 2 will test the hypothesis that brain activity and connectivity during baseline task performance is associated with the subsequent response to THC and HD-tDCS. This highly innovative project will improve our understanding of the mechanisms involved in cannabis-impaired decision-making, which will inform CUD management and address a growing public health concern.