Sensitivity to Intravenous Ethanol: Neuroimaging and Behavioral Phenotypes

对静脉注射乙醇的敏感性：神经影像和行为表型

基本信息

批准号：
8269633
负责人：
Eric D Claus
金额：
$ 19.64万
依托单位：
THE MIND RESEARCH NETWORK
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-06-01 至 2014-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8269633
关键词：
Acclimatization Accounting Acute Advocate Alcohol consumption Alcohol dependence Alcohols Animals Anterior Area Base of the Brain Behavior Behavioral Biological Markers Blood Blood alcohol level measurement Brain Characteristics Data Detection Disinhibition Dopamine Environment Ethanol Event-Related Potentials Feasibility Studies Functional Magnetic Resonance Imaging Future Genetic Genetic Variation Goals Heart Rate Heavy Drinking Human Impulsivity Incentives Individual Inferior frontal gyrus Infusion procedures Intoxication Intravenous Lateral Limb structure Literature Measurement Measures Motivation Motor Neurobiology Neurocognitive Nucleus Accumbens Oral Outcome Patient Self-Report Phenotype Physiological Recording of previous events Recruitment Activity Research Risk Sedation procedure Staging Time Translations Ventral Striatum alcohol cue alcohol effect alcohol exposure alcohol response alcohol sensitivity base binge drinking blood oxygenation level dependent response cognitive control drinking drinking behavior endophenotype high risk indexing neuroimaging neuromechanism novel pharmacokinetic model programs relating to nervous system response young adult

项目摘要

DESCRIPTION (provided by applicant): Individual variability in alcohol sensitivity is among the most widely studied endophenotypes for alcohol dependence. However, little is known about brain mechanisms relevant for alcohol sensitivity. Research on human alcohol sensitivity phenotypes has often relied on self-report measures and conventional oral alcohol administration paradigms, both of which may introduce considerable measurement error, thus decreasing sensitivity for detecting genetic and neural correlates. The proposed study will examine neural markers of alcohol sensitivity in the context of an alcohol challenge paradigm that incorporates highly controlled intravenous ethanol infusion. The broad aims of this proposal include a) developing our approach for integrating fMRI and infusion; b) examining feasibility of studying neural correlates of alcohol sensitivity in this context; and c) estimating effect sizes to inform power analyses for future studies. Heavy-drinking young adults will participate in two infusion sessions: a baseline "acclimation" session and an fMRI session. Physiologically- Based Pharmacokinetic (PBPK) modeling will be used to establish a peak target blood alcohol concentration (BAC) of 0.06 1 0.005 g% within 15 minutes. This BAC will be maintained (clamped) for 90 minutes. Alcohol sensitivity indices will include traditional self-report measures; heart rate response during infusion; and serial measures of subjective intoxication (stimulation/sedation) across the session. We will examine these indicators in relation to BOLD responses during tasks that engage incentive motivation and cognitive control networks, incorporating repeated assessments across the BAC time course. Both traditional and brain-based measures of alcohol sensitivity will be examined in relation to self-reported drinking. By examining neural phenotypes in the context of acute alcohol exposure, we hope to identify brain-based alcohol sensitivity phenotypes that are potentially more sensitive to genetic variation and to behavioral outcomes as compared to traditional measures. )

描述（由申请人提供）：酒精敏感性的个人变异性是酒精依赖性最广泛研究的内表型。但是，关于与酒精敏感性相关的大脑机制知之甚少。人类酒精敏感性表型的研究通常依赖于自我报告措施和常规的口服酒精给药范例，这两者都可能引入相当大的测量误差，从而降低了检测遗传和神经相关性的敏感性。拟议的研究将在酒精挑战范式的背景下检查酒精敏感性的神经标志物，该范式融合了高度控制的静脉注射乙醇输注。该提案的广泛目的包括a）开发我们整合fMRI和输液的方法； b）检查在这种情况下研究酒精敏感性神经相关性的可行性； c）估计效果大小，以告知电源分析以进行未来的研究。大批饮食的年轻人将参加两次输液课程：基线“适应”会议和一个fMRI会议。基于生理的药代动力学（PBPK）建模将在15分钟内建立0.06 1 0.005 g％的峰值血液酒精浓度（BAC）。该BAC将维持（夹紧）90分钟。酒精敏感性指数将包括传统的自我报告措施；输注过程中的心率反应；和整个会议上主观中毒（刺激/镇静）的序列度量。我们将检查这些指标与涉及激励动机和认知控制网络的任务中的大胆响应有关，并在BAC时间过程中重复评估。传统和基于大脑的酒精敏感性测量方法都将与自我报告的饮酒有关。通过在急性酒精暴露的背景下检查神经表型，我们希望鉴定基于脑的酒精敏感性表型，这些表型与传统措施相比，对遗传变异和行为结果可能更敏感。）