Spatiotemporal Brain Imaging of Alcohol Effects on Inhibitory Control

酒精对抑制控制影响的时空脑成像

• 批准号: 8898591
• 负责人: KSENIJA MARINKOVIC
• 金额: $ 43.31万
• 依托单位: SAN DIEGO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8898591
• 关键词: Accounting; Acute; Addictive Behavior; Address; Affect; Agreement; Alcohol abuse; Alcohol consumption; Alcohol dependence; Alcoholic Intoxication; Alcoholism; Alcohols; Alleles; Anterior; Attenuated; Behavior; Behavioral; Brain imaging; Characteristics; Complex; Conflict (Psychology); Data; Decision Making; Dependence; Detection; Development; Electroencephalography; Environment; Executive Dysfunction; Family; Family history of; Frequencies; Functional Magnetic Resonance Imaging; Gender; Genes; Genetic; Genetic Markers; Genetic Polymorphism; Genetic Predisposition to Disease; Genotype; Goals; Health; Impairment; Impulsivity; Individual; Inferior; Intoxication; Investigation; Lateral; Literature; Maintenance; Maps; Measures; Medial; Mediating; Methods; Monitor; Multimodal Imaging; Nature; Neurobiology; Other Genetics; Pattern; Pharmaceutical Preparations; Pharmacogenetics; Play; Populations at Risk; Prefrontal Cortex; Prevention strategy; Process; Recording of previous events; Recruitment Activity; Regulation; Resolution; Rewards; Risk; Role; Self-control as a personality trait; Signal Pathway; Signal Transduction; Source; Specific qualifier value; Staging; System; Time; Validation; addiction; alcohol effect; base; behavior influence; blood oxygen level dependent; cingulate cortex; cognitive control; design; drinking; encephalography; executive function; gamma-Aminobutyric Acid; hemodynamics; insight; interest; meetings; neural circuit; neuroimaging; novel; novelty processing; relating to nervous system; response; restraint; spatiotemporal; system architecture; trait

DESCRIPTION (provided by applicant): Executive functions are vulnerable to alcohol intoxication as it interferes with goal-directed behavior, ability to evaluate conflicting demands, inhibit impulsive responses, and optimize behavior. These impairments may result in a decreased capacity to exert self-restraint, contributing to increased drinking and dependence. Patterns of alcohol consumption and the risk for dependence are characterized by inter individual variability as the environment interacts with genetic susceptibility such as family history of alcoholism. Dopaminergic (DA) system mediates development and maintenance of addictive behaviors via reward regulation. However, the neurofunctional basis of DA-ergic influence on the top-down regulatory influence and its interaction with alcohol and impulsivity traits is poorly understood. The overall goal of this project is to use the multimodal imaging to examine the neurobiological basis of gene x environment interactions in the population at risk during inhibitory control and alcohol challenge. Its design includes well-defined functional polymorphisms regulating DA and GABA that are relevant to inhibitory control and alcoholism. The proposed paradigms recruit prefrontal circuitry shown to be sensitive to genotypes of interest in our preliminary investigations. Our multimodal approach comprises functional magnetic resonance imaging (fMRI) that provides spatial maps of activity related to conflict-inducing tasks, whereas the excellent temporal resolution of magneto- and encephalography (MEG/EEG) elucidates the timing and the oscillatory dynamics of alcohol-related abnormalities. Converging with our fMRI studies, the anatomically-constrained MEG approach indicates that the anterior cingulate cortex (ACC) is especially vulnerable to alcohol effects during conflict processing. Alcohol attenuates theta oscillations estimated to the ACC. Furthermore, oscillatory synchrony between the ACC and lateral prefrontal cortex (PFC) is dysregulated by alcohol, possibly underlying impaired inhibitory control. Our preliminary data indicate that the prefrontal neurofunctional systems underlying decision making, response inhibition, and error processing are differentially associated with the functional COMT Val158Met polymorphism during intoxication. Given these interactive contributions, we propose to obtain a rich set of complementary measures in individuals with a positive vs. negative family history of alcoholism. Behavioral and multimodal neuroimaging measures of inhibitory control and novelty processing will be obtained during alcohol challenge and will be analyzed as a function of genetic markers relevant to DA and GABA signaling and dispositional traits. The confluence of information will be analyzed separately and in synergy and will provide multidimensional insight into the basic mechanisms underlying alcohol-induced impairment of inhibitory control in real time as a function of family history and genetic makeup, with implications for individualized prevention strategies and pharmacogenetics.

描述（由申请人提供）：执行功能很容易受到酒精醉酒的影响，因为它会干扰目标指导的行为，评估需求矛盾的能力， 抑制冲动反应并优化行为。这些障碍可能导致施加自我约束的能力降低，导致饮酒和依赖性增加。随着环境与诸如酒精中毒家族史之类的遗传易感性相互作用，饮酒模式和依赖风险的特征是个性变化。多巴胺能（DA）系统通过奖励调节介导了成瘾行为的发展和维持。然而，对DA-ARGIC的影响对自上而下的调节影响的神经功能基础及其与酒精和冲动性状的相互作用知之甚少。该项目的总体目标是使用多模式成像检查在抑制性控制和酒精挑战期间，基因X环境相互作用的神经生物学基础。它的设计包括与抑制性控制和酒精中毒相关的调节DA和GABA的明确定义的功能多态性。在我们的初步研究中，提出的范式募集了对感兴趣的基因型敏感的前额叶回路。 我们的多模式方法包括功能性磁共振成像（FMRI），提供与诱导冲突的任务相关的活动的空间图，而磁性和脑电图（MEG/EEG）的极佳时间分辨率阐明了酗酒和振动性均质的亚伯纳属性的振动动力学。在我们的功能磁共振成像研究中，解剖上约束的MEG方法表明，在冲突处理过程中，前扣带回皮层（ACC）尤其容易受到酒精效应的影响。酒精会削弱估计为ACC的theta振荡。此外，ACC和外侧前额叶皮层（PFC）之间的振荡同步因酒精失调，可能是抑制性控制受损的基础。我们的初步数据表明，决策制定，响应抑制和错误处理的前额叶神经功能系统与功能性COMT Val158met多态性在中毒过程中有不同的相关性。鉴于这些互动贡献，我们建议在酗酒和负面家族史的个人中获得丰富的互补措施。在酒精挑战期间将获得抑制性控制和新颖性处理的行为和多模式神经影像学测量，并将作为与DA和GABA信号传导和性格性状相关的遗传标记的函数进行分析。信息的汇合将分别分析和协同作用，并将为酒精诱导的抑制性控制的基本机制实时提供多维见解，这是家族史和遗传构成的函数，对个性化的预防策略和药物遗传学的影响。