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中毒的影响，因为它会干扰目标导向的行为、评估相互冲突的需求的能力、 抑制冲动反应，优化行为。这些障碍可能会导致自我克制能力下降，从而导致酗酒和依赖性增加。由于环境与遗传易感性（例如酗酒家族史）相互作用，饮酒模式和依赖风险具有个体间差异。多巴胺能（DA）系统通过奖励调节介导成瘾行为的发展和维持。然而，人们对 DA 能影响自上而下的调节影响及其与酒精和冲动特征的相互作用的神经功能基础知之甚少。该项目的总体目标是利用多模态成像来检查抑制控制和酒精挑战期间高危人群中基因 x 环境相互作用的神经生物学基础。其设计包括明确的功能多态性调节 DA 和 GABA，这些多态性与抑制控制和酒精中毒相关。所提出的范式招募了前额叶回路，在我们的初步调查中，该回路对感兴趣的基因型敏感。 我们的多模态方法包括功能磁共振成像（fMRI），它提供与诱发冲突的任务相关的活动的空间图，而磁图和脑图（MEG/EEG）出色的时间分辨率则阐明了与酒精相关的任务的时间和振荡动力学。异常。与我们的功能磁共振成像研究相结合，解剖学限制的 MEG 方法表明，前扣带皮层 (ACC) 在冲突处理过程中特别容易受到酒精的影响。酒精会减弱 ACC 估计的 θ 振荡。此外，酒精会使 ACC 和外侧前额皮质 (PFC) 之间的振荡同步失调，这可能是抑制控制受损的原因。我们的初步数据表明，作为决策、反应抑制和错误处理基础的前额叶神经功能系统与中毒期间功能性 COMT Val158Met 多态性存在差异相关。鉴于这些互动贡献，我们建议针对具有阳性和阴性酗酒家族史的个体获得一套丰富的补充措施。抑制控制和新奇处理的行为和多模式神经影像学测量将在酒精挑战期间获得，并将作为与 DA 和 GABA 信号传导和性格特征相关的遗传标记的函数进行分析。这些信息的汇合将被单独和协同分析，并将提供对酒精引起的抑制控制损伤的基本机制的多维见解，作为家族史和基因组成的函数，对个体化预防策略和药物遗传学具有影响。