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Spatiotemporal Brain Imaging of Alcohol Effects on Inhibitory Control

酒精对抑制控制影响的时空脑成像

基本信息

批准号：
9120742
负责人：
KSENIJA MARINKOVIC
金额：
$ 44.6万
依托单位：
SAN DIEGO STATE UNIVERSITY
依托单位国家：
美国
项目类别：
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/9120742
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 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 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 gene environment interaction genetic makeup hemodynamics individualized prevention insight interest meetings neural circuit neuroimaging novel novelty processing relating to nervous system response restraint spatiotemporal system architecture temporal measurement trait trait impulsivity

项目摘要

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，