Neuroimaging in the Oklahoma Family Health Patterns Project

俄克拉荷马州家庭健康模式项目中的神经影像学

• 批准号: 8259691
• 负责人: William R Lovallo
• 金额: --
• 依托单位: OKLAHOMA CITY VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8259691
• 关键词: Address; Adoption; Affective; Age-Years; Alcohol abuse; Alcohol dependence; Alcoholism; Alcohols; Amygdaloid structure; Animal Model; Anterior; Area; Attention; Behavior; Behavior Disorders; Behavioral; Behavioral inhibition; Brain; Brain imaging; Brain region; Caring; Characteristics; Clinical; Cognition; Cognitive; Color; Communication; Conflict (Psychology); Corpus striatum structure; Cues; Data; Data Analyses; Data Set; Decision Making; Development; Disinhibition; Dorsal; Drug Exposure; Emotional; Environment; Event; Face; Failure; Family; Family health status; Family history of; Functional Magnetic Resonance Imaging; Funding; Future; Gambling; Goals; Health; Health Care Costs; Healthcare Systems; Heavy Drinking; High Prevalence; Homeostasis; Image; Impulsive Behavior; Individual; Inferior; Inherited; Institutes; Insula of Reil; Iowa; Knowledge; Label; Laboratories; Lead; Left; Limbic System; Literature; Medial; Midbrain structure; Military Personnel; Modeling; Monitor; Motor; Neuraxis; Nucleus Accumbens; Oklahoma; Outcome; Paper; Parents; Pattern; Persons; Physiological; Prefrontal Cortex; Process; Reaction; Recording of previous events; Regulation; Relative (related person); Rewards; Risk; Risk Behaviors; Risk Factors; Risk-Taking; Scanning; Secondary to; Services; Signal Transduction; Societies; Stimulus; Structure; Structure of precentral sulcus; Substance Use Disorder; Symptoms; System; Temperament; Testing; Time; Twin Multiple Birth; Veterans; Wit; Work; alcohol use disorder; alcoholism therapy; anti social; avoidance behavior; base; cingulate gyrus; classical conditioning; cognitive control; combat; discounting; disorder risk; drinking; emotional stimulus; executive function; hedonic; high risk; indexing; neuroimaging; parent project; pre-clinical; problem drinker; psychologic; response; social; trait; young adult

DESCRIPTION (provided by applicant): Our long-term goal is to develop a better understanding of central nervous system characteristics of persons at risk for alcoholism. Many Veteran alcoholics begin heavy drinking during their time in military service, and the VA is responsible for their care. Despite a large clinical literature on alcoholism, far less is known about the preclinical characteristics of persons at greatest risk for the disorder. In response to this information deficit, we instituted the Oklahoma Family Health Patterns Project to study nonabusing young adults with and without a family history of alcoholism. Persons with a positive family history are four times as likely to develop alcohol use disorders as those with no such history, and this risk doubles in persons who also have antisocial characteristics. Twin-adoption studies show that a tendency toward alcoholism and disinhibited and antisocial behavior traits that are coinherited. Persons with both a positive family history and personal evidence of behavioral disinhibition are accordingly considered to be at High Risk of future alcoholism, and those lacking these factors are considered at Low Risk. Our major hypothesis is that High Risk persons have altered brain mechanisms that serve to produce normal emotional responses to the environment and have deficient regulation of overt behavior. While evidence points to altered communication between the limbic system and prefrontal cortex, confirmatory neuroimaging is lacking. This application is subsumed under two aims: Aim I addresses altered affective reactivity associated with a high risk for alcoholism, and focuses on amygdala functional connectivity and anticipatory affective responses. Our discovery of amygdalar hypoactivation in High Risk persons viewing emotional faces suggests a possible deficit in affective response to social cues. A meaningful extension of this finding is to contrast the risk groups in functional amygdala connectivity. Inadequate processing of affective cues in High Risk persons may be consistent with a tendency to engage in risky behaviors and to subject themselves to negative consequences of drinking. We will examine group differences in specific connections, using the amygdala as the starting point of a network that includes the insula, the dorsal ACC, and the ventromedial PFC. The presence of amygdalar hypoactivation to emotional faces raises the question of how general this activation difference is. Therefore subjects will undergo a task that probes brain responses to anticipation of positive, negative, or neutral outcomes in a Pavlovian conditioning paradigm. This provides a second probe of emotional responsivity using a wider range of stimuli. We predict that the High Risk subjects will have less relative amygdala activation in anticipation of negative outcomes and greater relative activation in anticipation of positive ones in: caudate n., amygdala, ACC, and the insula. Aim II addresses disinhibited regulation of behavior associated with a high risk for alcoholism using three tasks that tap executive function, decision-making, and behavioral regulation. Executive controls will be tested using the Stroop response conflict task, sensitive to altered function in the cognitive control regions of the anterior cingulate gyrus, dorsolateral prefrontal cortex, and the left inferior precentral sulcus. Risky decision-making is examined using a delay discounting task examining functioning of the extended amygdala, nucleus accumbens, caudate, ventromedial prefrontal cortex, and ventral anterior cingulate gyrus. Behavioral disinhibition will be examined with a stop-signal task examining cognitive control regions of the anterior cingulate gyrus, dorsolateral prefrontal cortex, and the left inferior precentral sulcus. The planned studies are expected to yield new information concerning altered processing of emotional stimuli and behavioral disinhibition in young adults at high risk for future alcoholism. PUBLIC HEALTH RELEVANCE: Relevance to Veterans Health Treatment of alcoholism is a major health care cost for the VA system. Alcoholism often manifests in persons 18-30 years of age (Babor, Hofmann et al., 1992), a time that coincides with military service and perhaps combat exposure. As a result, the VA system is responsible for large numbers of veterans with alcohol and other substance use disorders that began during the period of active military service. Studies of persons at elevated risk for alcoholism can increase our knowledge of antecedent factors, contribute to models of alcoholism development, and aid in predicting who is most at risk.

描述（由申请人提供）： 我们的长期目标是更好地了解酗酒风险人群的中枢神经系统特征。许多退伍军人酗酒者在服兵役期间开始酗酒，退伍军人管理局负责照顾他们。尽管有大量关于酗酒的临床文献，但人们对酗酒风险最大的人的临床前特征知之甚少。为了应对这种信息缺失，我们发起了俄克拉荷马州家庭健康模式项目，以研究有或没有酗酒家族史的非虐待年轻人。有阳性家族史的人患酒精使用障碍的可能性是没有家族史的人的四倍，而对于同样具有反社会特征的人来说，这种风险加倍。双胞胎收养研究表明，酗酒倾向、放纵和反社会行为特征是共同遗传的。因此，具有阳性家族史和行为去抑制个人证据的人被认为未来酗酒的高风险，而缺乏这些因素的人被认为是低风险。我们的主要假设是，高风险人群已经改变了对环境产生正常情绪反应的大脑机制，并且对公开行为的调节不足。虽然证据表明边缘系统和前额叶皮层之间的沟通发生了变化，但缺乏确认性的神经影像学检查。该应用程序包含两个目标：目标 I 解决与酗酒高风险相关的情感反应改变，并重点关注杏仁核功能连接和预期情感反应。我们发现，高危人群在观看情绪化面孔时杏仁核活性低下，这表明他们对社交线索的情感反应可能存在缺陷。这一发现的一个有意义的扩展是对比危险群体的杏仁核功能连接。高风险人群对情感线索的处理不充分可能与从事危险行为和遭受饮酒负面后果的倾向一致。我们将使用杏仁核作为包括岛叶、背侧 ACC 和腹内侧 PFC 的网络的起点，检查特定连接的群体差异。杏仁核对情绪化面孔的激活不足引发了这样一个问题：这种激活差异有多普遍。因此，受试者将接受一项任务，在巴甫洛夫条件范式中探测大脑对积极、消极或中性结果预期的反应。这提供了使用更广泛的刺激来进行情绪反应的第二次探索。我们预测，高风险受试者在预期负面结果时杏仁核的相对激活程度较低，而在预期正面结果时杏仁核的相对激活程度较高：尾状核、杏仁核、ACC 和岛叶。目标 II 通过利用执行功能、决策和行为调节的三项任务来解决与酗酒高风险相关的行为的去抑制调节。执行控制将使用斯特鲁普反应冲突任务进行测试，该任务对前扣带回、背外侧前额叶皮层和左下中央前沟的认知控制区域的功能改变敏感。使用延迟贴现任务检查扩展杏仁核、伏核、尾状核、腹内侧前额叶皮层和腹侧前扣带回的功能来检查风险决策。将通过停止信号任务来检查行为去抑制，该任务检查前扣带回、背外侧前额叶皮层和左下中央前沟的认知控制区域。计划中的研究预计将产生有关未来酗酒高风险的年轻人情绪刺激处理改变和行为去抑制的新信息。 公共卫生相关性： 与退伍军人健康的相关性 酗酒治疗是退伍军人管理局系统的一项主要医疗保健费用。酗酒通常出现在 18-30 岁的人身上（Babor，Hofmann 等人，1992），这个时期恰逢服兵役，或许还有参战经历。因此，退伍军人管理局系统要对大量在现役期间开始患有酒精和其他药物滥用疾病的退伍军人负责。对酗酒高风险人群的研究可以增加我们对先行因素的了解，有助于建立酗酒发展模型，并有助于预测谁的风险最大。