Neuroimaging in the Oklahoma Family Health Patterns Project

描述（由申请人提供）：我们的目标是更好地了解有酗酒风险的人的中枢神经系统特征。尽管有大量关于酒精中毒的临床文献，但对最有可能患上这种疾病的人的临床前特征知之甚少。俄克拉荷马州家庭健康模式项目研究了有和没有酗酒家族史的健康年轻人。有阳性家族史的人发展酒精使用障碍的可能性是没有这种历史的人的四倍，并且这种风险在也有反社会和去抑制特征的人中加倍。这两种倾向是共同遗传的。同时具有阳性家族史和行为抑制解除的个人证据的人相应地被认为是未来酒精中毒的高风险，而缺乏这些因素的人被认为是低风险。我们的主要假设是，高风险的人已经改变了大脑机制，这些机制有助于对环境产生正常的情绪反应，并且对公开行为的调节不足。虽然有证据表明边缘系统和前额皮质之间的交流发生了变化，但缺乏证实性的神经影像学。这项修订后的申请遵循了我们最近的发现，即有酗酒家族史的人与没有酗酒家族史的人相比，在静息状态下局部脑葡萄糖代谢存在差异。初步发现，在参与获得视觉信息的结构中，FH+比FH-具有更大的FDG摄取（Rt. Middle & Sup.温度脑回）和获得奖励或评估奖励值以做出相关决定（左扣带回和尾状核）。这组结构和功能与下丘脑中看到的更大的激活是一致的，下丘脑可能在获得这种奖励的准备中发挥相关作用。相比之下，在涉及前额叶调节控制的功能中，FH-比FH+具有更大的FDG摄取：右额下回参与情绪和自主神经表达的调节。该区域与涉及意识自主调节的功能密切相关，该功能与眶额皮质一起向下丘脑和脑干输入。右额中回通过与背外侧前额叶皮层的广泛联系参与执行功能。这项研究将扩展静息数据库，以允许对与高危人群静息代谢差异相关的脑区网络的静息代谢活动进行网络分析。本研究将在我们的两个风险组中进行基于种子的违约模式和反违约模式函数的相关分析。计划中的研究预计将产生新的信息，涉及未来酗酒高风险的年轻人的认知，决策和行为调节的大脑区域的功能改变。

DESCRIPTION (provided by applicant): Our goal is to develop a better understanding of central nervous system characteristics of persons at risk for alcoholism. Despite a large clinical literature on alcoholism, far less is known about the preclinical characteristics of persons at greatest risk for the disorder. The Oklahoma Family Health Patterns Project studies healthy 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 and disinhibitory characteristics. The two tendencies 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 revised application pursues our recent finding that persons with a family history of alcoholism have differences in regional brain glucose metabolism in the resting state as compared to their counterparts with no such history. Preliminary findings are that FH+ have greater FDG uptake than FH- in structures involved in obtaining visual information (Rt. Middle & Sup. temp. gyrus) and obtaining rewards or assessing reward value to make relevant decisions (Left Cingulate and Caudate). This set of structures and functions is compatible with the greater activation seen in the hypothalamus, which may play a related role in preparation for obtaining such rewards. In contrast FH- have greater FDG uptake than FH+ in functions involving prefrontal regulatory controls: The right inferior frontal gyrus is involved in regulation of emotional and autonomic expression. This region is closely associated with functions involving conscious autonomic regulation in conjunction with the orbital frontal cortex having inputs to the hypothalamus and brainstem. The right middle frontal gyrus is involved in executive functions via extensive connections to the dorsolateral prefrontal cortex. This study will expand the resting database to allow a network analysis of resting metabolic activity of a network of brain areas concerned with resting metabolic differences in High-Risk persons. The present study will carry out a seed- based correlational analysis of default-mode and anti-default-mode function in our two risk groups. The planned studies are expected to yield new information concerning altered functioning in brain regions involved with cognition, decision-making, and behavioral regulation in young adults at high risk for future alcoholism.