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，但人们对酒精中毒高危人群的临床前特征知之甚少。俄克拉何马州家庭健康模式项目研究了有或没有家族酗酒史的健康年轻人。有阳性家族史的人发生酒精使用障碍的可能性是没有家族史的人的四倍，而具有反社会和去抑制特征的人的这种风险翻倍。这两种倾向是共同遗传的。因此，具有阳性家族史和个人行为抑制解除证据的人被认为是未来酗酒的高风险人群，而缺乏这些因素的人被认为是低风险人群。我们的主要假设是，高风险人群改变了大脑机制，这些机制有助于对环境产生正常的情绪反应，并且缺乏对公开行为的调节。虽然有证据表明边缘系统和前额叶皮层之间的交流发生了改变，但缺乏确证性的神经影像学。这项修订后的应用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，静息状态下脑区域葡萄糖代谢存在差异。初步发现FH+比FH-在获取视觉信息的结构（中高温度回）和获得奖励或评估奖励价值以做出相关决策的结构（左扣带和尾状回）中有更大的FH-摄取。这组结构和功能与下丘脑的更大激活是相容的，下丘脑可能在准备获得这种奖励方面起着相关的作用。相反，在涉及前额叶调节控制的功能中，FH-比FH+摄取更多的FDG：右侧额下回参与情绪和自主表达的调节。该区域与有意识的自主调节功能密切相关，并与向下丘脑和脑干输入信息的眶额皮质相连。右侧额叶中回通过与背外侧前额叶皮层的广泛连接参与执行功能。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有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群体中进行基于种子的违约模式和反违约模式功能的相关性分析。计划中的研究预计将获得有关未来酗酒高风险年轻人的认知、决策和行为调节脑区功能改变的新信息。

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.