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: 8204431
• 负责人: William R Lovallo
• 金额: $ 18.75万
• 依托单位: UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-12-02 至 2013-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8204431
• 关键词: Adoption; Affective; Alcohol abuse; Alcohol dependence; Alcoholism; Area; Attention; Behavior; Behavior Disorders; Behavioral; Brain; Brain Stem; Brain region; Characteristics; Clinical; Cognition; Communication; Conscious; Cues; Data Set; Databases; Decision Making; Deoxyglucose; Disinhibition; Emotional; Environment; Family; Family health status; Family history of; Fluorine; Functional Magnetic Resonance Imaging; Future; Goals; Heavy Drinking; High Prevalence; Homeostasis; Hypothalamic structure; Image; Individual; Inferior frontal gyrus; Inherited; Label; Lead; Left; Limbic System; Literature; Maps; Medial; Metabolic; Metabolic Activation; Metabolism; Middle frontal gyrus structure; Monitor; Neuraxis; Oklahoma; Parahippocampal Gyrus; Parents; Pathway Analysis; Pattern; Persons; Play; Positron-Emission Tomography; Prefrontal Cortex; Preparation; Process; Public Health; Recording of previous events; Regulation; Relative (related person); Rest; Rewards; Risk; Risk Behaviors; Risk Factors; Role; Sample Size; Sampling; Secondary to; Seeds; Societies; Stimulus; Structure; Substance Use Disorder; Symptoms; Temperament; Time; Twin Multiple Birth; Work; alcohol use disorder; anti social; base; brain metabolism; cingulate cortex; cognitive control; cognitive function; disorder risk; executive function; frontal lobe; glucose metabolism; hedonic; high risk; motivated behavior; neuroimaging; parent project; pre-clinical; problem drinker; public health relevance; response; social; uptake; visual information; volunteer; young adult

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. PUBLIC HEALTH RELEVANCE: Alcohol abuse and dependence are behavioral disorders that are a burden to society. Despite a large literature on persons with alcohol dependence, much less is known about the preclinical characteristics of persons at greatest risk for the disorder, especially those with inherited risk factors. The present study examines resting brain metabolism in persons with a positive family history of alcoholism who also have disinhibited and antisocial tendencies that place them at High Risk of future alcoholism. Studies of High Risk individuals are valuable in characterizing behavioral characteristics of those who are vulnerable to alcoholism free of central nervous system effects secondary to heavy drinking. The proposed positron emission tomography study will provide new and useful information on the underlying brain functional characteristics of these High Risk individuals.

描述（由申请人提供）：我们的目标是更好地了解酗酒风险人群的中枢神经系统特征。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。俄克拉荷马州家庭健康模式项目研究有或没有酗酒家族史的健康年轻人。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，而对于同时具有反社会和去抑制特征的人来说，这种风险加倍。这两种倾向是共同继承的。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。这个修订后的申请延续了我们最近的发现，即有酗酒家族史的人与没有酗酒家族史的人相比，在静息状态下的区域大脑葡萄糖代谢存在差异。初步发现，在涉及获取视觉信息（中回和上温回）以及获得奖励或评估奖励价值以做出相关决策（左扣带回和尾状核）的结构中，FH+ 比 FH- 具有更多的 FDG 摄取。这组结构和功能与下丘脑中看到的更大的激活相一致，这可能在准备获得此类奖励方面发挥相关作用。相反，在涉及前额调节控制的功能中，FH- 比 FH+ 具有更多的 FDG 摄取：右额下回参与情绪和自主表达的调节。该区域与涉及有意识自主调节的功能密切相关，并与下丘脑和脑干的眶额皮质相结合。右额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，以便对与高危人群静息代谢差异相关的大脑区域网络的静息代谢活动进行网络分析。本研究将对我们两个风险组的违约模式和反违约模式功能进行基于种子的相关分析。计划中的研究预计将产生有关未来酗酒高风险的年轻人中涉及认知、决策和行为调节的大脑区域功能改变的新信息。 公共卫生相关性：酒精滥用和酒精依赖是行为障碍，给社会带来负担。尽管有大量关于酒精依赖者的文献，但人们对酒精依赖症风险最大的人的临床前特征知之甚少，尤其是那些具有遗传性危险因素的人。本研究检查了有酗酒家族史的人的静息大脑代谢，这些人也有去抑制和反社会倾向，这些倾向使他们未来酗酒的风险很高。对高风险个体的研究对于描述那些容易酗酒且不受大量饮酒继发的中枢神经系统影响的人的行为特征很有价值。拟议的正电子发射断层扫描研究将为这些高风险个体的潜在大脑功能特征提供新的有用信息。