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有酗酒风险的人的中枢神经系统特征。尽管关于酒精中毒的临床文献很大，但对疾病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项目研究健康的年轻人，有或没有酒精中毒家族史。具有积极家族病史的人的发展饮酒障碍的可能性是没有这种病史的人的四倍，并且这种风险在具有反社会和抑制特征的人中会增加一倍。这两种趋势是共同的。因此，拥有积极的家族史和个人行为抑制的个人证据的人被认为是未来酒精中毒的高风险，而缺乏这些因素的人则被认为是低风险。我们的主要假设是，高风险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，并对公开行为的调节不足。尽管证据表明边缘系统与前额叶皮层之间的通信发生了改变，但缺乏确认性神经影像。这项修订后的应用追求我们最近的发现，与没有这种历史的同行相比，静止状态的酗酒家族史的人在静止状态的区域葡萄糖代谢有所不同。初步的发现是，在获得视觉信息（Rt。Middle＆Sup。Temp。Gyrus）中，FH+的FDG吸收比FH-更大，并获得奖励或评估奖励价值以做出相关决策（左扣带和谨慎）。这组结构和功能与下丘脑中看到的更大的激活兼容，这可能在准备获得此类奖励方面起着相关的作用。相比之下，FH-在涉及前额叶调节控制的功能中具有比FH+更大的FDG摄取：右下额回与情绪和自主性表达的调节有关。该区域与涉及有意识的自主神经调节的功能与具有下丘脑和脑干的轨道额叶皮层结合使用。右侧额叶回旋通过与背外侧前额叶皮层的广泛连接参与执行功能。这项研究将扩大静止数据库，以允许对与高风险人群中静息代谢差异有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中的默认模式和反默认模式函数进行基于种子的相关分析。预计计划的研究将产生有关与认知，决策和行为调节有关的大脑区域功能改变的新信息，以使未来的酒精中毒风险高。 公共卫生相关性：酗酒和依赖性是对社会负担的行为障碍。尽管有关于酒精依赖人的大量文献，但对疾病风险最大的人的临床前特征，尤其是那些具有遗传危险因素的人的临床前特征的了解少得多。本研究研究了酗酒家族史的人的静息脑代谢，这些人也已经抑制了反社会的倾向，使他们面临未来酒精中毒的高风险。对高风险个体的研究对于表征那些容易受到酗酒的人的行为特征的有价值，而没有中枢神经系统的影响，其继发于大量饮酒。拟议的正电子发射断层扫描研究将提供有关这些高风险个体的潜在大脑功能特征的新的有用信息。