Developing Capacity for Biomedical Signal Processing and Integration of Cognitive

说明(由申请人提供)：确定基因对酒精相关结果中种族差异的影响是一个与公共卫生密切相关的主题。霍华德大学酒精研究中心(HUARC)的神经生理学部分自1997-2003年最初的资助项目期间以来一直开展神经生理学活动。霍华德大学加入了酒精中毒遗传学合作研究(COGA)，作为七个网站之一，通过确定与酒精依赖相关的临床内表型，探索对酒精中毒易感性的主要遗传影响。神经行为实验是在HUARC的一个结构良好的神经生理学实验室进行的，该实验室位于霍华德大学综合临床研究中心。在随后的资助项目期间(2003-2008年)，HUARC作为互动研究小组(IRPG)加入了以前的COGA网站，并继续研究与酒精依赖有关的遗传因素。HU IRPG网站进一步发展了EEG-ERP实验室，这是对现有分子神经药理学实验室的补充。作为这项研究的一部分，该中心采用了印第安纳呼吸酒精夹技术，这是一种创新的机制，可以研究酒精对大脑的影响。实验室的活动是在HUARC主任泰勒博士的领导下进行的。Nwulia博士(这项新提案的PI)是一名精神病学家和酒精遗传流行病学家，他一直与HUARC的研究人员密切合作。2009年，Nwulia博士被聘为HUARC神经生理学核心的一员，并利用统计计算方面的独特技能制定了这项建议，以增强HUARC在生物医学信号处理和整合行为功能数据以分析这一候选基因研究方面的能力。最近，进行了一项初步研究，以确定ADH1B1和ADH1B3等位基因变异的个体对酒精挑战的比较反应。共有161名参与者参加了这项研究。我们现在已经积累了大量的遗传、神经生理学(包括休息、眼球跟踪和关键跟踪任务EEG)和其他神经行为数据，这些数据可以为探索预测疾病风险所需的生理标记提供坚实的基础，并作为分子遗传学和表达研究的特征。这项R03建议将在未来两年用于以下方面：获得最先进的跨平台软件开发工具，用于在并行计算环境下对神经元功能数据进行建模和分析，适合处理神经信息学模拟的计算负担，并使开发的程序免费提供给科学界；处理我们迄今记录的EEG/ERP数据，并全面分析ADH1B*3基因多态对受控酒精暴露和神经行为结果之间关系的调节作用，以酒精挑战期间的脑电特征和主观反应为索引；并创建和维护一个大型数据库，其中包括提取的休息和事件相关脑电特征，以及认知和行为反应数据，这些数据在我们最近的酒精夹住期间与脑电同时记录，作为非裔美国人生物行为数据的来源，他们在行为的生物医学研究中往往代表不足。这些目标的实现可能会导致一项大型的独立R01研究，以开发和验证酒精疾病预后的生理标记以及分子遗传和表达研究的内表型。 公共卫生相关性：霍华德大学酒精研究中心(HUARC)的神经生理学核心参与了酒精中毒遗传学合作研究(COGA)的七个地点之一，通过确定酒精依赖的临床内表型来研究酒精中毒的主要遗传影响；在COGA拨款完成后，HUARC继续积累了大量的遗传学、神经生理学和神经行为数据。该项目的目标是：获得最先进的跨平台软件开发工具，用于在并行计算环境下对神经元功能数据进行建模和分析，适合处理高维神经生理数据的计算负担；处理我们迄今记录的EEG/ERP数据，并综合分析ADH1B*3基因多态性对受控酒精暴露与神经行为结果之间关系的调节作用；并创建和维护一个大型数据库，其中包括提取的脑电特征以及认知和行为反应数据，在我们最近的酒精夹住研究中与脑电同时记录，作为非裔美国人的生物行为信息来源，他们在生物医学研究中往往代表不足。这些目标的实现可能会导致一项大型的独立R01研究，以开发和验证酒精疾病预后的生理标记以及分子遗传和表达研究的内表型。

DESCRIPTION (provided by applicant): Identification of genetic influences on racial disparities in alcohol-related outcome is a subject of great public health relevance. The neurophysiology component of the Howard University Alcohol Research Center (HUARC) has conducted neurophysiology activities since the initial funding project period of 1997-2003. Howard University joined the Collaborative Study on the Genetics of Alcoholism (COGA) as one of seven sites to explore the major genetic influence on vulnerability to alcoholism through identifying clinical endophenotypes that are associated with alcohol dependence. Neurobehavioral experiments were conducted at HUARC in a well constructed neurophysiology laboratory, which is housed in the Howard University General Clinical Research Center. In the subsequent funding project period (2003-2008), HUARC joined the previous COGA sites as the Interactive Research Group (IRPG) and continued to examine the genetic factors associated with alcohol dependence. The HU IRPG site further developed the EEG-ERP laboratory, which is an addition to the existing molecular neuropharmacology laboratory. As part of this research, the Center incorporated the Indiana Breath Alcohol clamp technique, an innovative mechanism that allows for the study of the effects of alcohol on the brain. Activities in the lab have been conducted under the leadership of Dr. Taylor, Director of HUARC. Dr. Nwulia (PI of this new proposal) is a psychiatrist and an alcohol genetic epidemiologist, who has worked closely with researchers at the HUARC. In 2009, Dr. Nwulia was brought in as a member of the neurophysiology core of the HUARC, and brings unique skills in statistical computing to develop this proposal to enhance the HUARC capacity for biomedical signal processing and integration of behavioral function data for analysis of this candidate gene study. Most recently, a pilot study was conducted to determine the comparative responses to alcohol challenge among Individuals with variations in the ADH1B1 and ADH1B3 alleles. A total of 161 participants enrolled in this study. We have now accumulated extensive amount of genetic, neurophysiologic (including resting, eye tracking and critical tracking tasks EEG) and other neurobehavioral data, which could provide a solid basis to explore physiological markers needed to predict disease risk and serve as traits for molecular genetic and expression studies. This R03 proposal will be utilized over the next two years for the following: to acquire state-of-the-art cross-platform software development tools for modeling and analysis of neuronal functional data under a parallel computing environment, suitable for handling the computational burden of neuroinformatic simulations, and to make developed programs freely- available to the scientific community; to process EEG/ERP data we have recorded so far and conduct a comprehensive analysis of the moderating effects of ADH1B*3 polymorphisms on the relationship between controlled alcohol exposure and neurobehavioral outcomes, indexed by EEG features and subjective responses during alcohol challenge; and to create and maintain a large database of extracted resting and event-related EEG features, and cognitive and behavioral response data, recorded simultaneously with EEG during our recent alcohol clamping, studies to serve as a resource of biobehavioral data of African Americans, who are often under-represented in biomedical studies of behavior. Accomplishment of these goals could lead to a large independent R01 study for development and validation of physiological markers for alcohol disease prognosis and endophenotypes for molecular genetic and expression studies. PUBLIC HEALTH RELEVANCE: The neurophysiology core of Howard University Alcohol Research Center (HUARC) was involved as one of seven sites of the Collaborative Study on the Genetics of Alcoholism (COGA), studying the major genetic influence to alcoholism through identification of clinical endophenotypes of alcohol dependence; and after the completion of COGA grant, HUARC has continued to accumulate extensive amount of genetic, neurophysiologic and neurobehavioral data. The goals of this project are: to acquire state-of-the-art cross-platform software development tools for modeling and analysis of neuronal functional data, under a parallel computing environment, suitable for handling the computational burden of high-dimensional neurophysiological data; to process EEG/ERP data we have recorded so far and conduct a comprehensive analysis of the moderating effects of ADH1B*3 polymorphisms on the relationship between controlled alcohol exposure and neurobehavioral outcomes; and to create and maintain a large database of extracted EEG features, and cognitive and behavioral response data, recorded simultaneously with EEG during our recent alcohol clamping studies, to serve as a resource for biobehavioral information on African Americans, who are often under- represented in biomedical studies. Accomplishment of these goals could lead to a large independent R01 study for development and validation of physiological markers for alcohol disease prognosis and endophenotypes for molecular genetic and expression studies.