Developing Capacity for Biomedical Signal Processing and Integration of Cognitive

描述（由申请人提供）：识别酒精相关结果中种族差异的遗传影响是一个具有重大公共卫生相关性的主题。霍华德大学酒精研究中心（HUARC）的神经生理学部分自1997年至2003年的初始资助项目期间进行了神经生理学活动。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，通过识别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。神经行为实验在HUARC的一个构造良好的神经生理学实验室中进行，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加入了以前的COGA网站作为互动研究小组（IRPG），并继续研究与酒精依赖相关的遗传因素。HU IRPG研究中心进一步开发了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州呼吸酒精钳技术，这是一种创新的机制，可以研究酒精对大脑的影响。实验室的活动在HUARC主任Taylor博士的领导下进行。Nwulia博士是一位精神病学家和酒精遗传流行病学家，他与HUARC的研究人员密切合作。2009年，Nwulia博士作为HUARC神经生理学核心的一员加入，并带来了统计计算方面的独特技能，以开发该提案，以增强HUARC生物医学信号处理和整合行为功能数据的能力，用于分析该候选基因研究。最近，进行了一项初步研究，以确定ADH 1B 1和ADH 1B 3等位基因变异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。我们已经积累了大量的遗传学、神经生理学（包括静息、眼动和关键跟踪任务EEG）和其他神经行为学数据，这些数据可以为探索预测疾病风险所需的生理标志物提供坚实的基础，并作为分子遗传和表达研究的特征。该R 03提案将在未来两年内用于以下方面：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，适用于处理神经信息学模拟的计算负担，并将开发的程序免费提供给科学界;处理我们迄今为止记录的EEG/ERP数据，并通过EEG特征和酒精挑战时的主观反应，全面分析ADH 1B *3多态性对控制性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，其中包含提取的静息和事件相关EEG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钳制期间与EEG同时记录，这些研究作为非裔美国人生物行为数据的资源，他们在行为的生物医学研究中往往代表性不足。这些目标的实现可能会导致一个大型的独立R 01研究，用于酒精疾病预后的生理标志物的开发和验证，以及用于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）的神经生理学核心作为酒精中毒遗传学合作研究（COGA）的七个研究点之一，通过识别酒精依赖的临床内表型来研究酒精中毒的主要遗传影响;在完成COGA资助后，HUARC继续积累了大量的遗传、神经生理和神经行为数据。本项目的目标是：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，适用于处理高维神经生理数据的计算负担;处理我们迄今为止记录的EEG/ERP数据，并对ADH 1B * 的调节作用进行全面分析控制性酒精暴露与神经行为结果关系的3个多态性;并创建和维护一个大型数据库，其中包含提取的EEG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钳制研究中与EEG同时记录，以作为非裔美国人生物行为信息的资源，他们在生物医学研究中的代表性往往不足。这些目标的实现可能会导致一个大型的独立R 01研究，用于酒精疾病预后的生理标志物的开发和验证，以及用于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.