Neural and genetic mechanisms of cognition in externalizing behavior.

描述（由申请人提供）：药物滥用的主要风险之一是一般倾向于外化行为（EB），这是一个广泛的类别，包括冲动，反社会行为，攻击，以及药物滥用。因此，了解外化行为所涉及的心理和生物学机制对于了解药物滥用以及成功预防和治疗药物滥用的发展至关重要。外化行为受到强烈的遗传影响，因此基因研究很好地阐明了其生物学基础。该研究将采用遗传和神经影像学方法，以研究与外化行为相关的认知模式相关的神经生物学机制。众所周知，外化行为与认知缺陷有关，包括智力低下和工作记忆差（即在分心的情况下在脑海中保存和处理信息的能力）。人们对影响这些认知缺陷的具体基因知之甚少，但与神经递质多巴胺相关的基因可能很重要，因为多巴胺既影响外化行为，也影响工作记忆等认知功能。这项拟议中的研究将收集60个人的DNA，以确定多巴胺能基因的变异。研究人员将对参与者的外化行为水平进行评估，并在他们从事工作记忆任务时使用功能性磁共振成像（fMRI）扫描他们的大脑。fMRI数据将提供人们在执行这些任务时的大脑活动图，然后可以对这些图进行分析，以确定大脑活动如何与外化行为相关联，以及这些关联如何受到特定基因的影响。这项研究将是一项试点研究，允许估计参与者的数量，包括男性和女性，这将是一项更大的研究所需要的，该研究可以严格检验关于外化行为中遗传对认知影响的假设。

DESCRIPTION (provided by applicant): One of the major risks for drug abuse is a general predisposition to externalizing behavior (EB), which is a broad category that includes impulsivity, antisocial behavior, and aggression, as well as drug abuse. Understanding the psychological and biological mechanisms involved in externalizing behavior is therefore important for understanding drug abuse and for the development of successful prevention and treatment of drug abuse. Externalizing behavior is strongly genetically influenced, and genetic research is therefore well placed to illuminate its biological basis. The proposed research will use both genetic and neuroimaging methods, in order to investigate the neurobiological mechanisms involved in patterns of cognition associated with externalizing behavior. Externalizing behavior is known to be associated with cognitive deficits, including low intelligence and poor working memory (which is the ability to hold and manipulate information in mind, despite distraction). Little is known about the specific genes that influence these cognitive deficits, but genes related to the neurotransmitter dopamine are likely to be important because dopamine influences both externalizing behavior and cognitive functions like working memory. The proposed study will collect DNA from 60 people in order to identify variations in dopaminergic genes. Participants will be assessed for level of externalizing behavior and will have their brains scanned using functional magnetic resonance imaging (fMRI) while they are engaged in a working memory task. The fMRI data will provide maps of brain activity when people engage in these tasks, which can then be analyzed to determine how brain activity is associated with externalizing behavior and how these associations are influenced by specific genes. This study will be a pilot study allowing estimation of the number of participants, both male and female, that will be needed in a larger study that can rigorously test hypotheses regarding genetic effects on cognition in externalizing behavior. PUBLIC HEALTH RELEVANCE: The proposed research is relevant to public health in that externalizing behavior represents the shared risk for a number of common disorders, including drug dependence, alcohol dependence, antisocial personality disorder, conduct disorder, and ADHD. Any findings regarding the neural and genetic mechanisms that underlie externalizing behavior will have immediate impact for basic and applied research that could lead to improvements in the prevention and treatment of these disorders and their subclinical manifestations (such as antisocial behavior and drug abuse).