Variability in Brain Function Underlying Motivated Behavior in Adolescence

青春期动机行为背后的大脑功能变异

• 批准号: 8554309
• 负责人: BEATRIZ LUNA
• 金额: $ 18.13万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-26 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8554309
• 关键词: 3' Untranslated Regions; Adolescence; Adolescent; Adolescent Behavior; Adolescent Development; Adult; Age; Area; Base of the Brain; Behavior; Behavioral; Behavioral Genetics; Biological; Brain; Brain imaging; Brain region; Catechols; Clinical; Cognitive; Collaborations; Complex; Corpus striatum structure; Data; Development; Dopamine; Education; Enrollment; Enzymes; Functional Magnetic Resonance Imaging; Future; Genes; Genetic; Genetic Polymorphism; Genotype; Image; Incentives; Individual; Individual Differences; Knowledge; Literature; Mediating; Methodology; Methyltransferase; Methyltransferase Gene; Neurobiology; Neurosciences; Neurotransmitters; Nucleotides; Parents; Participant; Pattern; Phase; Population; Positioning Attribute; Prefrontal Cortex; Process; Psychopathology; Publishing; Recruitment Activity; Research; Rest; Rewards; Risk-Taking; Role; Saliva; Sample Size; Sampling; Seeds; Series; Shapes; Single Nucleotide Polymorphism; Support System; Synapses; System; Tandem Repeat Sequences; Time; Variant; Ventral Striatum; age related; base; cognitive control; dopamine system; dopamine transporter; emerging adult; gene function; genetic variant; interest; motivated behavior; neural circuit; neurobiological mechanism; neurodevelopment; neuroimaging; novel; parent grant; relating to nervous system; response; reward processing; statistics; trafficking; trait; translational neuroscience; transmission process

DESCRIPTION (provided by applicant): Adolescence is a unique period of development characterized by heightened risk-taking indicating continued limitations in cognitive control and reward related behaviors as well as vulnerabilities for the emergence of psychopathology. Studies have shown significant developmental changes in frontostriatal function underlying reward and cognitive behaviors from adolescence to adulthood. However, the core mechanisms influencing the development of these processes are not well understood. Dopamine (DA) is a key neurotransmitter in the modulation of cognitive and reward-related processing in frontostriatal regions of the brain. During adolescence, the DA system demonstrates unique immaturities which may contribute to limitations in reward processing during this time. Imaging genetics studies have shown that subtle allelic variations in specific genes that directly impact DA processing, can have profound impact on behaviorally relevant neural activity. How genetically-driven variability in DA processing interacts with age-related differences in DA availablity are not well understood limiting our ability to understand variability in developmental trajectories of motivated complex behavior. Incorporating imaging genetics with brain-imaging studies during adolescent development can help clarify known age-related differences in reward processing and cognitive control as well as contribute to our basic understanding of DA's effect on behavior. Two crucial enzymes involved in the synaptic trafficking of DA and likely to have impact on reward and cognitive control systems are catechol-o-methyltransferase (COMT) and the dopamine transporter (DAT1). Because these enzymes have differential effects on PFC and striatum, investigating effects of their genotypic variation offers a new way to examine the integrity of frontostriatal networks. We will obtain saliva samples from subjects in our ongoing parent grant investigating behavioral and neuroimaging evidence for the effects of reward processing on the development of cognitive control. We will study a single nucleotide polymorphism (val158met) in the COMT gene, and a variable-nucleotide tandem repeat (VNTR) polymorphism of the SLC6A3 gene within the context of the development neural systems underlying incentive-based cognitive control. The specific aims of this revision are to 1) characterize the influence of genetically-driven DA variation expressed through SLC6A3 and COMT on brain function underlying reward processing and cognitive control; 2) To identify differences in the influence of genetically- driven variation on resulting behaviorally-relevant neural circuitry in adolescence compared to adulthood. Multiple regression and multi-variate imaging statistics methodologies will be used to explore age and genotype effects and interactions. This integrative neuroscience approach will allow greater understanding of associations between genes and the function of behaviorally relevant neural systems and support inferences about resulting behavioral implications, within a framework of adolescent development.

描述(由申请人提供)：青春期是一个独特的发展时期，其特点是高度冒险，表明认知控制和与奖励有关的行为持续受到限制，以及出现精神病理学的脆弱性。研究表明，从青春期到成年期，额纹状体功能、潜在的奖励和认知行为都发生了显着的发展变化。然而，影响这些进程发展的核心机制还没有得到很好的理解。多巴胺(DA)是调节大脑额纹状体区域认知和奖赏相关处理的关键神经递质。在青春期，DA系统表现出独特的不成熟，这可能导致这一时期奖励处理的局限性。成像遗传学研究表明，直接影响DA处理的特定基因的细微等位基因变化可以对行为相关的神经活动产生深远影响。DA加工中的遗传变异如何与年龄相关的DA可获得性差异相互作用尚不清楚，这限制了我们理解发育过程中的变异的能力 有动机的复杂行为的轨迹。将成像遗传学与青春期大脑成像研究相结合，有助于澄清已知的与年龄相关的奖赏加工和认知控制差异，并有助于我们基本理解DA对行为的影响。参与多巴胺突触运输的两种关键酶是儿茶酚-O-甲基转移酶(COMT)和多巴胺转运体(DAT1)，它们可能对奖赏和认知控制系统产生影响。由于这些酶对PFC和纹状体有不同的影响，研究它们的基因变异的影响为检测额纹状体网络的完整性提供了一种新的方法。我们将从正在进行的父母拨款中获取受试者的唾液样本，调查奖励处理对认知控制发展的影响的行为和神经成像证据。我们将研究COMT基因的单核苷酸多态(Val158met)和SLC6A3基因的可变核苷酸串联重复序列(VNTR)多态，在基于激励的认知控制基础上的神经系统发育的背景下。这项修订的具体目的是1)表征通过SLC6A3和COMT表达的遗传驱动的DA变异对潜在的奖励处理和认知控制的大脑功能的影响；2)确定与成年相比，遗传驱动的变异对青春期由此产生的行为相关神经回路的影响的差异。将使用多元回归和多变量成像统计方法来探索年龄和基因型的影响和相互作用。这种综合的神经科学方法将使人们能够更好地了解基因与行为相关神经系统功能之间的联系，并在青少年发展的框架内支持对由此产生的行为影响的推断。