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Effect of genetics on reward learning and generalization of associations in aging

遗传学对奖励学习和衰老关联泛化的影响

基本信息

批准号：
8787983
负责人：
MARK A GLUCK
金额：
$ 7.52万
依托单位：
RUTGERS THE STATE UNIV OF NJ NEWARK
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-01-01 至 2016-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8787983
关键词：
Adult Affect Age Aging Alleles Animals Attention Baby Booms Brain region Brain-Derived Neurotrophic Factor Businesses Clinical Code Cognition Cognitive Cognitive Science Cognitive aging Computer Simulation Corpus striatum structure Data Dissociation Dopamine Economics Elderly Environment Feedback Food Genes Genetic Genetic Polymorphism Genetic Variation Genotype Goals Guidelines Health Healthcare Heterogeneity Hippocampus (Brain)Homozygote Impaired cognition Impairment Independent Living Individual Individual Differences Intervention Investments Judgment Knowledge Lead Learning Link Longevity Marketing Modeling Molecular Genetics Outcome Participant Patients Performance Persons Pharmacological Treatment Phase Phenotype Population Process Psychological reinforcement Relative (related person)Research Resources Retirement Rewards Shapes System Technology Testing Trust abstracting age effect age related base classical conditioning cognitive function cognitive process cognitive training cohort computerized conditioning dopamine transporter experience genetic makeup genetic variant healthy aging insight interest meetings neurobiological mechanism neurochemistry novel personalized intervention skills social treatment program valylvaline young adult

项目摘要

DESCRIPTION (provided by applicant): This proposed study will examine the effects of aging on reward-based associative learning and generalization and how these relationships vary by common genetic polymorphisms. The ability to acquire new skills and apply those experiences to predict positive outcomes in novel situations is essential at all ages, enabling people to make critical economic decisions or social judgments. For example, people often select stocks based on wins and losses in the market, and the integration of these reinforcement outcomes over multiple experiences can help when navigating new investments, such as retirement planning. Similarly, this proposal focuses on frontostriatal-based learning (i.e., acquiring new associations from feedback) and hippocampal- based generalization (i.e., context-dependent transfer). These processes remain relatively understudied in cognitive aging, which is surprising given their relevance to adults of all ages. Our focus on the dissociation between learning and generalization is particularly relevant to older adults because these processes call on different brain regions that are differentially affected by healthy aging. Here, 175 younger and 175 older adults will complete a variety of learning and generalization tasks that have been validated to assess frontostriatal and hippocampal function. Older adults are predicted to show greater age-related deficits on learning than generalization, adding to data that healthy aging affects the striatal system more than the hippocampus (Aim 1). Consistent with evidence of heterogeneity of cognitive function in healthy aging, we will also show that some seniors do better than others during learning and/or generalization. Because genetic polymorphisms can reveal important individual differences in cognitive function, this study will also examine genetic components that may support individual differences in learning and generalization; notably, the dopamine transport gene (DAT1), which is most abundant in the striatum, and the gene coding for Brain-Derived Neurotrophic Factor (BDNF) that has highest expression in the hippocampus. It is expected that a functional polymorphism in DAT1 will predict individual differences in frontostriatal learning, whereas a functional polymorphism in BDNF will predict individual differences in hippocampal generalization (Aim 2.1). Finally, this study will examine whether healthy aging modulates these genetic effects on cognitive function, by testing a recent hypothesis that aging magnifies the functional significance of genetic variants on cognition (Aim 2.2). It is predicted that genotypic differences on cognition will be larger in older than younger adults. The identification of cognitively relevant genes, and age-related differences therein, brings promise to refine knowledge about neurobiological mechanisms of cognition and may help to explain heterogeneity of cognitive function in old age. Understanding the mechanisms underlying individual differences in vulnerability to cognitive decline may, in turn, inform cognitive training and pharmacological treatment programs aimed at maximizing cognitive functioning in old age. These goals are increasingly important as the number of older adults in the world population steadily rises.

描述（由申请人提供）：这项拟议的研究将研究衰老对基于奖励的联想学习和泛化的影响，以及这些关系如何因常见的遗传多态性而变化。获得新技能并运用这些经验来预测新情况下的积极结果的能力对于所有年龄段的人来说都是至关重要的，这使人们能够做出关键的经济决策或社会判断。例如，人们经常根据市场上的输赢来选择股票，而这些强化结果与多种经验的整合可以在引导新投资（例如退休计划）时有所帮助。同样，该提案侧重于基于额纹状体的学习（即获取新的关联）来自反馈）和基于海马的泛化（即上下文相关的转移）。这些过程在认知衰老中的研究相对较少，考虑到它们与所有年龄段的成年人的相关性，这是令人惊讶的。我们对学习和泛化之间分离的关注与老年人尤其相关，因为这些过程需要不同的大脑区域，而这些区域会受到健康衰老的不同影响。在这里，175 名年轻人和 175 名老年人将完成各种学习和泛化任务，这些任务已被验证可以评估额纹状体和海马功能。预计老年人在学习方面会表现出比泛化更大的与年龄相关的缺陷，这进一步表明健康老龄化对纹状体系统的影响大于对海马体的影响（目标 1）。与健康老龄化中认知功能异质性的证据一致，我们还将表明，一些老年人在学习和/或概括方面比其他人做得更好。由于遗传多态性可以揭示认知功能中重要的个体差异，因此本研究还将检查可能支持学习和泛化方面个体差异的遗传成分；值得注意的是，纹状体中最丰富的多巴胺转运基因（DAT1）和海马体中表达量最高的脑源性神经营养因子（BDNF）编码基因。预计 DAT1 的功能多态性将预测额纹状体学习的个体差异，而 BDNF 的功能多态性将预测海马泛化的个体差异（目标 2.1）。最后，本研究将通过测试最近的假设，即衰老会放大遗传变异对认知的功能意义（目标 2.2），来检验健康衰老是否会调节这些遗传对认知功能的影响。据预测，老年人的认知基因型差异将比年轻人更大。认知相关基因及其与年龄相关的差异的识别，有望完善有关认知的神经生物学机制的知识，并可能有助于解释老年认知功能的异质性。了解认知能力下降的个体差异背后的机制可能反过来为旨在最大化老年认知功能的认知训练和药物治疗计划提供信息。随着世界人口中老年人数量的稳步增加，这些目标变得越来越重要。