Development of Neural Systems Underlying Learning and Response to Novelty

描述（由申请人提供）：这是一份经过修订的K01提案，旨在培养神经影像学应用于基于环境统计的学习发展调查的专业知识，即频率和基于关联的学习。候选人制定了详细的职业发展计划，包括教学课程、神经影像学研讨会、持续的监督、培训和咨询领域专家。拟议的培训将在康奈尔大学威尔医学院的萨克勒研究所进行。萨克勒拥有几位世界知名的认知发育神经科学家，是少数几个完全致力于利用神经成像技术进行发育研究的设施之一。在之前的工作中，我们发现纹状体参与简单的基于频率的学习，海马体参与联想学习。我们将检验这样一个假设：虽然这些形式的学习在发育早期是完整的，但在学习过程中有效维护信息的能力，以及在新信息违反所学信息时调整行为的能力，随着潜在神经回路（如额纹状体和额海马体回路）的组织，发展得更加缓慢。在刺激呈现和/或与其他刺激相关联的频率上的统计操作将是主要的操作。婴儿的扫视潜伏期，儿童、青少年和成人的扫视潜伏期和反应时间将被用作行为依赖的测量。在另一个单独的会议上，将使用功能性磁共振成像（fMRI）和弥散张量成像（DTI）对相同的儿童，青少年和成人进行评估，以评估大脑区域招募的变化以及这些区域之间作为学习和发展功能的连接。这些研究对早产和极低出生体重（VLBW, < 1500克）的儿童具有重要意义，这些儿童在围产期非常容易发生轻微的纹状体和海马损伤，大约40%的儿童会有一些学习障碍。通过跟踪该电路在典型发育过程中学习功能的变化，这些研究将为临床研究奠定基础，这些临床研究可以确定精确的学习中断（特定于纹状体或海马电路）以及相关结果和早产儿和VLBW人群的学习障碍。K01研究将提供一种方法，通过这种方法可以约束对未来临床研究数据的解释。

DESCRIPTION (provided by applicant): This is a revised K01 proposal designed to foster expertise in the application of neuroimaging to a developmental investigation of learning based on environmental statistics, namely frequency and association-based learning. The candidate has formulated a detailed career development plan composed of didactic coursework, neuroimaging workshops, and ongoing supervision, training, and consultation with field experts. The proposed training will be conducted at the Sackler Institute at the Weill Medical College of Cornell University. The Sackler houses several world-renowned cognitive developmental neuroscientists and is one of the few facilities dedicated entirely to developmental research using neuroimaging technology. In previous work, we found the striatum to be involved in simple frequency-based learning and the hippocampus to be involved in associative learning. We will test the hypothesis that while these forms of learning are intact early in development, the ability to efficiently maintain information during learning and adjust behavior when learned information is violated by novel information develops more gradually as the underlying neural circuitry (e.g., frontostriatal and frontohippocampal circuits) is organized. Statistical manipulations in the frequency with which stimuli are presented and/or associated with other stimuli will be the primary manipulation. Saccade latency in infants, and both saccade latency and reaction times in children, adolescents, and adults will be used as behavioral dependent measures. In a separate session, functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI)will be used with the same children, adolescents, and adults to assess changes in the recruitment of brain areas and in connectivity between these areas as a function of learning and development. These studies have significant implications for children born preterm and very low birth weight (VLBW, < 1500 grams) who are highly susceptible to subtle striatal and hippocampal injury in the perinatal period, and approximately 40% of who will have some learning disability. By tracking changes in the learning functions of this circuitry across typical development, these studies will lay the foundation for clinical studies that can identify precise learning disruption (specific to striatal or hippocampal circuitry) and associated outcomes and learning disabilities in this preterm and VLBW population. The K01 studies will provide a means by which interpretations of data from future clinical studies can be constrained.