Eyeblink Conditioning in Infants and Adults

描述（由申请人提供）：回忆能力在出生后第一年的下半年发生了巨大的变化。在此期间，表现有很大的差异：一些婴儿在长时间的延迟后回忆起来，而另一些则没有。个体差异的一个潜在因素可能是神经基质发育状态的可变性，特别是海马体的成分。虽然没有直接测量海马功能的方法用于正常发育的人类婴儿，但一种有希望的间接测量方法是追踪眨眼条件反射，这是已知的海马体依赖性，使任务的表现成为人类婴儿海马体发育的一个很好的候选标记。尽管有这种潜力，但还没有研究表明，在生命的第一年里，痕迹眨眼条件反射的变化，这是海马体发育的重要时期。拟议的研究是第一个这样的研究，也是第一个关于海马体发育（通过跟踪眨眼条件反射的年龄相关变化来测量）和通过识别（使用事件相关电位：erp测量）和回忆（通过诱导和延迟模仿测量）评估的长期记忆之间关系的一系列调查。该提案的第一个目标是检查第一年下半年在延迟（标准和长）和跟踪眨眼条件反射任务中的表现变化。由于与任务相关的神经结构（分别是小脑和海马体）的不同发育，延迟条件反射表现的变化预计比跟踪条件反射表现的变化更快。第二个具体目的是比较婴儿在延迟和追踪条件反射任务上的表现与成人的表现，以确定行为的相对功能成熟度。因为追踪眨眼条件反射可以在整个生命周期和物种之间进行测试（更典型的是，不同的种群必须在不同的任务上进行测试），它可以用来检查记忆发展的连续性和非连续性。由于这项任务可以跨物种使用，因此它具有巨大的潜力，可以“诊断”已知存在记忆缺陷的特殊人类婴儿群体（例如，母亲患有糖尿病的婴儿；足月前出生但其他方面健康的婴儿）的记忆障碍的具体来源。因此，作为海马体发育标志的微量眨眼条件反射的发展对基础研究和转化研究具有重要的前景。回忆的能力在一岁后的下半年发生了巨大的变化。在这个早期阶段，记忆障碍在高危人群的行为中表现得很明显，包括糖尿病母亲的婴儿和足月前出生但其他方面健康的婴儿。一个与规范性发展和行为缺陷相关的因素是海马体的完整性。本研究的目的是测试痕迹眨眼条件反射作为海马体完整性的可能标记或探针，从而建立用于早期诊断和治疗的任务。

DESCRIPTION (provided by applicant): The ability to recall changes dramatically in the 2nd half of the 1st year of life. During this period there is great variability in performance: some infants recall after long delays, whereas others do not. One factor underlying individual differences may be variability in the developmental status of the neural substrate, specifically components of the hippocampus. Although there are no direct measures of hippocampal functioning for use with typically developing human infants, a promising indirect measure is trace eyeblink conditioning, which is known to be hippocampally dependent, making performance on the task an excellent candidate as a marker for hippocampal development in human infants. In spite of this potential, there have been no studies of changes in trace eyeblink conditioning across the 1st year of life, a period of substantial & significant hippocampal development. The proposed research is the first such study & also is the first in what will be a series of investigations of relations between hippocampal development (as measured by age-related changes in trace eyeblink conditioning) & long-term memory assessed via recognition (measured using event- related potentials: ERPs) & recall (measured by elicited & deferred imitation). The first aim of the proposal is to examine changes in performance on delay (standard & long) & trace eyeblink conditioning tasks across the latter half of the first year. Due to differential development of the neural structures implicated in the tasks (cerebellum & hippocampus, respectively), delay conditioning performance is expected to change more rapidly than trace conditioning performance. The second specific aim is to compare infants' performance on delay & trace conditioning tasks with that of adults' to determine relative functional maturity of behavior. Because trace eyeblink conditioning can be tested across the lifespan & across species (more typically, different populations must be tested on different tasks), it can be used to examine continuities & discontinuities in memory development. Because the task can be used across species, it has enormous potential to "diagnose" the specific source of memory impairment in special populations of human infants known to experience memory deficits (e.g., infants of diabetic mothers; infants born prior to term but otherwise healthy). Development of trace eyeblink conditioning as a marker for hippocampal development thus holds significant promise for basic as well as translational research. The ability to recall changes dramatically in the 2nd half of the 1st year of life. At this early age, impairments in memory are apparent in the behavior of at-risk groups, including infants of diabetic mothers and infants born prior to term but otherwise healthy. One factor implicated in both normative development and behavioral deficits is the integrity of the hippocampus. The proposed research is to test trace eyeblink conditioning as a possible marker or probe of the integrity of the hippocampus, thereby establishing the task for use in early diagnosis and treatment.