Hippocampal-Memory Network Development and Episodic Memory in Early Childhood

描述(申请人提供)：记忆是一种基石能力，我们在此基础上建立对我们自己和周围世界的知识。记忆力的缺陷，无论多么微小，都会对人生成功和心理健康产生重大影响。关于成年人记忆的神经基础，已经有大量的研究。这项研究表明，情景记忆依赖于大脑中位于颞叶、顶叶和前额叶的区域组成的分布式网络，其中海马体起着关键的、不可替代的作用。相比之下，很少有研究研究儿童早期记忆发展的神经机制。这尤其令人遗憾，因为行为研究表明，这是情节记忆显著而快速发展的时期。此外，来自非人类灵长类动物的神经解剖学数据表明，海马体的结构发育至少持续到出生后5岁。尽管这一发现在理论上与功能发展和行为记忆表现的改善有关，但它尚未得到实证检验。因此，尽管我们知道成年人的记忆过程和相关的神经回路，但明显缺乏对其早期功能成熟的系统研究。这不仅造成了科学理解上的差距，也阻碍了干预技术的发展，这些技术将促进或改善那些有损伤风险的人的记忆。这项建议的目的是描述早期儿童时期海马体介导的情节记忆网络的结构和功能的变化，此时儿童的情节记忆能力最强。基本的假设是，情节记忆的发展是海马体及其渐进的、整合的参与和与皮质区域分离的变化的结果。为了验证这一假说，我们将1)确定海马子区域的变化如何有助于儿童早期记忆能力的年龄相关改善，2)确定海马体如何与皮质区域整合以建立成熟的记忆网络并稳定儿童早期的记忆表现，以及3)确定在情节记忆行为改善之前的神经变化，这将成为儿童早期记忆干预的目标。为了实现这一目标，我们将从超高分辨率结构MRI、高分辨率静息状态功能MRI以及使用队列序贯设计对175名4-8岁儿童的情景记忆能力的行为评估中获得数据。这种多模式和纵向的方法将允许识别导致与年龄相关的行为变化的神经轨迹。对儿童记忆发展的系统研究对理解记忆具有重要意义，并将为记忆受损高危人群和被诊断为影响海马体和记忆的神经发育障碍的人群提供有针对性的干预(和预防)策略的关键信息。

DESCRIPTION (provided by applicant): Memory is a cornerstone ability upon which we build knowledge of ourselves and the world around us. Failures in memory, no matter how small, can significantly impact life success and mental health. A large body of research exists regarding the neural bases of memory in adults. This work indicates episodic memory relies on a distributed network of brain regions within temporal, parietal and prefrontal cortices, with the hippocampus playing a critical and irreplaceable role. In contrast, very few studies have examined neural mechanisms underlying memory development in early childhood. This is particularly unfortunate as behavioral research suggests this is a time of significant and rapid development in episodic memory. Additionally, neuroanatomical data from non-human primates have shown that structural development of the hippocampus continues at least through the 5th year postnatally. Although this finding has been theoretically linked to functional development and improvements in behavioral memory performance, it has not yet been examined empirically. Thus, despite all we know about memory processes and associated neural circuitry in adults, the systematic study of its functional maturation early in life is notably absent. This not only poses a gap in scientific understanding but also a barrier to development of intervention techniques that would facilitate or improve memory in those at-risk for impairment. The goal of this proposal is to characterize changes in the structure and function of the hippocampally-mediated episodic memory network during early childhood, when gains in episodic memory are greatest. The primary hypothesis is that episodic memory development results from changes in the hippocampus and its progressive, integrative participation and segregation with cortical areas. In order to test this hypothesis, we will 1) determine how changes in sub regions of the hippocampus contribute to age-related improvements in memory ability during early childhood, 2) determine how the hippocampus becomes integrated with cortical areas to establish a mature memory network and stabilize memory performance in early childhood and 3) identify neural changes that precede behavioral improvements in episodic memory, which will serve as targets for memory intervention in early childhood. To achieve this goal, we will acquire data from ultra-high resolution structural MRI, high resolution resting-state functional MRI, and behavioral assessments of episodic memory ability from a sample of 175 4-to 8-year-old using a cohort-sequential design. This multimodal and longitudinal approach will allow for the identification of neural trajectories that lead to age- related changes in behavior. Systematic study of memory development in childhood has important implications for understanding memory in general and will provide critical information for targeted intervention (and prevention) strategies for populations at-risk for memory impairment and those diagnosed with neurodevelopmental disorders known to affect the hippocampus and memory.