Understanding and improving hippocampal neuroplasticity through allocentric spatial navigation training

长期以来，增强健康年轻人的日常学习和记忆能力一直是学术研究和商业企业难以实现的目标。可以说，经验依赖可塑性研究的最重要目标之一是“远迁移”，指的是经验/训练的可推广和灵活的认知益处，其延伸超出训练背景并进入真实的世界。大量关于环境富集（EE）的文献表明，神经脆弱的动物和人类（例如，脑损伤、早产儿）表现出经验依赖性神经可塑性变化，一些研究显示伴随的行为改善。但在健康的年轻人身上，存在着明显的差距。我们研究计划的长期愿景是了解EE对HC和远距离转移的机制，更好地了解HC如何机械地支持远距离转移。一小部分有前途的研究指出，非中心空间导航可以实现这一目标。Allocentric空间导航-从“鸟瞰”导航需要创建一个人的环境的心理地图-被称为强大的激活和增强的大脑。(HC)使用这种类型导航的人有更大的HC，不太容易受到加速老化过程的影响。将非中心空间导航与EE相结合（即，密集的、持续新颖的和吸引人的认知刺激）抵消了健康年轻和老年男性成年人的正常HC下降，并具有适度的记忆增加。因此，拟议的研究计划将需要提供一个allocentric空间导航范式，以健康的年轻男性成年人利用的原则EE。全面，高度敏感和具体的“远转移”记忆的结果（包括模式生成和分离、定位和陈述性记忆）将与HC和相关区域的全面MRI成像一起沿着进行（包括容积、DTI、MRS、CVR和ASL）。在项目1中，性能将与一般化的非目标EE控制协议进行比较。据推测，密集allocentric空间导航将导致结构和功能HC的变化，这反过来又会引起普遍的增强学习和记忆。通过增加训练强度（项目2），假设这些发现将被放大，具有更强大的远距离转移和HC记忆关联。对研究结果的次级亚组分析将允许探索已知影响HC的因素（例如，年龄、教育）。项目2的研究结果将为下一阶段的研究奠定基础，在更广泛的人口样本中探索上述机制，包括老年人和女性，并采取更细粒度的方法来研究认知和神经变化强度的影响。

Enhancing everyday learning and memory capacity in healthy young adults has long been an elusive goal of academic research and commercial enterprise. Arguably, one of the most important aims of research in experience dependent plasticity is “far transfer”, referring to generalizable and flexible cognitive benefits of experience/training that extend beyond the training context and into the real world. A large body of literature on environmental enrichment (EE) shows that neurologically vulnerable animals and humans (e.g., brain injured, pre-mature) demonstrate experience-dependent neuroplastic change, with some studies showing concomitant behavioural improvements. But there is a notable gap when it comes to healthy young adults. The long-term vision of our research program is to understand mechanisms of EE on the HC and on far transfer, with a greater understanding of how the HC mechanistically supports far transfer. A small body of promising research points to allocentric spatial navigation to achieve this. Allocentric spatial navigation - navigation from a “bird's eye view” necessitating the creation of a mental map of one's environment - is known to robustly activate and enhance the hippocampi.(HC) Those who use this type of navigation have larger HC that are less vulnerable to accelerated aging processes. Combining allocentric spatial navigation with EE (i.e., intensive, continuously novel and engaging cognitive stimulation) has been found to offset normal HC decline in healthy young and older male adults and with modest memory increases. Therefore, the proposed program of research will entail the delivery of an allocentric spatial navigation paradigm to healthy young male adults harnessing the principles of EE. Comprehensive, highly sensitive and specific “far transfer' memory outcomes (including pattern generation and separation, location and declarative memory) will be administered along with comprehensive MRI imaging of the HC and related regions (including volumetric, DTI, MRS, CVR and ASL). In Project 1, performance will be compared to a generalized, non-targeted EE control protocol. It is hypothesized that intensive allocentric spatial navigation will result in structural and functional HC changes that will in turn give rise to generalizable enhancements to learning and memory. By augmenting the intensity of training (Project 2), it is hypothesized that these findings will be amplified, with more robust far transfer and HC-memory associations. Secondary sub-group analyses of the findings will permit exploration of factors known to affect the HC (e.g., age, education). Project 2 findings will provide groundwork for a next stage of research exploring the above mechanisms in a broader demographic sample, including older adults and females, and taking a more fine-grained approach to the impact of intensity of cognitive and neural changes.**