Understanding and improving hippocampal neuroplasticity through allocentric spatial navigation training

长期以来，提高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一个最重要的目的是“远迁移”，指的是经验/培训的可概括性和灵活性的认知益处，这些好处超出了培训的背景，进入了现实世界。大量关于环境丰富(EE)的文献表明，神经学上脆弱的动物和人类(例如，脑损伤、早熟)表现出经验依赖性的神经可塑性变化，一些研究表明伴随而来的行为改善。但当涉及到健康的年轻人时，有一个明显的差距。我们研究计划的长期愿景是了解EE对HC和关于FAR转移的机制，并更好地了解HC如何从机械上支持FAR转移。有一小部分有希望的研究指出，异地空间导航可以实现这一点。分心空间导航--从“鸟瞰”中导航，需要创建一个人所处环境的心理地图--众所周知，它可以有力地激活和增强海马体。(HC)使用这种导航的人有更大的HC，不太容易受到加速衰老过程的影响。研究发现，将异地空间导航与EE(即密集、持续的新奇和引人入胜的认知刺激)相结合，可以抵消健康的年轻和老年男性正常的HC下降，并伴随着适度的记忆增加。因此，拟议的研究计划将需要向健康的年轻男性提供一个利用EE原理的分配中心空间导航范例。全面、高度敏感和特定的“远迁移”记忆结果(包括模式产生和分离、位置和陈述性记忆)将与HC和相关区域(包括容量、DTI、MRS、CVR和ASL)的全面MRI成像一起进行管理。在项目1中，性能将与通用的、非目标的EE控制协议进行比较。据推测，密集的同位空间导航将导致结构和功能上的HC变化，进而导致学习和记忆的普遍增强。通过增加训练的强度(项目2)，假设这些发现将被放大，并与更强大的远距离迁移和HC-记忆联系。对结果的次级分组分析将允许探索已知的影响HC的因素(例如，年龄、教育程度)。项目2的发现将为下一阶段的研究提供基础，在包括老年人和女性在内的更广泛的人口样本中探索上述机制，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.