Understanding and improving hippocampal neuroplasticity through allocentric spatial navigation training

通过异中心空间导航训练了解和改善海马神经可塑性

• 批准号: RGPIN-2017-06615
• 负责人: Green, Robin
• 金额: $ 1.82万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=681259
• 关键词: Understanding; improving; hippocampal; neuroplasticity; through

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.**

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最重要的目标之一是“远转移”，指的是经验/训练的可推广和灵活的认知益处，这种益处超越了训练环境，延伸到现实世界。大量关于环境富集（EE）的文献表明，神经脆弱的动物和人类（如脑损伤、早产儿）表现出经验依赖的神经可塑性变化，一些研究显示伴随的行为改善。但在健康的年轻人中，这一比例存在显著差距。我们研究项目的长期愿景是了解情感表达对HC和远端迁移的影响机制，更深入地了解HC如何从机制上支持远端迁移。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。异中心空间导航——从“鸟瞰图”进行导航，需要在脑海中创建一个环境地图——被认为可以有力地激活和增强海马体。（HC）使用这种导航方式的人的HC更大，更不容易加速衰老过程。研究发现，将异心空间导航与情感表达（即密集、持续新颖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，并伴有适度的记忆增加。因此，拟议的研究计划将需要利用情感表达原则向健康年轻男性提供一个非中心空间导航范式。全面、高度敏感和特定的“远转移”记忆结果（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（包括体积、DTI、MRS、CVR和ASL）的全面MRI成像一起进行。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，密集的非中心空间导航将导致结构和功能上的HC变化，从而导致学习和记忆的普遍增强。通过增加训练强度（项目2），假设这些发现将被放大，具有更强大的远迁移和hc -记忆关联。二级亚组分析的结果将允许探索已知的影响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，并采取更细致的方法来研究认知和神经变化强度的影响**