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空间导航中海马轴的梯度拓扑规律及其老化的神经影像机制
其他题名Gradient topology pattern along hippocampal axis and its aging in spatial navigation: Neuroimaging mechanisms in spatial navigation: Neuroimaging mechanisms
张家鑫
导师左西年 ; 李会杰
2023-06
摘要空间导航作为日常生活中必不可少的综合性认知功能,在人类健康老化过程中,较早地出现退化并极易在高龄阶段丧失。大量已有研究表明:海马为空间导航能力提供了关键性的神经功能支撑,而这一区域本身又展现出极大的老化敏感性与异质性。因此,阐明海马子区域的差异性老化及其在空间导航过程中的不同贡献及其内在机制是深入理解海马与空间导航的关键。本文提出海马轴的梯度拓扑规律,刻画海马功能组织特性,沿自头至尾的海马轴连续建模海马相关的认知过程。具体而言,轴的一端(海马尾部)加工具体的、实例化的信息,另一轴端(海马头部)加工抽象的、一般化的信息,轴中间位置功能则由其距离头尾端点的拓扑距离决定。本文构建了自然情景空间导航的磁共振功能影像研究范式,采用横纵结合的实验设计,实现对上述梯度规律的验证。 为了验证人类海马的拓扑梯度规律,研究一收集了30名青年人的行为与磁共振扫描数据,青年人的空间导航成绩随着学习不断提升,表明了实验范式的有效性与空间导航行为成绩的学习效应。借助体素间相似性分析、表征相似性分析、多体素模式分析等技术,我们测量到了空间导航过程中海马表征粒度梯度、表征组织梯度和表征映射梯度。在表征粒度梯度上,在空间导航过程中,海马头部到尾部呈现出表征粒度的降低,反映了海马位置域的尺度变化,即该区域的体素对多大空间范围做出反应,这种尺度从海马头部到尾部逐渐减小;而在表征组织梯度上,海马从头到尾表现出从概念化到实例化的信息组织方式过渡,这允许海马兼顾多个抽象尺度上的信息以帮助导航,例如具体的路线与相同规则的路线组;而在表征映射关系上,我们仅仅在尾部发现了神经表征与刺激的一一映射关系,这意味着在海马尾部上,信息被具体地、与刺激对应的表征出来了,而非多对一或一对多的映射关系。为了对比青年人与老年人的海马梯度差异,研究二在研究一数据基础上,另招募30名老年人参与者,对比青年人与老年人的空间导航成绩,发现老年人的空间导航功能损伤,并且在海马轴的三个梯度上均表现出了明显的变平,包括整体梯度水平改变和海马头尾功能差异减小。对比青年人来看,老年人头尾的功能差异减小主要来自于海马头部功能的损伤。横断数据可能仅仅反映了个体差异,而纵向数据才能更为准确地反映老化改变,因此研究三对老年人进行了间隔2年的追踪,通过对比两次来访的数据,本研究发现老年人表征粒度梯度的整体水平在两年间持续老化,而表征组织与表征映射梯度保持稳定。 本研究系统地探讨了海马的功能,提出了海马的梯度拓扑组织规律,验证了在空间导航过程中,海马轴上所存在的三个维度梯度,包括表征粒度、表征组织、表征映射梯度。未来的研究有望将此海马的梯度拓扑规律推广至其他认知领域,为开展海马研究提供一个统一的、指导性的研究框架。此外,利用横断与纵向数据,本研究明确了老化因素对海马功能梯度的影响,发现在个体衰老过程中,海马功能梯度将持续变缓,这一过程的主导因素来自海马头部老化。
其他摘要Spatial navigation, an essential and integrated cognitive function in daily life, degenerates early in healthy aging and is highly susceptible to loss of deficits at advanced ages. Numerous studies have shown that the hippocampus provides critical neurological support for spatial navigation, and this region itself exhibits great aging sensitivity and heterogeneity. Therefore, elucidating the differential aging of hippocampal sub-regions and their different contributions to spatial navigation processes and their underlying mechanisms is key to a deeper understanding of the hippocampus and spatial navigation. In this paper, we propose a gradient topology law of the hippocampal axis to characterize the functional organization of the hippocampus and model hippocampus-related cognitive processes continuously along the hippocampal axis from head to tail. Specifically, one end of the axis (hippocampal tail) processes concrete and instantiated information, the other end of the axis (hippocampal head) processes abstract and generalized information, and the middle position function of the axis is determined by its topological distance from the head and tail endpoints. In this paper, we construct a paradigm for MRI functional imaging studies of natural situational spatial navigation, and use a combined cross一sectional and longitudinal experimental design to achieve verification of the above gradient law. In Study 1, behavioral and MRI scan data were collected from 30 young people, and the spatial navigation performance of the young people kept improving with learning, indicating the validity of the experimental paradigm and the learning effect of the behavioral performance of spatial navigation. With the help of inter-voxel similarity analysis, representational similarity analysis, and multi-voxel pattern analysis, we measured functional gradients in three dimensions of the hippocampus during spatial navigation, including representational granularity gradient, representational organization gradient, and representational mapping gradient. On the representational granularity gradient, the hippocampus showed a decrease in representational granularity from head to tail during spatial navigation, reflecting a change in the scale of the hippocampal location domain, i.e., how large a spatial extent the voxels in this region respond to, which gradually decreases from the head to tail of the hippocampus; and on the representational organization gradient, the hippocampus showed a transition from conceptual to instantiated information organization from head to tail, which allows the hippocampus to take into account information on multiple abstract scales to aid navigation, such as specific routes versus groups of routes with the same rules; and in terms of representational mapping relationships, we found a one-to-one mapping of neural representations to stimuli only in the caudal region, implying that information was represented concretely and correspondingly to stimuli in the hippocampal caudal region, rather than in a many-to-one or one-to-many mapping relationship. In Study 2, based on the data from Study 1, another 30 elderly participants were recruited to compare the spatial navigation performance of young people with that of the elderly, and it was evident that spatial navigation was impaired in the elderly. And a significant flattening was demonstrated on all three gradients of the hippocampal axis, including an overall gradient level change and a reduction in the difference in hippocampal cephalocaudal function. This reduction in cephalocaudal function was mainly due to the impairment of hippocampal head function when comparing the results in young adults. Study 3 followed older adults at 2-year intervals, and by comparing the data from the two visits, this study found that the overall level of representational size gradient in older adults continued to age over the two years, while the representational tissue and representational mapping gradients remained stable. In this study, we systematically explored the function of the hippocampus and proposed the law of gradient topology in the hippocampus, and we verified the three dimensional gradients, including representational granularity, representational organization, and representational mapping gradients, present in the hippocampal axis during spatial navigation. Future research is expected to extend this hippocampal gradient topological law to other cognitive domains and provide a unified and guiding research framework for conducting hippocampal research. In addition, using cross-sectional and longitudinal data, we clarified the influence of aging factors on the hippocampal functional gradient, which will continue to slow down during individual aging, and the dominant factor of this process may come from damage to the hippocampal head.
关键词空间导航 老化 海马轴 功能梯度 磁共振成像
学位类型博士
语种中文
学位名称理学博士
学位专业认知神经科学
学位授予单位中国科学院大学
学位授予地点中国科学院心理研究所
文献类型学位论文
条目标识符http://ir.psych.ac.cn/handle/311026/46219
专题认知与发展心理学研究室
推荐引用方式
GB/T 7714
张家鑫. 空间导航中海马轴的梯度拓扑规律及其老化的神经影像机制[D]. 中国科学院心理研究所. 中国科学院大学,2023.
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