人口老龄化问题是全球范围内面临的一项严峻挑战，在该背景下，老化相关认知和脑疾病严重威胁老年人健康，认知功能老化与脑老化基础研究因此显得尤为重要。该领域研究不仅有助于揭示认知老化的规律、探究相关神经机制，更为制定有效的干预方案提供了理论基础。
情景记忆（Episodic Memory，EM）是指对特定事件的经历和相关背景信息进行编码、存储和回忆的认知能力，容易受到老化的影响。深入研究情景记忆如何受到年龄的影响及其神经机制，对于解释老年人情景记忆功能下降的机理具有重要意义。既往基于功能磁共振成像（Functional Magnetic Resonance Imaging，fMRI）研究发现，老年人的情景记忆下降与前额叶、内侧颞叶、海马、后内侧皮层、视觉皮层为主的广泛脑区的功能异常有关，体现为激活下降与功能失连接等；随着神经影像技术的发展，发现了情景记忆的加工涉及多个初级感知觉皮层与跨模态皮层之间的广泛交流，相关加工系统体现出层级化加工模式。由于老化进程中的网络去分化，不同功能层级的分离逐渐模糊，这可能与情景记忆的衰退存在关联，但迄今为止尚未有研究从脑功能层级化老化的角度对情景记忆衰退的脑功能机制进行详细探讨。
功能梯度（Functional Gradient，FG）是一种以连续的视角量化脑功能的层级化组织模式的指标，鉴于脑功能明显的层级化分布模式，应用该方法可以将复杂的脑功能拆分为多个低维成分，为皮层功能的基本组织模式提供深刻洞察。静息态功能梯度容易受到年龄的影响，相关发育研究发现12岁左右的个体从以初级感知觉皮层之间的分离为主导的梯度转变为以初级感知觉皮层与跨模态皮层之间的分离为主导的梯度，这种梯度翻转现象反映了脑功能成熟与认知能力发展。有研究观察到老年人群出现了与12岁前儿童相似的梯度模式，但这种现象是否反映了普遍的脑功能老化特征尚不明确。任务态功能梯度反映了任务特异性的脑功能组织模式，能够更加准确地刻画特定条件下的功能层级化特征，然而迄今为止，尚未有研究对情景记忆任务态功能梯度模式进行深入的探讨和系统的分析。另一方面，厘清复杂脑功能的底层结构基础是神经科学领域的重要目标之一，已有研究通过探讨白质纤维网络与静息态功能网络的耦合关系，间接解释了功能梯度的分布特征。然而，目前仍然缺乏关于脑结构与功能梯度之间，特别是在任务状态下关联的直接证据。
在上述研究背景下，本研究基于大样本、多模态脑影像数据，结合功能梯度、逐步功能连接等功能连接组学的前沿数据分析方法，从探明静息态功能梯度的老化规律与情景记忆的关系出发，深入探索情景记忆任务态脑功能梯度的特异性模式与老化规律，最终厘清情景记忆任务态功能梯度的脑结构基础，并综合探讨情景记忆衰退的功能梯度特征。本研究包括三个子研究，具体研究内容如下：
研究一：情景记忆衰退与静息态功能梯度的关系。本研究旨在探索静息态功能梯度的老化规律，以及功能梯度的老化是否与情景记忆的衰退有关，以探明静息态功能梯度对情景记忆的影响。结果显示，静息态下老年人的平均梯度模式与12岁前的儿童更加接近，即梯度1为初级感知觉皮层之间分离的梯度，而梯度2为初级感知觉与跨模态皮层分离的梯度。梯度模式的差异在一定程度上解释了老年人认知功能的个体差异，例如与12岁前的儿童相似的梯度模式带来了老化初期更好的基于视觉的情景记忆表现，但同时也伴随着更强的情景记忆表现下降，而与年轻成年人的梯度模式（梯度1为初级感知觉与跨模态皮层分离的梯度，梯度2为初级感知觉皮层之间分离的梯度）相似的个体则在老化进程中表现出良好的保持。
研究二：情景记忆衰退与任务态功能梯度的关系。本研究基于老年人群的情景记忆任务表现与任务态fMRI数据，结合功能梯度与逐步功能连接分析方法，阐明情景记忆任务的两个关键阶段——编码阶段与再认阶段的功能梯度老化趋势，以及击中与漏报的功能层级化特征差异，以厘清情景记忆任务态功能梯度与情景记忆衰退之间的联系。结果显示，老年人在编码和再认阶段的功能梯度相较于静息态发生了一定程度的重组，但全局组织模式基本保持一致，并且任务态两个阶段的梯度模式非常相似。在编码阶段，初级感知觉皮层与跨模态皮层的分离梯度（梯度2）更重要，而再认阶段则更多涉及初级感知觉皮层间的分离梯度（梯度1），这表明老年人在不同任务阶段对脑功能组织的调用程度存在差异。另一方面，正确的记忆表现出在编码阶段更高的梯度2的解释率、再认阶段梯度1更强的压缩，以及需要更长的神经连接路径，但随着老化的进程，路径步长变短和终点梯度值的增加反映了网络去分化的特点。这些结果揭示了老年人在情景记忆任务中的特异性功能组织变化。
研究三：情景记忆相关功能梯度的脑结构基础。本研究旨在确认老化过程中灰质结构共变网络和两种白质网络（白质纤维数量网络，白质纤维长度网络）的衰退模式，并探讨这些结构网络指标对情景记忆任务态两阶段功能梯度的支持。结果显示，老年人群在灰质结构共变网络和白质纤维网络方面均存在显著的退化，腹内侧前额叶对海马与腹侧视觉皮层的补偿在老化进程中逐渐增强。脑结构对情景记忆任务态的功能梯度有着稳定的预测能力，且更高的结构共变强度、更多的白质纤维数量，尤其是有着更多长程纤维数量的区域对情景记忆任务态的功能梯度有着更好的预测性能。白质纤维长度的分布相较于其他两种结构网络，对功能梯度的组织方式具有更好的预测性能。此外，海马亚区的功能梯度与任务表现之间的关系并未受到白质纤维长度特征的显著影响，凸显了功能梯度在任务表现中独立于脑结构特征的支持作用。
综上所述，本研究的创新性成果包括：（1）通过老年人静息态的梯度模式差异解释了情景记忆表现的个体差异。（2）创新性地通过计算功能梯度，从脑功能层级化的角度揭示情景记忆衰退相关的脑功能基础。（3）强调了白质纤维长度对情景记忆任务态下的功能梯度组织模式的重要性。通过上述对功能梯度老化规律的探索，为深入理解情景记忆衰退的脑功能机制提供了重要证据，也为后续开发基于脑功能层级化特征的情景记忆提升手段提供了一定程度的理论依据。

The issue of population aging is a significant global challenge, with age-related cognitive decline and brain diseases posing severe threats to the health of the elderly. In this context, understanding the cognitive and brain aging processes becomes critically important. Research in this field not only helps uncover the patterns of cognitive aging and explore the underlying neural mechanisms but also provides a theoretical foundation for developing effective intervention strategies.
Episodic memory (EM) refers to the cognitive ability to encode, store, and recall specific events and associated contextual information, and it is particularly vulnerable to aging. A thorough investigation of how episodic memory is affected by aging and its neural mechanisms is crucial for understanding the decline in episodic memory function in the elderly. Previous studies using functional magnetic resonance imaging (fMRI) have revealed that the decline in episodic memory in older adults is associated with functional abnormalities in widespread brain regions, including the prefrontal cortex, medial temporal lobe, hippocampus, posterior medial cortex, and visual cortex. These abnormalities manifest as reduced activation and disrupted functional connectivity. With advancements in neuroimaging technology, it has been discovered that episodic memory processing involves extensive communication between primary sensory cortices and transmodal cortices, with these processing systems exhibiting a hierarchical organization. The network dedifferentiation observed during aging leads to a blurring of the distinction between different functional hierarchies, which may be associated with the decline in episodic memory. However, no studies have yet explored the neural mechanisms of episodic memory decline from the perspective of hierarchical brain function aging.
Functional gradient (FG) is a metric that quantifies the hierarchical organization of brain function from a continuous perspective, providing significant insights into the fundamental organizational patterns of cortical function. Resting-state functional gradients are sensitive to aging. Developmental studies have found that around the age of 12, individuals experience a reversal from a gradient dominated by the separation between primary sensory cortices to one dominated by the separation between primary sensory cortices and transmodal cortices. This gradient reversal phenomenon reflects brain functional maturation and cognitive development. Some studies have observed that older adults exhibit a gradient pattern similar to that of children under 12 years old, but whether this phenomenon reflects a general characteristic of brain functional aging remains unclear. Task-state functional gradients reflect task-specific brain functional organization patterns and can more accurately characterize functional hierarchical features under specific conditions. However, no studies have yet systematically analyzed the task-state functional gradient patterns during episodic memory tasks. Additionally, understanding the underlying structural basis of complex brain functions is a critical goal in neuroscience. Previous research has indirectly explained the distribution characteristics of functional gradients by investigating the coupling relationship between white matter fiber networks and resting-state functional networks. However, there is still a lack of direct evidence regarding the association between brain structure and functional gradients, particularly under task conditions.
Against this research backdrop, this study utilizes large-scale, multimodal brain imaging data, combined with cutting-edge data analysis methods in functional connectome, such as functional gradients and stepwise functional connectivity. The study aims to explore the relationship between the aging patterns of resting-state functional gradients and episodic memory, delve into the specific patterns and aging trends of task-state brain functional gradients during episodic memory tasks, and ultimately elucidate the structural basis of task-state functional gradients in episodic memory, providing a comprehensive understanding of the functional gradient characteristics of episodic memory decline. This research consists of three studies with the following specific research content:
Study 1: The Relationship Between Episodic Memory Decline and Resting-State Functional Gradients. This study aims to explore the aging patterns of resting-state functional gradients and whether these aging patterns are related to the decline in episodic memory. The results indicate that the average gradient pattern in older adults is more similar to that of children under 12 years old, with Gradient 1 representing the separation between primary sensory cortices and Gradient 2 representing the separation between primary sensory and transmodal cortices. The differences in gradient patterns partially explain individual differences in cognitive function among older adults. For instance, individuals with a gradient pattern similar to that of children under 12 exhibit better performance in the visual-based episodic memory in the early stages of aging, but this is accompanied by a more pronounced decline in episodic memory performance. In contrast, individuals with a gradient pattern similar to that of young adults (where Gradient 1 represents the separation between primary sensory and transmodal cortices, and Gradient 2 represents the separation between primary sensory cortices) exhibit better maintenance of cognitive function during aging.
Study 2: The Relationship Between Episodic Memory Decline and Task-State Functional Gradients. This study examines the task performance of episodic memory in older adults using task-state fMRI data and functional gradient analysis, combined with stepwise functional connectivity. It elucidates the aging trends of functional gradients in two key stages of episodic memory tasks—encoding and recognition—and the differences in functional hierarchy features between hits and misses, to clarify the relationship between task-state functional gradients and episodic memory decline. The results reveal that the functional gradients during the encoding and recognition stages undergo some degree of reorganization compared to the resting state, but the overall organizational pattern remains largely consistent, with similar gradient patterns in both task stages. During the encoding stage, the gradient of separation between primary sensory and transmodal cortices (Gradient 2) is more important, while the recognition stage involves more of the gradient of separation between primary sensory cortices (Gradient 1). This indicates that older adults exhibit differential recruitment of brain functional organization during different task stages. Furthermore, correct memory performance is associated with a higher explanatory rate of Gradient 2 during encoding, a stronger compression of Gradient 1 during recognition, and longer neural connection paths. However, with aging, the shortening of path length and the increase in endpoint gradient values reflect the characteristic of network dedifferentiation. These results reveal the specific functional organizational changes in older adults during episodic memory tasks.
Study 3: The Structural Basis of Functional Gradients Related to Episodic Memory. This study aims to confirm the patterns of decline in gray matter structural covariance networks and two types of white matter networks (white matter fiber number network and white matter fiber length network) during aging and to explore the support of these structural network indicators for the task-state functional gradients in the two stages of episodic memory. The results indicate that older adults exhibit significant degradation in both gray matter structural covariance networks and white matter fiber networks, with compensatory strengthening of the ventromedial prefrontal cortex's role in connecting the hippocampus and ventral visual cortex during aging. Brain structure has a stable predictive capacity for task-state functional gradients in episodic memory, with higher structural covariance strength and more white matter fibers, especially regions with more long-range fibers, offering better predictive performance for task-state functional gradients. The distribution of white matter fiber length, compared to the other two structural networks, provides better predictive performance for the organization of functional gradients. Additionally, the relationship between hippocampal subregion functional gradients and task performance is not significantly influenced by the characteristics of white matter fiber length, highlighting the independent support role of functional gradients in task performance.
In summary, the innovative contributions of this study include: (1) Explaining individual differences in episodic memory performance through differences in gradient patterns during resting-state in elderly individuals. (2) Revealing the neural basis of episodic memory decline from the perspective of brain functional hierarchy by calculating functional gradients. (3) Emphasizing the importance of white matter fiber length in the organization of functional gradient patterns during episodic memory tasks. This exploration of the aging patterns of functional gradients provides crucial evidence for a deeper understanding of the neural mechanisms underlying episodic memory decline and offers a theoretical foundation for the future development of strategies to enhance episodic memory based on hierarchical brain function characteristics.