认知与发展心理学研究室知识库

外侧前额叶皮层是人脑中重要脑区，其结构和功能具有复杂性和多样性。不仅负责执行功能、记忆、推理等多种认知功能，也是随龄最先衰退脑区之一，并展现终生可塑性。研究外侧前额叶皮层功能层级组织及其随龄变化，探索延缓认知和脑老化干预方法，对于维持日常生活及提升老年人生活质量具有重要意义。以往研究聚焦于分析离散脑区及其功能定位，极大推进了对认知老化及可塑性的理解，同时也限制了对大脑在老化过程中整体功能是如何协同变化的认识。近年，神经科学研究更关注脑区内及脑区间的连续性变化(即功能连接梯度)，这种研究方法允许我们更全面理解脑区内部和脑区间的变异性，并描述出空间连续统一的层级组织结构，该结构促进我们深入理解认知功能如何产生以及在不同加工层级间过渡。本研究基于静息态功能连接，旨在探索外侧前额叶皮层功能层级组织及其老化效应，并通过对老年人实施游戏化认知干预，探讨外侧前额叶功能层级组 织在老化过程中的可塑性。

研究一采用两个独立数据集，通过静息态功能连接和扩散图嵌入技术，捕捉并验证了外侧前额叶皮层功能连接梯度的宏观空间分布模式。发现外侧前额叶皮层功能连接主梯度整体呈头-尾分布。进一步分析显示，外侧前额叶皮层主梯度与功能网络对应，表现从感觉运动网络到默认网络的分层组织模式。这种分布模式反映了外侧前额叶皮层在处理感知运动到抽象认知过程中的连续性变化。此外，外侧前额叶皮层功能连接主梯度与其体积和表面积存在显著正相关。

研究二利用成人生命周期公开数据库，探讨外侧前额叶皮层功能连接梯度在成人毕生发展过程中的变化。结果发现，老年人的外侧前额叶皮层功能层级组织形式保持与青年和中年人一致的头-尾分布模式。进一步分析发现，额极和背外侧前额叶区域，老年人梯度值显著低于青年和中年人。同时，梯度轴两端的距离，老年人也显著小于青年和中年人。外侧前额叶梯度与执行功能相关分析显示，外侧前额叶头部梯度分数越高、尾部梯度分数越低，老年人的执行功能越好。

研究三探讨认知游戏和认知运动游戏干预对老年人外侧前额叶皮层功能层级组织的潜在影响。100名符合纳入标准健康老年人被随机分到认知游戏干预组、认知运动游戏干预组及对照组。两个干预组接受每周 2 次、每次 1 小时、为期 3 个月的干预，对照组干预期间保持正常的生活方式。干预前后，评估了被试的执行功能评估并进行了磁共振成像扫描。结果显示，与对照组相比，经 3 个月干预，两个干预组老年人在抑制、切换、工作记忆及总体执行功能上显著提升。然而，在外侧前额叶皮层功能层级组织方面，两个干预组与对照组相比没有显著差异。

综上所述，本文系统描述并验证了外侧前额叶皮层头-尾主梯度，该梯度随增龄表现出压缩模式，且展现出可塑性的个体差异。这些发现不仅为外侧前额叶皮层沿头-尾轴线组织的原则提供了更多证据，也为我们理解老化过程中外侧前额叶皮层层级结构变化及执行功能衰退机制提供了新视角，同时增强了我们对于外侧前额叶皮层在认知老化过程中可塑性的认识。

The lateral prefrontal cortex is a crucial region of the human brain, and its structure and function are complex and diverse. The lateral prefrontal lobe is not only responsible for a variety of cognitive functions such as executive function, memory, reasoning, etc., it is also one of the first brain areas to decline with age, and exhibits lifelong plasticity. Delving into the functional hierarchical organization of the lateral prefrontal cortex, examining its changes with age, and exploring interventions to mitigate cognitive and brain aging is crucial for maintaining daily living activities and augmenting quality of life in older adults. Previous research has mainly focused on analyzing discrete brain regions and their functional localization. This approach has greatly advanced the understanding of cognitive aging and plasticity, but it also limits the understanding of how the overall brain function changes collaboratively during the aging process. In recent years, neuroscience research has paid more attention to the continuous changes within and between brain regions (i.e., functional connectivity gradients), offering a more nuanced view of intra- and inter-regional variability. This approach reveals a spatially continuous, unified hierarchical organizational structure, enriching our indepth understanding of how cognitive functions arise and transition between different levels of processing. Employing resting-state functional connectivity data, this study aims to explore the functional hierarchical organization of the lateral prefrontal cortex and its aging effects, and to explore the plasticity of the functional hierarchical organization of the lateral prefrontal cortex in the aging process by implementing gamified cognitive intervention for older adults.

In Study 1, we used two independent datasets to capture and verify the macroscopic spatial distribution pattern of functional connectivity gradients in the lateral prefrontal cortex through resting-state functional connectivity and diffusion map embedding techniques. The results indicated that the main gradient of functional connectivity in the lateral prefrontal cortex showed an overall rostral-caudal distribution. Further analysis revealed that the principal gradient of the lateral prefrontal cortex corresponds to functional networks, exhibiting a hierarchical organization from the sensorimotor networks to the default network. This distribution pattern reflects the continuous changes in the lateral prefrontal cortex from processing sensory-motor to abstract cognition. Furthermore, the main gradient of functional connectivity in the lateral prefrontal cortex was significantly positively correlated with its volume and surface area.

In Study 2, we used the Adult Lifespan Dataset to explore the changes in the functional connectivity gradient of the lateral prefrontal cortex during adult lifespan. The findings reveal that the functional hierarchical organization of the lateral prefrontal cortex in older adults preserved a rostro-caudal distribution, consistent with patterns identified in middle-aged and young adults. Further analysis found that in the frontal pole and dorsolateral prefrontal regions, the gradient values in older adults were significantly lower than those in young and middle-aged adults. At the same time, the distance between the two ends of the gradient axis is also significantly smaller for older adults than young and middle-aged individuals. Correlation analysis between lateral prefrontal gradient and executive function shows that the higher the gradient score in the rostro of the lateral prefrontal lobe and the caudal the gradient score in the tail, the better the executive function of older adults.

Study 3 is an intervention study that aims to explore the potential effects of cognitive game and cognitive exergame intervention on the functional hierarchical organization of the lateral prefrontal cortex in older adults. One hundred healthy older adults who met the inclusion criteria were randomly assigned to cognitive game intervention group, cognitive exergame intervention group, or control group. The two intervention groups received intervention twice a week for 1 hour each time for 3 months, and the control group maintained a normal lifestyle during the intervention period. Before and after the intervention, participants underwent executive function assessments and magnetic resonance imaging scans. The findings indicated that compared to the control group, after 3 months of intervention, older adults in the two intervention groups had significant improvements in inhibition, task switch, working memory and overall executive function. Nonetheless, no significant alterations in the hierarchical organization of the lateral prefrontal cortex were detected in the intervention groups relative to the control group.

In summary, this paper systematically describes and validates the rostro-caudal main gradient in the lateral prefrontal cortex, which exhibits a compression pattern with age and individual differences in plasticity. These findings not only affirm the organizational principles of the rostro-caudal axis within the lateral prefrontal cortex, but also provide a new perspective for us to understand the changes in the hierarchical structure of the lateral prefrontal cortex and the mechanism of executive function decline during aging, while enhancing Improve our understanding of the plasticity of the lateral prefrontal cortex in cognitive aging.