遗忘型轻度认知损伤与老年性痴呆内隐与外显记忆的神经环路机制- - 结合任务与静息的功能磁共振成像研究

The proposed project will combine cross-sectional and longitudinal designs, and employ both task-related and resting-state fMRI techniques, and the data will be collected from Alzheimer's Disease patients (AD), amnesic Mild Cognitive Impairment subjects (aMCI), and elderly normal controls (NC). Based on the previous findings that aMCI and AD demonstrated impaired explicit memory (especially the most impaired associative episodic memory) but intact implicit memory, we will take the interdisciplinary strengths from psychology, neural computation and medicine to investigate their brain activations in specific regions while the subjects are performing these memory tasks, and then will adopt the correlation analysis and Bayesian network learning approach to compute the functional connectivity and effective connectivity among these activated brain regions. Relying on the neural network knowledge derived from task-related fMRI data, we will try to find corresponding memory network during baseline resting-state, and then using this intrinsic connectivity to predict the development of memory impairment within 3 years follow up. ..We predict there will be a visual memory network beginning from occipital visual cortex going through fusiform gyrus to mesial temporal lobe (MTL), and finally reaching prefrontal cortex (PFC). Graded deficits are expected along this connectivity stream with the progression of disease, among which, the connectivity between hippocampus and PFC which related to the retrieval of episodic associations is expected to be the most significantly affected one...The proposed project has the potential to find a distributed memory network, and to provide novel insights into understanding the brain pathological mechanism of dementia. Beyond these theoretical impacts, it will also provide scientific evidences for early detection of AD and for application of cognitive training to patients.

采用横断与纵向追踪设计相结合，任务下fMRI和静息态fMRI技术相结合，以遗忘型轻度认知损伤（aMCI）、老年性痴呆（AD）和正常老年对照为研究对象，以aMCI和AD内隐记忆保留、外显记忆受损（特别是联结记忆受损最为严重）为切入点，发挥心理学、神经计算科学和医学的学科交叉优势，观察任务下激活的关键脑区，采用相关分析和贝叶斯网络学习方法计算它们之间的功能连接和有效连接，进而以此指导建立静息态下对应的记忆网络，并探索其对未来记忆障碍发生发展的预测。.预期会发现从视觉皮层出发到梭状回再到海马等内侧颞叶区域，最终到达前额皮层的记忆环路。疾病对该环路上脑区及其连接的影响逐渐加大，其中负责联结提取的海马- - 前额通路将受到最显著的影响。..该研究不仅有助于揭示记忆的神经环路基础，而且会推动对痴呆病理机制的深入理解，同时为AD早期识别和认知干预提供科学依据。

采用任务态结合静息态神经成像技术(fMRI与ERP)，以遗忘型轻度认知损伤（aMCI）、老年性痴呆（AD）和正常老年对照为研究对象，以aMCI和AD内隐记忆保留、外显记忆受损（特别是联结记忆受损最为严重）为切入点，发挥心理学、神经计算科学和医学的学科交叉优势，考察了外显和内隐任务下激活的关键脑区，探索了MCI在外显任务态下脑区连接异常，建立静息态下对应的记忆网络并探索了MCI的相应损伤（包括功能连接和有效连接）。. 研究结果证实了存在从视觉皮层出发到梭状回再到海马等内侧颞叶区域，最终到达前额皮层的记忆环路，而且发现MCI负责联结提取的海马--前额通路受损最为严重。此外，我们还开展以认知训练为主的综合干预，发现海马--前额通路在干预后连接增强，并与外显记忆成绩提升之间存在显著相关，进一步证实了上述记忆通路的存在。. 同时利用系列研究发现的与aMCI外显提取受损对应的脑神经通路作为标记物，我们探索了其在aMCI早期识别方面的价值，比如在DMST任务中左侧额区P3结合对干扰项目的RT能够实现对aMCI识别敏感性达到87.5%， 特异性达到83.3%。. 特别值得一提的是，受aMCI内隐记忆和基于熟悉感的提取加工相对保留的启发，我们探索了一体化编码加工方式对联结记忆老化的影响。结果发现一体化编码能够增强熟悉性在联结记忆提取中的作用，从而促进了老年人外显联结记忆改善。一体化策略有别于以往传统的记忆训练策略（传统记忆策略定向基于“回想”的提取过程和在海马--前额通路的改善），就为aMCI的认知干预提供了新的思路。. 上述系列研究成果深入揭示了内隐和外显记忆的神经环路基础，推动了对痴呆病理机制的进一步理解，同时为AD早期识别和认知干预提供科学依据。

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