探讨脑皮层短程纤维连接密度在脑白质高信号个体认知储备机制中的作用

White matter hyperintensities (WMHs) which are detected as hyperintensity areas onT2-weighted MRI are commonly found in elderly individuals. However, the cognitivedysfunction relating to WMHs are not well corresponded with the pathological severity of the disease. Therefore, some cognitive reserve (CR) mechanisms are hypothesized to partly preserve an efficient functioning in the brain with WMHs by utilizing the existing neural network, and thus confound the association between WMHs and cognitive consequences. However, the cognitive reserve is largely considered as a conceptual and hypothetical process, to date. Its specific mechanism as well as the structural basis for mediating the reserve mechanism is still unclear. On the other hand, the cortical short-range fiberswhich occupy the peripheral WM regions adjacent to cortex are considered to be mostly spared from WMH pathology. More importantly, compared with large long-range fiber bundles, the short-range fibers that show higher synapticplasticity are more flexible under the CR effects (e.g., education, work activities, etc.) and can realize more versatile neural pathways. Therefore, it’s possible that the short-range fibers are recruited as alternative neural pathways (or, “latent” connections) to limit the clinicalconsequence of WMHs. As our preliminary work, we originally proposed the tool of cortical fiber connectivity density (FiCD) mapping, which is the only method that realizes a group-level vertex-wise statistical analysis of cortical structural connectivity, and we found that even small subcortical ischemic lesions could be related to corresponding decreased cortical FiCD value. On this basis, we performed a preliminary analysis on the short-range fiber connectivity density (SFiCD) of individuals with WMHs, and observed its correlative relationship to cognitive performance. Therefore, in the proposed study, we aim to further examine whether the cortical short-range connectivity is possibly served as a mediator of CR process, and thus related to limiting the cognitive consequence of WMHs. The findings of this study are hoped to help us better understand the mechanisms of CR and brain plasticityin response to white matter pathology, as well as the neurobiology of aging and related cognitive decline.

脑白质高信号（WMH）对认知的损害作用存在很大的不确定性。对此，前人假设性提出：个体具有利用神经网络对脑损伤进行自适应补偿的能力，从而缓冲WMH的临床认知结局，即所谓认知储备机制，但此过程的神经结构基础目前尚不明确。WMH通常选择性破坏多由长连接构成的深部脑白质，而浅表的皮层下短程纤维连接具有更强的可塑性和路径灵活性，容易被认知储备因素（如教育等）塑造，因而有可能在WMH状态下作为替代连接被募集，来缓冲认知损害效应。此假设得到我们前期实验的支持。此外，我们之前创建的FiCD测绘，实现了在体素级别对皮层结构连接的统计分析，并在已发表研究中证实即使较小的皮层下缺血灶也能够引起皮层连接密度的变化。基于以上，本研究旨在探索皮层短程连接是否可能在WMH个体中充当认知储备的介体，并与维持正常认知功能有关。研究结果将对我们认识WMH相关认知损害的病机，以及衰老过程中认知减退和代偿的神经机制具有重要意义。

脑白质高信号（WMH）作为一种可检测的神经系统病变，在老年个体中具有极高的发病率。然而，WMH对认知的损害作用存在很大的不确定性，即相当一部分老年个体尽管表现出较严重的脑WMH病变负荷，其认知功能减退却并不显著。对此，前人假设性提出：个体具有利用神经网络对脑损伤进行自适应补偿的能力，从而缓冲WMH的临床认知结局，但此过程的神经结构基础目前尚不明确。另一方面，WMH通常选择性破坏多由长连接构成的深部脑白质，而浅表的皮层下短程白质纤维，依其具有更强的可塑性和路径灵活性的特点，容易被认知储备因素（如教育等）塑造，因而有可能在WMH状态下作为替代连接被募集，来缓冲认知损害效应。基于上述假设，本研究主要内容包括如下三方面：1）借助前期所创建并优化的SFiCD分析方法，探讨了WMH个体中脑皮层短程纤维连接密度（SFiCD）是否存在变化；2）探讨WMH个体皮层SFiCD的变化的神经生物学及临床意义；3）判断WMH个体皮层短程连接在脑老化过程中的认知代偿及储备意义。研究结果及数据表明：脑白质高信号个体中皮层短程纤维连接存在变化，且此变化以脑枕叶的短程连接增强为特征；基于上述分析结论，本研究进一步发现脑白质高信号个体中皮层短程纤维连接异常与老年人在执行功能以及髓鞘化相关代谢物水平存在特定关联；此外，本研究证实了皮层短程连接在脑老化过程中存在增强的情况，因而为支持短程连接的认知功能代偿作用机制提供依据，同时发现该过程与认知储备因素并不存在明确的依赖关系，因此表明皮层短程连接在认知储备过程中的中介作用尚不能肯定。这些发现揭示了在老年个体中可能存在对皮层短程连接的募集增强的情况，并构成代偿机制，以此抵抗脑老化过程中的认识功能衰退。因此，该研究结果将对我们认识WMH相关认知损害的病机，以及进一步了解老龄化过程中的人脑可塑性及其神经代偿机制提供帮助。