Grieder Matthias, Wang Danny J J, Dierks Thomas, Wahlund Lars-Olof, Jann Kay
Translational Research Center, University Hospital of Psychiatry, University of Bern, Bern, Switzerland.
USC Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA, United States.
Front Neurosci. 2018 Oct 23;12:770. doi: 10.3389/fnins.2018.00770. eCollection 2018.
The human resting-state is characterized by spatially coherent brain activity at a low temporal frequency. The default mode network (DMN), one of so-called resting-state networks, has been associated with cognitive processes that are directed toward the self, such as introspection and autobiographic memory. The DMN's integrity appears to be crucial for mental health. For example, patients with Alzheimer's disease or other psychiatric conditions show disruptions of functional connectivity within the brain regions of the DMN. However, in prodromal or early stages of Alzheimer's disease, physiological alterations are sometimes elusive, despite manifested cognitive impairment. While functional connectivity assesses the signal correlation between brain areas, multi-scale entropy (MSE) measures the complexity of the blood-oxygen level dependent signal within an area and thus might show local changes before connectivity is affected. Hence, we investigated alterations of functional connectivity and MSE within the DMN in fifteen mild Alzheimer's disease patients as compared to fourteen controls. Potential associations of MSE with functional connectivity and cognitive abilities [i.e., mini-mental state examination (MMSE)] were assessed. A moderate decrease of DMN functional connectivity between posterior cingulate cortex and right hippocampus in Alzheimer's disease was found, whereas no differences were evident for whole-network functional connectivity. In contrast, the Alzheimer's disease group yielded lower global DMN-MSE than the control group. The most pronounced regional effects were localized in left and right hippocampi, and this was true for most scales. Moreover, MSE significantly correlated with functional connectivity, and DMN-MSE correlated positively with the MMSE in Alzheimer's disease. Most interestingly, the right hippocampal MSE was positively associated with semantic memory performance. Thus, our results suggested that cognitive decline in Alzheimer's disease is reflected by decreased signal complexity in DMN nodes, which might further lead to disrupted DMN functional connectivity. Additionally, altered entropy in Alzheimer's disease found in the majority of the scales indicated a disturbance of both local information processing and information transfer between distal areas. Conclusively, a loss of nodal signal complexity potentially impairs synchronization across nodes and thus preempts functional connectivity changes. MSE presents a putative functional marker for cognitive decline that might be more sensitive than functional connectivity alone.
人类静息状态的特征是在低时间频率下具有空间连贯的大脑活动。默认模式网络（DMN）是所谓的静息状态网络之一，与指向自我的认知过程有关，如内省和自传体记忆。DMN的完整性似乎对心理健康至关重要。例如，患有阿尔茨海默病或其他精神疾病的患者在DMN的脑区中表现出功能连接的中断。然而，在阿尔茨海默病的前驱期或早期，尽管存在明显的认知障碍，但生理改变有时难以捉摸。虽然功能连接评估脑区之间的信号相关性，但多尺度熵（MSE）测量一个区域内血氧水平依赖信号的复杂性，因此可能在连接性受到影响之前显示局部变化。因此，我们研究了15名轻度阿尔茨海默病患者与14名对照相比，DMN内功能连接和MSE的改变。评估了MSE与功能连接和认知能力[即简易精神状态检查表（MMSE）]之间的潜在关联。发现阿尔茨海默病患者后扣带回皮质与右侧海马之间的DMN功能连接有中度下降，而全网络功能连接没有明显差异。相比之下，阿尔茨海默病组的整体DMN-MSE低于对照组。最明显的区域效应位于左右海马，大多数尺度都是如此。此外，MSE与功能连接显著相关，在阿尔茨海默病中DMN-MSE与MMSE呈正相关。最有趣的是，右侧海马MSE与语义记忆表现呈正相关。因此，我们的结果表明，阿尔茨海默病中的认知衰退反映为DMN节点中信号复杂性的降低，这可能进一步导致DMN功能连接中断。此外，在大多数尺度上发现的阿尔茨海默病中熵的改变表明局部信息处理和远端区域之间信息传递的紊乱。总之，节点信号复杂性的丧失可能会损害节点之间的同步，从而先于功能连接变化。MSE提出了一种认知衰退的假定功能标志物，可能比单独的功能连接更敏感。
