Abstract
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.
Highlights
Brain activity during the human resting-state shows spatially coherent patterns at a low temporal frequency (Biswal et al, 1995; Raichle et al, 2001)
Using one-sided t-test assuming that Functional Connectivity (FC) is lower in Alzheimer’s disease (AD) than controls we found a significantly reduced connection between posterior cingulate cortex (PCC) and R-Hipp (t = 1.90, p = 0.034)
The validity analysis for entropy at every scale revealed that for scales 1–20 (0.625–0.031 Hz) we observed a complex behavior of signal fluctuations (Supplementary Figure 1). This is comprehensible since our fMRI comprised 400 volumes and coarse sampling at scales 20 and above would produce very short time-series for Multi-Scale Entropy (MSE) computation (20 time-points at scale 20) which renders it unreliable
Summary
Brain activity during the human resting-state shows spatially coherent patterns at a low temporal frequency (Biswal et al, 1995; Raichle et al, 2001). The temporal anti-correlation between task-positive (i.e., RSNs resembling functional networks engaged during task execution) and the task-negative RSN (increased activity in absence of a task, i.e., DMN), normally found in healthy subjects, is attenuated in progressed stages of AD (Fox et al, 2005; Weiler et al, 2017). This inability to switch between the task-positive RSNs and the DMN is hypothesized to be related to cognitive impairment in AD. Koch et al (2012) have corroborated the DMN’s relevance in AD by demonstrating the diagnostic power of DMN connectivity strength to separate AD from healthy controls, while the prediction of mild cognitive impairment (MCI) was less obvious
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