Alzheimer’s disease (AD) is a degenerative brain disease with a high and irreversible incidence. In recent years, because brain signals have complex nonlinear dynamics, there has been growing interest in studying complex changes in the time series of brain signals in patients with AD. We reviewed studies of complexity analyses of single-channel time series from electroencephalogram (EEG), magnetoencephalogram (MEG), and functional magnetic resonance imaging (fMRI) in AD and determined future research directions. A systematic literature search for 2000–2019 was performed in the Web of Science and PubMed databases, resulting in 126 identified studies. Compared to healthy individuals, the signals from AD patients have less complexity and more predictable oscillations, which are found mainly in the left parietal, occipital, right frontal, and temporal regions. This complexity is considered a potential biomarker for accurately responding to the functional lesion in AD. The current review helps to reveal the patterns of dysfunction in the brains of patients with AD and to investigate whether signal complexity can be used as a biomarker to accurately respond to the functional lesion in AD. We proposed further studies in the signal complexities of AD patients, including investigating the reliability of complexity algorithms and the spatial patterns of signal complexity. In conclusion, the current review helps to better understand the complexity of abnormalities in the AD brain and provide useful information for AD diagnosis.

The hippocampus is generally reported as one of the regions most impacted by Alzheimer’s disease (AD) and is closely associated with memory function and orientation. Undirected functional connectivity (FC) alterations occur in patients with mild cognitive impairment (MCI) and AD, and these alterations have been the subject of many studies. However, abnormal patterns of directed FC remain poorly understood. In this study, to identify changes in directed FC between the hippocampus and other brain regions, Granger causality analysis (GCA) based on voxels was applied to resting-state functional magnetic resonance imaging (rs-fMRI) data from 29 AD, 65 MCI, and 30 normal control (NC) subjects. The results showed significant differences in the patterns of directed FC among the three groups. There were fewer brain regions showing changes in directed FC with the hippocampus in the MCI group than the NC group, and these regions were mainly located in the temporal lobe, frontal lobe, and cingulate cortex. However, regarding the abnormalities in directed FC in the AD group, the number of affected voxels was greater, the size of the clusters was larger, and the distribution was wider. Most of the abnormal connections were unidirectional and showed hemispheric asymmetry. In addition, we also investigated the correlations between the abnormal directional FCs and cognitive and clinical measurement scores in the three groups and found that some of them were significantly correlated. This study revealed abnormalities in the transmission and reception of information in the hippocampus of MCI and AD patients and offer insight into the neurophysiological mechanisms underlying MCI and AD.

Emerging research indicates interruptions in the wiring organization of the brain network in Mild cognitive impairment (MCI) and Alzheimer's disease (AD). Due to the important role of rich-club organization in distinguishing abnormalities of AD patients and the close relationship between structural connectivity (SC) and functional connectivity (FC), our study examined whether changes in SC-FC coupling and the relationship with abnormal rich-club organizations during the development of diseases may contribute to the pathophysiology of AD. Structural diffusion-tensor imaging (DTI) and resting-state functional magnetic resonance imaging (fMRI) were performed in 38 normal controls (NCs), 40 MCI patients and 19 AD patients. Measures of the rich-club structure and its role in global structural–functional coupling were administered. Our study found decreased levels of feeder and local connectivity in MCI and AD patients, which were the main contributing factors to the lower efficiency of the brain structural network. Another important finding was that we have more accurately characterized the changing pattern of functional brain dynamics. The enhanced coupling between SC and FC in MCI and AD patients might be due to disruptions in optimal structural organization. More interestingly, we also found increases in the SC-FC coupling for feeder and local connections in MCI and AD patients. SC-FC coupling also showed significant differences between MCI and AD patients, mainly between the abnormal feeder connections. The connection density and coupling strength were significantly correlated with clinical metrics in patients. The present findings enhanced our understanding of the neurophysiologic mechanisms associated with MCI and AD.

Structural and functional differences between the brains of female and male adults have been well documented. However, potential sex differences in the patterns of rich-club organization and the coupling between their structural connectivity (SC) and functional connectivity (FC) remain to be determined. In this study, functional magnetic resonance imaging and diffusion tensor imaging techniques were combined to examine sex differences in rich-club organization. Females had a stronger SC-FC coupling than males. Moreover, stronger SC-FC coupling in the females was primarily located in feeder connections and non–rich-club nodes of the left inferior frontal gyrus and inferior parietal lobe and the right superior frontal gyrus and superior parietal gyrus, whereas higher coupling strength in males was primarily located in rich-club connections and rich-club node of the right insula, and non-rich-club nodes of the left hippocampus and the right parahippocampal gyrus. Sex-specific patterns in correlations were also shown between SC-FC coupling and cognitive function, including working memory and reasoning ability. The topological changes in rich-club organization provide novel insight into sex-specific effects on white matter connections that underlie a potential network mechanism of sex-based differences in cognitive function.

Structural and functional differences in brain hemispheric asymmetry have been well documented between female and male adults. However, potential differences in the connectivity patterns of the rich-club organization of hemispheric structural networks in females and males remain to be determined. In this study, diffusion tensor imaging was used to construct hemispheric structural networks in healthy subjects, and graph theoretical analysis approaches were applied to quantify hemisphere and gender differences in rich-club organization. The results showed that rich-club organization was consistently observed in both hemispheres of female and male adults. Moreover, a reduced level of connectivity was found in the left hemisphere. Notably, rightward asymmetries were mainly observed in feeder and local connections among one hub region and peripheral regions, many of which are implicated in visual processing and spatial attention functions. Additionally, significant gender differences were revealed in the rich-club, feeder, and local connections in rich-club organization. These gender-related hub and peripheral regions are involved in emotional, sensory, and cognitive control functions. The topological changes in rich-club organization provide novel insight into the hemisphere and gender effects on white matter connections and underlie a potential network mechanism of hemisphere- and gender-based differences in visual processing, spatial attention and cognitive control.