Abnormal information interaction in multilayer directed network based on cross-frequency integration of mild cognitive impairment and Alzheimer's disease.

Mild cognitive impairment (MCI) and Alzheimer's disease (AD) have been reported to result in abnormal cross-frequency integration. However, previous studies have failed to consider specific abnormalities in receiving and outputting information among frequency bands during integration. Here, we investigated heterogeneity in receiving and outputting information during cross-frequency integration in patients. The results showed that during cross-frequency integration, information interaction first increased and then decreased, manifesting in the heterogeneous distribution of inter-frequency nodes for receiving information. A possible explanation was that due to damage to some inter-frequency hub nodes, intra-frequency nodes gradually became new inter-frequency nodes, whereas original inter-frequency nodes gradually became new inter-frequency hub nodes. Notably, damage to the brain regions that receive information between layers was often accompanied by a strengthened ability to output information and the emergence of hub nodes for outputting information. Moreover, an important compensatory mechanism assisted in the reception of information in the cingulo-opercular and auditory networks and in the outputting of information in the visual network. This study revealed specific abnormalities in information interaction and compensatory mechanism during cross-frequency integration, providing important evidence for understanding cross-frequency integration in patients with MCI and AD.

Analysis of Dynamic Network Reconfiguration in Adults with Attention-Deficit/Hyperactivity Disorder Based Multilayer Network.

Attention-deficit/hyperactivity disorder (ADHD) has been reported exist abnormal topology structure in the brain network. However, these studies often treated the brain as a static monolithic structure, and dynamic characteristics were ignored. Here, we investigated how the dynamic network reconfiguration in ADHD patients differs from that in healthy people. Specifically, we acquired resting-state functional magnetic resonance imaging data from a public dataset including 40 ADHD patients and 50 healthy people. A novel model of a "time-varying multilayer network" and metrics of recruitment and integration were applied to describe group differences. The results showed that the integration scores of ADHD patients were significantly lower than those of controls at every level. The recruitment scores were lower than healthy people except for the whole-brain level. It is worth noting that the subcortical network and the thalamus in ADHD patients exhibited reduced alliance preference both within and between functional networks. In addition, we also found that recruitment and integration coefficients showed a significant correlation with symptom severity in some regions. Our results demonstrate that the capability to communicate within or between some functional networks is impaired in ADHD patients. These evidences provide a new opportunity for studying the characteristics of ADHD brain networks.

Complexity Analysis of EEG, MEG, and fMRI in Mild Cognitive Impairment and Alzheimer's Disease: A Review.

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.

Abnormal and Changing Information Interaction in Adults with Attention-Deficit/Hyperactivity Disorder Based on Network Motifs.

Network motif analysis approaches provide insights into the complexity of the brain's functional network. In recent years, attention-deficit/hyperactivity disorder (ADHD) has been reported to result in abnormal information interactions in macro- and micro-scale functional networks. However, most existing studies remain limited due to potentially ignoring meso-scale topology information. To address this gap, we aimed to investigate functional motif patterns in ADHD to unravel the underlying information flow and analyze motif-based node roles to characterize the different information interaction methods for identifying the abnormal and changing lesion sites of ADHD. The results showed that the interaction functions of the right hippocampus and the right amygdala were significantly increased, which could lead patients to develop mood disorders. The information interaction of the bilateral thalamus changed, influencing and modifying behavioral results. Notably, the capability of receiving information in the left inferior temporal and the right lingual gyrus decreased, which may cause difficulties for patients in processing visual information in a timely manner, resulting in inattention. This study revealed abnormal and changing information interactions based on network motifs, providing important evidence for understanding information interactions at the meso-scale level in ADHD patients.

Abnormal Spatial and Temporal Overlap of Time-Varying Brain Functional Networks in Patients with Schizophrenia.

Schizophrenia (SZ) is a complex psychiatric disorder with unclear etiology and pathological features. Neuroscientists are increasingly proposing that schizophrenia is an abnormality in the dynamic organization of brain networks. Previous studies have found that the dynamic brain networks of people with SZ are abnormal in both space and time. However, little is known about the interactions and overlaps between hubs of the brain underlying spatiotemporal dynamics. In this study, we aimed to investigate different patterns of spatial and temporal overlap of hubs between SZ patients and healthy individuals. Specifically, we obtained resting-state functional magnetic resonance imaging data from the public dataset for 43 SZ patients and 49 healthy individuals. We derived a representation of time-varying functional connectivity using the Jackknife Correlation (JC) method. We employed the Betweenness Centrality (BC) method to identify the hubs of the brain's functional connectivity network. We then applied measures of temporal overlap, spatial overlap, and hierarchical clustering to investigate differences in the organization of brain hubs between SZ patients and healthy controls. Our findings suggest significant differences between SZ patients and healthy controls at the whole-brain and subnetwork levels. Furthermore, spatial overlap and hierarchical clustering analysis showed that quasi-periodic patterns were disrupted in SZ patients. Analyses of temporal overlap revealed abnormal pairwise engagement preferences in the hubs of SZ patients. These results provide new insights into the dynamic characteristics of the network organization of the SZ brain.

Functional Integration and Segregation in a Multilayer Network Model of Patients with Schizophrenia.

Research has shown that abnormal brain networks in patients with schizophrenia appear at different frequencies, but the relationship between these different frequencies is unclear. Therefore, it is necessary to use a multilayer network model to evaluate the integration of information from different frequency bands. To explore the mechanism of integration and separation in the multilayer network of schizophrenia, we constructed multilayer frequency brain network models in 50 patients with schizophrenia and 69 healthy subjects, and the entropy of the multiplex degree (EMD) and multilayer clustering coefficient (MCC) were calculated. The results showed that the ability to integrate and separate information in the multilayer network of patients was significantly higher than that of normal people. This difference was mainly reflected in the default mode network, sensorimotor network, subcortical network, and visual network. Among them, the subcortical network was different in both MCC and EMD outcomes. Furthermore, differences were found in the posterior cingulate gyrus, hippocampus, amygdala, putamen, pallidum, and thalamus. The thalamus and posterior cingulate gyrus were associated with the patient's symptom scores. Our results showed that the cross-frequency interaction ability of patients with schizophrenia was significantly enhanced, among which the subcortical network was the most active. This interaction may serve as a compensation mechanism for intralayer dysfunction.

A hybrid deep neural network for classification of schizophrenia using EEG Data.

Schizophrenia is a serious mental illness that causes great harm to patients, so timely and accurate detection is essential. This study aimed to identify a better feature to represent electroencephalography (EEG) signals and improve the classification accuracy of patients with schizophrenia and healthy controls by using EEG signals. Our research method involves two steps. First, the EEG time series is preprocessed, and the extracted time-domain and frequency-domain features are transformed into a sequence of red-green-blue (RGB) images that carry spatial information. Second, we construct hybrid deep neural networks (DNNs) that combine convolution neural networks and long short-term memory to address RGB images to classify schizophrenic patients and healthy controls. The results show that the fuzzy entropy (FuzzyEn) feature is more significant than the fast Fourier transform (FFT) feature in brain topography. The deep learning (DL) method that we propose achieves an average accuracy of 99.22% with FuzzyEn and an average accuracy of 96.34% with FFT. These results show that the best effect is to extract fuzzy features as input features from EEG time series and then use a hybrid DNN for classification. Compared with the most advanced methods in this field, significant improvements have been achieved.

Dynamic Changes of Brain Networks during Working Memory Tasks in Schizophrenia.

Electroencephalograph (EEG) signals and graph theory measures have been widely used to characterize the brain functional networks of healthy individuals and patients by calculating the correlations between different electrodes over an entire time series. Although EEG signals have a high temporal resolution and can provide relatively stable results, the process of constructing and analyzing brain functional networks is inevitably complicated by high time complexity. Our goal in this research was to distinguish the brain function networks of schizophrenia patients from those of healthy participants during working memory tasks. Consequently, we utilized a method involving microstates, which are each characterized by a unique topography of electric potentials over an entire channel array, to reduce the dimension of the EEG signals during working memory tasks and then compared and analyzed the brain functional networks using the microstates time series (MTS) and original time series (OTS) of the schizophrenia patients and healthy individuals. We found that the right frontal and parietal-occipital regions neurons of the schizophrenia patients were less active than those of the healthy participants during working memory tasks. Notably, compared with OTS, the time needed to construct the brain functional networks was significantly reduced by using MTS. In conclusion, our results show that, like OTS, MTS can well distinguish the brain functional network of schizophrenia patients from those of healthy individuals during working memory tasks while greatly decreasing time complexity. MTS can thus provide a method for characterizing the original time series for the construction and analysis of EEG brain functional networks.

Phosphodiesterase 4D Gene Modifies the Functional Network of Patients With Mild Cognitive Impairment and Alzheimer's Disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that is affected by several genetic variants. It has been demonstrated that genetic variants affect brain organization and function. In this study, using whole genome-wide association studies (GWAS), we analyzed the functional magnetic resonance imaging and genetic data from the Alzheimer's Disease Neuroimaging Initiative dataset (ADNI) dataset and identified genetic variants associated with the topology of the functional brain network http://www.adni-info.org. We found three novel loci (rs2409627, rs9647533, and rs11955845) in an intron of the phosphodiesterase 4D (PDE4D) gene that contribute to abnormalities in the topological organization of the functional network. In particular, compared to the wild-type genotype, the subjects carrying the PDE4D variants had altered network properties, including a significantly reduced clustering coefficient, small-worldness, global and local efficiency, a significantly enhanced path length and a normalized path length. In addition, we found that all global brain network attributes were affected by PDE4D variants to different extents as the disease progressed. Additionally, brain regions with alterations in nodal efficiency due to the variations in PDE4D were predominant in the limbic lobe, temporal lobe and frontal lobes. PDE4D has a great effect on memory consolidation and cognition through long-term potentiation (LTP) effects and/or the promotion of inflammatory effects. PDE4D variants might be a main reasons underlyling for the abnormal topological properties and cognitive impairment. Furthermore, we speculated that PDE4D is a risk factor for neural degenerative diseases and provided important clues for the earlier detection and therapeutic intervention for AD.

Graph-based network analysis of resting-state fMRI: test-retest reliability of binarized and weighted networks.

In the past decade, resting-state functional magnetic resonance imaging (rs-fMRI) and graph-based measures have been widely used to quantitatively characterize the architectures of brain functional networks in healthy individuals and in patients with abnormalities related to psychopathic and neurological disorders. To accurately evaluate the topological organization of brain functional networks, the definition of the nodes and edges for the construction of functional networks is critical. Furthermore, both types of brain functional networks (binarized networks and weighted networks) are widely used to analyze topological organization. However, how to best select the network type is still debated. Consequently, we investigated the test-retest reliability of brain functional networks with binarized and weighted edges using two independent datasets and four strategies for defining nodes. We revealed fair to good reliability for a majority of network topological attributes and overall higher reliabilities for weighted networks than for binarized networks. For regional nodal efficiency, weighted networks also showed higher reliability across nodes. Thus, our findings imply that weighted networks contain more information, leading to more stable results. In addition, we found that the reliability of brain functional networks was influenced by the node definition strategy and that more precise of nodal definition were associated with higher reliability. The time effect of reliability was restricted, as no differences between long-term and short-term reliability were observed. In conclusion, our results suggest that weighted networks have better reliability because they reflect more topological information, implying broader applications of weighted networks related to normal and disordered function of the human brain.

Altered Directed Functional Connectivity of the Hippocampus in Mild Cognitive Impairment and Alzheimer's Disease: A Resting-State fMRI Study.

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.

Dynamic Complexity of Spontaneous BOLD Activity in Alzheimer's Disease and Mild Cognitive Impairment Using Multiscale Entropy Analysis.

Alzheimer's disease (AD) is characterized by progressive deterioration of brain function among elderly people. Studies revealed aberrant correlations in spontaneous blood oxygen level-dependent (BOLD) signals in resting-state functional magnetic resonance imaging (rs-fMRI) over a wide range of temporal scales. However, the study of the temporal dynamics of BOLD signals in subjects with AD and mild cognitive impairment (MCI) remains largely unexplored. Multiscale entropy (MSE) analysis is a method for estimating the complexity of finite time series over multiple time scales. In this research, we applied MSE analysis to investigate the abnormal complexity of BOLD signals using the rs-fMRI data from the Alzheimer's disease neuroimaging initiative (ADNI) database. There were 30 normal controls (NCs), 33 early MCI (EMCI), 32 late MCI (LMCI), and 29 AD patients. Following preprocessing of the BOLD signals, whole-brain MSE maps across six time scales were generated using the Complexity Toolbox. One-way analysis of variance (ANOVA) analysis on the MSE maps of four groups revealed significant differences in the thalamus, insula, lingual gyrus and inferior occipital gyrus, superior frontal gyrus and olfactory cortex, supramarginal gyrus, superior temporal gyrus, and middle temporal gyrus on multiple time scales. Compared with the NC group, MCI and AD patients had significant reductions in the complexity of BOLD signals and AD patients demonstrated lower complexity than that of the MCI subjects. Additionally, the complexity of BOLD signals from the regions of interest (ROIs) was found to be significantly associated with cognitive decline in patient groups on multiple time scales. Consequently, the complexity or MSE of BOLD signals may provide an imaging biomarker of cognitive impairments in MCI and AD.