Brain Dynamics Altered by Photic Stimulation in Patients with Alzheimer’s Disease and Mild Cognitive Impairment

Individuals with mild cognitive impairment (MCI) are at high risk of developing Alzheimer’s disease (AD). Repetitive photic stimulation (PS) is commonly used in routine electroencephalogram (EEG) examinations for rapid assessment of perceptual functioning. This study aimed to evaluate neural oscillatory responses and nonlinear brain dynamics under the effects of PS in patients with mild AD, moderate AD, severe AD, and MCI, as well as healthy elderly controls (HC). EEG power ratios during PS were estimated as an index of oscillatory responses. Multiscale sample entropy (MSE) was estimated as an index of brain dynamics before, during, and after PS. During PS, EEG harmonic responses were lower and MSE values were higher in the AD subgroups than in HC and MCI groups. PS-induced changes in EEG complexity were less pronounced in the AD subgroups than in HC and MCI groups. Brain dynamics revealed a “transitional change” between MCI and Mild AD. Our findings suggest a deficiency in brain adaptability in AD patients, which hinders their ability to adapt to repetitive perceptual stimulation. This study highlights the importance of combining spectral and nonlinear dynamical analysis when seeking to unravel perceptual functioning and brain adaptability in the various stages of neurodegenerative diseases.     

Decreased Resting-State Functional Complexity in Elderly with Subjective Cognitive Decline

Individuals with subjective cognitive decline (SCD) are at high risk of developing preclinical or clinical state of Alzheimer’s disease (AD). Resting state functional magnetic resonance imaging, which can indirectly reflect neuron activities by measuring the blood-oxygen-level-dependent (BOLD) signals, is promising in the early detection of SCD. This study aimed to explore whether the nonlinear complexity of BOLD signals can describe the subtle differences between SCD and normal aging, and uncover the underlying neuropsychological implications of these differences. In particular, we introduce amplitude-aware permutation entropy (AAPE) as the novel measure of brain entropy to characterize the complexity in BOLD signals in each brain region of the Brainnetome atlas. Our results demonstrate that AAPE can reflect the subtle differences between both groups, and the SCD group presented significantly decreased complexities in subregions of the superior temporal gyrus, the inferior parietal lobule, the postcentral gyrus, and the insular gyrus. Moreover, the results further reveal that lower complexity in SCD may correspond to poorer cognitive performance or even subtle cognitive impairment. Our findings demonstrated the effectiveness and sensitiveness of the novel brain entropy measured by AAPE, which may serve as the potential neuroimaging marker for exploring the subtle changes in SCD.     

Construction and Application of Functional Brain Network Based on Entropy

Functional brain network (FBN) is an intuitive expression of the dynamic neural activity interaction between different neurons, neuron clusters, or cerebral cortex regions. It can characterize the brain network topology and dynamic properties. The method of building an FBN to characterize the features of the brain network accurately and effectively is a challenging subject. Entropy can effectively describe the complexity, non-linearity, and uncertainty of electroencephalogram (EEG) signals. As a relatively new research direction, the research of the FBN construction method based on EEG data of fatigue driving has broad prospects. Therefore, it is of great significance to study the entropy-based FBN construction. We focus on selecting appropriate entropy features to characterize EEG signals and construct an FBN. On the real data set of fatigue driving, FBN models based on different entropies are constructed to identify the state of fatigue driving. Through analyzing network measurement indicators, the experiment shows that the FBN model based on fuzzy entropy can achieve excellent classification recognition rate and good classification stability. In addition, when compared with the other model based on the same data set, our model could obtain a higher accuracy and more stable classification results even if the length of the intercepted EEG signal is different.     

基于自适应模板法的脑电信号转移熵分析

脑电信号是一种产生机理相当复杂且非常微弱的随机信号, 综合反映了大脑组织的脑电活动及大脑的功能状态. 由于脑电信号的微弱性, 传统的基本模板方法在脑电信号分析上得到了良好的应用. 为进一步提升分析脑电信号的性能, 提出了一种新的基于自适应模板的转移熵方法并分析了青少年脑电与成年人脑电信号. 结果表明: 对于青少年脑电还是成年人脑电, 与基本模板法相比, 基于自适应模板法的转移熵可以更显著地表示脑电信号的耦合作用, 并且具有更好的区分度, 这将能更好地捕捉到信号中的动态信息、系统动力学复杂性的改变. 同时, 该方法将更有利于医学临床诊断的辅助检测, 对脑电信号是否处于病理状态的诊断提供了新的更好的判断依据.     

Exploring the Alterations in the Distribution of Neural Network Weights in Dementia Due to Alzheimer’s Disease

Alzheimer’s disease (AD) is a neurodegenerative disorder which has become an outstanding social problem. The main objective of this study was to evaluate the alterations that dementia due to AD elicits in the distribution of functional network weights. Functional connectivity networks were obtained using the orthogonalized Amplitude Envelope Correlation (AEC), computed from source-reconstructed resting-state eletroencephalographic (EEG) data in a population formed by 45 cognitive healthy elderly controls, 69 mild cognitive impaired (MCI) patients and 81 AD patients. Our results indicated that AD induces a progressive alteration of network weights distribution; specifically, the Shannon entropy (SE) of the weights distribution showed statistically significant between-group differences (p < 0.05, Kruskal-Wallis test, False Discovery Rate corrected). Furthermore, an in-depth analysis of network weights distributions was performed in delta, alpha, and beta-1 frequency bands to discriminate the weight ranges showing statistical differences in SE. Our results showed that lower and higher weights were more affected by the disease, whereas mid-range connections remained unchanged. These findings support the importance of performing detailed analyses of the network weights distribution to further understand the impact of AD progression on functional brain activity.     

基于脑电图的大脑功能性网络分析

利用脑电图数据建立了大脑功能性网络.分析了该网络的复杂网络统计特征，发现它的聚类系数远大于相应随机网络，明显具有小世界网络的特征，其度分布也接近于无标度网络.进一步验证了大脑功能性网络的复杂网络特性，发现患者的各项复杂网络特征指数与正常人相比有明显不同.定义了大脑神经网络信息熵及神经网络标准信息熵的概念，发现脑病患者的大脑神经网络信息熵明显小于正常人.从一个全新的角度量度了大脑的复杂网络特征，并提示了临床脑病诊疗的判断依据. 关键词： 脑电图 大脑功能性网络 复杂网络统计特征 信息熵     

BFF: Bayesian,Fiducial, and Frequentist Analysis of Cognitive Engagement among Cognitively Impaired Older Adults

Engagement in cognitively demanding activities is beneficial to preserving cognitive health. Our goal was to demonstrate the utility of frequentist, Bayesian, and fiducial statistical methods for evaluating the robustness of effects in identifying factors that contribute to cognitive engagement for older adults experiencing cognitive decline. We collected a total of 504 observations across two longitudinal waves of data from 28 cognitively impaired older adults. Participants’ systolic blood pressure responsivity, an index of cognitive engagement, was continuously sampled during cognitive testing. Participants reported on physical and mental health challenges and provided hair samples to assess chronic stress at each wave. Using the three statistical paradigms, we compared results from six model testing levels and longitudinal changes in health and stress predicting changes in cognitive engagement. Findings were mostly consistent across the three paradigms, providing additional confidence in determining effects. We extend selective engagement theory to cognitive impairment, noting that health challenges and stress appear to be important moderators. Further, we emphasize the utility of the Bayesian and fiducial paradigms for use with relatively small sample sizes because they are not based on asymptotic distributions. In particular, the fiducial paradigm is a useful tool because it provides more information than p values without the need to specify prior distributions, which may unduly influence the results based on a small sample. We provide the R code used to develop and implement all models.     

FMRI connectivity analysis of acupuncture effects on the whole brain network in mild cognitive impairment patients

The increased risk for the elderly with mild cognitive impairment (MCI) to progress to Alzheimer's disease makes it an appropriate condition for investigation. While the use of acupuncture as a complementary therapeutic method for treating MCI is popular in certain parts of the world, the underlying mechanism is still elusive. We sought to investigate the acupuncture effects on the functional connectivity throughout the entire brain in MCI patients compared to healthy controls (HC). The functional magnetic resonance imaging experiment was performed with two different paradigms, namely, deep acupuncture (DA) and superficial acupuncture (SA), at acupoint KI3. We first identified regions showing abnormal functional connectivity in the MCI group compared to HC during the resting state and subsequently tested whether these regions could be modulated by acupuncture. Then, we made the comparison of MCI vs. HC to test whether there were any specific modulatory patterns in the poststimulus resting brain between the two groups. Finally, we made the comparisons of DA vs. SA in each group to test the effect of acupuncture with different needling depths. We found the temporal regions (hippocampus, thalamus, fusiform gyrus) showing abnormal functional connectivity during the resting state. These regions are implicated in memory encoding and retrieving. Furthermore, we found significant changes in functional connectivity related with the abnormal regions in MCI patients following acupuncture. Compared to HC, the correlations related with the temporal regions were enhanced in the poststimulus resting brain in MCI patients. Compared to SA, significantly increased correlations related with the temporal regions were found for the DA condition. The enhanced correlations in the memory-related brain regions following acupuncture may be related to the purported therapeutically beneficial effects of acupuncture for the treatment of MCI. The heterogeneous modulatory patterns between DA and SA may suggest that deep muscle insertion of acupuncture is necessary to achieve the appreciable clinical effect.     

Non-Gaussian diffusion MRI assessment of brain microstructure in mild cognitive impairment and Alzheimer’s disease

We report the first application of a novel diffusion-based MRI method, called diffusional kurtosis imaging (DKI), to investigate changes in brain tissue microstructure in patients with mild cognitive impairment (MCI) and AD and in cognitively intact controls. The subject groups were characterized and compared in terms of DKI-derived metrics for selected brain regions using analysis of covariance with a Tukey multiple comparison correction. Receiver operating characteristic (ROC) and binary logistic regression analyses were used to assess the utility of regional diffusion measures, alone and in combination, to discriminate each pair of subject groups. ROC analyses identified mean and radial kurtoses in the anterior corona radiata as the best individual discriminators of MCI from controls, with the measures having an area under the ROC curve (AUC) of 0.80 and 0.82, respectively. The next best discriminators of MCI from controls were diffusivity and kurtosis (both mean and radial) in the prefrontal white matter (WM), with each measure having an AUC between 0.77 and 0.79. Finally, the axial diffusivity in the hippocampus was the best overall discriminator of MCI from AD, having an AUC of 0.90. These preliminary results suggest that non-Gaussian diffusion MRI may be beneficial in the assessment of microstructural tissue damage at the early stage of MCI and may be useful in developing biomarkers for the clinical staging of AD.     

Microcanonical and Canonical Ensembles for fMRI Brain Networks in Alzheimer’s Disease

This paper seeks to advance the state-of-the-art in analysing fMRI data to detect onset of Alzheimer’s disease and identify stages in the disease progression. We employ methods of network neuroscience to represent correlation across fMRI data arrays, and introduce novel techniques for network construction and analysis. In network construction, we vary thresholds in establishing BOLD time series correlation between nodes, yielding variations in topological and other network characteristics. For network analysis, we employ methods developed for modelling statistical ensembles of virtual particles in thermal systems. The microcanonical ensemble and the canonical ensemble are analogous to two different fMRI network representations. In the former case, there is zero variance in the number of edges in each network, while in the latter case the set of networks have a variance in the number of edges. Ensemble methods describe the macroscopic properties of a network by considering the underlying microscopic characterisations which are in turn closely related to the degree configuration and network entropy. When applied to fMRI data in populations of Alzheimer’s patients and controls, our methods demonstrated levels of sensitivity adequate for clinical purposes in both identifying brain regions undergoing pathological changes and in revealing the dynamics of such changes.     

A preliminary study of functional abnormalities in aMCI subjects during different episodic memory tasks

Functional magnetic resonance imaging (fMRI) is an important imaging modality to understand the neurodegenerative course of mild cognitive impairment (MCI) and early Alzheimer's disease (AD), because the memory dysfunction may occur before structural degeneration is obvious. In this research, we investigated the functional abnormalities of subjects with amnestic MCI (aMCI) using three episodic memory paradigms that are relevant to different memory domains in both encoding and recognition phases. Both whole-brain analysis and region-of-interest (ROI) analysis of the medial temporal lobes (MTL), which are central to the memory formation and retrieval, were used to compare the efficiency of the different memory paradigms and the functional difference between aMCI subjects and normal control subjects. We also investigated the impact of using different functional activation measurements in ROI analysis. This pilot study could facilitate the use of fMRI activations in the MTL as a marker for early detection and monitoring progression of AD.     

基于Kendall改进的同步算法癫痫脑网络分析

提出了一种基于Kendall等级相关改进的同步算法IRC(inverse rank correlation).Kendall等级相关是非线性动力学分析的一般化算法,可有效地度量变量间的非线性相关性.复杂网络的研究已逐渐深入到社会科学的各个领域,脑网络的研究已经成为当今脑功能研究的热点.利用改进的IRC算法,基于脑电EEG(electroencephalogram)数据来构建大脑功能性网络.对构建的脑功能网络的度指标进行了分析,以调查癫痫脑功能网络是否异于正常人.结果显示:使用该改进的算法能够对癫痫和正常脑功能网络显著区分,且只需要记录很短的脑电数据.实验结果数据表明,该方法适用于区分癫痫和正常脑组织网络度指标,它可有助于进一步地加深对大脑的神经动力学行为的研究,并为临床诊断提供有效工具.     

Working Memory Decline in Alzheimer’s Disease Is Detected by Complexity Analysis of Multimodal EEG-fNIRS

Alzheimer’s disease (AD) is characterized by working memory (WM) failures that can be assessed at early stages through administering clinical tests. Ecological neuroimaging, such as Electroencephalography (EEG) and functional Near Infrared Spectroscopy (fNIRS), may be employed during these tests to support AD early diagnosis within clinical settings. Multimodal EEG-fNIRS could measure brain activity along with neurovascular coupling (NC) and detect their modifications associated with AD. Data analysis procedures based on signal complexity are suitable to estimate electrical and hemodynamic brain activity or their mutual information (NC) during non-structured experimental paradigms. In this study, sample entropy of whole-head EEG and frontal/prefrontal cortex fNIRS was evaluated to assess brain activity in early AD and healthy controls (HC) during WM tasks (i.e., Rey–Osterrieth complex figure and Raven’s progressive matrices). Moreover, conditional entropy between EEG and fNIRS was evaluated as indicative of NC. The findings demonstrated the capability of complexity analysis of multimodal EEG-fNIRS to detect WM decline in AD. Furthermore, a multivariate data-driven analysis, performed on these entropy metrics and based on the General Linear Model, allowed classifying AD and HC with an AUC up to 0.88. EEG-fNIRS may represent a powerful tool for the clinical evaluation of WM decline in early AD.     

Choosing Strategies to Deal with Artifactual EEG Data in Children with Cognitive Impairment

Rett syndrome is a disease that involves acute cognitive impairment and, consequently, a complex and varied symptomatology. This study evaluates the EEG signals of twenty-nine patients and classify them according to the level of movement artifact. The main goal is to achieve an artifact rejection strategy that performs well in all signals, regardless of the artifact level. Two different methods have been studied: one based on the data distribution and the other based on the energy function, with entropy as its main component. The method based on the data distribution shows poor performance with signals containing high amplitude outliers. On the contrary, the method based on the energy function is more robust to outliers. As it does not depend on the data distribution, it is not affected by artifactual events. A double rejection strategy has been chosen, first on a motion signal (accelerometer or EEG low-pass filtered between 1 and 10 Hz) and then on the EEG signal. The results showed a higher performance when working combining both artifact rejection methods. The energy-based method, to isolate motion artifacts, and the data-distribution-based method, to eliminate the remaining lower amplitude artifacts were used. In conclusion, a new method that proves to be robust for all types of signals is designed.     

EEG-Based Emotion Recognition by Exploiting Fused Network Entropy Measures of Complex Networks across Subjects

It is well known that there may be significant individual differences in physiological signal patterns for emotional responses. Emotion recognition based on electroencephalogram (EEG) signals is still a challenging task in the context of developing an individual-independent recognition method. In our paper, from the perspective of spatial topology and temporal information of brain emotional patterns in an EEG, we exploit complex networks to characterize EEG signals to effectively extract EEG information for emotion recognition. First, we exploit visibility graphs to construct complex networks from EEG signals. Then, two kinds of network entropy measures (nodal degree entropy and clustering coefficient entropy) are calculated. By applying the AUC method, the effective features are input into the SVM classifier to perform emotion recognition across subjects. The experiment results showed that, for the EEG signals of 62 channels, the features of 18 channels selected by AUC were significant (p < 0.005). For the classification of positive and negative emotions, the average recognition rate was 87.26%; for the classification of positive, negative, and neutral emotions, the average recognition rate was 68.44%. Our method improves mean accuracy by an average of 2.28% compared with other existing methods. Our results fully demonstrate that a more accurate recognition of emotional EEG signals can be achieved relative to the available relevant studies, indicating that our method can provide more generalizability in practical use.     

Effects of Tau and Sampling Frequency on the Regularity Analysis of ECG and EEG Signals Using ApEn and SampEn Entropy Estimators

Electrocardiography (ECG) and electroencephalography (EEG) signals provide clinical information relevant to determine a patient’s health status. The nonlinear analysis of ECG and EEG signals allows for discovering characteristics that could not be found with traditional methods based on amplitude and frequency. Approximate entropy (ApEn) and sampling entropy (SampEn) are nonlinear data analysis algorithms that measure the data’s regularity, and these are used to classify different electrophysiological signals as normal or pathological. Entropy calculation requires setting the parameters r (tolerance threshold), m (immersion dimension), and τ (time delay), with the last one being related to how the time series is downsampled. In this study, we showed the dependence of ApEn and SampEn on different values of τ, for ECG and EEG signals with different sampling frequencies (F_s), extracted from a digital repository. We considered four values of F_s (128, 256, 384, and 512 Hz for the ECG signals, and 160, 320, 480, and 640 Hz for the EEG signals) and five values of τ (from 1 to 5). We performed parametric and nonparametric statistical tests to confirm that the groups of normal and pathological ECG and EEG signals were significantly different (p < 0.05) for each F and τ value. The separation between the entropy values of regular and irregular signals was variable, demonstrating the dependence of ApEn and SampEn with F_s and τ. For ECG signals, the separation between the conditions was more robust when using SampEn, the lowest value of F_s, and τ larger than 1. For EEG signals, the separation between the conditions was more robust when using SampEn with large values of F_s and τ larger than 1. Therefore, adjusting τ may be convenient for signals that were acquired with different F_s to ensure a reliable clinical classification. Furthermore, it is useful to set τ to values larger than 1 to reduce the computational cost.     

基于虚拟开车环境的自闭症儿童脑电样本熵

自闭症谱系障碍是一种涉及感觉、情感、记忆、语言、智力、动作等认知功能和执行功能障碍的精神疾病. 本文从神经工效学角度出发, 用虚拟开车环境作为复杂多任务激励源将大脑系统与人体动作控制等有机地结合起来, 通过对脑电信号的滑动平均样本熵分析来探索自闭症儿童在虚拟开车环境中的脑活动特征. 研究发现不论是休息状态还是开车状态, 自闭症患者的滑动平均样本熵总体上低于健康者, 尤其在前额叶、颞叶、顶叶和枕叶功能区, 表明自闭症儿童的行为适应性较低. 不过, 自闭症患者的开车状态与健康受试者的休息状态比较接近, 表明虚拟开车环境或许有助于自闭症患者的干预治疗. 此外, 自闭症患者在颞叶区呈现显著性右半球优势性. 本研究为进一步深入开展自闭症疾病的机理研究及其诊断、评估和干预等研究提供一种新的研究思路.     

Approximate Entropy of Brain Network in the Study of Hemispheric Differences

Human brain, a dynamic complex system, can be studied with different approaches, including linear and nonlinear ones. One of the nonlinear approaches widely used in electroencephalographic (EEG) analyses is the entropy, the measurement of disorder in a system. The present study investigates brain networks applying approximate entropy (ApEn) measure for assessing the hemispheric EEG differences; reproducibility and stability of ApEn data across separate recording sessions were evaluated. Twenty healthy adult volunteers were submitted to eyes-closed resting EEG recordings, for 80 recordings. Significant differences in the occipital region, with higher values of entropy in the left hemisphere than in the right one, show that the hemispheres become active with different intensities according to the performed function. Besides, the present methodology proved to be reproducible and stable, when carried out on relatively brief EEG epochs but also at a 1-week distance in a group of 36 subjects. Nonlinear approaches represent an interesting probe to study the dynamics of brain networks. ApEn technique might provide more insight into the pathophysiological processes underlying age-related brain disconnection as well as for monitoring the impact of pharmacological and rehabilitation treatments.     

基于弹性变分模态分解的癫痫脑电信号分类方法

癫痫脑电信号分类对于癫痫诊治具有重要意义.为了实现病灶性与非病灶性癫痫脑电信号的分类,本文利用弹性网回归重构变分模态分解算法,提出弹性变分模态分解算法并将其应用到所提癫痫脑电信号分类方法中.该方法先将原信号分割成多个子信号,并对各子信号进行弹性变分模态分解,然后从分解后的不同变分模态函数中提取精细复合多尺度散布熵作为特征,最后利用支持向量机进行分类.针对癫痫脑电的公共数据集,最终的实验结果表明,准确率、灵敏度和特异度三个性能指标分别达到92.54%,93.22%和91.86%.     

Analysis of cross-correlations in electroencephalogram signals as an approach to proactive diagnosis of schizophrenia

We apply flicker-noise spectroscopy (FNS), a time series analysis method operating on structure functions and power spectrum estimates, to study the clinical electroencephalogram (EEG) signals recorded in children/adolescents (11 to 14 years of age) with diagnosed schizophrenia-spectrum symptoms at the National Center for Psychiatric Health (NCPH) of the Russian Academy of Medical Sciences. The EEG signals for these subjects were compared with the signals for a control sample of chronically depressed children/adolescents. The purpose of the study is to look for diagnostic signs of subjects’ susceptibility to schizophrenia in the FNS parameters for specific electrodes and cross-correlations between the signals simultaneously measured at different points on the scalp. Our analysis of EEG signals from scalp-mounted electrodes at locations F₃ and F₄, which are symmetrically positioned in the left and right frontal areas of cerebral cortex, respectively, demonstrates an essential role of frequency-phase synchronization, a phenomenon representing specific correlations between the characteristic frequencies and phases of excitations in the brain. We introduce quantitative measures of frequency-phase synchronization and systematize the values of FNS parameters for the EEG data. The comparison of our results with the medical diagnoses for 84 subjects performed at NCPH makes it possible to group the EEG signals into 4 categories corresponding to different risk levels of subjects’ susceptibility to schizophrenia. We suggest that the introduced quantitative characteristics and classification of cross-correlations may be used for the diagnosis of schizophrenia at the early stages of its development.