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.     

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.     

Investigation on Identifying Implicit Learning Event from EEG Signal Using Multiscale Entropy and Artificial Bee Colony

The way people learn will play an essential role in the sustainable development of the educational system for the future. Utilizing technology in the age of information and incorporating it into how people learn can produce better learners. Implicit learning is a type of learning of the underlying rules without consciously seeking or understanding the rules; it is commonly seen in small children while learning how to speak their native language without learning grammar. This research aims to introduce a processing system that can systematically identify the relationship between implicit learning events and their Encephalogram (EEG) signal characteristics. This study converted the EEG signal from participants while performing cognitive task experiments into Multiscale Entropy (MSE) data. Using MSE data from different frequency bands and channels as features, the system explored a wide range of classifiers and observed their performance to see how they classified the features related to participants’ performance. The Artificial Bee Colony (ABC) method was used for feature selection to improve the process to make the system more efficient. The results showed that the system could correctly identify the differences between participants’ performance using MSE data and the ABC method with 95% confidence.     

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.     

Multiscale Permutation Lempel–Ziv Complexity Measure for Biomedical Signal Analysis: Interpretation and Application to Focal EEG Signals

This paper analyses the complexity of electroencephalogram (EEG) signals in different temporal scales for the analysis and classification of focal and non-focal EEG signals. Futures from an original multiscale permutation Lempel–Ziv complexity measure (MPLZC) were obtained. MPLZC measure combines a multiscale structure, ordinal analysis, and permutation Lempel–Ziv complexity for quantifying the dynamic changes of an electroencephalogram (EEG). We also show the dependency of MPLZC on several straight-forward signal processing concepts, which appear in biomedical EEG activity via a set of synthetic signals. The main material of the study consists of EEG signals, which were obtained from the Bern-Barcelona EEG database. The signals were divided into two groups: focal EEG signals (n = 100) and non-focal EEG signals (n = 100); statistical analysis was performed by means of non-parametric Mann–Whitney test. The mean value of MPLZC results in the non-focal group are significantly higher than those in the focal group for scales above 1 (p < 0.05). The result indicates that the non-focal EEG signals are more complex. MPLZC feature sets are used for the least squares support vector machine (LS-SVM) classifier to classify into the focal and non-focal EEG signals. Our experimental results confirmed the usefulness of the MPLZC method for distinguishing focal and non-focal EEG signals with a classification accuracy of 86%.     

Reduced System Complexity of Heart Rate Dynamics in Patients with Hyperthyroidism: A Multiscale Entropy Analysis

Studying heart rate dynamics would help understand the effects caused by a hyperkinetic heart in patients with hyperthyroidism. By using a multiscale entropy (MSE) analysis of heart rate dynamics derived from one-channel electrocardiogram recording, we aimed to compare the system complexity of heart rate dynamics between hyperthyroid patients and control subjects. A decreased MSE complexity index (CI) computed from MSE analysis reflects reduced system complexity. Compared with the control subjects (n = 37), the hyperthyroid patients (n = 37) revealed a significant decrease (p < 0.001) in MSE CI (hyperthyroid patients 10.21 ± 0.37 versus control subjects 14.08 ± 0.21), sample entropy for each scale factor (from 1 to 9), and high frequency power (HF) as well as a significant increase (p < 0.001) in low frequency power (LF) in normalized units (LF%) and ratio of LF to HF (LF/HF). In conclusion, besides cardiac autonomic dysfunction, the system complexity of heart rate dynamics is reduced in hyperthyroidism. This finding implies that the adaptability of the heart rate regulating system is impaired in hyperthyroid patients. Additionally, it might explain the exercise intolerance experienced by hyperthyroid patients. In addition, hyperthyroid patients and control subjects could be distinguished by the MSE CI computed from MSE analysis of heart rate dynamics.     

The Value of Heart Rhythm Complexity in Identifying High-Risk Pulmonary Hypertension Patients

Pulmonary hypertension (PH) is a fatal disease—even with state-of-the-art medical treatment. Non-invasive clinical tools for risk stratification are still lacking. The aim of this study was to investigate the clinical utility of heart rhythm complexity in risk stratification for PH patients. We prospectively enrolled 54 PH patients, including 20 high-risk patients (group A; defined as WHO functional class IV or class III with severely compromised hemodynamics), and 34 low-risk patients (group B). Both linear and non-linear heart rate variability (HRV) variables, including detrended fluctuation analysis (DFA) and multiscale entropy (MSE), were analyzed. In linear and non-linear HRV analysis, low frequency and high frequency ratio, DFAα1, MSE slope 5, scale 5, and area 6–20 were significantly lower in group A. Among all HRV variables, MSE scale 5 (AUC: 0.758) had the best predictive power to discriminate the two groups. In multivariable analysis, MSE scale 5 (p = 0.010) was the only significantly predictor of severe PH in all HRV variables. In conclusion, the patients with severe PH had worse heart rhythm complexity. MSE parameters, especially scale 5, can help to identify high-risk PH patients.     

The Systematic Bias of Entropy Calculation in the Multi-Scale Entropy Algorithm

Entropy indicates irregularity or randomness of a dynamic system. Over the decades, entropy calculated at different scales of the system through subsampling or coarse graining has been used as a surrogate measure of system complexity. One popular multi-scale entropy analysis is the multi-scale sample entropy (MSE), which calculates entropy through the sample entropy (SampEn) formula at each time scale. SampEn is defined by the “logarithmic likelihood” that a small section (within a window of a length m) of the data “matches” with other sections will still “match” the others if the section window length increases by one. “Match” is defined by a threshold of r times standard deviation of the entire time series. A problem of current MSE algorithm is that SampEn calculations at different scales are based on the same matching threshold defined by the original time series but data standard deviation actually changes with the subsampling scales. Using a fixed threshold will automatically introduce systematic bias to the calculation results. The purpose of this paper is to mathematically present this systematic bias and to provide methods for correcting it. Our work will help the large MSE user community avoiding introducing the bias to their multi-scale SampEn calculation results.     

Generalized Ordinal Patterns and the KS-Entropy

Ordinal patterns classifying real vectors according to the order relations between their components are an interesting basic concept for determining the complexity of a measure-preserving dynamical system. In particular, as shown by C. Bandt, G. Keller and B. Pompe, the permutation entropy based on the probability distributions of such patterns is equal to Kolmogorov–Sinai entropy in simple one-dimensional systems. The general reason for this is that, roughly speaking, the system of ordinal patterns obtained for a real-valued “measuring arrangement” has high potential for separating orbits. Starting from a slightly different approach of A. Antoniouk, K. Keller and S. Maksymenko, we discuss the generalizations of ordinal patterns providing enough separation to determine the Kolmogorov–Sinai entropy. For defining these generalized ordinal patterns, the idea is to substitute the basic binary relation ≤ on the real numbers by another binary relation. Generalizing the former results of I. Stolz and K. Keller, we establish conditions that the binary relation and the dynamical system have to fulfill so that the obtained generalized ordinal patterns can be used for estimating the Kolmogorov–Sinai entropy.     

Multiscale Entropy Analysis of Short Signals: The Robustness of Fuzzy Entropy-Based Variants Compared to Full-Length Long Signals

Multiscale entropy (MSE) analysis is a fundamental approach to access the complexity of a time series by estimating its information creation over a range of temporal scales. However, MSE may not be accurate or valid for short time series. This is why previous studies applied different kinds of algorithm derivations to short-term time series. However, no study has systematically analyzed and compared their reliabilities. This study compares the MSE algorithm variations adapted to short time series on both human and rat heart rate variability (HRV) time series using long-term MSE as reference. The most used variations of MSE are studied: composite MSE (CMSE), refined composite MSE (RCMSE), modified MSE (MMSE), and their fuzzy versions. We also analyze the errors in MSE estimations for a range of incorporated fuzzy exponents. The results show that fuzzy MSE versions—as a function of time series length—present minimal errors compared to the non-fuzzy algorithms. The traditional multiscale entropy algorithm with fuzzy counting (MFE) has similar accuracy to alternative algorithms with better computing performance. For the best accuracy, the findings suggest different fuzzy exponents according to the time series length.     

Consciousness Detection in a Complete Locked-in Syndrome Patient through Multiscale Approach Analysis

Completely locked-in state (CLIS) patients are unable to speak and have lost all muscle movement. From the external view, the internal brain activity of such patients cannot be easily perceived, but CLIS patients are considered to still be conscious and cognitively active. Detecting the current state of consciousness of CLIS patients is non-trivial, and it is difficult to ascertain whether CLIS patients are conscious or not. Thus, it is important to find alternative ways to re-establish communication with these patients during periods of awareness, and one such alternative is through a brain–computer interface (BCI). In this study, multiscale-based methods (multiscale sample entropy, multiscale permutation entropy and multiscale Poincaré plots) were applied to analyze electrocorticogram signals from a CLIS patient to detect the underlying consciousness level. Results from these different methods converge to a specific period of awareness of the CLIS patient in question, coinciding with the period during which the CLIS patient is recorded to have communicated with an experimenter. The aim of the investigation is to propose a methodology that could be used to create reliable communication with CLIS patients.     

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.     

Modified multiscale entropy for short-term time series analysis

Multiscale entropy (MSE) is a prevalent algorithm used to measure the complexity of a time series. Because the coarse-graining procedure reduces the length of a time series, the conventional MSE algorithm applied to a short-term time series may yield an imprecise estimation of entropy or induce undefined entropy. To overcome this obstacle, the modified multiscale entropy (MMSE) was developed. The coarse-graining procedure was replaced with a moving-average procedure and a time delay was incorporated for constructing template vectors in calculating sample entropy. For conducting short-term time series analysis, this study shows that the MMSE algorithm is more reliable than the conventional MSE.     

Application of Generalized Composite Multiscale Lempel–Ziv Complexity in Identifying Wind Turbine Gearbox Faults

Wind turbine gearboxes operate in harsh environments; therefore, the resulting gear vibration signal has characteristics of strong nonlinearity, is non-stationary, and has a low signal-to-noise ratio, which indicates that it is difficult to identify wind turbine gearbox faults effectively by the traditional methods. To solve this problem, this paper proposes a new fault diagnosis method for wind turbine gearboxes based on generalized composite multiscale Lempel–Ziv complexity (GCMLZC). Within the proposed method, an effective technique named multiscale morphological-hat convolution operator (MHCO) is firstly presented to remove the noise interference information of the original gear vibration signal. Then, the GCMLZC of the filtered signal was calculated to extract gear fault features. Finally, the extracted fault features were input into softmax classifier for automatically identifying different health conditions of wind turbine gearboxes. The effectiveness of the proposed method was validated by the experimental and engineering data analysis. The results of the analysis indicate that the proposed method can identify accurately different gear health conditions. Moreover, the identification accuracy of the proposed method is higher than that of traditional multiscale Lempel–Ziv complexity (MLZC) and several representative multiscale entropies (e.g., multiscale dispersion entropy (MDE), multiscale permutation entropy (MPE) and multiscale sample entropy (MSE)).     

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.     

Analysis of complex time series using refined composite multiscale entropy

Multiscale entropy (MSE) is an effective algorithm for measuring the complexity of a time series that has been applied in many fields successfully. However, MSE may yield an inaccurate estimation of entropy or induce undefined entropy because the coarse-graining procedure reduces the length of a time series considerably at large scales. Composite multiscale entropy (CMSE) was recently proposed to improve the accuracy of MSE, but it does not resolve undefined entropy. Here we propose a refined composite multiscale entropy (RCMSE) to improve CMSE. For short time series analyses, we demonstrate that RCMSE increases the accuracy of entropy estimation and reduces the probability of inducing undefined entropy.     

On the α-q-Mutual Information and the α-q-Capacities

The measures of information transfer which correspond to non-additive entropies have intensively been studied in previous decades. The majority of the work includes the ones belonging to the Sharma–Mittal entropy class, such as the Rényi, the Tsallis, the Landsberg–Vedral and the Gaussian entropies. All of the considerations follow the same approach, mimicking some of the various and mutually equivalent definitions of Shannon information measures, and the information transfer is quantified by an appropriately defined measure of mutual information, while the maximal information transfer is considered as a generalized channel capacity. However, all of the previous approaches fail to satisfy at least one of the ineluctable properties which a measure of (maximal) information transfer should satisfy, leading to counterintuitive conclusions and predicting nonphysical behavior even in the case of very simple communication channels. This paper fills the gap by proposing two parameter measures named the α-q-mutual information and the α-q-capacity. In addition to standard Shannon approaches, special cases of these measures include the α-mutual information and the α-capacity, which are well established in the information theory literature as measures of additive Rényi information transfer, while the cases of the Tsallis, the Landsberg–Vedral and the Gaussian entropies can also be accessed by special choices of the parameters α and q. It is shown that, unlike the previous definition, the α-q-mutual information and the α-q-capacity satisfy the set of properties, which are stated as axioms, by which they reduce to zero in the case of totally destructive channels and to the (maximal) input Sharma–Mittal entropy in the case of perfect transmission, which is consistent with the maximum likelihood detection error. In addition, they are non-negative and less than or equal to the input and the output Sharma–Mittal entropies, in general. Thus, unlike the previous approaches, the proposed (maximal) information transfer measures do not manifest nonphysical behaviors such as sub-capacitance or super-capacitance, which could qualify them as appropriate measures of the Sharma–Mittal information transfer.     

A Quantitative Comparison between Shannon and Tsallis–Havrda–Charvat Entropies Applied to Cancer Outcome Prediction

In this paper, we propose to quantitatively compare loss functions based on parameterized Tsallis–Havrda–Charvat entropy and classical Shannon entropy for the training of a deep network in the case of small datasets which are usually encountered in medical applications. Shannon cross-entropy is widely used as a loss function for most neural networks applied to the segmentation, classification and detection of images. Shannon entropy is a particular case of Tsallis–Havrda–Charvat entropy. In this work, we compare these two entropies through a medical application for predicting recurrence in patients with head–neck and lung cancers after treatment. Based on both CT images and patient information, a multitask deep neural network is proposed to perform a recurrence prediction task using cross-entropy as a loss function and an image reconstruction task. Tsallis–Havrda–Charvat cross-entropy is a parameterized cross-entropy with the parameter α . Shannon entropy is a particular case of Tsallis–Havrda–Charvat entropy for α=1 . The influence of this parameter on the final prediction results is studied. In this paper, the experiments are conducted on two datasets including in total 580 patients, of whom 434 suffered from head–neck cancers and 146 from lung cancers. The results show that Tsallis–Havrda–Charvat entropy can achieve better performance in terms of prediction accuracy with some values of α .     

An ESR Framework for the Study of Consciousness

I will argue that, in an interdisciplinary study of consciousness, epistemic structural realism (ESR) can offer a feasible philosophical background for the study of consciousness and its associated neurophysiological phenomena in neuroscience and cognitive science while also taking into account the mathematical structures involved in this type of research. Applying the ESR principles also to the study of the neurophysiological phenomena associated with free will (or rather conscious free choice) and with various alterations of consciousness (AOCs) generated by various pathologies such as epilepsy would add explanatory value to the matter. This interdisciplinary approach would be in tune with Quine’s well known idea that philosophy is not simple conceptual analysis but is continuous with science and actually represents an abstract branch of the empirical research. The ESR could thus resonate with scientific models of consciousness such as the global neuronal workspace model (inspired by the global workspace theory—GWT) and the integrated information theory (IIT) model. While structural realism has already been employed in physics or biology, its application as a meta-theory contextualising and relating various scientific findings on consciousness is new indeed. Out of the two variants: ontic structural realism (OSR) and epistemic structural realism (ESR), the latter can be considered more suitable for the study of consciousness and its associated neurophysiological phenomena because it removes the pressure of the still unanswered ‘What is consciousness?’ ontological question and allows us to concentrate instead on the ‘What can we know about consciousness?’ epistemological question.     

Are Words the Quanta of Human Language? Extending the Domain of Quantum Cognition

In previous research, we showed that ‘texts that tell a story’ exhibit a statistical structure that is not Maxwell–Boltzmann but Bose–Einstein. Our explanation is that this is due to the presence of ‘indistinguishability’ in human language as a result of the same words in different parts of the story being indistinguishable from one another, in much the same way that ’indistinguishability’ occurs in quantum mechanics, also there leading to the presence of Bose–Einstein rather than Maxwell–Boltzmann as a statistical structure. In the current article, we set out to provide an explanation for this Bose–Einstein statistics in human language. We show that it is the presence of ‘meaning’ in ‘texts that tell a story’ that gives rise to the lack of independence characteristic of Bose–Einstein, and provides conclusive evidence that ‘words can be considered the quanta of human language’, structurally similar to how ‘photons are the quanta of electromagnetic radiation’. Using several studies on entanglement from our Brussels research group, we also show, by introducing the von Neumann entropy for human language, that it is also the presence of ‘meaning’ in texts that makes the entropy of a total text smaller relative to the entropy of the words composing it. We explain how the new insights in this article fit in with the research domain called ‘quantum cognition’, where quantum probability models and quantum vector spaces are used in human cognition, and are also relevant to the use of quantum structures in information retrieval and natural language processing, and how they introduce ‘quantization’ and ‘Bose–Einstein statistics’ as relevant quantum effects there. Inspired by the conceptuality interpretation of quantum mechanics, and relying on the new insights, we put forward hypotheses about the nature of physical reality. In doing so, we note how this new type of decrease in entropy, and its explanation, may be important for the development of quantum thermodynamics. We likewise note how it can also give rise to an original explanatory picture of the nature of physical reality on the surface of planet Earth, in which human culture emerges as a reinforcing continuation of life.