The use of the eye-fixation-related potential to investigate visual perception in professional domains with high attentional demand: a literature review.

INTRODUCTION: Visual attention is a cognitive skill related to visual perception and neural activity, and also moderated by expertise, in time-constrained professional domains (e.g., aviation, driving, sport, surgery). However, the contribution of both perceptual and neural processes on performance has been studied separately in the literature. DEVELOPMENT: We defend an integration of visual and neural signals to offer a more complete picture of the visual attention displayed by professionals of different skill levels when performing free-viewing tasks. Specifically, we propose to zoom the analysis in data related to the quiet eye and P300 component jointly, as a novel signal processing approach to evaluate professionals' visual attention. CONCLUSION: This review highlights the advantages of using portable eye trackers and electroencephalogram systems altogether, as a promising technique for a better understanding of early cognitive components related to attentional processes. Altogether, the eye-fixation-related potentials method may provide a better understanding of the cognitive mechanisms employed by the participants in natural settings, revealing what visual information is of interest for participants and distinguishing the neural bases of visual attention between targets and non-targets whenever they perceive a stimulus during free viewing experiments.

Connectivity-based Meta-Bands: A new approach for automatic frequency band identification in connectivity analyses.

The majority of electroencephalographic (EEG) and magnetoencephalographic (MEG) studies filter and analyse neural signals in specific frequency ranges, known as "canonical" frequency bands. However, this segmentation, is not exempt from limitations, mainly due to the lack of adaptation to the neural idiosyncrasies of each individual. In this study, we introduce a new data-driven method to automatically identify frequency ranges based on the topological similarity of the frequency-dependent functional neural network. The resting-state neural activity of 195 cognitively healthy subjects from three different databases (MEG: 123 subjects; EEG1: 27 subjects; EEG2: 45 subjects) was analysed. In a first step, MEG and EEG signals were filtered with a narrow-band filter bank (1 Hz bandwidth) from 1 to 70 Hz with a 0.5 Hz step. Next, the connectivity in each of these filtered signals was estimated using the orthogonalized version of the amplitude envelope correlation to obtain the frequency-dependent functional neural network. Finally, a community detection algorithm was used to identify communities in the frequency domain showing a similar network topology. We have called this approach the "Connectivity-based Meta-Bands" (CMB) algorithm. Additionally, two types of synthetic signals were used to configure the hyper-parameters of the CMB algorithm. We observed that the classical approaches to band segmentation are partially aligned with the underlying network topologies at group level for the MEG signals, but they are missing individual idiosyncrasies that may be biasing previous studies, as revealed by our methodology. On the other hand, the sensitivity of EEG signals to reflect this underlying frequency-dependent network structure is limited, revealing a simpler frequency parcellation, not aligned with that defined by the "canonical" frequency bands. To the best of our knowledge, this is the first study that proposes an unsupervised band segmentation method based on the topological similarity of functional neural network across frequencies. This methodology fully accounts for subject-specific patterns, providing more robust and personalized analyses, and paving the way for new studies focused on exploring the frequency-dependent structure of brain connectivity.

Validation of a predictive model for obstructive sleep apnea in people with Down syndrome.

Detecting obstructive sleep apnea (OSA) is important to both prevent significant comorbidities in people with Down syndrome (DS) and untangle contributions to other behavioral and mental health diagnoses. However, laboratory-based polysomnograms are often poorly tolerated, unavailable, or not covered by health insurance for this population. In previous work, our team developed a prediction model that seemed to hold promise in identifying which people with DS might not have significant apnea and, consequently, might be able to forgo a diagnostic polysomnogram. In this study, we sought to validate these findings in a novel set of participants with DS. We recruited an additional 64 participants with DS, ages 3-35 years. Caregivers completed the same validated questionnaires, and our study team collected vital signs, physical exam findings, and medical histories that were previously shown to be predictive. Patients then had a laboratory-based polysomnogram. The best modeling had a validated negative predictive value of 50% for an apnea-hypopnea index (AHI) > 1/hTST and 73.7% for AHI >5/hTST. The positive predictive values were 60% and 39.1%, respectively. As such, a clinically reliable screening tool for OSA in people with DS was not achieved. Patients with DS should continue to be monitored for OSA according to current healthcare guidelines.

Covering the Gap Between Sleep and Cognition - Mechanisms and Clinical Examples.

A growing number of studies have shown the strong relationship between sleep and different cognitive processes, especially those that involve memory consolidation. Traditionally, these processes were attributed to mechanisms related to the macroarchitecture of sleep, as sleep cycles or the duration of specific stages, such as the REM stage. More recently, the relationship between different cognitive traits and specific waves (sleep spindles or slow oscillations) has been studied. We here present the most important physiological processes induced by sleep, with particular focus on brain electrophysiology. In addition, recent and classical literature were reviewed to cover the gap between sleep and cognition, while illustrating this relationship by means of clinical examples. Finally, we propose that future studies may focus not only on analyzing specific waves, but also on the relationship between their characteristics as potential biomarkers for multiple diseases.

Airflow Analysis in the Context of Sleep Apnea.

The airflow (AF) is a physiological signal involved in the overnight polysomnography (PSG) that reflects the respiratory activity. This signal is able to show the particularities of sleep apnea and is therefore used to define apneic events. In this regard, a growing number of studies have shown the usefulness of employing the overnight airflow as the only or combined information source for diagnosing sleep apnea in both children and adults. Due to its easy acquisition and interpretation, this biosignal has been widely analyzed by means of different signal processing techniques. In this chapter, we review the main methodological approaches applied to characterize and extract relevant information from this signal. In view of the results, we can conclude that the overnight airflow successfully reflects the particularities caused by the occurrence of apneic and hypopneic events and provides useful information for obtaining relevant biomarkers that characterize this disease.

Oximetry Indices in the Management of Sleep Apnea: From Overnight Minimum Saturation to the Novel Hypoxemia Measures.

Obstructive sleep apnea (OSA) is a multidimensional disease often underdiagnosed due to the complexity and unavailability of its standard diagnostic method: the polysomnography. Among the alternative abbreviated tests searching for a compromise between simplicity and accurateness, oximetry is probably the most popular. The blood oxygen saturation (SpO2) signal is characterized by a near-constant profile in healthy subjects breathing normally, while marked drops (desaturations) are linked to respiratory events. Parameterization of the desaturations has led to a great number of indices of severity assessment commonly used to assist in OSA diagnosis. In this chapter, the main methodologies used to characterize the overnight oximetry profile are reviewed, from visual inspection and simple statistics to complex measures involving signal processing and pattern recognition techniques. We focus on the individual performance of each approach, but also on the complementarity among the great amount of indices existing in the state of the art, looking for the most relevant oximetric feature subset. Finally, a quick overview of SpO2-based deep learning applications for OSA management is carried out, where the raw oximetry signal is analyzed without previous parameterization. Our research allows us to conclude that all the methodologies (conventional, time, frequency, nonlinear, and hypoxemia-based) demonstrate high ability to provide relevant oximetric indices, but only a reduced set provide non-redundant complementary information leading to a significant performance increase. Finally, although oximetry is a robust tool, greater standardization and prospective validation of the measures derived from complex signal processing techniques are still needed to homogenize interpretation and increase generalizability.

Conventional Machine Learning Methods Applied to the Automatic Diagnosis of Sleep Apnea.

The overnight polysomnography shows a range of drawbacks to diagnose obstructive sleep apnea (OSA) that have led to the search for artificial intelligence-based alternatives. Many classic machine learning methods have been already evaluated for this purpose. In this chapter, we show the main approaches found in the scientific literature along with the most used data to develop the models, useful and large easily available databases, and suitable methods to assess performances. In addition, a range of results from selected studies are presented as examples of these methods. Very high diagnostic performances are reported in these results regardless of the approaches taken. This leads us to conclude that conventional machine learning methods are useful techniques to develop new OSA diagnosis simplification proposals and to act as benchmark for other more recent methods such as deep learning.

Deep-Learning Model Based on Convolutional Neural Networks to Classify Apnea-Hypopnea Events from the Oximetry Signal.

Automated analysis of the blood oxygen saturation (SpO2) signal from nocturnal oximetry has shown usefulness to simplify the diagnosis of obstructive sleep apnea (OSA), including the detection of respiratory events. However, the few preceding studies using SpO2 recordings have focused on the automated detection of respiratory events versus normal respiration, without making any distinction between apneas and hypopneas. In this sense, the characteristics of oxygen desaturations differ between obstructive apnea and hypopnea episodes. In this chapter, we use the SpO2 signal along with a convolutional neural network (CNN)-based deep-learning architecture for the automatic identification of apnea and hypopnea events. A total of 398 SpO2 signals from adult OSA patients were used for this purpose. A CNN architecture was trained using 30-s epochs from the SpO2 signal for the automatic classification of three classes: normal respiration, apnea, and hypopnea. Then, the apnea index (AI), the hypopnea index (HI), and the apnea-hypopnea index (AHI) were obtained by aggregating the outputs of the CNN for each subject (AICNN, HICNN, and AHICNN). This model showed a promising diagnostic performance in an independent test set, with 80.3% 3-class accuracy and 0.539 3-class Cohen's kappa for the classification of respiratory events. Furthermore, AICNN, HICNN, and AHICNN showed a high agreement with the values obtained from the standard PSG: 0.8023, 0.6774, and 0.8466 intra-class correlation coefficients (ICCs), respectively. This suggests that CNN can be used to analyze SpO2 recordings for the automated diagnosis of OSA in at-home oximetry tests.

Headache-related circuits and high frequencies evaluated by EEG, MRI, PET as potential biomarkers to differentiate chronic and episodic migraine: Evidence from a systematic review.

BACKGROUND: The diagnosis of migraine is mainly clinical and self-reported, which makes additional examinations unnecessary in most cases. Migraine can be subtyped into chronic (CM) and episodic (EM). Despite the very high prevalence of migraine, there are no evidence-based guidelines for differentiating between these subtypes other than the number of days of migraine headache per month. Thus, we consider it timely to perform a systematic review to search for physiological evidence from functional activity (as opposed to anatomical structure) for the differentiation between CM and EM, as well as potential functional biomarkers. For this purpose, Web of Science (WoS), Scopus, and PubMed databases were screened. FINDINGS: Among the 24 studies included in this review, most of them (22) reported statistically significant differences between the groups of CM and EM. This finding is consistent regardless of brain activity acquisition modality, ictal stage, and recording condition for a wide variety of analyses. That speaks for a supramodal and domain-general differences between CM and EM that goes beyond a differentiation based on the days of migraine per month. Together, the reviewed studies demonstrates that electro- and magneto-physiological brain activity (M/EEG), as well as neurovascular and metabolic recordings from functional magnetic resonance imaging (fMRI) and positron emission tomography (PET), show characteristic patterns that allow to differentiate between CM and EM groups. CONCLUSIONS: Although a clear brain activity-based biomarker has not yet been identified to distinguish these subtypes of migraine, research is approaching headache specialists to a migraine diagnosis based not only on symptoms and signs reported by patients. Future studies based on M/EEG should pay special attention to the brain activity in medium and fast frequency bands, mainly the beta band. On the other hand, fMRI and PET studies should focus on neural circuits and regions related to pain and emotional processing.

Abnormal meta-state activation of dynamic brain networks across the Alzheimer spectrum.

The characterization of the distinct dynamic functional connectivity (dFC) patterns that activate in the brain during rest can help to understand the underlying time-varying network organization. The presence and behavior of these patterns (known as meta-states) have been widely studied by means of functional magnetic resonance imaging (fMRI). However, modalities with high-temporal resolution, such as electroencephalography (EEG), enable the characterization of fast temporally evolving meta-state sequences. Mild cognitive impairment (MCI) and dementia due to Alzheimer's disease (AD) have been shown to disrupt spatially localized activation and dFC between different brain regions, but not much is known about how they affect meta-state network topologies and their network dynamics. The main hypothesis of the study was that MCI and dementia due to AD alter normal meta-state sequences by inducing a loss of structure in their patterns and a reduction of their dynamics. Moreover, we expected that patients with MCI would display more flexible behavior compared to patients with dementia due to AD. Thus, the aim of the current study was twofold: (i) to find repeating, distinctly organized network patterns (meta-states) in neural activity; and (ii) to extract information about meta-state fluctuations and how they are influenced by MCI and dementia due to AD. To accomplish these goals, we present a novel methodology to characterize dynamic meta-states and their temporal fluctuations by capturing aspects based on both their discrete activation and the continuous evolution of their individual strength. These properties were extracted from 60-s resting-state EEG recordings from 67 patients with MCI due to AD, 50 patients with dementia due to AD, and 43 cognitively healthy controls. First, the instantaneous amplitude correlation (IAC) was used to estimate instantaneous functional connectivity with a high temporal resolution. We then extracted meta-states by means of graph community detection based on recurrence plots (RPs), both at the individual- and group-level. Subsequently, a diverse set of properties of the continuous and discrete fluctuation patterns of the meta-states was extracted and analyzed. The main novelty of the methodology lies in the usage of Louvain GJA community detection to extract meta-states from IAC-derived RPs and the extended analysis of their discrete and continuous activation. Our findings showed that distinct dynamic functional connectivity meta-states can be found on the EEG time-scale, and that these were not affected by the oscillatory slowing induced by MCI or dementia due to AD. However, both conditions displayed a loss of meta-state modularity, coupled with shorter dwell times and higher complexity of the meta-state sequences. Furthermore, we found evidence that meta-state sequencing is not entirely random; it shows an underlying structure that is partially lost in MCI and dementia due to AD. These results show evidence that AD progression is associated with alterations in meta-state switching, and a degradation of dynamic brain flexibility.

Heart rate variability spectrum characteristics in children with sleep apnea.

BACKGROUND: Classic spectral analysis of heart rate variability (HRV) in pediatric sleep apnea-hypopnea syndrome (SAHS) traditionally evaluates the very low frequency (VLF: 0-0.04 Hz), low frequency (LF: 0.04-0.15 Hz), and high frequency (HF: 0.15-0.40 Hz) bands. However, specific SAHS-related frequency bands have not been explored. METHODS: One thousand seven hundred and thirty-eight HRV overnight recordings from two pediatric databases (0-13 years) were evaluated. The first one (981 children) served as training set to define new HRV pediatric SAHS-related frequency bands. The associated relative power (RP) were computed in the test set, the Childhood Adenotonsillectomy Trial database (CHAT, 757 children). Their relationships with polysomnographic variables and diagnostic ability were assessed. RESULTS: Two new specific spectral bands of pediatric SAHS within 0-0.15 Hz were related to duration of apneic events, number of awakenings, and wakefulness after sleep onset (WASO), while an adaptive individual-specific new band from HF was related to oxyhemoglobin desaturations, arousals, and WASO. Furthermore, these new spectral bands showed improved diagnostic ability than classic HRV. CONCLUSIONS: Novel spectral bands provide improved characterization of pediatric SAHS. These findings may pioneer a better understanding of the effects of SAHS on cardiac function and potentially serve as detection biomarkers. IMPACT: New specific heart rate variability (HRV) spectral bands are identified and characterized as potential biomarkers in pediatric sleep apnea. Spectral band BW1 (0.001-0.005 Hz) is related to macro sleep disruptions. Spectral band BW2 (0.028-0.074 Hz) is related to the duration of apneic events. An adaptive spectral band within the respiratory range, termed ABW3, is related to oxygen desaturations. The individual and collective diagnostic ability of these novel spectral bands outperforms classic HRV bands.

Wavelet Analysis of Overnight Airflow to Detect Obstructive Sleep Apnea in Children.

This study focused on the automatic analysis of the airflow signal (AF) to aid in the diagnosis of pediatric obstructive sleep apnea (OSA). Thus, our aims were: (i) to characterize the overnight AF characteristics using discrete wavelet transform (DWT) approach, (ii) to evaluate its diagnostic utility, and (iii) to assess its complementarity with the 3% oxygen desaturation index (ODI3). In order to reach these goals, we analyzed 946 overnight pediatric AF recordings in three stages: (i) DWT-derived feature extraction, (ii) feature selection, and (iii) pattern recognition. AF recordings from OSA patients showed both lower detail coefficients and decreased activity associated with the normal breathing band. Wavelet analysis also revealed that OSA disturbed the frequency and energy distribution of the AF signal, increasing its irregularity. Moreover, the information obtained from the wavelet analysis was complementary to ODI3. In this regard, the combination of both wavelet information and ODI3 achieved high diagnostic accuracy using the common OSA-positive cutoffs: 77.97%, 81.91%, and 90.99% (AdaBoost.M2), and 81.96%, 82.14%, and 90.69% (Bayesian multi-layer perceptron) for 1, 5, and 10 apneic events/hour, respectively. Hence, these findings suggest that DWT properly characterizes OSA-related severity as embedded in nocturnal AF, and could simplify the diagnosis of pediatric OSA.

Neurofeedback Training Based on Motor Imagery Strategies Increases EEG Complexity in Elderly Population.

Neurofeedback training (NFT) has shown promising results in recent years as a tool to address the effects of age-related cognitive decline in the elderly. Since previous studies have linked reduced complexity of electroencephalography (EEG) signal to the process of cognitive decline, we propose the use of non-linear methods to characterise changes in EEG complexity induced by NFT. In this study, we analyse the pre- and post-training EEG from 11 elderly subjects who performed an NFT based on motor imagery (MI-NFT). Spectral changes were studied using relative power (RP) from classical frequency bands (delta, theta, alpha, and beta), whilst multiscale entropy (MSE) was applied to assess EEG-induced complexity changes. Furthermore, we analysed the subject's scores from Luria tests performed before and after MI-NFT. We found that MI-NFT induced a power shift towards rapid frequencies, as well as an increase of EEG complexity in all channels, except for C3. These improvements were most evident in frontal channels. Moreover, results from cognitive tests showed significant enhancement in intellectual and memory functions. Therefore, our findings suggest the usefulness of MI-NFT to improve cognitive functions in the elderly and encourage future studies to use MSE as a metric to characterise EEG changes induced by MI-NFT.

Erratum: Martín-Montero et al. Bispectral Analysis of Heart Rate Variability to Characterize and Help Diagnose Pediatric Sleep Apnea. Entropy 2021, 23, 1016.

The author wishes to make the following correction to this paper [...].

Bispectral Analysis of Heart Rate Variability to Characterize and Help Diagnose Pediatric Sleep Apnea.

Pediatric obstructive sleep apnea (OSA) is a breathing disorder that alters heart rate variability (HRV) dynamics during sleep. HRV in children is commonly assessed through conventional spectral analysis. However, bispectral analysis provides both linearity and stationarity information and has not been applied to the assessment of HRV in pediatric OSA. Here, this work aimed to assess HRV using bispectral analysis in children with OSA for signal characterization and diagnostic purposes in two large pediatric databases (0-13 years). The first database (training set) was composed of 981 overnight ECG recordings obtained during polysomnography. The second database (test set) was a subset of the Childhood Adenotonsillectomy Trial database (757 children). We characterized three bispectral regions based on the classic HRV frequency ranges (very low frequency: 0-0.04 Hz; low frequency: 0.04-0.15 Hz; and high frequency: 0.15-0.40 Hz), as well as three OSA-specific frequency ranges obtained in recent studies (BW1: 0.001-0.005 Hz; BW2: 0.028-0.074 Hz; BWRes: a subject-adaptive respiratory region). In each region, up to 14 bispectral features were computed. The fast correlation-based filter was applied to the features obtained from the classic and OSA-specific regions, showing complementary information regarding OSA alterations in HRV. This information was then used to train multi-layer perceptron (MLP) neural networks aimed at automatically detecting pediatric OSA using three clinically defined severity classifiers. Both classic and OSA-specific MLP models showed high and similar accuracy (Acc) and areas under the receiver operating characteristic curve (AUCs) for moderate (classic regions: Acc = 81.0%, AUC = 0.774; OSA-specific regions: Acc = 81.0%, AUC = 0.791) and severe (classic regions: Acc = 91.7%, AUC = 0.847; OSA-specific regions: Acc = 89.3%, AUC = 0.841) OSA levels. Thus, the current findings highlight the usefulness of bispectral analysis on HRV to characterize and diagnose pediatric OSA.

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.

Exploring EEG Spectral Patterns in Episodic and Chronic Migraine During the Interictal State: Determining Frequencies of Interest in the Resting State.

OBJECTIVE: The analysis of particular (electroencephalographic) EEG frequency bands has revealed new insights relative to the neural dynamics that, when studying the EEG spectrum as a whole, would have remained hidden. This study is aimed at characterizing spectral resting state EEG patterns for assessing possible differences of episodic and chronic migraine during the interictal period. For that purpose, a novel methodology for analyzing specific frequencies of interest was performed. METHODS: Eighty-seven patients with migraine (45 with episodic and 42 with chronic migraine) and 39 age- and sex-matched controls performed a resting-state EEG recording. Spectral measures were computed using conventional frequency bands. Additionally, particular frequency bands were determined to distinguish between controls and migraine patients, as well as between migraine subgroups. RESULTS: Frequencies ranging from 11.6 Hz to 12.8 Hz characterized migraine as a whole, with differences evident in the central and left parietal regions (controlling for false discovery rate). An additional band between 24.1 Hz and 29.8 Hz was used to discriminate between migraine subgroups. Interestingly, the power in this band was positively correlated with time from onset in episodic migraine, but no correlation was found for chronic migraine. CONCLUSIONS: Specific frequency bands were proposed to identify the spectral characteristics of the electrical brain activity in migraine during the interictal stage. Our findings support the importance of discriminating between migraine subgroups to avoid hiding relevant features in migraine.

Effective Fundus Image Decomposition for the Detection of Red Lesions and Hard Exudates to Aid in the Diagnosis of Diabetic Retinopathy.

Diabetic retinopathy (DR) is characterized by the presence of red lesions (RLs), such as microaneurysms and hemorrhages, and bright lesions, such as exudates (EXs). Early DR diagnosis is paramount to prevent serious sight damage. Computer-assisted diagnostic systems are based on the detection of those lesions through the analysis of fundus images. In this paper, a novel method is proposed for the automatic detection of RLs and EXs. As the main contribution, the fundus image was decomposed into various layers, including the lesion candidates, the reflective features of the retina, and the choroidal vasculature visible in tigroid retinas. We used a proprietary database containing 564 images, randomly divided into a training set and a test set, and the public database DiaretDB1 to verify the robustness of the algorithm. Lesion detection results were computed per pixel and per image. Using the proprietary database, 88.34% per-image accuracy (ACCi), 91.07% per-pixel positive predictive value (PPVp), and 85.25% per-pixel sensitivity (SEp) were reached for the detection of RLs. Using the public database, 90.16% ACCi, 96.26% PPV_p, and 84.79% SEp were obtained. As for the detection of EXs, 95.41% ACCi, 96.01% PPV_p, and 89.42% SE_p were reached with the proprietary database. Using the public database, 91.80% ACCi, 98.59% PPVp, and 91.65% SEp were obtained. The proposed method could be useful to aid in the diagnosis of DR, reducing the workload of specialists and improving the attention to diabetic patients.

Relationship between the Presence of the ApoE ε4 Allele and EEG Complexity along the Alzheimer's Disease Continuum.

Alzheimer's disease (AD) is the most prevalent cause of dementia, being considered a major health problem, especially in developed countries. Late-onset AD is the most common form of the disease, with symptoms appearing after 65 years old. Genetic determinants of AD risk are vastly unknown, though, ε 4 allele of the ApoE gene has been reported as the strongest genetic risk factor for AD. The objective of this study was to analyze the relationship between brain complexity and the presence of ApoE ε 4 alleles along the AD continuum. For this purpose, resting-state electroencephalography (EEG) activity was analyzed by computing Lempel-Ziv complexity (LZC) from 46 healthy control subjects, 49 mild cognitive impairment subjects, 45 mild AD patients, 44 moderate AD patients and 33 severe AD patients, subdivided by ApoE status. Subjects with one or more ApoE ε 4 alleles were included in the carriers subgroups, whereas the ApoE ε 4 non-carriers subgroups were formed by subjects without any ε 4 allele. Our results showed that AD continuum is characterized by a progressive complexity loss. No differences were observed between AD ApoE ε 4 carriers and non-carriers. However, brain activity from healthy subjects with ApoE ε 4 allele (carriers subgroup) is more complex than from non-carriers, mainly in left temporal, frontal and posterior regions (p-values < 0.05, FDR-corrected Mann-Whitney U-test). These results suggest that the presence of ApoE ε 4 allele could modify the EEG complexity patterns in different brain regions, as the temporal lobes. These alterations might be related to anatomical changes associated to neurodegeneration, increasing the risk of suffering dementia due to AD before its clinical onset. This interesting finding might help to advance in the development of new tools for early AD diagnosis.

Correction: Martínez-Cagigal, V.; Santamaría-Vázquez, E.; Hornero, R. Asynchronous Control of P300-Based Brain-Computer Interfaces Using Sample Entropy. Entropy 2019, 21, 230.

Figure 5 of the original paper contains errors [...].