Exploring the disruptions of the neurophysiological organization in Alzheimer's disease: An integrative approach.

BACKGROUND AND OBJECTIVE: Alzheimer's disease (AD) is a neurological disorder that impairs brain functions associated with cognition, memory, and behavior. Noninvasive neurophysiological techniques like magnetoencephalography (MEG) and electroencephalography (EEG) have shown promise in reflecting brain changes related to AD. These techniques are usually assessed at two levels: local activation (spectral, nonlinear, and dynamic properties) and global synchronization (functional connectivity, frequency-dependent network, and multiplex network organization characteristics). Nonetheless, the understanding of the organization formed by the existing relationships between these levels, henceforth named neurophysiological organization, remains unexplored. This work aims to assess the alterations AD causes in the resting-state neurophysiological organization. METHODS: To that end, three datasets from healthy controls (HC) and patients with dementia due to AD were considered: MEG database (55 HC and 87 patients with AD), EEG1 database (51 HC and 100 patients with AD), and EEG2 database (45 HC and 82 patients with AD). To explore the alterations induced by AD in the relationships between several features extracted from M/EEG data, association networks (ANs) were computed. ANs are graphs, useful to quantify and visualize the intricate relationships between multiple features. RESULTS: Our results suggested a disruption in the neurophysiological organization of patients with AD, exhibiting a greater inclination towards the local activation level; and a significant decrease in the complexity and diversity of the ANs (p-value ¡ 0.05, Mann-Whitney U-test, Bonferroni correction). This effect might be due to a shift of the neurophysiological organization towards more regular configurations, which may increase its vulnerability. Moreover, our findings support the crucial role played by the local activation level in maintaining the stability of the neurophysiological organization. Classification performance exhibited accuracy values of 83.91%, 73.68%, and 72.65% for MEG, EEG1, and EEG2 databases, respectively. CONCLUSION: This study introduces a novel, valuable methodology able to integrate parameters characterize different properties of the brain activity and to explore the intricate organization of the neurophysiological organization at different levels. It was noted that AD increases susceptibility to changes in functional neural organization, suggesting a greater ease in the development of severe impairments. Therefore, ANs could facilitate a deeper comprehension of the complex interactions in brain function from a global standpoint.

Attention-based deep learning framework for automatic fundus image processing to aid in diabetic retinopathy grading.

BACKGROUND AND OBJECTIVE: Early detection and grading of Diabetic Retinopathy (DR) is essential to determine an adequate treatment and prevent severe vision loss. However, the manual analysis of fundus images is time consuming and DR screening programs are challenged by the availability of human graders. Current automatic approaches for DR grading attempt the joint detection of all signs at the same time. However, the classification can be optimized if red lesions and bright lesions are independently processed since the task gets divided and simplified. Furthermore, clinicians would greatly benefit from explainable artificial intelligence (XAI) to support the automatic model predictions, especially when the type of lesion is specified. As a novelty, we propose an end-to-end deep learning framework for automatic DR grading (5 severity degrees) based on separating the attention of the dark structures from the bright structures of the retina. As the main contribution, this approach allowed us to generate independent interpretable attention maps for red lesions, such as microaneurysms and hemorrhages, and bright lesions, such as hard exudates, while using image-level labels only. METHODS: Our approach is based on a novel attention mechanism which focuses separately on the dark and the bright structures of the retina by performing a previous image decomposition. This mechanism can be seen as a XAI approach which generates independent attention maps for red lesions and bright lesions. The framework includes an image quality assessment stage and deep learning-related techniques, such as data augmentation, transfer learning and fine-tuning. We used the architecture Xception as a feature extractor and the focal loss function to deal with data imbalance. RESULTS: The Kaggle DR detection dataset was used for method development and validation. The proposed approach achieved 83.7 % accuracy and a Quadratic Weighted Kappa of 0.78 to classify DR among 5 severity degrees, which outperforms several state-of-the-art approaches. Nevertheless, the main result of this work is the generated attention maps, which reveal the pathological regions on the image distinguishing the red lesions and the bright lesions. These maps provide explainability to the model predictions. CONCLUSIONS: Our results suggest that our framework is effective to automatically grade DR. The separate attention approach has proven useful for optimizing the classification. On top of that, the obtained attention maps facilitate visual interpretation for clinicians. Therefore, the proposed method could be a diagnostic aid for the early detection and grading of DR.

Unraveling motor imagery brain patterns using explainable artificial intelligence based on Shapley values.

BACKGROUND AND OBJECTIVE: Motor imagery (MI) based brain-computer interfaces (BCIs) are widely used in rehabilitation due to the close relationship that exists between MI and motor execution (ME). However, the underlying brain mechanisms of MI remain not well understood. Most MI-BCIs use the sensorimotor rhythms elicited in the primary motor cortex (M1) and somatosensory cortex (S1), which consist of an event-related desynchronization followed by an event-related synchronization. Consequently, this has resulted in systems that only record signals around M1 and S1. However, MI could involve a more complex network including sensory, association, and motor areas. In this study, we hypothesize that the superior accuracies achieved by new deep learning (DL) models applied to MI decoding rely on focusing on a broader MI activation of the brain. Parallel to the success of DL, the field of explainable artificial intelligence (XAI) has seen continuous development to provide explanations for DL networks success. The goal of this study is to use XAI in combination with DL to extract information about MI brain activation patterns from non-invasive electroencephalography (EEG) signals. METHODS: We applied an adaptation of Shapley additive explanations (SHAP) to EEGSym, a state-of-the-art DL network with exceptional transfer learning capabilities for inter-subject MI classification. We obtained the SHAP values from two public databases comprising 171 users generating left and right hand MI instances with and without real-time feedback. RESULTS: We found that EEGSym based most of its prediction on the signal of the frontal electrodes, i.e. F7 and F8, and on the first 1500 ms of the analyzed imagination period. We also found that MI involves a broad network not only based on M1 and S1, but also on the prefrontal cortex (PFC) and the posterior parietal cortex (PPC). We further applied this knowledge to select a 8-electrode configuration that reached inter-subject accuracies of 86.5% ± 10.6% on the Physionet dataset and 88.7% ± 7.0% on the Carnegie Mellon University's dataset. CONCLUSION: Our results demonstrate the potential of combining DL and SHAP-based XAI to unravel the brain network involved in producing MI. Furthermore, SHAP values can optimize the requirements for out-of-laboratory BCI applications involving real users.

Persistent sleep-disordered breathing independently contributes to metabolic syndrome in prepubertal children.

BACKGROUND: Obstructive sleep apnea (OSA) is a risk factor for metabolic syndrome (MetS) in adults, but its association in prepubertal children is still questionable due to the relatively limited cardiometabolic data available and the phenotypic heterogeneity. OBJECTIVE: To identify the role of OSA as a potential mediator of MetS in prepubertal children. METHODS: A total of 255 prepubertal children from the Childhood Adenotonsillectomy Trial were included, with standardized measurements taken before OSA treatment and 7 months later. MetS was defined if three or more of the following criteria were present: adiposity, high blood pressure, elevated glycemia, and dyslipidemia. A causal mediation analysis was conducted to assess the effect of OSA treatment on MetS. RESULTS: OSA treatment significantly impacted MetS, with the apnea-hypopnea index emerging as mediator (p = .02). This mediation role was not detected for any of the individual risk factors that define MetS. We further found that the relationship between MetS and OSA is ascribable to respiratory disturbance caused by the apnea episodes, while systemic inflammation as measured by C-reactive protein, is mediated by desaturation events and fragmented sleep. In terms of evolution, patients with MetS were significantly more likely to recover after OSA treatment (odds ratio = 2.56, 95% confidence interval [CI] 1.20-5.46; risk ratio = 2.06, 95% CI 1.19-3.54) than the opposite, patients without MetS to develop it. CONCLUSION: The findings point to a causal role of OSA in the development of metabolic dysfunction, suggesting that persistent OSA may increase the risk of MetS in prepubertal children. This mediation role implies a need for developing screening for MetS in children presenting OSA symptoms.

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.

A deep learning model based on the combination of convolutional and recurrent neural networks to enhance pulse oximetry ability to classify sleep stages in children with sleep apnea.

Characterization of sleep stages is essential in the diagnosis of sleep-related disorders but relies on manual scoring of overnight polysomnography (PSG) recordings, which is onerous and labor-intensive. Accordingly, we aimed to develop an accurate deep-learning model for sleep staging in children suffering from pediatric obstructive sleep apnea (OSA) using pulse oximetry signals. For this purpose, pulse rate (PR) and blood oxygen saturation (SpO2) from 429 childhood OSA patients were analyzed. A CNN-RNN architecture fed with PR and SpO2 signals was developed to automatically classify wake (W), non-Rapid Eye Movement (NREM), and REM sleep stages. This architecture was composed of: (i) a convolutional neural network (CNN), which learns stage-related features from raw PR and SpO2 data; and (ii) a recurrent neural network (RNN), which models the temporal distribution of the sleep stages. The proposed CNN-RNN model showed a high performance for the automated detection of W/NREM/REM sleep stages (86.0% accuracy and 0.743 Cohen's kappa). Furthermore, the total sleep time estimated for each children using the CNN-RNN model showed high agreement with the manually derived from PSG (intra-class correlation coefficient = 0.747). These results were superior to previous works using CNN-based deep-learning models for automatic sleep staging in pediatric OSA patients from pulse oximetry signals. Therefore, the combination of CNN and RNN allows to obtain additional information from raw PR and SpO2 data related to sleep stages, thus being useful to automatically score sleep stages in pulse oximetry tests for children evaluated for suspected OSA.Clinical Relevance-This research establishes the usefulness of a CNN-RNN architecture to automatically score sleep stages in pulse oximetry tests for pediatric OSA diagnosis.

Assessing the Potential of Brain-Computer Interface Multiplayer Video Games using c-VEPs: A Pilot Study.

Video games have become a common and widespread form of entertainment, while non-invasive brain-computer interfaces (BCI) are emerging as potential alternative communication technologies. Combining BCIs and video games can enhance the gaming experience and make it accessible to motor-disabled individuals. Recently, code-modulated visual evoked potentials (c-VEP) have been proposed as a novel control signal able to achieve high performance with short calibration times. However, there are still no video games that use c-VEPs as a control signal. The aim of this pilot study is to develop an implementation of the 'Connect 4' multiplayer video game using a c-VEP-based BCI and test it with 10 healthy users. Participants were paired to compete in matches and carried out individual tasks. The results showed that the participants were able to control the game with an average accuracy of 94.10% and a selection time of 5.25 seconds per command, outperforming previous approaches. This suggests that the proposed video game is feasible and c-VEPs can provide smooth BCI control.

Nonparametric Early Stopping Detection for c-VEP-based Brain-Computer Interfaces: A Pilot Study.

Brain-computer interface (BCI) systems based on code-modulated visual evoked potentials (c-VEP) stand out for achieving excellent command selection accuracies with very short calibration times. One of the natural steps to democratize their use in plug-and-play environments is to develop early stopping algorithms. These methods allow real-time detection of the minimum number of code repetitions needed to provide reliable selections. However, such techniques are scarce in the current state-of-the-art for c-VEP-based BCI systems based on the classical circular shifting paradigm. Here, a novel nonparametric early stopping method is proposed, which approximates the distribution of unattended commands to a normal distribution and issues a selection when the correlation of the command is considered an outlier. The proposal has been evaluated offline with 15 healthy users, achieving an average accuracy of 97.08% and a speed of 1.37 s/command. Likewise, the algorithm has also been evaluated with an additional user in an online way, as a proof of concept to validate its technical feasibility, achieving an average accuracy of 96.88% with a speed of 1.67 s/command. These results suggest that the real time application of the proposed algorithm is feasible, significantly reducing the required selection time without compromising accuracy.

ECG-based convolutional neural network in pediatric obstructive sleep apnea diagnosis.

Obstructive sleep apnea (OSA) is a prevalent respiratory condition in children and is characterized by partial or complete obstruction of the upper airway during sleep. The respiratory events in OSA induce transient alterations of the cardiovascular system that ultimately can lead to increased cardiovascular risk in affected children. Therefore, a timely and accurate diagnosis is of utmost importance. However, polysomnography (PSG), the standard diagnostic test for pediatric OSA, is complex, uncomfortable, costly, and relatively inaccessible, particularly in low-resource environments, thereby resulting in substantial underdiagnosis. Here, we propose a novel deep-learning approach to simplify the diagnosis of pediatric OSA using raw electrocardiogram tracing (ECG). Specifically, a new convolutional neural network (CNN)-based regression model was implemented to automatically predict pediatric OSA by estimating its severity based on the apnea-hypopnea index (AHI) and deriving 4 OSA severity categories. For this purpose, overnight ECGs from 1,610 PSG recordings obtained from the Childhood Adenotonsillectomy Trial (CHAT) database were used. The database was randomly divided into approximately 60%, 20%, and 20% for training, validation, and testing, respectively. The diagnostic performance of the proposed CNN model largely outperformed the most accurate previous algorithms that relied on ECG-derived features (4-class Cohen's kappa coefficient of 0.373 versus 0.166). Specifically, for AHI cutoff values of 1, 5, and 10 events/hour, the binary classification achieved sensitivities of 84.19%, 76.67%, and 53.66%; specificities of 46.15%, 91.39%, and 98.06%; and accuracies of 75.92%, 86.96%, and 91.97%, respectively. Therefore, pediatric OSA can be readily identified by our proposed CNN model, which provides a simpler, faster, and more accessible diagnostic test that can be implemented in clinical practice.

Influence of spatial frequency in visual stimuli for cVEP-based BCIs: evaluation of performance and user experience.

Code-modulated visual evoked potentials (c-VEPs) are an innovative control signal utilized in brain-computer interfaces (BCIs) with promising performance. Prior studies on steady-state visual evoked potentials (SSVEPs) have indicated that the spatial frequency of checkerboard-like stimuli influences both performance and user experience. Spatial frequency refers to the dimensions of the individual squares comprising the visual stimulus, quantified in cycles (i.e., number of black-white squares pairs) per degree of visual angle. However, the specific effects of this parameter on c-VEP-based BCIs remain unexplored. Therefore, the objective of this study is to investigate the role of spatial frequency of checkerboard-like visual stimuli in a c-VEP-based BCI. Sixteen participants evaluated selection matrices with eight spatial frequencies: C001 (0 c/°, 1×1 squares), C002 (0.15 c/°, 2×2 squares), C004 (0.3 c/°, 4×4 squares), C008 (0.6 c/°, 8×8 squares), C016 (1.2 c/°, 16×16 squares), C032 (2.4 c/°, 32×32 squares), C064 (4.79 c/°, 64×64 squares), and C128 (9.58 c/°, 128×128 squares). These conditions were tested in an online spelling task, which consisted of 18 trials each conducted on a 3×3 command interface. In addition to accuracy and information transfer rate (ITR), subjective measures regarding comfort, ocular irritation, and satisfaction were collected. Significant differences in performance and comfort were observed based on different stimulus spatial frequencies. Although all conditions achieved mean accuracy over 95% after 2.1 s of trial duration, C016 stood out in terms user experience. The proposed condition not only achieved a mean accuracy of 96.53% and 164.54 bits/min with a trial duration of 1.05s, but also was reported to be significantly more comfortable than the traditional C001 stimulus. Since both features are key for BCI development, higher spatial frequencies than the classical black-to-white stimulus might be more adequate for c-VEP systems. Hence, we assert that the spatial frequency should be carefully considered in the development of future applications for c-VEP-based BCIs.

Prediction of the Sleep Apnea Severity Using 2D-Convolutional Neural Networks and Respiratory Effort Signals.

The high prevalence of sleep apnea and the limitations of polysomnography have prompted the investigation of strategies aimed at automated diagnosis using a restricted number of physiological measures. This study aimed to demonstrate that thoracic (THO) and abdominal (ABD) movement signals are useful for accurately estimating the severity of sleep apnea, even if central respiratory events are present. Thus, we developed 2D-convolutional neural networks (CNNs) jointly using THO and ABD to automatically estimate sleep apnea severity and evaluate the central event contribution. Our proposal achieved an intraclass correlation coefficient (ICC) = 0.75 and a root mean square error (RMSE) = 10.33 events/h when estimating the apnea-hypopnea index, and ICC = 0.83 and RMSE = 0.95 events/h when estimating the central apnea index. The CNN obtained accuracies of 94.98%, 79.82%, and 81.60% for 5, 15, and 30 events/h when evaluating the complete apnea hypopnea index. The model improved when the nature of the events was central: 98.72% and 99.74% accuracy for 5 and 15 events/h. Hence, the information extracted from these signals using CNNs could be a powerful tool to diagnose sleep apnea, especially in subjects with a high density of central apnea events.

An explainable deep-learning model to stage sleep states in children and propose novel EEG-related patterns in sleep apnea.

Automatic deep-learning models used for sleep scoring in children with obstructive sleep apnea (OSA) are perceived as black boxes, limiting their implementation in clinical settings. Accordingly, we aimed to develop an accurate and interpretable deep-learning model for sleep staging in children using single-channel electroencephalogram (EEG) recordings. We used EEG signals from the Childhood Adenotonsillectomy Trial (CHAT) dataset (n = 1637) and a clinical sleep database (n = 980). Three distinct deep-learning architectures were explored to automatically classify sleep stages from a single-channel EEG data. Gradient-weighted Class Activation Mapping (Grad-CAM), an explainable artificial intelligence (XAI) algorithm, was then applied to provide an interpretation of the singular EEG patterns contributing to each predicted sleep stage. Among the tested architectures, a standard convolutional neural network (CNN) demonstrated the highest performance for automated sleep stage detection in the CHAT test set (accuracy = 86.9% and five-class kappa = 0.827). Furthermore, the CNN-based estimation of total sleep time exhibited strong agreement in the clinical dataset (intra-class correlation coefficient = 0.772). Our XAI approach using Grad-CAM effectively highlighted the EEG features associated with each sleep stage, emphasizing their influence on the CNN's decision-making process in both datasets. Grad-CAM heatmaps also allowed to identify and analyze epochs within a recording with a highly likelihood to be misclassified, revealing mixed features from different sleep stages within these epochs. Finally, Grad-CAM heatmaps unveiled novel features contributing to sleep scoring using a single EEG channel. Consequently, integrating an explainable CNN-based deep-learning model in the clinical environment could enable automatic sleep staging in pediatric sleep apnea tests.

Gene Co-Expression Networks Offer New Perspectives on Sepsis Pathophysiology.

Sepsis is among the most common causes of death in intensive care units. Septic shock is a type of circulatory shock that shows signs and symptoms that are similar to non-septic shock. Despite the impact of shock on patients and the economic burden, knowledge of the pathophysiology of septic shock is scarce. In this context, weighted gene co-expression network analysis can help to elucidate the molecular mechanisms of this condition. The gene expression dataset used in this study was downloaded from the Gene Expression Omnibus, which contains 80 patients with septic shock, 33 patients with non-septic shock, and 15 healthy controls. Our novel analysis revealed five gene modules specific for patients with septic shock and three specific gene modules for patients with non-septic shock. Interestingly, genes related to septic shock were mainly involved in the immune system and endothelial cells, while genes related to non-septic shock were primarily associated with endothelial cells. Together, the results revealed the specificity of the genes related to the immune system in septic shock. The novel approach developed here showed its potential to identify critical pathways for the occurrence and progression of these conditions while offering new treatment strategies and effective therapies.

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.

Combining brain-computer interfaces and multiplayer video games: an application based on c-VEPs.

Introduction and objective: Video games are crucial to the entertainment industry, nonetheless they can be challenging to access for those with severe motor disabilities. Brain-computer interfaces (BCI) systems have the potential to help these individuals by allowing them to control video games using their brain signals. Furthermore, multiplayer BCI-based video games may provide valuable insights into how competitiveness or motivation affects the control of these interfaces. Despite the recent advancement in the development of code-modulated visual evoked potentials (c-VEPs) as control signals for high-performance BCIs, to the best of our knowledge, no studies have been conducted to develop a BCI-driven video game utilizing c-VEPs. However, c-VEPs could enhance user experience as an alternative method. Thus, the main goal of this work was to design, develop, and evaluate a version of the well-known 'Connect 4' video game using a c-VEP-based BCI, allowing 2 users to compete by aligning 4 same-colored coins vertically, horizontally or diagonally. Methods: The proposed application consists of a multiplayer video game controlled by a real-time BCI system processing 2 electroencephalograms (EEGs) sequentially. To detect user intention, columns in which the coin can be placed was encoded with shifted versions of a pseudorandom binary code, following a traditional circular shifting c-VEP paradigm. To analyze the usability of our application, the experimental protocol comprised an evaluation session by 22 healthy users. Firstly, each user had to perform individual tasks. Afterward, users were matched and the application was used in competitive mode. This was done to assess the accuracy and speed of selection. On the other hand, qualitative data on satisfaction and usability were collected through questionnaires. Results: The average accuracy achieved was 93.74% ± 1.71%, using 5.25 seconds per selection. The questionnaires showed that users felt a minimal workload. Likewise, high satisfaction values were obtained, highlighting that the application was intuitive and responds quickly and smoothly. Conclusions: This c-VEP based multiplayer video game has reached suitable performance on 22 users, supported by high motivation and minimal workload. Consequently, compared to other versions of "Connect 4" that utilized different control signals, this version has exhibited superior performance.

Electrical analysis of logical complexity: an exploratory eeg study of logically valid/invalid deducive inference.

INTRODUCTION: Logically valid deductive arguments are clear examples of abstract recursive computational procedures on propositions or on probabilities. However, it is not known if the cortical time-consuming inferential processes in which logical arguments are eventually realized in the brain are in fact physically different from other kinds of inferential processes. METHODS: In order to determine whether an electrical EEG discernible pattern of logical deduction exists or not, a new experimental paradigm is proposed contrasting logically valid and invalid inferences with exactly the same content (same premises and same relational variables) and distinct logical complexity (propositional truth-functional operators). Electroencephalographic signals from 19 subjects (24.2 ± 3.3 years) were acquired in a two-condition paradigm (100 trials for each condition). After the initial general analysis, a trial-by-trial approach in beta-2 band allowed to uncover not only evoked but also phase asynchronous activity between trials. RESULTS: showed that (i) deductive inferences with the same content evoked the same response pattern in logically valid and invalid conditions, (ii) mean response time in logically valid inferences is 61.54% higher, (iii) logically valid inferences are subjected to an early (400 ms) and a late reprocessing (600 ms) verified by two distinct beta-2 activations (p-value < 0,01, Wilcoxon signed rank test). CONCLUSION: We found evidence of a subtle but measurable electrical trait of logical validity. Results put forward the hypothesis that some logically valid deductions are recursive or computational cortical events.

Quantification of the robustness of functional neural networks: application to the characterization of Alzheimer's disease continuum.

Objective.Brain connectivity networks are usually characterized in terms of properties coming from the complex network theory. Using new measures to summarize the attributes of functional connectivity networks can be an important step for their better understanding and characterization, as well as to comprehend the alterations associated with neuropsychiatric and neurodegenerative disorders. In this context, the main objective of this study was to introduce a novel methodology to evaluate network robustness, which was subsequently applied to characterize the brain activity in the Alzheimer's disease (AD) continuum.Approach.Functional connectivity networks were built using 478 electroencephalographic and magnetoencephalographic resting-state recordings from three different databases. These functional connectivity networks computed in the conventional frequency bands were modified simulating an iterative attack procedure using six different strategies. The network changes caused by these attacks were evaluated by means of Spearman's correlation. The obtained results at the conventional frequency bands were aggregated in a correlation surface, which was characterized in terms of four gradient distribution properties: mean, variance, skewness, and kurtosis.Main results.The new proposed methodology was able to consistently quantify network robustness. Our results showed statistically significant differences in the inherent ability of the network to deal with attacks (i.e. differences in network robustness) between controls, mild cognitive impairment subjects, and AD patients for the three different databases. In addition, we found a significant correlation between mini-mental state examination scores and the changes in network robustness.Significance.To the best of our knowledge, this is the first study which assesses the robustness of the functional connectivity network in the AD continuum. Our findings consistently evidence the loss of network robustness as the AD progresses for the three databases. Furthermore, the changes in this complex network property may be related with the progressive deterioration in brain functioning due to AD.

ITACA: An open-source framework for Neurofeedback based on Brain-Computer Interfaces.

BACKGROUND AND OBJECTIVE: Neurofeedback (NF) is a paradigm that allows users to self-modulate patterns of brain activity. It is implemented with a closed-loop brain-computer interface (BCI) system that analyzes the user's brain activity in real-time and provides continuous feedback. This paradigm is of great interest due to its potential as a non-pharmacological and non-invasive alternative to treat non-degenerative brain disorders. Nevertheless, currently available NF frameworks have several limitations, such as the lack of a wide variety of real-time analysis metrics or overly simple training scenarios that may negatively affect user performance. To overcome these limitations, this work proposes ITACA: a novel open-source framework for the design, implementation and evaluation of NF training paradigms. METHODS: ITACA is designed to be easy-to-use, flexible and attractive. Specifically, ITACA includes three different gamified training scenarios with a choice of five brain activity metrics as real-time feedback. Among them, novel metrics based on functional connectivity and network theory stand out. It is complemented with five different computerized versions of widespread cognitive assessment tests. To validate the proposed framework, a computational efficiency analysis and an NF training protocol focused on frontal-medial theta modulation were conducted. RESULTS: Efficiency analysis proved that all implemented metrics allow an optimal feedback update rate for conducting NF sessions. Furthermore, conducted NF protocol yielded results that support the use of ITACA in NF research studies. CONCLUSIONS: ITACA implements a wide variety of features for designing, conducting and evaluating NF studies with the goal of helping researchers expand the current state-of-the-art in NF training.