Multidimensional Biomechanics-Based Score to Assess Disease Progression in Duchenne Muscular Dystrophy.

(1) Background: Duchenne (DMD) is a rare neuromuscular disease that progressively weakens muscles, which severely impairs gait capacity. The Six Minute-Walk Test (6MWT), which is commonly used to evaluate and monitor the disease's evolution, presents significant variability due to extrinsic factors such as patient motivation, fatigue, and learning effects. Therefore, there is a clear need for the establishment of precise clinical endpoints to measure patient mobility. (2) Methods: A novel score (6M+ and 2M+) is proposed, which is derived from the use of a new portable monitoring system capable of carrying out a complete gait analysis. The system includes several biomechanical sensors: a heart rate band, inertial measurement units, electromyography shorts, and plantar pressure insoles. The scores were obtained by processing the sensor signals and via gaussian-mixture clustering. (3) Results: The 6M+ and 2M+ scores were evaluated against the North Star Ambulatory Assessment (NSAA), the gold-standard for measuring DMD, and six- and two-minute distances. The 6M+ and 2M+ tests led to superior distances when tested against the NSAA. The 6M+ test and the 2M+ test in particular were the most correlated with age, suggesting that these scores better characterize the gait regressions in DMD. Additionally, the 2M+ test demonstrated an accuracy and stability similar to the 6M+ test. (4) Conclusions: The novel monitoring system described herein exhibited good usability with respect to functional testing in a clinical environment and demonstrated an improvement in the objectivity and reliability of monitoring the evolution of neuromuscular diseases.

The Kappa Opioid Receptor and the Sleep of Reason: Cortico-Subcortical Imbalance Following Salvinorin-A.

BACKGROUND: The mechanisms through which kappa opioid receptor (KOR) agonists induce psychotomimetic effects are largely unknown, although the modulation of this receptor has attracted attention for its clinical use. In this work, we characterize the neuropharmacological effects of salvinorin-A, a highly selective KOR agonist. METHODS: Changes in multimodal electroencephalography, single-photon emission computed tomography, and subjective effects following the acute administration of salvinorin-A are reported. The study included 2 sub-studies that employed a double-blind, crossover, randomized, placebo-controlled design. RESULTS: The electroencephalography measures showed a marked increase in delta and gamma waves and a decrease in alpha waves while subjects were under the effect of salvinorin-A. Regarding single-photon emission computed tomography measures, significant decreases in regional cerebral blood flow were detected in multiple regions of the frontal, temporal, parietal, and occipital cortices. Significant regional cerebral blood flow increases were observed in some regions of the medial temporal lobe, including the amygdala, the hippocampal gyrus, and the cerebellum. The pattern of subjective effects induced by salvinorin-A was similar to those observed in relation to other psychotomimetic drugs but with an evidently dissociative nature. No dysphoric effects were reported. CONCLUSION: The salvinorin-A-mediated KOR agonism induced dramatic psychotomimetic effects along with a generalized decrease in cerebral blood flow and electric activity within the cerebral cortex.

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

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

A Tailored and Engaging mHealth Gamified Framework for Nutritional Behaviour Change.

Mobile health applications (apps) have been shown to be effective for improving eating habits. However, most of the existing apps rely on calorie and nutrient counting which have several limitations including the difficulty in sustaining long-term use, inaccuracy, and the risk of developing eating disorders. We designed and developed a mHealth framework for nutritional behaviour change, integrated into the CarpeDiem app, that focuses on the intake of key food groups which are known to have a higher impact on health indicators instead of the intake of nutrients. This framework is mainly based on a gamified system that delivers personalized dietary missions to the user and provides motivational recommendations that help the user to achieve these missions. Its design was guided by an evidenced-based theory of behavioural change, the HAPA model, and it is also characterized by the personalization of the system and the use of a recommender system based on advanced artificial intelligence techniques. Overall, the approach used in the present app could foster a sustained improvement of eating habits among the general population, which is the main challenge of dietary interventions, decreasing the risk of developing the chronic diseases associated with unhealthy dietary habits.

Influence of the number of trials on evoked motor cortical activity in EEG recordings.

Objective. Improvements in electroencephalography enable the study of the localization of active brain regions during motor tasks. Movement-related cortical potentials (MRCPs), and event-related desynchronization (ERD) and synchronization are the main motor-related cortical phenomena/neural correlates observed when a movement is elicited. When assessing neurological diseases, averaging techniques are commonly applied to characterize motor related processes better. In this case, a large number of trials is required to obtain a motor potential that is representative enough of the subject's condition. This study aimed to assess the effect of a limited number of trials on motor-related activity corresponding to different upper limb movements (elbow flexion/extension, pronation/supination and hand open/close).Approach. An open dataset consisting on 15 healthy subjects was used for the analysis. A Monte Carlo simulation approach was applied to analyse, in a robust way, different typical time- and frequency-domain features, topography, and low-resolution electromagnetic tomography.Main results. Grand average potentials, and topographic and tomographic maps showed few differences when using fewer trials, but shifts in the localization of motor-related activity were found for several individuals. MRCP and beta ERD features were more robust to a limited number of trials, yielding differences lower than 20% for cases with 50 trials or more. Strong correlations between features were obtained for subsets above 50 trials. However, the inter-subject variability increased as the number of trials decreased. The elbow flexion/extension movement showed a more robust performance for a limited number of trials, both in population and in individual-based analysis.Significance. Our findings suggested that 50 trials can be an appropriate number to obtain stable motor-related features in terms of differences in the averaged motor features, correlation, and changes in topography and tomography.

Improving the ripple classification in focal pediatric epilepsy: identifying pathological high-frequency oscillations by Gaussian mixture model clustering.

Objective. High-frequency oscillations (HFOs) have emerged as a promising clinical biomarker for presurgical evaluation in childhood epilepsy. HFOs are commonly classified in stereo-encephalography as ripples (80-200 Hz) and fast ripples (200-500 Hz). Ripples are less specific and not so directly associated with epileptogenic activity because of their physiological and pathological origin. The aim of this paper is to distinguish HFOs in the ripple band and to improve the evaluation of the epileptogenic zone (EZ).Approach. This study constitutes a novel modeling approach evaluated in ten patients from Sant Joan de Deu Pediatric Hospital (Barcelona, Spain), with clearly-defined seizure onset zones (SOZ) during presurgical evaluation. A subject-by-subject basis analysis is proposed: a probabilistic Gaussian mixture model (GMM) based on the combination of specific ripple features is applied for estimating physiological and pathological ripple subpopulations.Main Results. Clear pathological and physiological ripples are identified. Features differ considerably among patients showing within-subject variability, suggesting that individual models are more appropriate than a traditional whole-population approach. The difference in rates inside and outside the SOZ for pathological ripples is significantly higher than when considering all the ripples. These significant differences also appear in signal segments without epileptiform activity. Pathological ripple rates show a sharp decline from SOZ to non-SOZ contacts and a gradual decrease with distance.Significance. This novel individual GMM approach improves ripple classification and helps to refine the delineation of the EZ, as well as being appropriate to investigate the interaction of epileptogenic and propagation networks.

SGM: a novel time-frequency algorithm based on unsupervised learning improves high-frequency oscillation detection in epilepsy.

OBJECTIVE: We propose a novel automated method called the S-Transform Gaussian Mixture detection algorithm (SGM) to detect high-frequency oscillations (HFO) combining the strengths of different families of previously published detectors. APPROACH: This algorithm does not depend on parameter tuning on a subject (or database) basis, uses time-frequency characteristics, and relies on non-supervised classification to determine if the events standing out from the baseline activity are HFO or not. SGM consists of three steps: the first stage computes the signal baseline using the entropy of the autocorrelation; the second uses the S-Transform to obtain several time-frequency features (area, entropy, and time and frequency widths); and in the third stage Gaussian mixture models cluster time-frequency features to decide if events correspond to HFO-like activity. To validate the SGM algorithm we tested its performance in simulated and real environments. MAIN RESULTS: We assessed the algorithm on a publicly available simulated stereoelectroencephalographic (SEEG) database with varying signal-to-noise ratios (SNR), obtaining very good results for medium and high SNR signals. We further tested the SGM algorithm on real signals from patients with focal epilepsy, in which HFO detection was performed visually by experts, yielding a high agreement between experts and SGM. SIGNIFICANCE: The SGM algorithm displayed proper performance in simulated and real environments and therefore can be used for non-supervised detection of HFO. This non-supervised algorithm does not require previous labelling by experts or parameter adjustment depending on the subject or database considered. SGM is not a computationally intensive algorithm, making it suitable to detect and characterize HFO in long-term SEEG recordings.

Alterations in EEG connectivity in healthy young adults provide an indicator of sleep depth.

Current sleep analyses have used electroencephalography (EEG) to establish sleep intensity through linear and nonlinear measures. Slow wave activity (SWA) and entropy are the most commonly used markers of sleep depth. The purpose of this study is to evaluate changes in brain EEG connectivity during sleep in healthy subjects and compare them with SWA and entropy. Four different connectivity metrics: coherence (MSC), synchronization likelihood (SL), cross mutual information function (CMIF), and phase locking value (PLV), were computed focusing on their correlation with sleep depth. These measures provide different information and perspectives about functional connectivity. All connectivity measures revealed to have functional changes between the different sleep stages. The averaged CMIF seemed to be a more robust connectivity metric to measure sleep depth (correlations of 0.78 and 0.84 with SWA and entropy, respectively), translating greater linear and nonlinear interdependences between brain regions especially during slow wave sleep. Potential changes of brain connectivity were also assessed throughout the night. Connectivity measures indicated a reduction of functional connectivity in N2 as sleep progresses. The validation of connectivity indexes is necessary because they can reveal the interaction between different brain regions in physiological and pathological conditions and help understand the different functions of deep sleep in humans.

Automated detection of epileptic ripples in MEG using beamformer-based virtual sensors.

OBJECTIVE: In epilepsy, high-frequency oscillations (HFOs) are expressively linked to the seizure onset zone (SOZ). The detection of HFOs in the noninvasive signals from scalp electroencephalography (EEG) and magnetoencephalography (MEG) is still a challenging task. The aim of this study was to automate the detection of ripples in MEG signals by reducing the high-frequency noise using beamformer-based virtual sensors (VSs) and applying an automatic procedure for exploring the time-frequency content of the detected events. APPROACH: Two-hundred seconds of MEG signal and simultaneous iEEG were selected from nine patients with refractory epilepsy. A two-stage algorithm was implemented. Firstly, beamforming was applied to the whole head to delimitate the region of interest (ROI) within a coarse grid of MEG-VS. Secondly, a beamformer using a finer grid in the ROI was computed. The automatic detection of ripples was performed using the time-frequency response provided by the Stockwell transform. Performance was evaluated through comparisons with simultaneous iEEG signals. MAIN RESULTS: ROIs were located within the seizure-generating lobes in the nine subjects. Precision and sensitivity values were 79.18% and 68.88%, respectively, by considering iEEG-detected events as benchmarks. A higher number of ripples were detected inside the ROI compared to the same region in the contralateral lobe. SIGNIFICANCE: The evaluation of interictal ripples using non-invasive techniques can help in the delimitation of the epileptogenic zone and guide placement of intracranial electrodes. This is the first study that automatically detects ripples in MEG in the time domain located within the clinically expected epileptic area taking into account the time-frequency characteristics of the events through the whole signal spectrum. The algorithm was tested against intracranial recordings, the current gold standard. Further studies should explore this approach to enable the localization of noninvasively recorded HFOs to help during pre-surgical planning and to reduce the need for invasive diagnostics.

Influence of metallic artifact filtering on MEG signals for source localization during interictal epileptiform activity.

OBJECTIVE: Medical intractable epilepsy is a common condition that affects 40% of epileptic patients that generally have to undergo resective surgery. Magnetoencephalography (MEG) has been increasingly used to identify the epileptogenic foci through equivalent current dipole (ECD) modeling, one of the most accepted methods to obtain an accurate localization of interictal epileptiform discharges (IEDs). Modeling requires that MEG signals are adequately preprocessed to reduce interferences, a task that has been greatly improved by the use of blind source separation (BSS) methods. MEG recordings are highly sensitive to metallic interferences originated inside the head by implanted intracranial electrodes, dental prosthesis, etc and also coming from external sources such as pacemakers or vagal stimulators. To reduce these artifacts, a BSS-based fully automatic procedure was recently developed and validated, showing an effective reduction of metallic artifacts in simulated and real signals (Migliorelli et al 2015 J. Neural Eng. 12 046001). The main objective of this study was to evaluate its effects in the detection of IEDs and ECD modeling of patients with focal epilepsy and metallic interference. APPROACH: A comparison between the resulting positions of ECDs was performed: without removing metallic interference; rejecting only channels with large metallic artifacts; and after BSS-based reduction. Measures of dispersion and distance of ECDs were defined to analyze the results. MAIN RESULTS: The relationship between the artifact-to-signal ratio and ECD fitting showed that higher values of metallic interference produced highly scattered dipoles. Results revealed a significant reduction on dispersion using the BSS-based reduction procedure, yielding feasible locations of ECDs in contrast to the other two approaches. SIGNIFICANCE: The automatic BSS-based method can be applied to MEG datasets affected by metallic artifacts as a processing step to improve the localization of epileptic foci.

Automatic BSS-based filtering of metallic interference in MEG recordings: definition and validation using simulated signals.

OBJECTIVE: One of the principal drawbacks of magnetoencephalography (MEG) is its high sensitivity to metallic artifacts, which come from implanted intracranial electrodes and dental ferromagnetic prosthesis and produce a high distortion that masks cerebral activity. The aim of this study was to develop an automatic algorithm based on blind source separation (BSS) techniques to remove metallic artifacts from MEG signals. APPROACH: Three methods were evaluated: AMUSE, a second-order technique; and INFOMAX and FastICA, both based on high-order statistics. Simulated signals consisting of real artifact-free data mixed with real metallic artifacts were generated to objectively evaluate the effectiveness of BSS and the subsequent interference reduction. A completely automatic detection of metallic-related components was proposed, exploiting the known characteristics of the metallic interference: regularity and low frequency content. MAIN RESULTS: The automatic procedure was applied to the simulated datasets and the three methods exhibited different performances. Results indicated that AMUSE preserved and consequently recovered more brain activity than INFOMAX and FastICA. Normalized mean squared error for AMUSE decomposition remained below 2%, allowing an effective removal of artifactual components. SIGNIFICANCE: To date, the performance of automatic artifact reduction has not been evaluated in MEG recordings. The proposed methodology is based on an automatic algorithm that provides an effective interference removal. This approach can be applied to any MEG dataset affected by metallic artifacts as a processing step, allowing further analysis of unusable or poor quality data.

Reduction of metallic interference in MEG signals using AMUSE.

Magnetoencephalography is a technique that can noninvasively measure the brain signal. There are many advantages of using this technique rather than similar procedures such as the EEG for the evaluation of medical diseases. However, one of its main problems is its high sensitivity to sources causing metallic distortion of the signal, and the removal of this type of artifacts remains unsolved. In this study a technique for reducing metallic interference was presented. This algorithm was based on AMUSE, a second order blind source separation method, and a procedure for choosing the artifactual independent components was also presented. The results showed that the elimination of these artifacts would be possible by means of the application of this AMUSE-based interference reduction procedure.