Colonic microbiota is associated with inflammation and host epigenomic alterations in inflammatory bowel disease.

Studies of inflammatory bowel disease (IBD) have been inconclusive in relating microbiota with distribution of inflammation. We report microbiota, host transcriptomics, epigenomics and genetics from matched inflamed and non-inflamed colonic mucosa [50 Crohn's disease (CD); 80 ulcerative colitis (UC); 31 controls]. Changes in community-wide and within-patient microbiota are linked with inflammation, but we find no evidence for a distinct microbial diagnostic signature, probably due to heterogeneous host-microbe interactions, and show only marginal microbiota associations with habitual diet. Epithelial DNA methylation improves disease classification and is associated with both inflammation and microbiota composition. Microbiota sub-groups are driven by dominant Enterbacteriaceae and Bacteroides species, representative strains of which are pro-inflammatory in vitro, are also associated with immune-related epigenetic markers. In conclusion, inflamed and non-inflamed colonic segments in both CD and UC differ in microbiota composition and epigenetic profiles.

Bifidobacterium longum 1714 as a translational psychobiotic: modulation of stress, electrophysiology and neurocognition in healthy volunteers.

The emerging concept of psychobiotics-live microorganisms with a potential mental health benefit-represents a novel approach for the management of stress-related conditions. The majority of studies have focused on animal models. Recent preclinical studies have identified the B. longum 1714 strain as a putative psychobiotic with an impact on stress-related behaviors, physiology and cognitive performance. Whether such preclinical effects could be translated to healthy human volunteers remains unknown. We tested whether psychobiotic consumption could affect the stress response, cognition and brain activity patterns. In a within-participants design, healthy volunteers (N=22) completed cognitive assessments, resting electroencephalography and were exposed to a socially evaluated cold pressor test at baseline, post-placebo and post-psychobiotic. Increases in cortisol output and subjective anxiety in response to the socially evaluated cold pressor test were attenuated. Furthermore, daily reported stress was reduced by psychobiotic consumption. We also observed subtle improvements in hippocampus-dependent visuospatial memory performance, as well as enhanced frontal midline electroencephalographic mobility following psychobiotic consumption. These subtle but clear benefits are in line with the predicted impact from preclinical screening platforms. Our results indicate that consumption of B. longum 1714 is associated with reduced stress and improved memory. Further studies are warranted to evaluate the benefits of this putative psychobiotic in relevant stress-related conditions and to unravel the mechanisms underlying such effects.

In-depth performance analysis of an EEG based neonatal seizure detection algorithm.

OBJECTIVE: To describe a novel neurophysiology based performance analysis of automated seizure detection algorithms for neonatal EEG to characterize features of detected and non-detected seizures and causes of false detections to identify areas for algorithmic improvement. METHODS: EEGs of 20 term neonates were recorded (10 seizure, 10 non-seizure). Seizures were annotated by an expert and characterized using a novel set of 10 criteria. ANSeR seizure detection algorithm (SDA) seizure annotations were compared to the expert to derive detected and non-detected seizures at three SDA sensitivity thresholds. Differences in seizure characteristics between groups were compared using univariate and multivariate analysis. False detections were characterized. RESULTS: The expert detected 421 seizures. The SDA at thresholds 0.4, 0.5, 0.6 detected 60%, 54% and 45% of seizures. At all thresholds, multivariate analyses demonstrated that the odds of detecting seizure increased with 4 criteria: seizure amplitude, duration, rhythmicity and number of EEG channels involved at seizure peak. Major causes of false detections included respiration and sweat artefacts or a highly rhythmic background, often during intermediate sleep. CONCLUSION: This rigorous analysis allows estimation of how key seizure features are exploited by SDAs. SIGNIFICANCE: This study resulted in a beta version of ANSeR with significantly improved performance.

Automated detection of perturbed cardiac physiology during oral food allergen challenge in children.

This paper investigates the fully automated computer-based detection of allergic reaction in oral food challenges using pediatric ECG signals. Nonallergic background is modeled using a mixture of Gaussians during oral food challenges, and the model likelihoods are used to determine whether a subject is allergic to a food type. The system performance is assessed on the dataset of 24 children (15 allergic and 9 nonallergic) totaling 34 h of data. The proposed detector correctly classified all nonallergic subjects (100% specificity) and 12 allergic subjects (80% sensitivity) and is capable of detecting allergy on average 17 min earlier than trained clinicians during oral food challenges, the gold standard of allergy diagnosis. Inclusion of the developed allergy classification platform during oral food challenges recorded would result in a 30% reduction of doses administered to allergic subjects. The results of study introduce the possibility to halt challenges earlier which can safely advance the state of clinical art of allergy diagnosis by reducing the overall exposure to the allergens.

An automated system for grading EEG abnormality in term neonates with hypoxic-ischaemic encephalopathy.

Automated analysis of the neonatal EEG has the potential to assist clinical decision making for neonates with hypoxic-ischaemic encephalopathy. This paper proposes a method of automatically grading the degree of abnormality in an hour long epoch of neonatal EEG. The automated grading system (AGS) was based on a multi-class linear classifier grading of short-term epochs of EEG which were converted into a long-term grading of EEG using a majority vote operation. The features used in the AGS were summary measurements of two sub-signals extracted from a quadratic time-frequency distribution: the amplitude modulation and instantaneous frequency. These sub-signals were based on a model of EEG as a multiplication of a coloured random process with a slowly varying pseudo-periodic waveform and may be related to macroscopic neurophysiological function. The 4 grade AGS had a classification accuracy of 83% compared to human annotation of the EEG (level of agreement, κ = 0.76). Features estimated on the developed sub-signals proved more effective at grading the EEG than measures based solely on the EEG and the incorporation of additional sub-grades based on EEG states into the AGS also improved performance.

EEG-based neonatal seizure detection with Support Vector Machines.

OBJECTIVE: The study presents a multi-channel patient-independent neonatal seizure detection system based on the Support Vector Machine (SVM) classifier. METHODS: A machine learning algorithm (SVM) is used as a classifier to discriminate between seizure and non-seizure EEG epochs. Two post-processing steps are proposed to increase both the temporal precision and the robustness of the system. The resulting system is validated on a large clinical dataset of 267 h of EEG data from 17 full-term newborns with seizures. RESULTS: The performance of the system using event-based metrics is reported. The system showed the best up-to-date performance of a neonatal seizure detection system. The system was able to achieve an average good detection rate of ~89% with one false seizure detection per hour, ~96% with two false detections per hour, or ~100% with four false detections per hour. An analysis of errors revealed sources of misclassification in terms of both missed seizures and false detections. CONCLUSIONS: The results obtained with the proposed SVM-based seizure detection system allow for its practical application in neonatal intensive care units. SIGNIFICANCE: The proposed SVM-based seizure detection system can greatly assist clinical staff, in a neonatal intensive care unit, to interpret the EEG. The system allows control of the final decision by choosing different confidence levels which makes it flexible for clinical needs. The obtained results may provide a reference for future seizure detection systems.

Performance assessment for EEG-based neonatal seizure detectors.

OBJECTIVE: This study discusses an appropriate framework to measure system performance for the task of neonatal seizure detection using EEG. The framework is used to present an extended overview of a multi-channel patient-independent neonatal seizure detection system based on the Support Vector Machine (SVM) classifier. METHODS: The appropriate framework for performance assessment of neonatal seizure detectors is discussed in terms of metrics, experimental setups, and testing protocols. The neonatal seizure detection system is evaluated in this framework. Several epoch-based and event-based metrics are calculated and curves of performance are reported. A new metric to measure the average duration of a false detection is proposed to accompany the event-based metrics. A machine learning algorithm (SVM) is used as a classifier to discriminate between seizure and non-seizure EEG epochs. Two post-processing steps proposed to increase temporal precision and robustness of the system are investigated and their influence on various metrics is shown. The resulting system is validated on a large clinical dataset of 267h. RESULTS: In this paper, it is shown how a complete set of metrics and a specific testing protocol are necessary to extensively describe neonatal seizure detection systems, objectively assess their performance and enable comparison with existing alternatives. The developed system currently represents the best published performance to date with an ROC area of 96.3%. The sensitivity and specificity were ~90% at the equal error rate point. The system was able to achieve an average good detection rate of ~89% at a cost of 1 false detection per hour with an average false detection duration of 2.7 min. CONCLUSIONS: It is shown that to accurately assess the performance of EEG-based neonatal seizure detectors and to facilitate comparison with existing alternatives, several metrics should be reported and a specific testing protocol should be followed. It is also shown that reporting only event-based metrics can be misleading as they do not always reflect the true performance of the system. SIGNIFICANCE: This is the first study to present a thorough method for performance assessment of EEG-based seizure detection systems. The evaluated SVM-based seizure detection system can greatly assist clinical staff, in a neonatal intensive care unit, to interpret the EEG.

Parallel artefact rejection for epileptiform activity detection in routine EEG.

The EEG signal is very often contaminated by electrical activity external to the brain. These artefacts make the accurate detection of epileptiform activity more difficult. A scheme developed to improve the detection of these artefacts (and hence epileptiform event detection) is introduced. A structure of parallel Support Vector Machine classifiers is assembled, one classifier tuned to perform the identification of epileptiform activity, the remainder trained for the detection of ocular and movement-related artefacts. This strategy enables an absolute reduction in false detection rate of 21.6% with the constraint of ensuring all epileptic events are recognized. Such a scheme is desirable given that sections of data which are heavily contaminated with artefact need not be excluded from analysis.

Predicting the neurodevelopmental outcome in newborns with hypoxic-ischaemic injury.

The prediction of outcome in newborns with hypoxic ischemic encephalopathy (HIE) is a problematic task. Here, the ability of a combination of clinical, heart rate and EEG measures to predict outcome at 2 years is investigated. One hour of EEG and ECG recordings were obtained from newborns 24 hours after birth. Each newborn was reassessed at 24 months to investigate their neurodevelopmental outcome. From the EEG and ECG recordings, a set of 12 features was extracted. To classify each baby's outcome this data, along with clinical information was fed to a support vector machine. On a per patient basis an ROC area of 0.768 was achieved with 73.68% of newborns being assigned the correct outcome. Overall, this system presents a promising step towards the use of multimodal data for the prediction of neurodevelopmental outcome in newborns with HIE.

Speech recognition features for EEG signal description in detection of neonatal seizures.

In this work, features which are usually employed in automatic speech recognition (ASR) are used for the detection of neonatal seizures in newborn EEG. Three conventional ASR feature sets are compared to the feature set which has been previously developed for this task. The results indicate that the thoroughly-studied spectral envelope based ASR features perform reasonably well on their own. Additionally, the SVM Recursive Feature Elimination routine is applied to all extracted features pooled together. It is shown that ASR features consistently appear among the top-rank features.

Heart rate based automatic seizure detection in the newborn.

This work investigates the efficacy of heart rate (HR) based measures for patient-independent, automatic detection of seizures in newborns. Sixty-two time-domain and frequency-domain features were extracted from the neonatal heart rate signal. These features were classified using a sophisticated support vector machine (SVM) scheme. The performance was evaluated on a large dataset of 208 h from 14 newborn infants. It was shown that the HR can be useful for the detection of neonatal seizures for certain patients yielding an area under the receiver operating characteristic (ROC) curve of up to 82%. On evaluating the system using multiple patients an average ROC area of 0.59 with sensitivity of 60% and specificity of 60%, were obtained. Feature selection was performed and in the majority of patients the performance was degraded. Further analysis of the feature weights found significant variability in feature ranking across all patients. Overall, the patient-independent system presented here was seen to perform well in some patients (2 out of 14) but performed poorly when tested on the entire group.

Gaussian mixture models for classification of neonatal seizures using EEG.

A real-time neonatal seizure detection system is proposed based on a Gaussian mixture model classifier. The system includes feature transformation techniques and classifier output postprocessing. The detector was evaluated on a database of 20 patients with 330 h of recordings. A detailed analysis of the choice of parameters for the detector is provided. A mean good detection rate of 79% was obtained with only 0.5 false detections per hour. A thorough review of all misclassified events was performed, from which a number of patterns causing false detections were identified.

EEG in the healthy term newborn within 12 hours of birth.

OBJECTIVE: To characterise and quantify the EEG during sleep in healthy newborns in the early newborn period. METHODS: Continuous multi-channel video-EEG data was recorded for up to 2 hours in normal newborns within 12 hours of birth. The total amount of active (AS) and quiet sleep (QS) was calculated in the first hour of recording. The EEG signal was quantitatively analysed for symmetry and synchrony. Spectral edge frequency (SEF), spectral entropy (H) and relative delta power (delta(R)) were calculated for a ten-minute segment of AS and QS in each recording. Paired t-test and Wilcoxon rank sum test were used for data analysis. RESULTS: Thirty normal newborn babies were studied, 10 within 6 hours of birth and 20 between 6 and 12 hours. All babies showed continuous symmetrical and synchronous EEG activity and well-developed sleep-wake cycling (SWC) with the median percentage of AS--48.5% and QS--36.6%. Quantitative EEG analysis of sleep epochs showed that SEF and H were significantly higher (p<0.0001) and delta(R) was significantly lower (p<0.0001) in AS than in QS. CONCLUSION: The normal newborn EEG shows symmetrical and synchronous continuous activity and well-developed SWC as early as within the first 6 hours of birth. Quantitative analysis of the EEG in the early postnatal period reveals differences in SEF, H and delta(R) for AS and QS periods. SIGNIFICANCE: These findings may have implications for quantitative analysis of the newborn EEG, including the EEG of babies with hypoxic ischaemic encephalopathy.