Deep transfer learning for improving single-EEG arousal detection

Datasets in sleep science present challenges for machine learning algorithms due to differences in recording setups across clinics. We investigate two deep transfer learning strategies for overcoming the channel mismatch problem for cases where two datasets do not contain exactly the same setup leading to degraded performance in single-EEG models. Specifically, we train a baseline model on multivariate polysomnography data and subsequently replace the first two layers to prepare the architecture for single-channel electroencephalography data. Using a fine-tuning strategy, our model yields similar performance to the baseline model (F1=0.682 and F1=0.694, respectively), and was significantly better than a comparable single-channel model. Our results are promising for researchers working with small databases who wish to use deep learning models pre-trained on larger databases.Comment: Accepted for presentation at EMBC202

Towards a Flexible Deep Learning Method for Automatic Detection of Clinically Relevant Multi-Modal Events in the Polysomnogram

Much attention has been given to automatic sleep staging algorithms in past years, but the detection of discrete events in sleep studies is also crucial for precise characterization of sleep patterns and possible diagnosis of sleep disorders. We propose here a deep learning model for automatic detection and annotation of arousals and leg movements. Both of these are commonly seen during normal sleep, while an excessive amount of either is linked to disrupted sleep patterns, excessive daytime sleepiness impacting quality of life, and various sleep disorders. Our model was trained on 1,485 subjects and tested on 1,000 separate recordings of sleep. We tested two different experimental setups and found optimal arousal detection was attained by including a recurrent neural network module in our default model with a dynamic default event window (F1 = 0.75), while optimal leg movement detection was attained using a static event window (F1 = 0.65). Our work show promise while still allowing for improvements. Specifically, future research will explore the proposed model as a general-purpose sleep analysis model.Comment: Accepted for publication in 41st International Engineering in Medicine and Biology Conference (EMBC), July 23-27, 201

Automatic sleep stage classification with deep residual networks in a mixed-cohort setting

Study Objectives: Sleep stage scoring is performed manually by sleep experts and is prone to subjective interpretation of scoring rules with low intra- and interscorer reliability. Many automatic systems rely on few small-scale databases for developing models, and generalizability to new datasets is thus unknown. We investigated a novel deep neural network to assess the generalizability of several large-scale cohorts. Methods: A deep neural network model was developed using 15684 polysomnography studies from five different cohorts. We applied four different scenarios: 1) impact of varying time-scales in the model; 2) performance of a single cohort on other cohorts of smaller, greater or equal size relative to the performance of other cohorts on a single cohort; 3) varying the fraction of mixed-cohort training data compared to using single-origin data; and 4) comparing models trained on combinations of data from 2, 3, and 4 cohorts. Results: Overall classification accuracy improved with increasing fractions of training data (0.25$\%$: 0.782 $\pm$ 0.097, 95$\%$ CI [0.777-0.787]; 100$\%$: 0.869 $\pm$ 0.064, 95$\%$ CI [0.864-0.872]), and with increasing number of data sources (2: 0.788 $\pm$ 0.102, 95$\%$ CI [0.787-0.790]; 3: 0.808 $\pm$ 0.092, 95$\%$ CI [0.807-0.810]; 4: 0.821 $\pm$ 0.085, 95$\%$ CI [0.819-0.823]). Different cohorts show varying levels of generalization to other cohorts. Conclusions: Automatic sleep stage scoring systems based on deep learning algorithms should consider as much data as possible from as many sources available to ensure proper generalization. Public datasets for benchmarking should be made available for future research.Comment: Author's original version. This article has been accepted for publication in SLEEP published by Oxford University Pres

Automatic Detection of Cortical Arousals in Sleep and their Contribution to Daytime Sleepiness

Cortical arousals are transient events of disturbed sleep that occur spontaneously or in response to stimuli such as apneic events. The gold standard for arousal detection in human polysomnographic recordings (PSGs) is manual annotation by expert human scorers, a method with significant interscorer variability. In this study, we developed an automated method, the Multimodal Arousal Detector (MAD), to detect arousals using deep learning methods. The MAD was trained on 2,889 PSGs to detect both cortical arousals and wakefulness in 1 second intervals. Furthermore, the relationship between MAD-predicted labels on PSGs and next day mean sleep latency (MSL) on a multiple sleep latency test (MSLT), a reflection of daytime sleepiness, was analyzed in 1447 MSLT instances in 873 subjects. In a dataset of 1,026 PSGs, the MAD achieved a F1 score of 0.76 for arousal detection, while wakefulness was predicted with an accuracy of 0.95. In 60 PSGs scored by multiple human expert technicians, the MAD significantly outperformed the average human scorer for arousal detection with a difference in F1 score of 0.09. After controlling for other known covariates, a doubling of the arousal index was associated with an average decrease in MSL of 40 seconds ($\beta$ = -0.67, p = 0.0075). The MAD outperformed the average human expert and the MAD-predicted arousals were shown to be significant predictors of MSL, which demonstrate clinical validity the MAD.Comment: 40 pages, 13 figures, 9 table

Inter-expert and intra-expert reliability in sleep spindle scoring

Objectives: To measure the inter-expert and intra-expert agreement in sleep spindle scoring, and to quantify how many experts are needed to build a reliable dataset of sleep spindle scorings. Methods: The EEG dataset was comprised of 400 randomly selected 115 s segments of stage 2 sleep from 110 sleeping subjects in the general population (57 ± 8, range: 42–72 years). To assess expert agreement, a total of 24 Registered Polysomnographic Technologists (RPSGTs) scored spindles in a subset of the EEG dataset at a single electrode location (C3-M2). Intra-expert and inter-expert agreements were calculated as F_1-scores, Cohen’s kappa (κ), and intra-class correlation coefficient (ICC). Results: We found an average intra-expert F_1-score agreement of 72 ± 7% (κ: 0.66 ± 0.07). The average inter-expert agreement was 61 ± 6% (κ: 0.52 ± 0.07). Amplitude and frequency of discrete spindles were calculated with higher reliability than the estimation of spindle duration. Reliability of sleep spindle scoring can be improved by using qualitative confidence scores, rather than a dichotomous yes/no scoring system. Conclusions: We estimate that 2–3 experts are needed to build a spindle scoring dataset with ‘substantial’ reliability (κ: 0.61–0.8), and 4 or more experts are needed to build a dataset with ‘almost perfect’ reliability (κ: 0.81–1). Significance: Spindle scoring is a critical part of sleep staging, and spindles are believed to play an important role in development, aging, and diseases of the nervous system

Effects of osteopontin inhibition on radiosensitivity of MDA-MB-231 breast cancer cells

<p>Abstract</p> <p>Background</p> <p>Osteopontin (OPN) is a secreted glycophosphoprotein that is overexpressed in various tumors, and high levels of OPN have been associated with poor prognosis of cancer patients. In patients with head and neck cancer, high OPN plasma levels have been associated with poor prognosis following radiotherapy. Since little is known about the relationship between OPN expression and radiosensitivity, we investigated the cellular and radiation induced effects of OPN siRNA in human MDA-MB-231 breast cancer cells.</p> <p>Methods</p> <p>MDA-MB-231 cells were transfected with OPN-specific siRNAs and irradiated after 24 h. To verify the OPN knockdown, we measured the OPN mRNA and protein levels using qRT-PCR and Western blot analysis. Furthermore, the functional effects of OPN siRNAs were studied by assays to assess clonogenic survival, migration and induction of apoptosis.</p> <p>Results</p> <p>Treatment of MDA-MB-231 cells with OPN siRNAs resulted in an 80% decrease in the OPN mRNA level and in a decrease in extracellular OPN protein level. Transfection reduced clonogenic survival to 42% (p = 0.008), decreased the migration rate to 60% (p = 0.15) and increased apoptosis from 0.3% to 1.7% (p = 0.04). Combination of OPN siRNA and irradiation at 2 Gy resulted in a further reduction of clonogenic survival to 27% (p < 0.001), decreased the migration rate to 40% (p = 0.03) and increased apoptosis to 4% (p < 0.005). Furthermore, OPN knockdown caused a weak radiosensitization with an enhancement factor of 1.5 at 6 Gy (p = 0.09) and a dose modifying factor (DMF₁₀) of 1.1.</p> <p>Conclusion</p> <p>Our results suggest that an OPN knockdown improves radiobiological effects in MDA-MB-231 cells. Therefore, OPN seems to be an attractive target to improve the effectiveness of radiotherapy.</p

Sleep-spindle detection: crowdsourcing and evaluating performance of experts, non-experts and automated methods

Sleep spindles are discrete, intermittent patterns of brain activity observed in human electroencephalographic data. Increasingly, these oscillations are of biological and clinical interest because of their role in development, learning and neurological disorders. We used an Internet interface to crowdsource spindle identification by human experts and non-experts, and we compared their performance with that of automated detection algorithms in data from middle- to older-aged subjects from the general population. We also refined methods for forming group consensus and evaluating the performance of event detectors in physiological data such as electroencephalographic recordings from polysomnography. Compared to the expert group consensus gold standard, the highest performance was by individual experts and the non-expert group consensus, followed by automated spindle detectors. This analysis showed that crowdsourcing the scoring of sleep data is an efficient method to collect large data sets, even for difficult tasks such as spindle identification. Further refinements to spindle detection algorithms are needed for middle- to older-aged subjects

MSED: A Multi-Modal Sleep Event Detection Model for Clinical Sleep Analysis

Study objective: Clinical sleep analysis require manual analysis of sleep patterns for correct diagnosis of sleep disorders. Several studies show significant variability in scoring discrete sleep events. We wished to investigate, whether an automatic method could be used for detection of arousals (Ar), leg movements (LM) and sleep disordered breathing (SDB) events, and if the joint detection of these events performed better than having three separate models. Methods: We designed a single deep neural network architecture to jointly detect sleep events in a polysomnogram. We trained the model on 1653 recordings of individuals, and tested the optimized model on 1000 separate recordings. The performance of the model was quantified by F1, precision, and recall scores, and by correlating index values to clinical values using Pearson's correlation coefficient. Results: F1 scores for the optimized model was 0.70, 0.63, and 0.62 for Ar, LM, and SDB, respectively. The performance was higher, when detecting events jointly compared to corresponding single-event models. Index values computed from detected events correlated well with manual annotations ($r^2$ = 0.73, $r^2$ = 0.77, $r^2$ = 0.78, respectively). Conclusion: Detecting arousals, leg movements and sleep disordered breathing events jointly is possible, and the computed index values correlates well with human annotations.Comment: 20 pages, 6 figure