Poul Jennum

Alexander Neergaard Olesen, Poul Jennum, Emmanuel Mignot et al.

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.

Alexander Neergaard Olesen, Poul Jennum, Emmanuel Mignot et al.

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.

Alexander Neergaard Olesen, Poul Jennum, Emmanuel Mignot et al.

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.

Alexander Neergaard Olesen, Stanislas Chambon, Valentin Thorey et al.

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.

Andreas Brink-Kjaer, Alexander Neergaard Olesen, Paul E. Peppard et al.

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 ($β$ = -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.

Alexander Neergaard Olesen, Poul Jennum, Paul Peppard et al.

We have developed an automatic sleep stage classification algorithm based on deep residual neural networks and raw polysomnogram signals. Briefly, the raw data is passed through 50 convolutional layers before subsequent classification into one of five sleep stages. Three model configurations were trained on 1850 polysomnogram recordings and subsequently tested on 230 independent recordings. Our best performing model yielded an accuracy of 84.1% and a Cohen's kappa of 0.746, improving on previous reported results by other groups also using only raw polysomnogram data. Most errors were made on non-REM stage 1 and 3 decisions, errors likely resulting from the definition of these stages. Further testing on independent cohorts is needed to verify performance for clinical use.

Jens B. Stephansen, Alexander N. Olesen, Mads Olsen et al.

Analysis of sleep for the diagnosis of sleep disorders such as Type-1 Narcolepsy (T1N) currently requires visual inspection of polysomnography records by trained scoring technicians. Here, we used neural networks in approximately 3,000 normal and abnormal sleep recordings to automate sleep stage scoring, producing a hypnodensity graph - a probability distribution conveying more information than classical hypnograms. Accuracy of sleep stage scoring was validated in 70 subjects assessed by six scorers. The best model performed better than any individual scorer (87% versus consensus). It also reliably scores sleep down to 5 instead of 30 second scoring epochs. A T1N marker based on unusual sleep-stage overlaps achieved a specificity of 96% and a sensitivity of 91%, validated in independent datasets. Addition of HLA-DQB1*06:02 typing increased specificity to 99%. Our method can reduce time spent in sleep clinics and automates T1N diagnosis. It also opens the possibility of diagnosing T1N using home sleep studies.