Automated scoring of pre-REM sleep in mice with deep learning

Reliable automation of the labor-intensive manual task of scoring animal sleep can facilitate the analysis of long-term sleep studies. In recent years, deep-learning-based systems, which learn optimal features from the data, increased scoring accuracies for the classical sleep stages of Wake, REM, and Non-REM. Meanwhile, it has been recognized that the statistics of transitional stages such as pre-REM, found between Non-REM and REM, may hold additional insight into the physiology of sleep and are now under vivid investigation. We propose a classification system based on a simple neural network architecture that scores the classical stages as well as pre-REM sleep in mice. When restricted to the classical stages, the optimized network showed state-of-the-art classification performance with an out-of-sample F1 score of 0.95 in male C57BL/6J mice. When unrestricted, the network showed lower F1 scores on pre-REM (0.5) compared to the classical stages. The result is comparable to previous attempts to score transitional stages in other species such as transition sleep in rats or N1 sleep in humans. Nevertheless, we observed that the sequence of predictions including pre-REM typically transitioned from Non-REM to REM reflecting sleep dynamics observed by human scorers. Our findings provide further evidence for the difficulty of scoring transitional sleep stages, likely because such stages of sleep are under-represented in typical data sets or show large inter-scorer variability. We further provide our source code and an online platform to run predictions with our trained network.

[1]  C. Gottesmann,et al.  Detection of seven sleep-waking stages in the rat , 1992, Neuroscience & Biobehavioral Reviews.

[2]  Isaac L. Chuang,et al.  Confident Learning: Estimating Uncertainty in Dataset Labels , 2019, J. Artif. Intell. Res..

[3]  Xiaomin Song,et al.  Time Series Data Augmentation for Deep Learning: A Survey , 2020, IJCAI.

[4]  Karine Lacourse,et al.  Massive online data annotation, crowdsourcing to generate high quality sleep spindle annotations from EEG data , 2020, Scientific Data.

[5]  Romain Tavenard,et al.  Data Augmentation for Time Series Classification using Convolutional Neural Networks , 2016 .

[6]  Genshiro A. Sunagawa,et al.  FASTER: an unsupervised fully automated sleep staging method for mice , 2013, Genes to cells : devoted to molecular & cellular mechanisms.

[7]  Amir Bashan,et al.  Network physiology reveals relations between network topology and physiological function , 2012, Nature Communications.

[8]  Miad Faezipour,et al.  Sleep Stage Classification Using EEG Signal Analysis: A Comprehensive Survey and New Investigation , 2016, Entropy.

[9]  U. Rajendra Acharya,et al.  A review of automated sleep stage scoring based on physiological signals for the new millennia , 2019, Comput. Methods Programs Biomed..

[10]  A. Gabrielli,et al.  Recent developments in automatic scoring of rodent sleep. , 2015, Archives italiennes de biologie.

[11]  Geoffrey E. Hinton,et al.  Deep Learning , 2015, Nature.

[12]  Charles G. Frye,et al.  Robust, automated sleep scoring by a compact neural network with distributional shift correction , 2019, PloS one.

[13]  A. F. Adams,et al.  The Survey , 2021, Dyslexia in Higher Education.

[14]  Jimmy Ba,et al.  Adam: A Method for Stochastic Optimization , 2014, ICLR.

[15]  R. C. Macridis A review , 1963 .

[16]  H. Heller,et al.  Scoring transitions to REM sleep in rats based on the EEG phenomena of pre-REM sleep: an improved analysis of sleep structure. , 1994, Sleep.

[17]  Stephan Bialonski,et al.  Automated Classification of Sleep Stages and EEG Artifacts in Mice with Deep Learning , 2018, ArXiv.

[18]  Kaiming He,et al.  Accurate, Large Minibatch SGD: Training ImageNet in 1 Hour , 2017, ArXiv.

[19]  Jack R. Smith,et al.  Automatic Analysis of Sleep Electroencephalograms by Hybrid Computation , 1969, IEEE Trans. Syst. Sci. Cybern..

[20]  J. van Leeuwen,et al.  Neural Networks: Tricks of the Trade , 2002, Lecture Notes in Computer Science.

[21]  Guigang Zhang,et al.  Deep Learning , 2016, Int. J. Semantic Comput..

[22]  The intermediate stage of sleep in mice , 1991, Physiology & Behavior.

[23]  Yijing Li,et al.  Learning from class-imbalanced data: Review of methods and applications , 2017, Expert Syst. Appl..

[24]  E. Mohammadi,et al.  Barriers and facilitators related to the implementation of a physiological track and trigger system: A systematic review of the qualitative evidence , 2017, International journal for quality in health care : journal of the International Society for Quality in Health Care.

[25]  Bingni W. Brunton,et al.  Sleep Identification Enabled by Supervised Training Algorithms (SIESTA): An open-source platform for automatic sleep staging of rodent polysomnographic data , 2020, bioRxiv.

[26]  Gari D Clifford,et al.  Supervised and Unsupervised Machine Learning for Automated Scoring of Sleep-Wake and Cataplexy in a Mouse Model of Narcolepsy. , 2019, Sleep.

[27]  Valter Tucci,et al.  A novel unsupervised analysis of electrophysiological signals reveals new sleep substages in mice , 2018, PLoS biology.

[28]  A. Malafosse,et al.  Genetic variation in EEG activity during sleep in inbred mice. , 1998, American journal of physiology. Regulatory, integrative and comparative physiology.

[29]  Kristofer E. Bouchard,et al.  Robust, automated sleep scoring by a compact neural network with distributional shift correction , 2019, bioRxiv.

[30]  Alexander J. Smola,et al.  Detecting and Correcting for Label Shift with Black Box Predictors , 2018, ICML.

[31]  Tiago H. Falk,et al.  Deep learning-based electroencephalography analysis: a systematic review , 2019, Journal of neural engineering.

[32]  Vladimir Svetnik,et al.  A Deep Learning Approach for Automated Sleep-Wake Scoring in Pre-Clinical Animal Models , 2020, Journal of Neuroscience Methods.

[33]  G. Ruigt,et al.  A large scale, high resolution, automated system for rat sleep staging. I. Methodology and technical aspects. , 1989, Electroencephalography and clinical neurophysiology.

[34]  Geoffrey I. Webb,et al.  Encyclopedia of Machine Learning and Data Mining , 2017, Encyclopedia of Machine Learning and Data Mining.

[35]  W C Dement,et al.  Real-time automated sleep scoring: validation of a microcomputer-based system for mice. , 1991, Sleep.

[36]  Kirsi-Marja Rytkönen,et al.  Automated sleep scoring in rats and mice using the naive Bayes classifier , 2011, Journal of Neuroscience Methods.

[37]  Alessandro Puiatti,et al.  Automated sleep scoring: A review of the latest approaches. , 2019, Sleep medicine reviews.

[38]  Hiroyuki Kitagawa,et al.  MC-SleepNet: Large-scale Sleep Stage Scoring in Mice by Deep Neural Networks , 2019, Scientific Reports.

[39]  Nitish Srivastava,et al.  Dropout: a simple way to prevent neural networks from overfitting , 2014, J. Mach. Learn. Res..

[40]  Sheng-Fu Liang,et al.  Development of a rule-based automatic five-sleep-stage scoring method for rats , 2019, BioMedical Engineering OnLine.

[41]  Lukasz Kaiser,et al.  Attention is All you Need , 2017, NIPS.

[42]  Taghi M. Khoshgoftaar,et al.  Survey on deep learning with class imbalance , 2019, J. Big Data.

[43]  Stanislas Chambon,et al.  A Deep Learning Architecture for Temporal Sleep Stage Classification Using Multivariate and Multimodal Time Series , 2017, IEEE Transactions on Neural Systems and Rehabilitation Engineering.

[44]  Pattern recognition applied to sleep state classification. , 1969, Electroencephalography and clinical neurophysiology.

[45]  A. Gabrielli,et al.  SCOPRISM: A new algorithm for automatic sleep scoring in mice , 2014, Journal of Neuroscience Methods.

[46]  Binqiang Zhao,et al.  O2U-Net: A Simple Noisy Label Detection Approach for Deep Neural Networks , 2019, 2019 IEEE/CVF International Conference on Computer Vision (ICCV).

[47]  Santosh Kumar Satapathy,et al.  A Comprehensive Survey and New Investigation on Sleep Disorder Detection Using EEG Signal , 2020 .

[48]  Chao Wu,et al.  DeepSleepNet: A Model for Automatic Sleep Stage Scoring Based on Raw Single-Channel EEG , 2017, IEEE Transactions on Neural Systems and Rehabilitation Engineering.

[49]  Joachim M. Buhmann,et al.  SPINDLE: End-to-end learning from EEG/EMG to extrapolate animal sleep scoring across experimental settings, labs and species , 2019, PLoS Comput. Biol..

[50]  Alaa Tharwat,et al.  Classification assessment methods , 2020, Applied Computing and Informatics.

[51]  C. Robert,et al.  Automated sleep staging systems in rats , 1999, Journal of Neuroscience Methods.

[52]  Germain Forestier,et al.  Deep learning for time series classification: a review , 2018, Data Mining and Knowledge Discovery.

[53]  Xue Ben,et al.  Deep Transformer Models for Time Series Forecasting: The Influenza Prevalence Case , 2020, ArXiv.

[54]  D. Neckelmann,et al.  The reliability and functional validity of visual and semiautomatic sleep/wake scoring in the Møll-Wistar rat. , 1994, Sleep.

[55]  Karim Benchenane,et al.  Improved sleep scoring in mice reveals human-like stages , 2018, bioRxiv.

[56]  Razvan Pascanu,et al.  On the difficulty of training recurrent neural networks , 2012, ICML.

[57]  Seiichi Uchida,et al.  An empirical survey of data augmentation for time series classification with neural networks , 2020, PloS one.

[58]  G. Paxinos,et al.  Paxinos and Franklin's the Mouse Brain in Stereotaxic Coordinates , 2012 .

[59]  Jürgen Schmidhuber,et al.  Long Short-Term Memory , 1997, Neural Computation.

[60]  J. Born,et al.  About sleep's role in memory. , 2013, Physiological reviews.

[61]  Victoria Booth,et al.  Open-source logic-based automated sleep scoring software using electrophysiological recordings in rats , 2009, Journal of Neuroscience Methods.

[62]  C. Gottesmann,et al.  The Transition from Slow-wave Sleep to Paradoxical Sleep: Evolving Facts and Concepts of the Neurophysiological Processes Underlying the Intermediate Stage of Sleep , 1996, Neuroscience & Biobehavioral Reviews.

[63]  Y. Urade,et al.  Algorithm for sleep scoring in experimental animals based on fast Fourier transform power spectrum analysis of the electroencephalogram , 2008 .

[64]  Geoffrey I. Webb,et al.  Encyclopedia of Machine Learning and Data Mining , 2017, Encyclopedia of Machine Learning and Data Mining.

[65]  S. Hewitt,et al.  2007 , 2018, Los 25 años de la OMC: Una retrospectiva fotográfica.

[66]  A. Giuditta,et al.  Characterization of Transition Sleep Episodes in Baseline EEG Recordings of Adult Rats , 1996, Physiology & Behavior.

[67]  E. Chibowski,et al.  Magnetic water treatment-A review of the latest approaches. , 2018, Chemosphere.