Sleep in patients with disorders of consciousness characterized by means of machine learning

Sleep has been proposed to indicate preserved residual brain functioning in patients suffering from disorders of consciousness (DOC) after awakening from coma. However, a reliable characterization of sleep patterns in this clinical population continues to be challenging given severely altered brain oscillations, frequent and extended artifacts in clinical recordings and the absence of established staging criteria. In the present study, we try to address these issues and investigate the usefulness of a multivariate machine learning technique based on permutation entropy, a complexity measure. Specifically, we used long-term polysomnography (PSG), along with video recordings in day and night periods in a sample of 23 DOC; 12 patients were diagnosed as Unresponsive Wakefulness Syndrome (UWS) and 11 were diagnosed as Minimally Conscious State (MCS). Eight hour PSG recordings of healthy sleepers (N = 26) were additionally used for training and setting parameters of supervised and unsupervised model, respectively. In DOC, the supervised classification (wake, N1, N2, N3 or REM) was validated using simultaneous videos which identified periods with prolonged eye opening or eye closure.The supervised classification revealed that out of the 23 subjects, 11 patients (5 MCS and 6 UWS) yielded highly accurate classification with an average F1-score of 0.87 representing high overlap between the classifier predicting sleep (i.e. one of the 4 sleep stages) and closed eyes. Furthermore, the unsupervised approach revealed a more complex pattern of sleep-wake stages during the night period in the MCS group, as evidenced by the presence of several distinct clusters. In contrast, in UWS patients no such clustering was found. Altogether, we present a novel data-driven method, based on machine learning that can be used to gain new and unambiguous insights into sleep organization and residual brain functioning of patients with DOC.

[1]  Trevor Hastie,et al.  The Elements of Statistical Learning , 2001 .

[2]  A. Schlögl,et al.  An E-Health Solution for Automatic Sleep Classification according to Rechtschaffen and Kales: Validation Study of the Somnolyzer 24 × 7 Utilizing the Siesta Database , 2005, Neuropsychobiology.

[3]  Susan G. Wardle,et al.  Decoding Dynamic Brain Patterns from Evoked Responses: A Tutorial on Multivariate Pattern Analysis Applied to Time Series Neuroimaging Data , 2016, Journal of Cognitive Neuroscience.

[4]  Steven Laureys,et al.  Sleep in disorders of consciousness. , 2010, Sleep medicine reviews.

[5]  E Donchin,et al.  A new method for off-line removal of ocular artifact. , 1983, Electroencephalography and clinical neurophysiology.

[6]  F. Giubilei,et al.  Sleep abnormalities in traumatic apallic syndrome. , 1995, Journal of neurology, neurosurgery, and psychiatry.

[7]  Manuel Schabus,et al.  Across the consciousness continuum—from unresponsive wakefulness to sleep , 2015, Front. Hum. Neurosci..

[8]  S. Dehaene,et al.  Information Sharing in the Brain Indexes Consciousness in Noncommunicative Patients , 2013, Current Biology.

[9]  The sleep cycle in coma: prognostic value. , 1968, Electroencephalography and clinical neurophysiology.

[10]  G. Chatrian,et al.  Electroencephalographic patterns resembling those of sleep in certain comatose states after injuries to the head. , 1963, Electroencephalography and clinical neurophysiology.

[11]  Steven Laureys,et al.  Electroencephalographic profiles for differentiation of disorders of consciousness , 2013, Biomedical engineering online.

[12]  H. Jasper,et al.  The ten-twenty electrode system of the International Federation. The International Federation of Clinical Neurophysiology. , 1999, Electroencephalography and clinical neurophysiology. Supplement.

[13]  A. Rechtschaffen,et al.  A manual of standardized terminology, technique and scoring system for sleep stages of human subjects , 1968 .

[14]  M. N. Nuwer,et al.  Assessment of digital EEG, quantitative EEG, and EEG brain mapping: Report of the American Academy of Neurology and the American Clinical Neurophysiology Society* , 1997, Neurology.

[15]  F. Fazekas,et al.  Cardiopulmonary arrest is the most frequent cause of the unresponsive wakefulness syndrome: A prospective population-based cohort study in Austria. , 2016, Resuscitation.

[16]  E. Wolpert A Manual of Standardized Terminology, Techniques and Scoring System for Sleep Stages of Human Subjects. , 1969 .

[17]  J. Giacino,et al.  The JFK Coma Recovery Scale-Revised: measurement characteristics and diagnostic utility. , 2004, Archives of physical medicine and rehabilitation.

[18]  Guy Lapalme,et al.  A systematic analysis of performance measures for classification tasks , 2009, Inf. Process. Manag..

[19]  G. Tononi,et al.  Electrophysiological correlates of behavioural changes in vigilance in vegetative state and minimally conscious state. , 2011, Brain : a journal of neurology.

[20]  B. Pompe,et al.  Permutation entropy: a natural complexity measure for time series. , 2002, Physical review letters.

[21]  R Core Team,et al.  R: A language and environment for statistical computing. , 2014 .

[22]  A. Chesson,et al.  The American Academy of Sleep Medicine (AASM) Manual for the Scoring of Sleep and Associated Events: Rules, Terminology and Technical Specifications , 2007 .

[23]  Steven Laureys,et al.  Sleep in the unresponsive wakefulness syndrome and minimally conscious state. , 2013, Journal of neurotrauma.

[24]  Monika Schönauer,et al.  Night sleep in patients with vegetative state , 2017, Journal of sleep research.

[25]  Gudrun Stockmanns,et al.  Electroencephalographic Order Pattern Analysis for the Separation of Consciousness and Unconsciousness: An Analysis of Approximate Entropy, Permutation Entropy, Recurrence Rate, and Phase Coupling of Order Recurrence Plots , 2008, Anesthesiology.

[26]  Walter G Sannita,et al.  Unresponsive wakefulness syndrome: a new name for the vegetative state or apallic syndrome , 2010, BMC medicine.

[27]  Max Kuhn,et al.  caret: Classification and Regression Training , 2015 .

[28]  Matthäus Staniek,et al.  Symbolic transfer entropy. , 2008, Physical review letters.

[29]  Mary M. Conte,et al.  Preservation of electroencephalographic organization in patients with impaired consciousness and imaging‐based evidence of command‐following , 2014, Annals of neurology.

[30]  Tal Galili,et al.  dendextend: an R package for visualizing, adjusting and comparing trees of hierarchical clustering , 2015, Bioinform..

[31]  Marcel Brun,et al.  Clustering Algorithms: On Learning, Validation, Performance, and Applications to Genomics , 2009, Current genomics.

[32]  A. Luxen,et al.  Automated Analysis of Background EEG and Reactivity During Therapeutic Hypothermia in Comatose Patients After Cardiac Arrest , 2014, Clinical EEG and neuroscience.

[33]  Gerald Pichler,et al.  Significance of circadian rhythms in severely brain-injured patients , 2017, Neurology.

[34]  Manuel Schabus,et al.  EEG entropy measures indicate decrease of cortical information processing in Disorders of Consciousness , 2016, Clinical Neurophysiology.

[35]  Davide Tonon,et al.  The importance of polysomnography in the evaluation of prolonged disorders of consciousness: sleep recordings more adequately correlate than stimulus-related evoked potentials with patients' clinical status. , 2014, Sleep medicine.

[36]  J. Giacino,et al.  The minimally conscious state: Definition and diagnostic criteria , 2002, Neurology.

[37]  J. Sleigh,et al.  Permutation entropy of the electroencephalogram: a measure of anaesthetic drug effect. , 2008, British journal of anaesthesia.

[38]  Klaus Nordhausen,et al.  The Elements of Statistical Learning: Data Mining, Inference, and Prediction, Second Edition by Trevor Hastie, Robert Tibshirani, Jerome Friedman , 2009 .

[39]  T. Åkerstedt,et al.  Subjective and objective sleepiness in the active individual. , 1990, The International journal of neuroscience.

[40]  B. Jennett,et al.  Assessment of coma and impaired consciousness. A practical scale. , 1974, Lancet.

[41]  Manuel Schabus,et al.  Night and day variations of sleep in patients with disorders of consciousness , 2017, Scientific Reports.