disorders of consciousness; classification; electrophysiology; TMS; functional neuroimaging; neuroethics
Abstract :
[en] Consciousness is a multidimensional construct with no widely accepted definition. Especially in pathological conditions, it is less clear what exactly is meant by (un)consciousness, how it can be reliably observed or measured. Here, we aim at (i) bringing together state of the art approaches to classification of single patients suffering from disorders of consciousness by means of motor-independent assessment of consciousness states with electrophysiology and functional neuroimaging, (ii) showing how each proposed metric translates into clinical practice and (iii) raising a discussion on the ethical aspects of consciousness measurements.We realize that when dealing with patients some issues commonly pertain to each method- ology discussed here, such as the overall clinical condition, clinical heterogeneity, and diagnostic uncertainty. When pre- dicting patients’ diagnosis, though, each method adopts a different approach to determine (a) a “gold standard” of the benchmark population upon which the metric is computed and (b) the generalization and replicability in the attempt to avoid overfitting. From an applied ethics perspective, the focus is, hence, on knowing what one is measuring and on the validity of measurements.We conclude that, when searching for consciousness in pathological conditions, confident diag- nosis can be based on the use of probabilistic predictions as well as on accumulative evidence stemming from multiple non-overlapping assessments with different modalities. A framework which will regulate the application order of these techniques (balancing their availability, sensitivity, and specificity, based on underlying clinical assumptions about a patient’s conscious state), is expected to ameliorate clinical management and further inform on the critical patterns of (un)consciousness.
Disciplines :
Neurosciences & behavior
Author, co-author :
Demertzi, Athina ; Université de Liège - ULiège > Centre de recherches du cyclotron
Sitt, Jacobo Diego
Sarasso, Simone
Pinxten, Wim
Language :
English
Title :
Measuring states of pathological (un)consciousness: research dimensions, clinical applications, and ethics
Bayne T, Hohwy J, Owen AM. Are there levels of consciousness? Trends Cogn Sci 2016;20:405-13.
Beckmann CF, DeLuca M, Devlin JT et al. Investigations into resting-state connectivity using independent component analysis. Philos Trans R Soc Lond B Biol Sci 2005;360:1001-13.
Bekinschtein TA, Dehaene S, Rohaut B. Neural signature of the conscious processing of auditory regularities. Proc Natl Acad Sci U S A 2009;106:1672-77.
Biswal BB, Van Kylen J, Hyde JS. Simultaneous assessment of flow and BOLD signals in resting-state functional connectivity maps. NMR Biomed 1997;10:165-70.
Boly M, Garrido MI, Gosseries O et al. Preserved feedforward but impaired top-down processes in the vegetative state. Science 2011;332:858-62.
Boly M, Tshibanda L, Vanhaudenhuyse A et al. Functional connectivity in the default network during resting state is preserved in a vegetative but not in a brain dead patient. Hum Brain Mapp 2009;30:2393-400.
Boveroux P, Vanhaudenhuyse A, Bruno MA et al. Breakdown of within- and between-network resting state functional magnetic resonance imaging connectivity during propofol-induced loss of consciousness. Anesthesiology 2010;113:1038-53.
Bruno M, Vanhaudenhuyse A, Schnakers C et al. Visual fixation in the vegetative state: an observational case series PET study. BMC Neurol 2010;10. https://www.ncbi.nlm.nih.gov/pubmed/ 23946194
Casali AG, Gosseries O, Rosanova M et al. A theoretically based index of consciousness independent of sensory processing and behavior. Sci Transl Med 2013;5:198ra105-198ra105.
Casarotto S, Comanducci A, Rosanova M et al. Stratification of unresponsive patients by an independently validated index of brain complexity. Ann Neurol 2016;80:718-29.
Clavagnier S, Falchier A, Kennedy H. Long-distance feedback projections to area V1: implications for multisensory integration, spatial awareness, and visual consciousness. Cogn Affect Behav Neurosci 2004;4:117-26.
Cruse D, Beukema S, Chennu S et al. The reliability of the N400 in single subjects: implications for patients with disorders of consciousness. NeuroImage Clin 2014;4:788-99.
Demertzi A, Antonopoulos G, Heine L et al. Intrinsic functional connectivity differentiates minimally conscious from unresponsive patients. Brain 2015;138:2619-31.
Demertzi A, Gomez F, Crone JS et al. Multiple fMRI system-level baseline connectivity is disrupted in patients with consciousness alterations. Cortex 2014;52:35-46.
Demertzi A, Ledoux D, Bruno M-A et al. Attitudes towards end-of-life issues in disorders of consciousness: a European survey. J Neurol 2011;258:1058-65.
Demertzi A, Liew C, Ledoux D et al. Dualism persists in the science of mind. Ann N Y Acad Sci 2009a;1157:1-9.
Demertzi A, Racine E, Bruno A et al. Pain perception in disorders of consciousness: neuroscience, clinical care, and ethics in dialogue. Neuroethics 2013;6:37-50.
Demertzi A, Schnakers C, Ledoux D et al. Different beliefs about pain perception in the vegetative and minimally conscious states: a European survey of medical and paramedical professionals. Prog Brain Res 2009b;177:329-38.
Demertzi A, Whitfield-Gabrieli S. Intrinsic brain activity and consciousness. In: Laureys S, Gosseries O, Tononi G (eds), The Neurology of Conciousness, 2nd edn. Elsevier, 2016, 95-105.
Eckert MA, Kamdar N V., Chang CE et al. A cross-modal system linking primary auditory and visual cortices: evidence from intrinsic fMRI connectivity analysis. Hum Brain Mapp 2008;29:848-57.
Engel AK, Fries P, Singer W. Dynamic predictions: oscillations and synchrony in top-down processing. Nat Rev Neurosci 2001;2:704-16.
Engemann D, Raimondo F, King J-R et al. Automated measurement and prediction of consciousness in vegetative and minimally conscious patients. ICML Work Stat Mach Learn Neurosci (Stamlins 2015).
Engemann D, Raimondo F, King J-R et al. (n.d.) Robust quantification of consciousness from clinical EEG.
Fridman EA, Schiff ND. Neuromodulation of the conscious state following severe brain injuries. Curr Opin Neurobiol 2014;29:172-77.
Gantner IS, Bodart O, Laureys S et al. Our rapidly changing understanding of acute and chronic disorders of consciousness: challenges for neurologists. Future Neurol 2013;8:43-54.
Giacino JT, Ashwal S, Childs N et al. The minimally conscious state: Definition and diagnostic criteria. Neurology 2002;58:349-53.
Giacino JT, Fins JJ, Laureys S et al. Disorders of consciousness after acquired brain injury: the state of the science. Nat Rev Neurol 2014;10:99-114.
Giacino JT, Kalmar K, Whyte J. The JFK Coma Recovery Scale - Revised: Measurement. 2004;85:2020-29.
Greicius MD, Srivastava G, Reiss AL et al. Default-mode network activity distinguishes Alzheimer's disease from healthy aging: evidence from functional MRI. Proc Natl Acad Sci U S A 2004;101:4637-42.
Gusnard DA, Raichle ME. Searching for a baseline: Functional imaging and the resting human brain. Nat Rev Neurosci 2001;2:685-94.
Harrison AH, Connolly JF. Finding a way in: a review and practical evaluation of fMRI and EEG for detection and assessment in disorders of consciousness. Neurosci Biobehav Rev 2013;37:1403-19.
Heine L, Soddu A, Gomez F et al. Resting state networks and consciousness: Alterations of multiple resting state network connectivity in physiological, pharmacological, and pathological consciousness states. Front Psychol 2012;3:1-12.
Ilmoniemi RJ, Virtanen J, Ruohonen J et al. Neuronal responses to magnetic stimulation reveal cortical reactivity and connectivity. Neuroreport 1997;8:3537-40.
Jennett B, Plum F. Persistent vegetative state after brain damage: a syndrome in search of a name. Lancet 1972;299:734-37.
Jox RJ, Bernat JL, Laureys S et al. Disorders of consciousness: responding to requests for novel diagnostic and therapeutic interventions. Lancet Neurol 2012;11:732-38.
Kahane G, Savulescu J. Brain damage and the moral significance of consciousness. J Med Philos 2009;34:6-26.
King JR, Faugeras F, Gramfort A et al. Single-trial decoding of auditory novelty responses facilitates the detection of residual consciousness. Neuroimage 2013a;83C:726-38.
King JR, Sitt JD, Faugeras F et al. Information sharing in the brain indexes consciousness in noncommunicative patients. Curr Biol 2013b;23:1914-19.
Kirsch M, Guldenmund P, Ali Bahri M et al. Sedation of patients with disorders of consciousness during neuroimaging: effects on resting state functional brain connectivity. Anesth Analg 2017;124:588-98.
Laird AR, Fox PM, Eickhoff SB et al. Behavioral interpretations of intrinsic connectivity networks. J Cogn Neurosci 2011;23:4022-37.
Laureys S, Boly M. What is it like to be vegetative or minimally conscious? Curr Opin Neurol 2007;20:609-13.
Laureys S, Celesia GG, Cohadon F et al. Unresponsive wakefulness syndrome: a new name for the vegetative state or apallic syndrome. BMC Med 2010;8:68.
Laureys S, Pellas F, Van Eeckhout P et al. The locked-in syndrome: what is it like to be conscious but paralyzed and voiceless? Prog Brain Res 2005;150:495-611.
Massimini M, Boly M, Casali A et al. A perturbational approach for evaluating the brain's capacity for consciousness. Prog Brain Res 2009;177:201-14.
Morlet D, Fischer C. MMN and novelty P3 in coma and other altered states of consciousness: a review. Brain Topogr 2014;27:467-79.
Naro A, Leo A, Buda A et al. Do you see me? The role of visual fixation in chronic disorders of consciousness differential diagnosis. Brain Res 2016;1653:59-66.
Noirhomme Q, Brecheisen R, Lesenfants D et al. “Look at my classifier's result”: Disentangling unresponsive from (minimally) conscious patients. Neuroimage 2017;145:288-303.
Noreika V, Jylhankangas € L, Moro L et al. Consciousness lost and found: subjective experiences in an unresponsive state. Brain Cogn 2011;77:327-34.
Pedregosa F, Varoquaux G, Gramfort A et al. Scikit-learn: Machine Learning in Python. Mach Learn 2012;12:2825-30.
Perrin F, Schnakers C, Schabus M et al. Brain response to one's own name in vegetative state, minimally conscious state, and locked-in syndrome. Arch Neurol 2006;63:562-69.
Peterson A. Consilience, clinical validation, and global disorders of consciousness. Neurosci Conscious 2016;2016:1-9. https://academic.oup.com/nc/article-lookup/doi/10.1093/nc/niw011 (17 March 2017, last accessed).
Peterson A, Cruse D, Naci L et al. Risk, diagnostic error, and the clinical science of consciousness. NeuroImage Clin 2015;7:588-97.
Posner JB, Saper CB, Schiff ND et al. Plum and Posner's Diagnosis of Stupor and Coma, 4th edn. New York: Oxford University Press, 2007.
Raichle ME, MacLeod AM, Snyder AZ et al. A default mode of brain function. Proc Natl Acad Sci U S A 2001;98:676-82.
Rohaut B, Faugeras F, Chausson N et al. Probing ERP correlates of verbal semantic processing in patients with impaired consciousness. Neuropsychologia 2015;66:279-92.
Sanders RD, Raz A, Banks MI et al. Is consciousness fragile? Br J Anaesth 2016;116:1-3.
Schnakers C, Vanhaudenhuyse A, Giacino J et al. Diagnostic accuracy of the vegetative and minimally conscious state: Clinical consensus versus standardized neurobehavioral assessment. BMC Neurol 2009;5:1-5.
Seel R, Sherer M, Whyte J et al. A practice parameter of the American Congress of Assessment Scales for disorders of consciousness: evidence- based recommendations for clinical practice and research. Arch Phys Med Rehabil 2010;91:1795-813.
Sergent C, Faugeras F, Rohaut B et al. Multidimensional cognitive evaluation of patients with disorders of consciousness using EEG: a proof of concept study. NeuroImage Clin 2016.
Seth AK, Dienes Z, Cleeremans A et al. Measuring consciousness: relating behavioural and neurophysiological approaches. Trends Cogn Sci 2008;12:314-21.
Shannon CE. A mathematical theory of communication. Bell Syst Tech J 1948;27:379-423.
Shea N, Bayne T. The vegetative state and the science of consciousness. Br J Philos Sci 2010;61:459-84.
Siclari F, LaRocque JJ, Postle BR et al. Assessing sleep consciousness within subjects using a serial awakening paradigm. Front Psychol 2013;4.
Sitt JD, King JR, Karoui IE et al. Large scale screening of neural signatures of consciousness in patients in a vegetative or minimally conscious state. Brain 2014;137:2258-70.
Smith SM, Fox PT, Miller KL et al. Correspondence of the brain's functional architecture during activation and rest. Proc Natl Acad Sci U S A 2009;106:13040-45.
Soddu A, Vanhaudenhuyse A, Bahri MA et al. Identifying the default-mode component in spatial IC analyses of patients with disorders of consciousness. Hum Brain Mapp 2012;33:778-96.
Stender J, Gosseries O, Bruno MA et al. Diagnostic precision of PET imaging and functional MRI in disorders of consciousness: a clinical validation study. Lancet Neurol 2014;6736:8-16.
The Multi-society Task Force on PVS. Medical aspects of the persistent vegetative state - 1. N Engl J Med 1994;330:1499-508.
Tononi G. An information integration theory of consciousness. BMC Neurosci 2004;5:42.
Tononi G, Boly M, Massimini M et al. Integrated information theory: from consciousness to its physical substrate. Nat Rev Neurosci 2016;17:450-61.
Vanhaudenhuyse A, Noirhomme Q, Tshibanda LJ-F et al. Default network connectivity reflects the level of consciousness in non-communicative brain-damaged patients. Brain 2010;133:161-71.
Weijer C, Peterson A, Webster F et al. Ethics of neuroimaging after serious brain injury. BMC Med Ethics 2014;15:41.