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Detecting awareness after severe brain injury

Abstract

Recent developments in functional neuroimaging have provided a number of new tools for assessing patients who clinically appear to be in a vegetative state. These techniques have been able to reveal awareness and even allow rudimentary communication in some patients who remain entirely behaviourally non-responsive. The implications of these results extend well beyond the immediate clinical and scientific findings to influencing legal proceedings, raising new ethical questions about the withdrawal of nutrition and hydration and providing new options for patients and families in that decision-making process. The findings have also motivated significant public discourse about the role of neuroscience research in society.

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Figure 1: Electroencephalography activity demonstrating command-following and awareness in a patient diagnosed as being in a vegetative state for 12 years.
Figure 2: Functional MRI-based communication in a patient diagnosed as being in a vegetative state for 12 years.

References

  1. 1

    Plum, F. & Posner, J. The Diagnosis of Stupor and Coma (Oxford Univ. Press, 1982).

    Google Scholar 

  2. 2

    Royal College of Physicians. The vegetative state: guidance on diagnosis and management. Clin. Med. 3, 249–254 (2003).

  3. 3

    Andrews, K., Murphy, L., Munday, R. & Littlewood, C. Misdiagnosis of the vegetative state: retrospective study in a rehabilitation unit. BMJ 313, 13–16 (1996).

    CAS  Article  Google Scholar 

  4. 4

    Childs, N. L., Mercer, W. N. & Childs, H. W. Accuracy of diagnosis of persistent vegetative state. Neurology 43, 1465–1467 (1993).

    CAS  Article  Google Scholar 

  5. 5

    Schnakers, C. et al. Diagnostic accuracy of the vegetative and minimally conscious state: clinical consensus versus standardized neurobehavioral assessment. BMC Neurol. 9, 35 (2009).

    Article  Google Scholar 

  6. 6

    Jennett, B. & Plum, F. Persistent vegetative state after brain damage. A syndrome in search of a name. Lancet 1, 734–737 (1972).

    CAS  Article  Google Scholar 

  7. 7

    Giacino, J. T. et al. The minimally conscious state: definition and diagnostic criteria. Neurology 58, 349–353 (2002).

    Article  Google Scholar 

  8. 8

    Owen, A. M. Detecting consciousness: a unique role for neuroimaging. Annu. Rev. Psychol. 64, 109–133 (2013).

    Article  Google Scholar 

  9. 9

    Owen, A. M. et al. Detecting awareness in the vegetative state. Science 313, 1402–1402 (2006).

    CAS  Article  Google Scholar 

  10. 10

    Monti, M. M. et al. Willful modulation of brain activity in disorders of consciousness. New Engl. J. Med. 362, 579–589 (2010).

    CAS  Article  Google Scholar 

  11. 11

    Cruse, D. et al. Bedside detection of awareness in the vegetative state: a cohort study. Lancet 378, 2088–2094 (2011).

    Article  Google Scholar 

  12. 12

    Boly, M. et al. When thoughts become action: an fMRI paradigm to study volitional brain activity in non-communicative brain injured patients. Neuroimage 36, 979–992 (2007).

    CAS  Article  Google Scholar 

  13. 13

    Aguirre, G. K., Detre, J. A., Alsop, D. C. & D'Esposito, M. The parahippocampus subserves topographical learning in man. Cereb. Cortex 6, 823–829 (1996).

    CAS  Article  Google Scholar 

  14. 14

    Ghaem, O. et al. Mental navigation along memorized routes activates the hippocampus, precuneus, and insula. Neuroreport 8, 739–744 (1997).

    CAS  Article  Google Scholar 

  15. 15

    Mellet, E. et al. Neural correlates of topographic mental exploration: the impact of route versus survey perspective learning. Neuroimage 12, 588–600 (2000).

    CAS  Article  Google Scholar 

  16. 16

    O'Craven, K. M. & Kanwisher, N. Mental imagery of faces and places activates corresponding stimulus-specific brain regions. J. Cogn. Neurosci. 12, 1013–1023 (2000).

    CAS  Article  Google Scholar 

  17. 17

    Ino, T. et al. Mental navigation in humans is processed in the anterior bank of the parieto-occipital sulcus. Neurosci. Lett. 322, 182–186 (2002).

    CAS  Article  Google Scholar 

  18. 18

    Owen, A. M. & Coleman, M. R. Functional neuroimaging of the vegetative state. Nature Rev. Neurosci. 9, 235–243 (2008).

    CAS  Article  Google Scholar 

  19. 19

    Bekinschtein, T. A., Manes, F. F., Villarreal, M., Owen, A. M. & Della-Maggiore, V. Functional imaging reveals movement preparatory activity in the vegetative state. Front. Hum. Neurosci. 5, 5 (2011).

    Article  Google Scholar 

  20. 20

    Monti, M. M., Coleman, M. R. & Owen, A. M. Executive functions in the absence of behavior: functional imaging of the minimally conscious state. Prog. Brain Res. 177, 249–260 (2009).

    Article  Google Scholar 

  21. 21

    Monti, M. M., Pickard, J. D. & Owen, A. M. Visual cognition in disorders of consciousness: from V1 to top-down attention. Hum. Brain Mapp. 34, 1245–1253 (2013).

    Article  Google Scholar 

  22. 22

    Zeman, A. The problem of unreportable awareness. Prog. Brain Res. 177, 1–9 (2009).

    Article  Google Scholar 

  23. 23

    Schnakers, C. et al. Voluntary brain processing in disorders of consciousness. Neurology 71, 1614–1620 (2008).

    CAS  Article  Google Scholar 

  24. 24

    Pfurtscheller, G. & Neuper, C. Motor imagery activates primary sensorimotor area in humans. Neurosci. Lett. 239, 65–68 (1997).

    CAS  Article  Google Scholar 

  25. 25

    Pfurtscheller, G., Scherer, R., Müller-Putz, G. R. & Lopes da Silva, F. H. Short-lived brain state after cued motor imagery in naive subjects. Eur. J. Neurosci. 28, 1419–1426 (2008).

    CAS  Article  Google Scholar 

  26. 26

    Pfurtscheller, G., Brunner, C., Schlögl, A. & Lopes da Silva, F. H. Mu rhythm (de)synchronization and EEG single-trial classification of different motor imagery tasks. Neuroimage 31, 153–159 (2006).

    CAS  Article  Google Scholar 

  27. 27

    Goldfine, A. et al. Reanalysis of “Bedside detection of awareness in the vegetative state: a cohort study”. Lancet 381, 289–291 (2013).

    Article  Google Scholar 

  28. 28

    Cruse, D. et al. Reanalysis of “Bedside detection of awareness in the vegetative state: a cohort study.” — authors' reply. Lancet 381, 291–292 (2013).

    Article  Google Scholar 

  29. 29

    Cruse, D. et al. Detecting awareness in the vegetative state: electroencephalographic evidence for attempted movements to command. PLoS ONE 7, e49933 (2012).

    CAS  Article  Google Scholar 

  30. 30

    Owen, A. M. & Coleman, M. R. Detecting awareness in the vegetative state. Ann. NY Acad. Sci. 1129, 130–138 (2008).

    Article  Google Scholar 

  31. 31

    Sorger, B., Reithler, J., Dahmen, B. & Goebel, R. A real-time fMRI-based spelling device immediately enabling robust motor-independent communication. Curr. Biol. 22, 1333–1338 (2012).

    CAS  Article  Google Scholar 

  32. 32

    Sorger, B., Dahmen, B., Reithler, J. & Gosseries, O. Another kind of 'BOLD Response': answering multiple-choice questions via online decoded single-trial brain signals. Prog. Brain Res. 177, 275–292 (2009).

    Article  Google Scholar 

  33. 33

    The Multi-Society Task Force on PVS. Medical aspects of the persistent vegetative state (I). New Engl. J. Med. 330, 1499–1508 (1994).

  34. 34

    The Multi-Society Task Force on PVS. Medical aspects of the persistent vegetative state (II). New Engl. J. Med. 330, 1572–1579 (1994).

  35. 35

    Jennett, B. The Vegetative State: Medical Facts, Ethical and Legal Dilemmas (Cambridge Univ. Press, 2002).

    Book  Google Scholar 

  36. 36

    Jennett, B. Thirty years of the vegetative state: clinical, ethical and legal problems. Prog. Brain Res. 150, 537–543 (2005).

    Article  Google Scholar 

  37. 37

    Walsh, F. Finding a voice for the brain injured. bbc.co.uk [online], (2012)

    Google Scholar 

  38. 38

    Teasdale, G. & Jennett, B. Assessment of coma and impaired consciousness. A practical scale. Lancet 2, 81–84 (1974).

    CAS  Article  Google Scholar 

  39. 39

    Giacino, J. T., Kalmar, K. & Whyte, J. The JFK Coma Recovery Scale-Revised: measurement characteristics and diagnostic utility. Arch. Phys. Med. Rehabil. 85, 2020–2029 (2004).

    Article  Google Scholar 

  40. 40

    Maguire, E. A., Frackowiak, R. S. & Frith, C. D. Recalling routes around london: activation of the right hippocampus in taxi drivers. J. Neurosci. 17, 7103–7110 (1997).

    CAS  Article  Google Scholar 

  41. 41

    Naci, L., Cusack, R., Jia, Z., V. & Owen, M. A. The brain's silent messenger: using selective attention to decode human thought for brain-based communication. J. Neurosci. 33, 9385–9393 (2013).

    CAS  Article  Google Scholar 

  42. 42

    Naci, L. & Owen, A. M. Making every word count for nonresponsive patients. JAMA Neurol. http://dx.doi.org/10.1001/jamaneurol.2013.3686 (2013).

  43. 43

    Fins, J. J. & Schiff, N. D. Shades of gray: new insights into the vegetative state. Hastings Cent. Rep. 36, 8 (2006).

    Article  Google Scholar 

  44. 44

    Giacino, J. T., Schnakers, C. & Rodriguez-Moreno, D. Behavioral assessment in patients with disorders of consciousness: gold standard or fool's gold? Prog. Brain Res. 177, 33–48 (2009).

    Article  Google Scholar 

  45. 45

    Laureys, S. & Schiff, N. D. Coma and consciousness: paradigms (re)framed by neuroimaging. Neuroimage 61, 478–491 (2012).

    Article  Google Scholar 

  46. 46

    Schnakers, C. et al. Cognitive function in the locked-in syndrome. J. Neurol. 255, 323–330 (2008).

    Article  Google Scholar 

  47. 47

    Hampshire, A. et al. Assessing residual reasoning ability in overtly non-communicative patients using fMRI. Neuroimage Clin. 2, 174–183 (2013).

    Google Scholar 

  48. 48

    Fins, J. J. The ethics of measuring and modulating consciousness: the imperative of minding time. Prog. Brain Res. 177, 371–382 (2009).

    Article  Google Scholar 

  49. 49

    Kahane, G. & Savulescu, J. Brain damage and the moral significance of consciousness. J. Med. Philos. 34, 6–26 (2009).

    PubMed  PubMed Central  Google Scholar 

  50. 50

    Coleman, M. R. et al. Towards the routine use of brain imaging to aid the clinical diagnosis of disorders of consciousness. Brain 132, 2541–2552 (2009).

    CAS  Article  Google Scholar 

  51. 51

    Di, H., Boly, M., Weng, X., Ledoux, D. & Laureys, S. Neuroimaging activation studies in the vegetative state: predictors of recovery? Clin. Med. 8, 502–507 (2008).

    Article  Google Scholar 

  52. 52

    Bruno, M.-A. et al. A survey on self-assessed well-being in a cohort of chronic locked-in syndrome patients: happy majority, miserable minority. BMJ Open 1, e000039 (2011).

    Article  Google Scholar 

  53. 53

    Laureys, S. et al. The locked-in syndrome: what is it like to be conscious but paralyzed and voiceless? Prog. Brain Res. 150, 495–511 (2005).

    Article  Google Scholar 

  54. 54

    Council for International Organization of Medical Sciences. International ethical guidelines for biomedical research involving human subjects. (CIOMS, 2002).

  55. 55

    UK Medical Research Council. Human tissue and biological samples for use in research — operational and ethical guidelines. (MRC, 2001).

  56. 56

    Fernandez, C. V., Skedgel, C. & Weijer, C. Considerations and costs of disclosing study findings to research participants. CMAJ 170, 1417–1419 (2004).

    Article  Google Scholar 

  57. 57

    Reilly, P. When should an investigator share raw data with the subjects? IRB 2, 4–5+ (1980).

    Article  Google Scholar 

  58. 58

    Shalowitz, D. I. & Miller, F. G. Disclosing individual results of clinical research: implications of respect for participants. JAMA 294, 737–740 (2005).

    CAS  Article  Google Scholar 

  59. 59

    Partridge, A. H. & Winer, E. P. Informing clinical trial participants about study results. JAMA 288, 363–365 (2002).

    Article  Google Scholar 

  60. 60

    US National Bioethics Advisory Commission. Research involving human biological materials: ethical issues and policy guidance. (NBAC, 1999).

  61. 61

    Canadian Institutes of Health Research. CIHR best practices for protecting privacy in health research. (CIHR, 2005).

  62. 62

    Buchanan, A. E. & Brock, D. W. Deciding for Others: the Ethics of Surrogate Decision Making (Studies in Philosophy and Health Policy) (Cambridge Univ. Press,1989).

    Google Scholar 

  63. 63

    Peterson, A. et al. Assessing decision-making capacity in the behaviorally nonresponsive patient with residual covert awareness. AJOB Neurosci. 4, 3–14 (2013).

    Article  Google Scholar 

  64. 64

    Laureys, S. et al. Unresponsive wakefulness syndrome: a new name for the vegetative state or apallic syndrome. BMC Med. 8, 68 (2010).

    Article  Google Scholar 

  65. 65

    Owen, A. M. et al. Response to comments on 'Detecting awareness in the vegetative state'. Science 315, 1221 (2007).

    CAS  Article  Google Scholar 

  66. 66

    Bardin, J. C. et al. Dissociations between behavioural and functional magnetic resonance imaging-based evaluations of cognitive function after brain injury. Brain 134, 769–782 (2011).

    Article  Google Scholar 

  67. 67

    Naci, L. et al. Brain–computer interfaces for communication with nonresponsive patients. Ann. Neurol. 72, 312–323 (2012).

    Article  Google Scholar 

  68. 68

    Chatelle, C. et al. Brain–computer interfacing in disorders of consciousness. Brain Inj. 26, 1510–1522 (2012).

    Article  Google Scholar 

  69. 69

    Hochberg, L. R. et al. Reach and grasp by people with tetraplegia using a neurally controlled robotic arm. Nature 485, 372–375 (2012).

    CAS  Article  Google Scholar 

  70. 70

    Guenther, F. H. et al. A wireless brain–machine interface for real-time speech synthesis. PLoS ONE 4, e8218 (2009).

    Article  Google Scholar 

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Acknowledgements

We thank G. B. Young and D. Cruse for their expert advice and assistance regarding the patient described in detail in this Perspective. This work was funded by awards to A.M.O. from the Canada Excellence Research Chair (CERC) Programme, the Canadian Institutes of Health Research (CIHR) and the Natural Sciences and Engineering Research Council of Canada (NSERC).

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Correspondence to Davinia Fernández-Espejo or Adrian M. Owen.

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Structural imaging in the vegetative and minimally conscious states (PDF 211 kb)

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Fernández-Espejo, D., Owen, A. Detecting awareness after severe brain injury. Nat Rev Neurosci 14, 801–809 (2013). https://doi.org/10.1038/nrn3608

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