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Functional neuroanatomy underlying the clinical subcategorization of minimally conscious state patients

Journal of Neurology volume 259, pages 1087–1098 (2012)Cite this article

Abstract

Patients in a minimally conscious state (MCS) show restricted signs of awareness but are unable to communicate. We assessed cerebral glucose metabolism in MCS patients and tested the hypothesis that this entity can be subcategorized into MCS− (i.e., patients only showing nonreflex behavior such as visual pursuit, localization of noxious stimulation and/or contingent behavior) and MCS+ (i.e., patients showing command following).

Patterns of cerebral glucose metabolism were studied using [18F]-fluorodeoxyglucose-PET in 39 healthy volunteers (aged 46 ± 18 years) and 27 MCS patients of whom 13 were MCS− (aged 49 ± 19 years; 4 traumatic; 21 ± 23 months post injury) and 14 MCS+ (aged 43 ± 19 years; 5 traumatic; 19 ± 26 months post injury). Results were thresholded for significance at false discovery rate corrected p < 0.05.

We observed a metabolic impairment in a bilateral subcortical (thalamus and caudate) and cortical (fronto-temporo-parietal) network in nontraumatic and traumatic MCS patients. Compared to MCS−, patients in MCS+ showed higher cerebral metabolism in left-sided cortical areas encompassing the language network, premotor, presupplementary motor, and sensorimotor cortices. A functional connectivity study showed that Broca’s region was disconnected from the rest of the language network, mesiofrontal and cerebellar areas in MCS− as compared to MCS+ patients.

The proposed subcategorization of MCS based on the presence or absence of command following showed a different functional neuroanatomy. MCS− is characterized by preserved right hemispheric cortical metabolism interpreted as evidence of residual sensory consciousness. MCS+ patients showed preserved metabolism and functional connectivity in language networks arguably reflecting some additional higher order or extended consciousness albeit devoid of clinical verbal or nonverbal expression.

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References

  1. Giacino JT, Ashwal S, Childs N et al (2002) The minimally conscious state: definition and diagnostic criteria. Neurology 58:349–353

    PubMed  Article  Google Scholar 

  2. Bruno MA, Vanhaudenhuyse A, Thibaut A et al (2011) From unresponsive wakefulness to minimally conscious PLUS and functional locked-in syndromes: recent advances in our understanding of disorders of consciousness. J Neurol

  3. Laureys S, Goldman S, Phillips C et al (1999) Impaired effective cortical connectivity in vegetative state: preliminary investigation using PET. Neuroimage 9:377–382

    PubMed  Article  CAS  Google Scholar 

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

    PubMed  Article  Google Scholar 

  5. Laureys S, Faymonville ME, Degueldre C et al (2000) Auditory processing in the vegetative state. Brain 123:1589–1601

    PubMed  Article  Google Scholar 

  6. Friston KJ, Penny WD, Glaser DE (2005) Conjunction revisited. Neuroimage 25:661–667

    PubMed  Article  Google Scholar 

  7. Genovese CR, Lazar NA, Nichols T (2002) Thresholding of statistical maps in functional neuroimaging using the false discovery rate. Neuroimage 15:870–878

    PubMed  Article  Google Scholar 

  8. Nakayama N, Okumura A, Shinoda J et al (2006) Relationship between regional cerebral metabolism and consciousness disturbance in traumatic diffuse brain injury without large focal lesions: an FDG-PET study with statistical parametric mapping analysis. J Neurol Neurosurg Psychiatr 77:856–862

    PubMed  Article  CAS  Google Scholar 

  9. Rudolf J, Ghaemi M, Ghaemi M et al (1999) Cerebral glucose metabolism in acute and persistent vegetative state. J Neurosurg Anesthesiol 11:17–24

    PubMed  Article  CAS  Google Scholar 

  10. Voss HU, Uluc AM, Dyke JP et al (2006) Possible axonal regrowth in late recovery from the minimally conscious state. J Clin Invest 116:2005–2011

    PubMed  Article  CAS  Google Scholar 

  11. Vanhaudenhuyse A, Noirhomme Q, Tshibanda LJ et al (2010) Default network connectivity reflects the level of consciousness in non-communicative brain-damaged patients. Brain 133:161–171

    PubMed  Article  Google Scholar 

  12. Laureys S (2005) The neural correlate of (un)awareness: lessons from the vegetative state. Trends Cogn Sci 9:556–559

    PubMed  Article  Google Scholar 

  13. Boly M, Faymonville ME, Schnakers C et al (2008) Perception of pain in the minimally conscious state with PET activation: an observational study. Lancet Neurol 7:1013–1020

    PubMed  Article  Google Scholar 

  14. Laureys S, Faymonville ME, Peigneux P et al (2002) Cortical processing of noxious somatosensory stimuli in the persistent vegetative state. Neuroimage 17:732–741

    PubMed  Article  CAS  Google Scholar 

  15. Boly M, Faymonville ME, Peigneux P et al (2004) Auditory processing in severely brain injured patients: differences between the minimally conscious state and the persistent vegetative state. Arch Neurol 61:233–238

    PubMed  Article  Google Scholar 

  16. Coleman MR, Rodd JM, Davis MH et al (2007) Do vegetative patients retain aspects of language comprehension? Evidence from fMRI. Brain 130:2494–2507

    PubMed  Article  Google Scholar 

  17. Laureys S, Perrin F, Faymonville ME et al (2004) Cerebral processing in the minimally conscious state. Neurology 63:916–918

    PubMed  Article  CAS  Google Scholar 

  18. Schiff ND, Rodriguez-Moreno D, Kamal A et al (2005) fMRI reveals large-scale network activation in minimally conscious patients. Neurology 64:514–523

    PubMed  Article  CAS  Google Scholar 

  19. Bruno MA, Vanhaudenhuyse A, Schnakers C et al (2010) Visual fixation in the vegetative state: an observational case series PET study. BMC Neurol 10:35

    PubMed  Article  Google Scholar 

  20. Kentridge RW, Nijboer TC, Heywood CA (2008) Attended but unseen: visual attention is not sufficient for visual awareness. Neuropsychologia 46:864–869

    PubMed  Article  CAS  Google Scholar 

  21. Tamietto M, Cauda F, Corazzini LL et al (2009) Collicular vision guides nonconscious behavior. J Cogn Neurosci 22:888–902

    Article  Google Scholar 

  22. Moreno DR, Schiff ND, Giacino J et al (2010) A network approach to assessing cognition in disorders of consciousness. Neurology 75:1871–1878

    Article  Google Scholar 

  23. Longoni F, Grande M, Hendrich V et al (2005) An fMRI study on conceptual, grammatical, and morpho-phonological processing. Brain Cogn 57:131–134

    PubMed  Article  Google Scholar 

  24. Vigneau M, Beaucousin V, Herve PY et al (2006) Meta-analyzing left hemisphere language areas: phonology, semantics, and sentence processing. Neuroimage 30:1414–1432

    PubMed  Article  CAS  Google Scholar 

  25. Davis MH, Johnsrude IS (2003) Hierarchical processing in spoken language comprehension. J Neurosci 23:3423–3431

    PubMed  CAS  Google Scholar 

  26. Hickok G, Poeppel D (2007) The cortical organization of speech processing. Nat Rev Neurosci 8:393–402

    PubMed  Article  CAS  Google Scholar 

  27. Riecker A, Mathiak K, Wildgruber D et al (2005) fMRI reveals two distinct cerebral networks subserving speech motor control. Neurology 64:700–706

    PubMed  Article  CAS  Google Scholar 

  28. Zhang J, Mitsis EM, Chu K, Newmark RE et al (2010) Statistical parametric mapping and cluster counting analysis of [18F] FDG-PET imaging in traumatic brain injury. J Neurotrauma 27(1):35–49

    PubMed  Article  Google Scholar 

  29. Gabrieli JD, Poldrack RA, Desmond JE (1998) The role of left prefrontal cortex in language and memory. Proc Natl Acad Sci USA. 95:906–913

    PubMed  Article  CAS  Google Scholar 

  30. Haggard P (2008) Human volition: towards a neuroscience of will. Nat Rev Neurosci 9:934–946

    PubMed  Article  CAS  Google Scholar 

  31. Haaland KY, Elsinger CL, Mayer AR et al (2004) Motor sequence complexity and performing hand produce differential patterns of hemispheric lateralization. J Cogn Neurosci 16:621–636

    PubMed  Article  Google Scholar 

  32. Gainotti G (2001) Disorders of emotional behaviour. J Neurol 248:743–749

    PubMed  Article  CAS  Google Scholar 

  33. Rushworth MF, Johansen-Berg H, Gobel SM et al (2003) The left parietal and premotor cortices: motor attention and selection. Neuroimage 20(Suppl 1):S89–S100

    PubMed  Article  Google Scholar 

  34. Gazzaniga MS (2000) Cerebral specialization and interhemispheric communication: does the corpus callosum enable the human condition? Brain 123(Pt 7):1293–1326

    PubMed  Article  Google Scholar 

  35. Turk DJ, Heatherton TF, Macrae CN et al (2003) Out of contact, out of mind: the distributed nature of the self. Ann NY Acad Sci 1001:65–78

    PubMed  Article  Google Scholar 

  36. Damasio AR (1998) Investigating the biology of consciousness. Philos Trans R Soc Lond B Biol Sci 353:1879–1882

    PubMed  Article  CAS  Google Scholar 

  37. Edelman GM (2004) Wider than the sky: The phenomenal gift of consciousness. Yale University Press, New Haven and London

    Google Scholar 

  38. Laureys S, Perrin F, Bredart S (2007) Self-consciousness in non-communicative patients. Conscious Cogn 16:722–741 (discussion 742–745)

    PubMed  Article  Google Scholar 

  39. Seth AK, Dienes Z, Cleeremans A et al (2008) Measuring consciousness: relating behavioural and neurophysiological approaches. Trends Cogn Sci 12:314–321

    PubMed  Article  Google Scholar 

  40. Majerus S, Bruno MA, Schnakers C et al (2009) The problem of aphasia in the assessment of consciousness in brain-damaged patients. Prog Brain Res 177:49–61

    PubMed  Article  Google Scholar 

  41. Monti MM, Vanhaudenhuyse A, Coleman MR et al (2010) Willful modulation of brain activity in disorders of consciousness. N. Engl J Med 362(7):579–589

    PubMed  Article  CAS  Google Scholar 

  42. Boly M, Garrido MA, Gosseries O et al (2011) Preserved feedforward but impaired top-down processes in the vegetative state. Science 332:858–862

    PubMed  Article  CAS  Google Scholar 

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Acknowledgments

The funding sources had no role in the study design, data collection, data analysis, data interpretation, or writing of this report. All authors had full access to all the data in the study and had final responsibility for the decision to submit for publication. This research was funded by the Belgian National Funds for Scientific Research (FNRS), the European Commission (Mindbridge, DISCOS, Marie-Curie Actions, DECODER & COST), the James McDonnell Foundation, the Mind Science Foundation, the French Speaking Community Concerted Research Action (ARC-06/11-340), the Fondation Médicale Reine Elisabeth, and the University of Liège. SL and MAB participated in the conception and design of this study. MAB, AV, CS, OG, PB, and MK acquired the data. SL, MAB, and MB analyzed and interpreted the data. MAB and SL drafted the manuscript. AV, CS, AD, OG, MS, GM, and RH revised the manuscript for intellectual content. SL and GM obtained funding. RH and GM provided administrative, technical, or material support, and SL supervised the study.

Conflict of interest

The authors declare that they have no competing interests.

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Affiliations

  1. Coma Science Group, Cyclotron Research Center, University of Liège, Sart-Tilman B30, 4000, Liège, Belgium

    Marie-Aurélie Bruno, Mélanie Boly, Audrey Vanhaudenhuyse, Caroline Schnakers, Olivia Gosseries, Pierre Boveroux, Murielle Kirsch, Athena Demertzi, Gustave Moonen & Steven Laureys

  2. Department of Neurology, University Hospital of Liège, Liège, Belgium

    Mélanie Boly, Gustave Moonen & Steven Laureys

  3. Research Center for Cognitive and Behavioral Neuroscience, University of Liège, Liège, Belgium

    Steve Majerus

  4. Department of Nuclear Medicine, University Hospital of Liège, Liège, Belgium

    Claire Bernard & Roland Hustinx

  5. Fund for Scientific Research FNRS, Brussels, Belgium

    Marie-Aurélie Bruno, Steve Majerus, Mélanie Boly, Audrey Vanhaudenhuyse, Caroline Schnakers, Olivia Gosseries & Steven Laureys

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  1. Marie-Aurélie Bruno
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  2. Steve Majerus
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  3. Mélanie Boly
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  4. Audrey Vanhaudenhuyse
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  13. Steven Laureys
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Correspondence to Steven Laureys.

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Bruno, MA., Majerus, S., Boly, M. et al. Functional neuroanatomy underlying the clinical subcategorization of minimally conscious state patients. J Neurol 259, 1087–1098 (2012). https://doi.org/10.1007/s00415-011-6303-7

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  • DOI: https://doi.org/10.1007/s00415-011-6303-7

Keywords

  • Coma
  • Consciousness
  • Minimally conscious state
  • Positron-emission tomography
  • Neuroanatomy