Functional MRI and Outcome in Traumatic Coma

  • Brian L. EdlowEmail author
  • Joseph T. Giacino
  • Ona Wu
Neurotrauma (J Levine)
Part of the following topical collections:
  1. Topical Collection on Neurotrauma


Advances in task-based functional MRI (fMRI), resting-state fMRI (rs-fMRI), and arterial spin labeling (ASL) perfusion MRI have occurred at a rapid pace in recent years. These techniques for measuring brain function have great potential to improve the accuracy of prognostication for civilian and military patients with traumatic coma. In addition, fMRI, rs-fMRI, and ASL perfusion MRI have provided novel insights into the pathophysiology of traumatic disorders of consciousness, as well as the mechanisms of recovery from coma. However, functional neuroimaging techniques have yet to achieve widespread clinical use as prognostic tests for patients with traumatic coma. Rather, a broad spectrum of methodological hurdles currently limits the feasibility of clinical implementation. In this review, we discuss the basic principles of fMRI, rs-fMRI, and ASL perfusion MRI and their potential applications as prognostic tools for patients with traumatic coma. We also discuss future strategies for overcoming the current barriers to clinical implementation.


Traumatic brain injury Traumatic axonal injury Coma Functional MRI Resting-state functional MRI Arterial spin labeling perfusion MRI Default mode network Traumatic coma 



The contents of this article were developed with support from the National Institutes of Health (R25NS065743), the Center for Integration of Medicine and Innovative Technology (Boston, MA, USA), and the National Institute on Disability and Rehabilitation Research, United States Department of Education (H133A120085; Spaulding–Harvard Traumatic Brain Injury Model System). However, the contents do not necessarily represent the policy of the Department of Education, and endorsement by the federal government should not be assumed.

Compliance with Ethics Guidelines

Conflict of Interest

Brian L. Edlow and Ona Wu declare that they have no conflict of interest.

Joseph T. Giacino has been a consultant for Craig Rehabilitation Hospital and Frazier Rehabilitation Hospital, has served as an expert witness consultant on five legal cases in the last 36 months involving patients with disorders of consciousness concerning diagnosis, prognosis, pain and suffering, and adequacy of treatment, and has received grant support from the James S. McDonnell Foundation.

Human and Animal Rights and Informed Consent

This article contains imaging data from a human subject that were acquired as part of a study approved by our hospital's Institutional Review Board. Informed consent for the study was provided by the subject's legal guardian.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Bruns Jr J, Hauser WA. The epidemiology of traumatic brain injury: a review. Epilepsia. 2003;44 Suppl 10:2–10.PubMedCrossRefGoogle Scholar
  2. 2.
    Faul M, Xu L, Wald MM, et al. Traumatic brain injury in the United States: emergency department visits, hospitalizations, and deaths. Atlanta: Centers for Disease Control and Prevention, National Center for Injury Prevention and Control; 2010.Google Scholar
  3. 3.
    Perel P, Arango M, Clayton T, et al. Predicting outcome after traumatic brain injury: practical prognostic models based on large cohort of international patients. BMJ. 2008;336:425–9.PubMedCrossRefGoogle Scholar
  4. 4.
    Bell RS, Vo AH, Neal CJ, et al. Military traumatic brain and spinal column injury: a 5-year study of the impact blast and other military grade weaponry on the central nervous system. J Trauma. 2009;66:S104–11.PubMedCrossRefGoogle Scholar
  5. 5.
    DuBose JJ, Barmparas G, Inaba K, et al. Isolated severe traumatic brain injuries sustained during combat operations: demographics, mortality outcomes, and lessons to be learned from contrasts to civilian counterparts. J Trauma. 2011;70:11–6. discussion 16-8.PubMedCrossRefGoogle Scholar
  6. 6.
    Jennett B, Plum F. Persistent vegetative state after brain damage. A syndrome in search of a name. Lancet. 1972;1:734–7.PubMedCrossRefGoogle Scholar
  7. 7.
    Giacino JT, Ashwal S, Childs N, et al. The minimally conscious state: definition and diagnostic criteria. Neurology. 2002;58:349–53.PubMedCrossRefGoogle Scholar
  8. 8.
    Katz DI, Polyak M, Coughlan D, et al. Natural history of recovery from brain injury after prolonged disorders of consciousness: outcome of patients admitted to inpatient rehabilitation with 1-4 year follow-up. Prog Brain Res. 2009;177:73–88.PubMedCrossRefGoogle Scholar
  9. 9.
    Zoroya G. For troops with brain trauma, a long journey back. Tampa: USA Today; 2010.
  10. 10.
    Nakase-Richardson R, Whyte J, Giacino JT, et al. Longitudinal outcome of patients with disordered consciousness in the NIDRR TBI Model Systems programs. J Neurotrauma. 2012;29:59–65.PubMedCrossRefGoogle Scholar
  11. 11.
    McNamee S, Howe L, Nakase-Richardson R, et al. Treatment of disorders of consciousness in the Veterans Health Administration polytrauma centers. J Head Trauma Rehabil. 2012;27:244–52.PubMedCrossRefGoogle Scholar
  12. 12.
    Skandsen T, Kvistad KA, Solheim O, et al. Prognostic value of magnetic resonance imaging in moderate and severe head injury: a prospective study of early MRI findings and one-year outcome. J Neurotrauma. 2011;28:691–9.PubMedCrossRefGoogle Scholar
  13. 13.
    Gennarelli TA, Spielman GM, Langfitt TW, et al. Influence of the type of intracranial lesion on outcome from severe head injury. J Neurosurg. 1982;56:26–32.PubMedCrossRefGoogle Scholar
  14. 14.
    Lammi MH, Smith VH, Tate RL, et al. The minimally conscious state and recovery potential: a follow-up study 2 to 5 years after traumatic brain injury. Arch Phys Med Rehabil. 2005;86:746–54.PubMedCrossRefGoogle Scholar
  15. 15.
    Estraneo A, Moretta P, Loreto V, et al. Late recovery after traumatic, anoxic, or hemorrhagic long-lasting vegetative state. Neurology. 2010;75:239–45.PubMedCrossRefGoogle Scholar
  16. 16.
    Luaute J, Maucort-Boulch D, Tell L, et al. Long-term outcomes of chronic minimally conscious and vegetative states. Neurology. 2010;75:246–52.PubMedCrossRefGoogle Scholar
  17. 17.
    Murray GD, Butcher I, McHugh GS, et al. Multivariable prognostic analysis in traumatic brain injury: results from the IMPACT study. J Neurotrauma. 2007;24:329–37.PubMedCrossRefGoogle Scholar
  18. 18.
    Firsching R, Woischneck D, Diedrich M, et al. Early magnetic resonance imaging of brainstem lesions after severe head injury. J Neurosurg. 1998;89:707–12.PubMedCrossRefGoogle Scholar
  19. 19.
    Lagares A, Ramos A, Perez-Nunez A, et al. The role of MR imaging in assessing prognosis after severe and moderate head injury. Acta Neurochir. 2009;151:341–56.PubMedCrossRefGoogle Scholar
  20. 20.
    Edlow BL, Wu O. Advanced neuroimaging in traumatic brain injury. Semin Neurol. 2012;32:372–98.Google Scholar
  21. 21.
    Andrews K, Murphy L, Munday R, et al. Misdiagnosis of the vegetative state: retrospective study in a rehabilitation unit. BMJ. 1996;313:13–6.PubMedCrossRefGoogle Scholar
  22. 22.
    Childs NL, Mercer WN, Childs HW. Accuracy of diagnosis of persistent vegetative state. Neurology. 1993;43:1465–7.PubMedCrossRefGoogle Scholar
  23. 23.
    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;9:35.PubMedCrossRefGoogle Scholar
  24. 24.
    Giacino JT, Kalmar K, Whyte J. The JFK Coma Recovery Scale-Revised: measurement characteristics and diagnostic utility. Arch Phys Med Rehabil. 2004;85:2020–9.PubMedCrossRefGoogle Scholar
  25. 25.
    Giacino JT, Kalmar K. The vegetative and minimally conscious states: a comparison of clinical features and functional outcome. J Head Trauma Rehabil. 1997;12:36–51.CrossRefGoogle Scholar
  26. 26.
    Giacino JT, Whyte J, Bagiella E, et al. Placebo-controlled trial of amantadine for severe traumatic brain injury. N Engl J Med. 2012;366:819–26.PubMedCrossRefGoogle Scholar
  27. 27.
    Whyte J, Myers R. Incidence of clinically significant responses to zolpidem among patients with disorders of consciousness: a preliminary placebo controlled trial. Am J Phys Med Rehabil. 2009;88:410–8.PubMedCrossRefGoogle Scholar
  28. 28.
    Schiff ND, Giacino JT, Kalmar K, et al. Behavioural improvements with thalamic stimulation after severe traumatic brain injury. Nature. 2007;448:600–3.PubMedCrossRefGoogle Scholar
  29. 29.
    Kwong KK, Belliveau JW, Chesler DA, et al. Dynamic magnetic resonance imaging of human brain activity during primary sensory stimulation. Proc Natl Acad Sci USA. 1992;89:5675–9.PubMedCrossRefGoogle Scholar
  30. 30.
    Ogawa S, Tank DW, Menon R, et al. Intrinsic signal changes accompanying sensory stimulation: functional brain mapping with magnetic resonance imaging. Proc Natl Acad Sci USA. 1992;89:5951–5.PubMedCrossRefGoogle Scholar
  31. 31.
    Detre JA, Wang J. Technical aspects and utility of fMRI using BOLD and ASL. Clin Neurophysiol. 2002;113:621–34.PubMedCrossRefGoogle Scholar
  32. 32.
    Laureys S, Schiff ND. Coma and consciousness: paradigms (re)framed by neuroimaging. NeuroImage. 2012;61:478–91.PubMedCrossRefGoogle Scholar
  33. 33.
    Donaldson DI, Buckner RL. Effective paradigm design. In: Jezzard P, Matthews PM, Smith SM, editors. Functional MRI: an introduction to methods. Oxford: Oxford University Press; 2001.Google Scholar
  34. 34.
    Kasahara M, Menon DK, Salmond CH, et al. Traumatic brain injury alters the functional brain network mediating working memory. Brain Inj. 2011;25:1170–87.PubMedCrossRefGoogle Scholar
  35. 35.
    Palacios EM, Sala-Llonch R, Junque C, et al. White matter integrity related to functional working memory networks in traumatic brain injury. Neurology. 2012;78:852–60.PubMedCrossRefGoogle Scholar
  36. 36.
    Kasahara M, Menon DK, Salmond CH, et al. Altered functional connectivity in the motor network after traumatic brain injury. Neurology. 2010;75:168–76.PubMedCrossRefGoogle Scholar
  37. 37.
    Newsome MR, Scheibel RS, Hanten G, et al. Brain activation while thinking about the self from another person's perspective after traumatic brain injury in adolescents. Neuropsychology. 2010;24:139–47.PubMedCrossRefGoogle Scholar
  38. 38.
    Owen AM, Coleman MR, Boly M, et al. Detecting awareness in the vegetative state. Science. 2006;313:1402.PubMedCrossRefGoogle Scholar
  39. 39.
    Newcombe VF, Williams GB, Scoffings D, et al. Aetiological differences in neuroanatomy of the vegetative state: insights from diffusion tensor imaging and functional implications. J Neurol Neurosurg Psychiatry. 2010;81:552–61.PubMedCrossRefGoogle Scholar
  40. 40.
    • Coleman MR, Davis MH, Rodd JM, et al. Towards the routine use of brain imaging to aid the clinical diagnosis of disorders of consciousness. Brain. 2009;132:2541–52. In this fMRI study of 41 patients in a VS (n = 22) and an MCS (n = 19), a passive language stimulus was used to investigate language networks. Hierarchical language-related fMRI activation patterns correlated with the degree of behavioral recovery 6 months after the fMRI scan.PubMedCrossRefGoogle Scholar
  41. 41.
    Coleman MR, Rodd JM, Davis MH, et al. Do vegetative patients retain aspects of language comprehension? Evidence from fMRI. Brain. 2007;130:2494–507.PubMedCrossRefGoogle Scholar
  42. 42.
    Monti MM, Pickard JD, Owen AM. Visual cognition in disorders of consciousness: From V1 to top-down attention. Hum Brain Mapp. 2013;34:1245–53.PubMedCrossRefGoogle Scholar
  43. 43.
    Rodriguez Moreno D, Schiff ND, Giacino J, et al. A network approach to assessing cognition in disorders of consciousness. Neurology. 2010;75:1871–8.PubMedCrossRefGoogle Scholar
  44. 44.
    Schiff ND, Rodriguez-Moreno D, Kamal A, et al. fMRI reveals large-scale network activation in minimally conscious patients. Neurology. 2005;64:514–23.PubMedCrossRefGoogle Scholar
  45. 45.
    Fernandez-Espejo D, Junque C, Vendrell P, et al. Cerebral response to speech in vegetative and minimally conscious states after traumatic brain injury. Brain Inj. 2008;22:882–90.PubMedCrossRefGoogle Scholar
  46. 46.
    Bekinschtein T, Leiguarda R, Armony J, et al. Emotion processing in the minimally conscious state. J Neurol Neurosurg Psychiatry. 2004;75:788.PubMedCrossRefGoogle Scholar
  47. 47.
    Bekinschtein T, Tiberti C, Niklison J, et al. Assessing level of consciousness and cognitive changes from vegetative state to full recovery. Neuropsychol Rehabil. 2005;15:307–22.PubMedCrossRefGoogle Scholar
  48. 48.
    Di HB, Yu SM, Weng XC, et al. Cerebral response to patient's own name in the vegetative and minimally conscious states. Neurology. 2007;68:895–9.PubMedCrossRefGoogle Scholar
  49. 49.
    Zhu J, Wu X, Gao L, et al. Cortical activity after emotional visual stimulation in minimally conscious state patients. J Neurotrauma. 2009;26:677–88.PubMedCrossRefGoogle Scholar
  50. 50.
    Qin P, Di H, Liu Y, et al. Anterior cingulate activity and the self in disorders of consciousness. Hum Brain Mapp. 2010;31:1993–2002.PubMedCrossRefGoogle Scholar
  51. 51.
    Fernandez-Espejo D, Junque C, Cruse D, et al. Combination of diffusion tensor and functional magnetic resonance imaging during recovery from the vegetative state. BMC Neurol. 2010;10:77.PubMedCrossRefGoogle Scholar
  52. 52.
    Heelmann V, Lippert-Gruner M, Rommel T, et al. Abnormal functional MRI BOLD contrast in the vegetative state after severe traumatic brain injury. Int J Rehabil Res. 2010;33:151–7.PubMedCrossRefGoogle Scholar
  53. 53.
    •• Monti MM, Vanhaudenhuyse A, Coleman MR, et al. Willful modulation of brain activity in disorders of consciousness. N Engl J Med. 2010;362:579–89. This study includes the largest cohort of patients with DOC to be assessed with spatial and motor imagery fMRI paradigms (n = 54). Five of 54 patients (all with TBI) had patterns of brain activation during the command-following paradigms that were similar to those of controls, and one patient in an MCS could link the two imagery tasks to “yes” and “no” answers.PubMedCrossRefGoogle Scholar
  54. 54.
    Bekinschtein TA, Manes FF, Villarreal M, et al. Functional imaging reveals movement preparatory activity in the vegetative state. Front Hum Neurosci. 2011;5:5.PubMedCrossRefGoogle Scholar
  55. 55.
    Bardin JC, Fins JJ, Katz DI, et al. Dissociations between behavioural and functional magnetic resonance imaging-based evaluations of cognitive function after brain injury. Brain. 2011;134:769–82.PubMedCrossRefGoogle Scholar
  56. 56.
    Bardin JC, Schiff ND, Voss HU. Pattern classification of volitional functional magnetic resonance imaging responses in patients with severe brain injury. Arch Neurol. 2012;69:176–81.PubMedCrossRefGoogle Scholar
  57. 57.
    Raichle ME, MacLeod AM, Snyder AZ, et al. A default mode of brain function. Proc Natl Acad Sci USA. 2001;98:676–82.PubMedCrossRefGoogle Scholar
  58. 58.
    Raichle ME, Snyder AZ. A default mode of brain function: a brief history of an evolving idea. NeuroImage. 2007;37:1083–90. discussion 97-9.PubMedCrossRefGoogle Scholar
  59. 59.
    Shulman GL, Fiez JA, Corbetta M, et al. Common blood flow changes across visual tasks: II. Decreases in cerebral cortex. J Cogn Neurosci. 1997;9:648–63.CrossRefGoogle Scholar
  60. 60.
    Binder JR, Frost JA, Hammeke TA, et al. Conceptual processing during the conscious resting state. A functional MRI study. J Cogn Neurosci. 1999;11:80–95.PubMedCrossRefGoogle Scholar
  61. 61.
    Seeley WW, Menon V, Schatzberg AF, et al. Dissociable intrinsic connectivity networks for salience processing and executive control. J Neurosci. 2007;27:2349–56.PubMedCrossRefGoogle Scholar
  62. 62.
    Tang L, Ge Y, Sodickson DK, et al. Thalamic resting-state functional networks: disruption in patients with mild traumatic brain injury. Radiology. 2011;260:831–40.PubMedCrossRefGoogle Scholar
  63. 63.
    Fox MD, Snyder AZ, Vincent JL, et al. The human brain is intrinsically organized into dynamic, anticorrelated functional networks. Proc Natl Acad Sci USA. 2005;102:9673–8.PubMedCrossRefGoogle Scholar
  64. 64.
    Biswal B, Yetkin FZ, Haughton VM, et al. Functional connectivity in the motor cortex of resting human brain using echo-planar MRI. Magn Reson Med. 1995;34:537–41.PubMedCrossRefGoogle Scholar
  65. 65.
    Fox MD, Greicius M. Clinical applications of resting state functional connectivity. Front Syst Neurosci. 2010;4:19.PubMedGoogle Scholar
  66. 66.
    Beckmann CF, Smith SM. Probabilistic independent component analysis for functional magnetic resonance imaging. IEEE Trans Med Imaging. 2004;23:137–52.PubMedCrossRefGoogle Scholar
  67. 67.
    Boly M, Phillips C, Tshibanda L, et al. Intrinsic brain activity in altered states of consciousness: how conscious is the default mode of brain function? Ann N Y Acad Sci. 2008;1129:119–29.PubMedCrossRefGoogle Scholar
  68. 68.
    Biswal BB, Mennes M, Zuo XN, et al. Toward discovery science of human brain function. Proc Natl Acad Sci USA. 2010;107:4734–9.PubMedCrossRefGoogle Scholar
  69. 69.
    Buckner RL, Andrews-Hanna JR, Schacter DL. The brain's default network: anatomy, function, and relevance to disease. Ann N Y Acad Sci. 2008;1124:1–38.PubMedCrossRefGoogle Scholar
  70. 70.
    Fransson P, Marrelec G. The precuneus/posterior cingulate cortex plays a pivotal role in the default mode network: evidence from a partial correlation network analysis. NeuroImage. 2008;42:1178–84.PubMedCrossRefGoogle Scholar
  71. 71.
    Sharp DJ, Beckmann CF, Greenwood R, et al. Default mode network functional and structural connectivity after traumatic brain injury. Brain. 2011;134:2233–47.PubMedCrossRefGoogle Scholar
  72. 72.
    Hillary FG, Slocomb J, Hills EC, et al. Changes in resting connectivity during recovery from severe traumatic brain injury. Int J Psychophysiol. 2011;82:115–23.PubMedCrossRefGoogle Scholar
  73. 73.
    Bonnelle V, Leech R, Kinnunen KM, et al. Default mode network connectivity predicts sustained attention deficits after traumatic brain injury. J Neurosci. 2011;31:13442–51.PubMedCrossRefGoogle Scholar
  74. 74.
    Bonnelle V, Ham TE, Leech R, et al. Salience network integrity predicts default mode network function after traumatic brain injury. Proc Natl Acad Sci USA. 2012;109:4690–5.PubMedCrossRefGoogle Scholar
  75. 75.
    Cauda F, Micon BM, Sacco K, et al. Disrupted intrinsic functional connectivity in the vegetative state. J Neurol Neurosurg Psychiatry. 2009;80:429–31.PubMedCrossRefGoogle Scholar
  76. 76.
    • Vanhaudenhuyse A, Noirhomme Q, Tshibanda LJ, et al. Default network connectivity reflects the level of consciousness in non-communicative brain-damaged patients. Brain. 2010;133:161–71. In this rs-fMRI study of patients in a coma (n = 5), in a VS (n = 4), in an MCS (n = 4), and with locked-in syndrome (n = 1), the strength of functional connectivity within the DMN correlated linearly with the level of consciousness.PubMedCrossRefGoogle Scholar
  77. 77.
    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.PubMedCrossRefGoogle Scholar
  78. 78.
    Teipel SJ, Bokde AL, Meindl T, et al. White matter microstructure underlying default mode network connectivity in the human brain. NeuroImage. 2010;49:2021–32.PubMedCrossRefGoogle Scholar
  79. 79.
    Greicius MD, Supekar K, Menon V, et al. Resting-state functional connectivity reflects structural connectivity in the default mode network. Cereb Cortex. 2009;19:72–8.PubMedCrossRefGoogle Scholar
  80. 80.
    Yan C, Liu D, He Y, et al. Spontaneous brain activity in the default mode network is sensitive to different resting-state conditions with limited cognitive load. PLoS One. 2009;4:e5743.PubMedCrossRefGoogle Scholar
  81. 81.
    Jo HJ, Saad ZS, Simmons WK, et al. Mapping sources of correlation in resting state FMRI, with artifact detection and removal. NeuroImage. 2010;52:571–82.PubMedCrossRefGoogle Scholar
  82. 82.
    Fernandez-Seara MA, Edlow BL, Hoang A, et al. Minimizing acquisition time of arterial spin labeling at 3T. Magn Reson Med. 2008;59:1467–71.PubMedCrossRefGoogle Scholar
  83. 83.
    Chen Y, Wang DJ, Detre JA. Test-retest reliability of arterial spin labeling with common labeling strategies. J Magn Reson Imaging. 2011;33:940–9.PubMedCrossRefGoogle Scholar
  84. 84.
    Kim J, Whyte J, Patel S, et al. Methylphenidate modulates sustained attention and cortical activation in survivors of traumatic brain injury: a perfusion fMRI study. Psychopharmacology. 2012;222:47–57.PubMedCrossRefGoogle Scholar
  85. 85.
    Kim J, Whyte J, Patel S, et al. Resting cerebral blood flow alterations in chronic traumatic brain injury: an arterial spin labeling perfusion FMRI study. J Neurotrauma. 2010;27:1399–411.PubMedCrossRefGoogle Scholar
  86. 86.
    Kim J, Whyte J, Patel S, et al. A perfusion fMRI study of the neural correlates of sustained-attention and working-memory deficits in chronic traumatic brain injury. Neurorehabil Neural Repair. 2012;26:870–80.PubMedCrossRefGoogle Scholar
  87. 87.
    • Liu AA, Voss HU, Dyke JP, et al. Arterial spin labeling and altered cerebral blood flow patterns in the minimally conscious state. Neurology. 2011;77:1518–23. In this ASL perfusion MRI study of patients in a traumatic MCS, CBF was preserved in the precuneus/posterior cingulate region but was decreased in the anterior nodes of the DMN (e.g., medial prefrontal cortex).PubMedCrossRefGoogle Scholar
  88. 88.
    Laureys S, Lemaire C, Maquet P, et al. Cerebral metabolism during vegetative state and after recovery to consciousness. J Neurol Neurosurg Psychiatry. 1999;67:121.PubMedCrossRefGoogle Scholar
  89. 89.
    Silva S, Alacoque X, Fourcade O, et al. Wakefulness and loss of awareness: brain and brainstem interaction in the vegetative state. Neurology. 2010;74:313–20.PubMedCrossRefGoogle Scholar
  90. 90.
    Brown EN, Lydic R, Schiff ND. General anesthesia, sleep, and coma. N Engl J Med. 2010;363:2638–50.PubMedCrossRefGoogle Scholar
  91. 91.
    Greicius MD, Kiviniemi V, Tervonen O, et al. Persistent default-mode network connectivity during light sedation. Hum Brain Mapp. 2008;29:839–47.PubMedCrossRefGoogle Scholar
  92. 92.
    Fukunaga M, Horovitz SG, van Gelderen P, et al. Large-amplitude, spatially correlated fluctuations in BOLD fMRI signals during extended rest and early sleep stages. Magn Reson Imaging. 2006;24:979–92.PubMedCrossRefGoogle Scholar
  93. 93.
    Wager TD, Atlas LY, Lindquist MA, et al. An fMRI-based neurologic signature of physical pain. N Engl J Med. 2013;368:1388–97.PubMedCrossRefGoogle Scholar
  94. 94.
    Moruzzi G, Magoun HW. Brain stem reticular formation and activation of the EEG. Electroencephalogr Clin Neurophysiol. 1949;1:455–73.PubMedGoogle Scholar
  95. 95.
    Steriade M. Arousal: revisiting the reticular activating system. Science. 1996;272:225–6.PubMedCrossRefGoogle Scholar
  96. 96.
    Edlow BL, Takahashi E, Wu O, et al. Neuroanatomic connectivity of the human ascending arousal system critical to consciousness and its disorders. J Neuropathol Exp Neurol. 2012;71:531–46.PubMedCrossRefGoogle Scholar
  97. 97.
    Edlow BL, Haynes RL, Takahashi E, et al. Disconnection of the ascending arousal system in traumatic coma. J Neuropathol Exp Neurol. 2013;72:505–23.PubMedCrossRefGoogle Scholar
  98. 98.
    Parvizi J, Damasio AR. Neuroanatomical correlates of brainstem coma. Brain. 2003;126:1524–36.PubMedCrossRefGoogle Scholar
  99. 99.
    Mazziotta J, Toga A, Evans A, et al. A probabilistic atlas and reference system for the human brain: International Consortium for Brain Mapping (ICBM). Philos Trans R Soc Lond B Biol Sci. 2001;356:1293–322.PubMedCrossRefGoogle Scholar
  100. 100.
    Ovadia-Caro S, Nir Y, Soddu A, et al. Reduction in inter-hemispheric connectivity in disorders of consciousness. PLoS One. 2012;7:e37238.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Department of NeurologyMassachusetts General HospitalBostonUSA
  2. 2.Department of Physical Medicine and RehabilitationSpaulding Rehabilitation HospitalCharlestownUSA
  3. 3.Athinoula A. Martinos Center for Biomedical ImagingMassachusetts General HospitalCharlestownUSA

Personalised recommendations