Brain Imaging and Behavior

, Volume 12, Issue 6, pp 1669–1677 | Cite as

White matter integrity correlates with residual consciousness in patients with severe brain injury

  • Lubin Wang
  • Yi Yang
  • Shanshan Chen
  • Mingmei Ge
  • Jianghong He
  • Zheng Yang
  • Pan LinEmail author
  • Xinhuai WuEmail author


Previous studies have suggested that white matter disruption plays an important role in disorders of consciousness (DOC) after severe brain injury. Nevertheless, the integrity of white matter architecture supporting consciousness and its relations with clinical severity in patients with DOC remain to be established. In this study, diffusion tensor imaging (DTI) data was collected from 14 DOC patients and 15 healthy control subjects. We combined tract-based spatial statistics (TBSS) with region of interest (ROI) analysis to examine differences of DTI metrics on white matter skeletons between DOC patients and healthy controls, and the association between white matter integrity and patients’ residual consciousness assessed by Coma Recovery Scale-Revised (CRS-R). We found that: (1) patients with DOC had widespread white matter integrity disruptions, especially in the fornix; (2) the alteration of white matter microstructure was mainly attributed to the increase in radial diffusivity, possibly reflecting demyelination; (3) the behavioral CRS-R assessment score was positively correlated with white matter integrity in the fornix, uncinate fasciculus, pontine crossing tract, and posterior limb of internal capsule. Our results suggest that despite the widespread abnormalities of white matter following severe brain injury, the impairment of consciousness is likely to result from disruptions of key pathways that link brain regions in distributed networks.


Disorder of consciousness Diffusion tensor imaging Tract-based spatial statistics Fornix Coma Recovery Scale-Revised 



This work was supported by the National Natural Science Foundation of China (61673391, 61473221, 81600919), and the Beijing Natural Science Foundation (7164302).

Compliance with ethical standards

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from the patients’ legal guardians and the normal control subjects in the study.


  1. Adams, J. H., Graham, D. I., & Jennett, B. (2000). The neuropathology of the vegetative state after an acute brain insult. Brain, 123 (Pt 7), 1327–1338.Google Scholar
  2. Adnan, A., Crawley, A., Mikulis, D., Moscovitch, M., Colella, B., & Green, R. (2013). Moderate-severe traumatic brain injury causes delayed loss of white matter integrity: evidence of fornix deterioration in the chronic stage of injury. Brain Injury, 27(12), 1415–1422. Scholar
  3. Assaf, Y., & Pasternak, O. (2008). Diffusion tensor imaging (DTI)-based white matter mapping in brain research: a review. Journal of Molecular Neuroscience, 34(1), 51–61. Scholar
  4. Baron, R. M., & Kenny, D. A. (1986). The moderator-mediator variable distinction in social psychological research: conceptual, strategic, and statistical considerations. Journal of Personality and Social Psychology, 51(6), 1173–1182.CrossRefGoogle Scholar
  5. Basser, P. J., & Pierpaoli, C. (1996). Microstructural and physiological features of tissues elucidated by quantitative-diffusion-tensor MRI. Journal of Magnetic Resonance. Series B, 111(3), 209–219.CrossRefGoogle Scholar
  6. Cavaliere, C., Aiello, M., Di Perri, C., Fernandez-Espejo, D., Owen, A. M., & Soddu, A. (2014). Diffusion tensor imaging and white matter abnormalities in patients with disorders of consciousness. Frontiers in Human Neuroscience, 8, 1028. Scholar
  7. Demertzi, A., Antonopoulos, G., Heine, L., Voss, H. U., Crone, J. S., de Los Angeles, C., et al. (2015). Intrinsic functional connectivity differentiates minimally conscious from unresponsive patients. Brain, 138(Pt 9), 2619–2631. Scholar
  8. Douet, V., & Chang, L. (2014). Fornix as an imaging marker for episodic memory deficits in healthy aging and in various neurological disorders. Frontiers in Aging Neuroscience, 6, 343. Scholar
  9. Fernandez-Espejo, D., Bekinschtein, T., Monti, M. M., Pickard, J. D., Junque, C., Coleman, M. R., et al. (2011). Diffusion weighted imaging distinguishes the vegetative state from the minimally conscious state. Neuroimage, 54(1), 103–112. Scholar
  10. Fernández-Espejo, D., Soddu, A., Cruse, D., Palacios, E. M., Junque, C., Vanhaudenhuyse, A., et al. (2012). A role for the default mode network in the bases of disorders of consciousness. Annals of Neurology, 72(3), 335–343. Scholar
  11. Gennarelli, T. A., Thibault, L. E., Adams, J. H., Graham, D. I., Thompson, C. J., & Marcincin, R. P. (1982). Diffuse axonal injury and traumatic coma in the primate. Annals of Neurology, 12(6), 564–574. Scholar
  12. Giacino, J. T., Ashwal, S., Childs, N., Cranford, R., Jennett, B., Katz, D. I., et al. (2002). The minimally conscious state: definition and diagnostic criteria. Neurology, 58(3), 349–353.CrossRefGoogle Scholar
  13. Giacino, J. T., Fins, J. J., Laureys, S., & Schiff, N. D. (2014). Disorders of consciousness after acquired brain injury: the state of the science. Nature Reviews. Neurology, 10(2), 99–114. Scholar
  14. Giacino, J. T., Kalmar, K., & Whyte, J. (2004). The JFK Coma Recovery Scale-Revised: Measurement characteristics and diagnostic utility. Archives of Physical Medicine and Rehabilitation, 85(12), 2020–2029. Scholar
  15. Kinnunen, K. M., Greenwood, R., Powell, J. H., Leech, R., Hawkins, P. C., Bonnelle, V., et al. (2011). White matter damage and cognitive impairment after traumatic brain injury. Brain, 134(Pt 2), 449–463. Scholar
  16. Lant, N. D., Gonzalez-Lara, L. E., Owen, A. M., & Fernandez-Espejo, D. (2016). Relationship between the anterior forebrain mesocircuit and the default mode network in the structural bases of disorders of consciousness. Neuroimage Clinic, 10, 27–35. Scholar
  17. Laureys, S., Owen, A. M., & Schiff, N. D. (2004). Brain function in coma, vegetative state, and related disorders. The Lancet Neurology, 3(9), 537–546. Scholar
  18. Le Bihan, D., Mangin, J. F., Poupon, C., Clark, C. A., Pappata, S., Molko, N., et al. (2001). Diffusion tensor imaging: concepts and applications. Journal of Magnetic Resonance Imaging, 13(4), 534–546.CrossRefGoogle Scholar
  19. Leemans, A., & Jones, D. K. (2009). The B-matrix must be rotated when correcting for subject motion in DTI data. Magnetic Resonance in Medicine, 61(6), 1336–1349. Scholar
  20. Mac Donald, C. L., Dikranian, K., Bayly, P., Holtzman, D., & Brody, D. (2007). Diffusion tensor imaging reliably detects experimental traumatic axonal injury and indicates approximate time of injury. The Journal of Neuroscience, 27(44), 11869–11876. Scholar
  21. Mori, S., Oishi, K., Jiang, H., Jiang, L., Li, X., Akhter, K., et al. (2008). Stereotaxic white matter atlas based on diffusion tensor imaging in an ICBM template. Neuroimage, 40(2), 570–582. Scholar
  22. Moscovitch, M., Cabeza, R., Winocur, G., & Nadel, L. (2016). Episodic memory and beyond: the hippocampus and neocortex in transformation. Annual Review of Psychology, 67(1), 105–134. doi.
  23. Newcombe, V., Chatfield, D., Outtrim, J., Vowler, S., Manktelow, A., Cross, J., et al. (2011). Mapping traumatic axonal injury using diffusion tensor imaging: correlations with functional outcome. PLoS ONE, 6(5), e19214. Scholar
  24. Newcombe, V. F. J., Williams, G. B., Scoffings, D., Cross, J., Carpenter, T. A., Pickard, J. D., et al. (2010). Aetiological differences in neuroanatomy of the vegetative state: insights from diffusion tensor imaging and functional implications. Journal of Neurology, Neurosurgery, and Psychiatry, 81(5), 552–561. Scholar
  25. Owen, A. M. (2014). Disorders of consciousness: Diagnostic accuracy of brain imaging in the vegetative state. Nature Reviews. Neurology, 10(7), 370–371. Scholar
  26. Perlbarg, V., Puybasset, L., Tollard, E., Lehericy, S., Benali, H., & Galanaud, D. (2009). Relation between brain lesion location and clinical outcome in patients with severe traumatic brain injury: a diffusion tensor imaging study using voxel-based approaches. Human Brain Mapping, 30(12), 3924–3933. Scholar
  27. Rutgers, D. R., Fillard, P., Paradot, G., Tadié, M., Lasjaunias, P., & Ducreux, D. (2008). Diffusion tensor imaging characteristics of the corpus callosum in mild, moderate, and severe traumatic brain injury. American Journal of Neuroradiology, 29(9), 1730–1735. Scholar
  28. Schiff, N. D. (2010). Recovery of consciousness after brain injury: a mesocircuit hypothesis. Trends in Neurosciences, 33(1), 1–9. Scholar
  29. Sidaros, A., Engberg, A. W., Sidaros, K., Liptrot, M. G., Herning, M., Petersen, P., et al. (2008). Diffusion tensor imaging during recovery from severe traumatic brain injury and relation to clinical outcome: a longitudinal study. Brain, 131(Pt 2), 559–572.
  30. Smith, S. M., Jenkinson, M., Johansen-Berg, H., Rueckert, D., Nichols, T. E., Mackay, C. E., et al. (2006). Tract-based spatial statistics: voxelwise analysis of multi-subject diffusion data. NeuroImage, 31(4), 1487–1505. Scholar
  31. Smith, S. M., & Nichols, T. E. (2009). Threshold-free cluster enhancement: addressing problems of smoothing, threshold dependence and localisation in cluster inference. Neuroimage, 44(1), 83–98. Scholar
  32. Song, S. K., Sun, S. W., Ju, W. K., Lin, S. J., Cross, A. H., & Neufeld, A. H. (2003). Diffusion tensor imaging detects and differentiates axon and myelin degeneration in mouse optic nerve after retinal ischemia. Neuroimage, 20(3), 1714–1722.CrossRefGoogle Scholar
  33. Tononi, G. (2008). Consciousness as integrated information: a provisional manifesto. The Biological Bulletin, 215(3), 216–242.CrossRefGoogle Scholar
  34. Tononi, G. (2012). Integrated information theory of consciousness: an updated account. Archives Italiennes de Biologie, 150(2–3), 56–90. Scholar
  35. Tsivilis, D., Vann, S. D., Denby, C., Roberts, N., Mayes, A. R., Montaldi, D., et al. (2008). A disproportionate role for the fornix and mammillary bodies in recall versus recognition memory. Nature Neuroscience, 11(7), 834–842. Scholar
  36. van der Eerden, A. W., Khalilzadeh, O., Perlbarg, V., Dinkel, J., Sanchez, P., Vos, P. E., et al. (2014). White matter changes in comatose survivors of anoxic ischemic encephalopathy and traumatic brain injury: comparative diffusion-tensor imaging study. Radiology, 270(2), 506–516. Scholar
  37. Vandekerckhove, M., Bulnes, L. C., & Panksepp, J. (2013). The emergence of primary anoetic consciousness in episodic memory. Frontiers in Behavioral Neuroscience, 7, 210. Scholar
  38. Wang, J. Y., Bakhadirov, K., Devous, M. D., Abdi, S., McColl, H., Moore, R. C., et al (2008). Diffusion tensor tractography of traumatic diffuse axonal injury. Archives of Neurology, 65(5), 619–626. Scholar
  39. Wannez, S., Heine, L., Thonnard, M., Gosseries, O., & Laureys, S. & Coma Science Group, c. (2017). The repetition of behavioral assessments in diagnosis of disorders of consciousness. Annals of Neurology, 81(6), 883–889,
  40. Weng, L., Xie, Q., Zhao, L., Zhang, R., Ma, Q., Wang, J., et al. (2017). Abnormal structural connectivity between the basal ganglia, thalamus, and frontal cortex in patients with disorders of consciousness. Cortex, 90, 71–87. Scholar
  41. Yeo, S. S., Chang, P. H., & Jang, S. H. (2013). The ascending reticular activating system from pontine reticular formation to the thalamus in the human brain. Frontiers in Human Neuroscience, 7, 416. Scholar
  42. Zheng, Z. S., Reggente, N., Lutkenhoff, E., Owen, A. M., & Monti, M. M. (2017). Disentangling disorders of consciousness: Insights from diffusion tensor imaging and machine learning. Human Brain Mapping, 38(1), 431–443. Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Cognitive and Mental Health Research CenterBeijing Institute of Basic Medical SciencesBeijingChina
  2. 2.Department of NeurosurgeryPLA Army General HospitalBeijingChina
  3. 3.Department of RadiologyPLA Army General HospitalBeijingChina
  4. 4.Key Laboratory of Cognitive Science, College of Biomedical EngineeringSouth-Central University for NationalitiesWuhanChina
  5. 5.Hubei Key Laboratory of Medical Information Analysis and Tumor Diagnosis & Treatment, College of Biomedical EngineeringSouth-Central University for NationalitiesWuhanChina

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