Abstract
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.
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References
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.
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. https://doi.org/10.3109/02699052.2013.823659.
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. https://doi.org/10.1007/s12031-007-0029-0.
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.
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.
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. https://doi.org/10.3389/fnhum.2014.01028.
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. https://doi.org/10.1093/brain/awv169.
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. https://doi.org/10.3389/fnagi.2014.00343.
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. https://doi.org/10.1016/j.neuroimage.2010.08.035.
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. https://doi.org/10.1002/ana.23635.
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. https://doi.org/10.1002/ana.410120611.
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.
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. https://doi.org/10.1038/nrneurol.2013.279.
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. https://doi.org/10.1016/j.apmr.2004.02.033.
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. https://doi.org/10.1093/brain/awq347.
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. https://doi.org/10.1016/j.nicl.2015.11.004.
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. https://doi.org/10.1016/s1474-4422(04)00852-x.
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.
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. https://doi.org/10.1002/mrm.21890.
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. https://doi.org/10.1523/JNEUROSCI.3647-07.2007.
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. https://doi.org/10.1016/j.neuroimage.2007.12.035.
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. https://doi.org/10.1146/annurev-psych-113011-143733. doi.
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. https://doi.org/10.1371/journal.pone.0019214.
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. https://doi.org/10.1136/jnnp.2009.196246.
Owen, A. M. (2014). Disorders of consciousness: Diagnostic accuracy of brain imaging in the vegetative state. Nature Reviews. Neurology, 10(7), 370–371. https://doi.org/10.1038/nrneurol.2014.102.
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. https://doi.org/10.1002/hbm.20817.
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. https://doi.org/10.3174/ajnr.A1213.
Schiff, N. D. (2010). Recovery of consciousness after brain injury: a mesocircuit hypothesis. Trends in Neurosciences, 33(1), 1–9. https://doi.org/10.1016/j.tins.2009.11.002.
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. https://doi.org/10.1093/brain/awm294.
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. https://doi.org/10.1016/j.neuroimage.2006.02.024.
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. https://doi.org/10.1016/j.neuroimage.2008.03.061.
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.
Tononi, G. (2008). Consciousness as integrated information: a provisional manifesto. The Biological Bulletin, 215(3), 216–242.
Tononi, G. (2012). Integrated information theory of consciousness: an updated account. Archives Italiennes de Biologie, 150(2–3), 56–90. https://doi.org/10.4449/aib.v149i5.1388.
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. https://doi.org/10.1038/nn.2149.
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. https://doi.org/10.1148/radiol.13122720.
Vandekerckhove, M., Bulnes, L. C., & Panksepp, J. (2013). The emergence of primary anoetic consciousness in episodic memory. Frontiers in Behavioral Neuroscience, 7, 210. https://doi.org/10.3389/fnbeh.2013.00210.
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. https://doi.org/10.1001/archneur.65.5.619.
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, https://doi.org/10.1002/ana.24962.
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. https://doi.org/10.1016/j.cortex.2017.02.011.
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. https://doi.org/10.3389/fnhum.2013.00416.
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. https://doi.org/10.1002/hbm.23370.
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This work was supported by the National Natural Science Foundation of China (61673391, 61473221, 81600919), and the Beijing Natural Science Foundation (7164302).
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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.
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Wang, L., Yang, Y., Chen, S. et al. White matter integrity correlates with residual consciousness in patients with severe brain injury. Brain Imaging and Behavior 12, 1669–1677 (2018). https://doi.org/10.1007/s11682-018-9832-1
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DOI: https://doi.org/10.1007/s11682-018-9832-1