Brain Structure and Function

, Volume 225, Issue 1, pp 441–459 | Cite as

Structural abnormalities in thalamo-prefrontal tracks revealed by high angular resolution diffusion imaging predict working memory scores in concussed children

  • Guido I. GubermanEmail author
  • Jean-Christophe Houde
  • Alain Ptito
  • Isabelle Gagnon
  • Maxime Descoteaux
Original Article


Because of their high prevalence, heterogeneous clinical presentation, and wide-ranging sequelae, concussions are a challenging neurological condition, especially in children. Shearing forces transmitted across the brain during concussions often result in white matter damage. The neuropathological impact of concussions has been discerned from animal studies and includes inflammation, demyelination, and axonal loss. These pathologies can overlap during the sub-acute stage of recovery. However, due to the challenges of accurately modeling complex white matter structure, these neuropathologies have not yet been differentiated in children in vivo. In the present study, we leveraged recent advances in diffusion imaging modeling, tractography, and tractometry to better understand the neuropathology underlying working memory problems in concussion. Studying a sample of 16 concussed and 46 healthy youths, we used novel tractography methods to isolate 11 working memory tracks. Along these tracks, we measured fractional anisotropy, diffusivities, track volume, apparent fiber density, and free water fraction. In three tracks connecting the right thalamus to the right dorsolateral prefrontal cortex (DLPFC), we found microstructural differences suggestive of myelin alterations. In another track connecting the left anterior-cingulate cortex with the left DLPFC, we found microstructural changes suggestive of axonal loss. Structural differences and tractography reconstructions were reproduced using test–retest analyses. White matter structure in the three thalamo-prefrontal tracks, but not the cingulo-prefrontal track, appeared to play a key role in working memory function. The present results improve understanding of working memory neuropathology in concussions, which constitutes an important step toward developing neuropathologically informed biomarkers of concussion in children.


Concussion Mild TBI Diffusion-weighted imaging Constrained spherical deconvolution 



We want to thank the participants and their parents for lending their time for this study. We also want to thank Dr. Jen-Kai Chen and Dr. Rajeet Singh Salujah for their contribution in the acquisition of this data.


Funding for this study came from: 1. a Vanier Canada Graduate Research award, the Fonds de Recherche du Quebec—Doctoral Training for Medical Students award, and the Tomlinson Doctoral Fellowship award (G. I. Guberman); 2. an Institutional Research Chair in Neuroinformatics and National Science and Engineering Research Council Discovery Grants (Dr. Descoteaux); 3. a Canadian Institutes of Health Research Grant (Dr. Ptito, Dr. Gagnon); 4. A Fonds de Recherche du Quebec senior clinical research scholar award, and support from the Research Institute of the McGill University Health Centre (Dr. Gagnon).

Compliance with ethical standards

Conflict of interest

The authors have no conflicts of interest to declare.

Ethics approval

Every participant provided informed written consent as approved by the ethics committee at McGill University, Montreal Neurological Institute.

Supplementary material

429_2019_2002_MOESM1_ESM.pdf (14.6 mb)
Supplementary file1 (PDF 14968 kb)
429_2019_2002_MOESM2_ESM.pdf (39 kb)
Supplementary file2 (PDF 38 kb)
429_2019_2002_MOESM3_ESM.pdf (53 kb)
Supplementary file3 (PDF 52 kb)
429_2019_2002_MOESM4_ESM.pdf (48 kb)
Supplementary file4 (PDF 48 kb)
429_2019_2002_MOESM5_ESM.pdf (55 kb)
Supplementary file5 (PDF 55 kb)
429_2019_2002_MOESM6_ESM.pdf (421 kb)
Supplementary file6 (PDF 420 kb)
429_2019_2002_MOESM7_ESM.docx (13.5 mb)
Supplementary file7 (DOCX 13804 kb)


  1. Abdel-Dayem HM, Abu-Judeh H, Kumar M, Atay S, Naddaf S, El-Zeftawy H, Luo JQ (1998) SPECT brain perfusion abnormalities in mild or moderate traumatic brain injury. Clin Nucl Med 23:309–317CrossRefGoogle Scholar
  2. Anderson CV, Wood DM, Bigler ED, Blatter DD (1996) Lesion volume, injury severity, and thalamic integrity following head injury. J Neurotrauma 13:59–65. CrossRefPubMedGoogle Scholar
  3. Andersson JLR, Sotiropoulos SN (2016) An integrated approach to correction for off-resonance effects and subject movement in diffusion MR imaging. Neuroimage 125:1063–1078. CrossRefPubMedPubMedCentralGoogle Scholar
  4. Avants BB, Epstein CL, Grossman M, Gee JC (2008) Symmetric diffeomorphic image registration with cross-correlation: evaluating automated labeling of elderly and neurodegenerative brain. Med Image Anal 12:26–41. CrossRefPubMedGoogle Scholar
  5. Avants BB, Tustison NJ, Song G, Cook PA, Klein A, Gee JC (2011) A reproducible evaluation of ANTs similarity metric performance in brain image registration. Neuroimage 54:2033–2044. CrossRefPubMedGoogle Scholar
  6. Bareyre F, Wahl F, McIntosh TK, Stutzmann JM (1997) Time course of cerebral edema after traumatic brain injury in rats: effects of riluzole and mannitol. J Neurotrauma 14:839–849. CrossRefPubMedGoogle Scholar
  7. Bayly PV, Cohen TS, Leister EP, Ajo D, Leuthardt EC, Genin GM (2005) Deformation of the human brain induced by mild acceleration. J Neurotrauma 22:845–856. CrossRefPubMedPubMedCentralGoogle Scholar
  8. Bigler ED, Maxwell WL (2012) Neuropathology of mild traumatic brain injury: relationship to neuroimaging findings. Brain Imaging Behav 6:108–136. CrossRefPubMedGoogle Scholar
  9. Bolkan SS et al (2017) Thalamic projections sustain prefrontal activity during working memory maintenance. Nat Neurosci 20:987–996. CrossRefPubMedPubMedCentralGoogle Scholar
  10. Budde MD, Janes L, Gold E, Turtzo LC, Frank JA (2011) The contribution of gliosis to diffusion tensor anisotropy and tractography following traumatic brain injury: validation in the rat using Fourier analysis of stained tissue sections. Brain 134:2248–2260. CrossRefPubMedPubMedCentralGoogle Scholar
  11. Carroll LJ et al (2004) Prognosis for mild traumatic brain injury: results of the WHO Collaborating Centre Task Force on Mild Traumatic Brain Injury. J Rehabil Med (43 Suppl):84–105CrossRefGoogle Scholar
  12. Cassidy JD et al (2004) Incidence, risk factors and prevention of mild traumatic brain injury: results of the WHO Collaborating Centre Task Force on Mild Traumatic Brain Injury. J Rehabil Med (43 Suppl):28–60CrossRefGoogle Scholar
  13. Chen JK, Johnston KM, Frey S, Petrides M, Worsley K, Ptito A (2004) Functional abnormalities in symptomatic concussed athletes: an fMRI study. Neuroimage 22:68–82. CrossRefPubMedGoogle Scholar
  14. Chen JK, Johnston KM, Collie A, McCrory P, Ptito A (2007) A validation of the post concussion symptom scale in the assessment of complex concussion using cognitive testing and functional MRI. J Neurol Neurosurg Psychiatry 78:1231–1238. CrossRefPubMedPubMedCentralGoogle Scholar
  15. Churchill NW, Hutchison MG, Richards D, Leung G, Graham SJ, Schweizer TA (2017) Neuroimaging of sport concussion: persistent alterations in brain structure and function at medical clearance. Sci Rep 7:8297. CrossRefPubMedPubMedCentralGoogle Scholar
  16. Daducci A, Canales-Rodriguez EJ, Zhang H, Dyrby TB, Alexander DC, Thiran JP (2015) Accelerated microstructure imaging via convex optimization (AMICO) from diffusion MRI data. Neuroimage 105:32–44. CrossRefPubMedGoogle Scholar
  17. Dean PJ, O'Neill D, Sterr A (2012) Post-concussion syndrome: prevalence after mild traumatic brain injury in comparison with a sample without head injury. Brain Inj 26:14–26. CrossRefPubMedGoogle Scholar
  18. Dell'Acqua F, Simmons A, Williams SC, Catani M (2013) Can spherical deconvolution provide more information than fiber orientations? Hindrance modulated orientational anisotropy, a true-tract specific index to characterize white matter diffusion. Hum Brain Mapp 34:2464–2483. CrossRefPubMedGoogle Scholar
  19. Descoteaux M, Deriche R, Knosche TR, Anwander A (2009) Deterministic and probabilistic tractography based on complex fibre orientation distributions. IEEE Trans Med Imaging 28:269–286. CrossRefPubMedGoogle Scholar
  20. Dodd AB, Epstein K, Ling JM, Mayer AR (2014) Diffusion tensor imaging findings in semi-acute mild traumatic brain injury. J Neurotrauma 31:1235–1248. CrossRefPubMedGoogle Scholar
  21. Douaud G et al (2011) DTI measures in crossing-fibre areas: increased diffusion anisotropy reveals early white matter alteration in MCI and mild Alzheimer's disease. Neuroimage 55:880–890. CrossRefPubMedGoogle Scholar
  22. Dyrby TB, Lundell H, Burke MW, Reislev NL, Paulson OB, Ptito M, Siebner HR (2014) Interpolation of diffusion weighted imaging datasets. Neuroimage 103:202–213. CrossRefPubMedGoogle Scholar
  23. Fan L et al (2016) the human brainnetome atlas: a new brain atlas based on connectional architecture. Cereb Cortex 26:3508–3526. CrossRefPubMedPubMedCentralGoogle Scholar
  24. Faul M, Xu L, Wald M, Coronado V (2010) Traumatic brain injury in the United States: emergency department visits, hospitalizations, and deaths. Centers for Disease Control and Prevention National Center for Injury Prevention and Control, AtlantaCrossRefGoogle Scholar
  25. Garyfallidis E et al (2014) Dipy, a library for the analysis of diffusion MRI data. Front Neuroinform 8:8. CrossRefPubMedPubMedCentralGoogle Scholar
  26. Ge Y et al (2009) Assessment of thalamic perfusion in patients with mild traumatic brain injury by true FISP arterial spin labelling MR imaging at 3T. Brain Inj 23:666–674. CrossRefPubMedGoogle Scholar
  27. Girard G, Whittingstall K, Deriche R, Descoteaux M (2014) Towards quantitative connectivity analysis: reducing tractography biases. Neuroimage 98:266–278. CrossRefPubMedGoogle Scholar
  28. Goswami R et al (2016) Frontotemporal correlates of impulsivity and machine learning in retired professional athletes with a history of multiple concussions. Brain Struct Funct 221:1911–1925. CrossRefPubMedGoogle Scholar
  29. Grossman EJ, Inglese M (2016) The role of thalamic damage in mild traumatic brain injury. J Neurotrauma 33:163–167. CrossRefPubMedPubMedCentralGoogle Scholar
  30. Grossman EJ et al (2012) Thalamus and cognitive impairment in mild traumatic brain injury: a diffusional kurtosis imaging study. J Neurotrauma 29:2318–2327. CrossRefPubMedPubMedCentralGoogle Scholar
  31. Guberman G (2019) Montreal Neurological Institute—pediatric concussion.
  32. Harsan LA et al (2006) Brain dysmyelination and recovery assessment by noninvasive in vivo diffusion tensor magnetic resonance imaging. J Neurosci Res 83:392–402. CrossRefPubMedGoogle Scholar
  33. Hayes JP, Bigler ED, Verfaellie M (2016) Traumatic brain injury as a disorder of brain connectivity. J Int Neuropsychol Soc 22:120–137. CrossRefPubMedPubMedCentralGoogle Scholar
  34. Henninger N et al (2007) Differential recovery of behavioral status and brain function assessed with functional magnetic resonance imaging after mild traumatic brain injury in the rat. Crit Care Med 35:2607–2614. CrossRefPubMedGoogle Scholar
  35. Hessen E, Nestvold K, Anderson V (2007) Neuropsychological function 23 years after mild traumatic brain injury: a comparison of outcome after paediatric and adult head injuries. Brain Inj 21:963–979. CrossRefPubMedGoogle Scholar
  36. Holland RL (2016) What makes a good biomarker? Adv Precis Med 1:66–77CrossRefGoogle Scholar
  37. Hulkower MB, Poliak DB, Rosenbaum SB, Zimmerman ME, Lipton ML (2013) A decade of DTI in traumatic brain injury: 10 years and 100 articles later. Am J Neuroradiol 34:2064–2074. CrossRefPubMedGoogle Scholar
  38. Jantzen KJ, Anderson B, Steinberg FL, Kelso JA (2004) A prospective functional MR imaging study of mild traumatic brain injury in college football players. Am J Neuroradiol 25:738–745PubMedGoogle Scholar
  39. Jeurissen B, Leemans A, Tournier JD, Jones DK, Sijbers J (2013) Investigating the prevalence of complex fiber configurations in white matter tissue with diffusion magnetic resonance imaging. Hum Brain Mapp 34:2747–2766. CrossRefPubMedGoogle Scholar
  40. Jones DK (2004) The effect of gradient sampling schemes on measures derived from diffusion tensor MRI: a Monte Carlo study. Magn Reson Med 51:807–815. CrossRefPubMedGoogle Scholar
  41. Jones DK, Knosche TR, Turner R (2013) White matter integrity, fiber count, and other fallacies: the do's and don'ts of diffusion MRI. Neuroimage 73:239–254. CrossRefPubMedGoogle Scholar
  42. Keightley ML, Saluja RS, Chen JK, Gagnon I, Leonard G, Petrides M, Ptito A (2014) A functional magnetic resonance imaging study of working memory in youth after sports-related concussion: is it still working? J Neurotrauma 31:437–451. CrossRefPubMedPubMedCentralGoogle Scholar
  43. Kristman VL et al (2014) Methodological issues and research recommendations for prognosis after mild traumatic brain injury: results of the International Collaboration on Mild Traumatic Brain Injury Prognosis. Arch Phys Med Rehabil 95:S265–277. CrossRefPubMedGoogle Scholar
  44. Landre N, Poppe CJ, Davis N, Schmaus B, Hobbs SE (2006) Cognitive functioning and postconcussive symptoms in trauma patients with and without mild TBI. Arch Clin Neuropsychol 21:255–273. CrossRefPubMedGoogle Scholar
  45. Lewine JD, Davis JT, Sloan JH, Kodituwakku PW, Orrison WW Jr (1999) Neuromagnetic assessment of pathophysiologic brain activity induced by minor head trauma. Am J Neuroradiol 20:857–866PubMedGoogle Scholar
  46. Little DM et al (2010) Thalamic integrity underlies executive dysfunction in traumatic brain injury. Neurology 74:558–564. CrossRefPubMedPubMedCentralGoogle Scholar
  47. Lovell MR et al (2006) Measurement of symptoms following sports-related concussion: reliability and normative data for the post-concussion scale. Appl Neuropsychol 13:166–174. CrossRefPubMedGoogle Scholar
  48. Mac Donald CL et al (2011) Detection of blast-related traumatic brain injury in U.S. military personnel. N Engl J Med 364:2091–2100. CrossRefPubMedPubMedCentralGoogle Scholar
  49. Mac Donald CL, Dikranian K, Bayly P, Holtzman D, Brody D (2007) Diffusion tensor imaging reliably detects experimental traumatic axonal injury and indicates approximate time of injury. J Neurosci 27:11869–11876. CrossRefPubMedPubMedCentralGoogle Scholar
  50. Maintz JA, Viergever MA (1998) A survey of medical image registration. Med Image Anal 2:1–36CrossRefGoogle Scholar
  51. Mayer AR et al (2018) Advanced biomarkers of pediatric mild traumatic brain injury: progress and perils. Neurosci Biobehav Rev. CrossRefPubMedPubMedCentralGoogle Scholar
  52. McAllister TW et al (1999) Brain activation during working memory 1 month after mild traumatic brain injury: a functional MRI study. Neurology 53:1300–1308CrossRefGoogle Scholar
  53. McAllister TW, Sparling MB, Flashman LA, Guerin SJ, Mamourian AC, Saykin AJ (2001) Differential working memory load effects after mild traumatic brain injury. Neuroimage 14:1004–1012. CrossRefPubMedGoogle Scholar
  54. McKee AC et al (2009) Chronic traumatic encephalopathy in athletes: progressive tauopathy after repetitive head injury. J Neuropathol Exp Neurol 68:709–735CrossRefGoogle Scholar
  55. McKinlay A, Corrigan J, Horwood LJ, Fergusson DM (2014) Substance abuse and criminal activities following traumatic brain injury in childhood, adolescence, and early adulthood. J Head Trauma Rehabil 29:498–506. CrossRefPubMedGoogle Scholar
  56. Meehan WP 3rd, Mannix RC, O'Brien MJ, Collins MW (2013) The prevalence of undiagnosed concussions in athletes. Clin J Sport Med 23:339–342. CrossRefPubMedPubMedCentralGoogle Scholar
  57. Mierzwa AJ, Marion CM, Sullivan GM, McDaniel DP, Armstrong RC (2015) Components of myelin damage and repair in the progression of white matter pathology after mild traumatic brain injury. J Neuropathol Exp Neurol 74:218–232. CrossRefPubMedPubMedCentralGoogle Scholar
  58. Mito R et al (2018) Fibre-specific white matter reductions in Alzheimer's disease and mild cognitive impairment. Brain. CrossRefPubMedGoogle Scholar
  59. Orlovska S, Pedersen MS, Benros ME, Mortensen PB, Agerbo E, Nordentoft M (2014) Head injury as risk factor for psychiatric disorders: a nationwide register-based follow-up study of 113,906 persons with head injury. Am J Psychiatry 171:463–469CrossRefGoogle Scholar
  60. Palacios E et al (2018) The evolution of white matter changes after mild traumatic brain injury: a DTI and NODDI study. bioRxiv. CrossRefGoogle Scholar
  61. Pardini JE, Pardini DA, Becker JT, Dunfee KL, Eddy WF, Lovell MR, Welling JS (2010) Postconcussive symptoms are associated with compensatory cortical recruitment during a working memory task. Neurosurgery 67:1020–1027. 1027–1028) CrossRefPubMedPubMedCentralGoogle Scholar
  62. Pasternak O, Sochen N, Gur Y, Intrator N, Assaf Y (2009) Free water elimination and mapping from diffusion MRI. Magn Reson Med 62:717–730. CrossRefGoogle Scholar
  63. Pasternak O, Shenton ME, Westin CF (2012) Estimation of extracellular volume from regularized multi-shell diffusion MRI. Med Image Comput Comput Assist Interv 15:305–312PubMedPubMedCentralGoogle Scholar
  64. Pasternak O, Kubicki M, Shenton ME (2016) vivo imaging of neuroinflammation in schizophrenia. Schizophr Res 173:200–212. CrossRefGoogle Scholar
  65. Peeters W, van den Brande R, Polinder S, Brazinova A, Steyerberg EW, Lingsma HF, Maas AI (2015) Epidemiology of traumatic brain injury in Europe. Acta Neurochir (Wien) 157:1683–1696. CrossRefGoogle Scholar
  66. Petrides M, Alivisatos B, Meyer E, Evans AC (1993) Functional activation of the human frontal cortex during the performance of verbal working memory tasks. Proc Natl Acad Sci USA 90:878–882CrossRefGoogle Scholar
  67. Petrides M, Frey S, Chen J-K (2001) Increased activation of the mid-dorsolateral frontal cortex during the monitoring of abstract visual and verbal stimuli. Neuroimage 6:721CrossRefGoogle Scholar
  68. Pierpaoli C, Basser PJ (1996) Toward a quantitative assessment of diffusion anisotropy. Magn Reson Med 36:893–906CrossRefGoogle Scholar
  69. Pierpaoli C, Barnett A, Pajevic S, Chen R, Penix LR, Virta A, Basser P (2001) Water diffusion changes in Wallerian degeneration and their dependence on white matter architecture. Neuroimage 13:1174–1185. CrossRefPubMedGoogle Scholar
  70. Powell JL, Parkes L, Kemp GJ, Sluming V, Barrick TR, Garcia-Finana M (2012) The effect of sex and handedness on white matter anisotropy: a diffusion tensor magnetic resonance imaging study. Neuroscience 207:227–242. CrossRefPubMedGoogle Scholar
  71. Raffelt DA et al (2012) Apparent Fibre Density: a novel measure for the analysis of diffusion-weighted magnetic resonance images. Neuroimage 59:3976–3994. CrossRefPubMedGoogle Scholar
  72. Raffelt DA, Tournier JD, Smith RE, Vaughan DN, Jackson G, Ridgway GR, Connelly A (2017) Investigating white matter fibre density and morphology using fixel-based analysis. Neuroimage 144:58–73. CrossRefPubMedPubMedCentralGoogle Scholar
  73. Sabet AA, Christoforou E, Zatlin B, Genin GM, Bayly PV (2008) Deformation of the human brain induced by mild angular head acceleration. J Biomech 41:307–315. CrossRefPubMedGoogle Scholar
  74. Salter H, Holland R (2014) Biomarkers: refining diagnosis and expediting drug development—reality, aspiration and the role of open innovation. J Intern Med 276:215–228. CrossRefPubMedGoogle Scholar
  75. Sharp DJ, Jenkins PO (2015) Concussion is confusing us all. Pract Neurol 15:172–186. CrossRefPubMedPubMedCentralGoogle Scholar
  76. Shenton ME et al (2012) A review of magnetic resonance imaging and diffusion tensor imaging findings in mild traumatic brain injury. Brain Imaging Behav 6:137–192. CrossRefPubMedPubMedCentralGoogle Scholar
  77. Smith SM (2002) Fast robust automated brain extraction. Hum Brain Mapp 17:143–155. CrossRefPubMedGoogle Scholar
  78. Spader HS et al (2018) Prospective study of myelin water fraction changes after mild traumatic brain injury in collegiate contact sports. J Neurosurg. CrossRefPubMedPubMedCentralGoogle Scholar
  79. Spinos P, Sakellaropoulos G, Georgiopoulos M, Stavridi K, Apostolopoulou K, Ellul J, Constantoyannis C (2010) Postconcussion syndrome after mild traumatic brain injury in Western Greece. J Trauma 69:789–794. CrossRefPubMedGoogle Scholar
  80. Stern CE, Owen AM, Tracey I, Look RB, Rosen BR, Petrides M (2000) Activity in ventrolateral and mid-dorsolateral prefrontal cortex during nonspatial visual working memory processing: evidence from functional magnetic resonance imaging. Neuroimage 11:392–399. CrossRefPubMedGoogle Scholar
  81. St-Jean S, Coupe P, Descoteaux M (2016) Non local spatial and angular matching: enabling higher spatial resolution diffusion MRI datasets through adaptive denoising. Med Image Anal 32:115–130. CrossRefPubMedGoogle Scholar
  82. Sun SW, Liang HF, Trinkaus K, Cross AH, Armstrong RC, Song SK (2006) Noninvasive detection of cuprizone induced axonal damage and demyelination in the mouse corpus callosum. Magn Reson Med 55:302–308. CrossRefPubMedGoogle Scholar
  83. Sun C, Wang Y, Cui R, Wu C, Li X, Bao Y, Wang Y (2018) Human thalamic-prefrontal peduncle connectivity revealed by diffusion spectrum imaging fiber tracking. Front Neuroanat 12:24. CrossRefPubMedPubMedCentralGoogle Scholar
  84. Sundman M, Doraiswamy PM, Morey RA (2015) Neuroimaging assessment of early and late neurobiological sequelae of traumatic brain injury: implications for CTE. Front Neurosci 9:334. CrossRefPubMedPubMedCentralGoogle Scholar
  85. Tournier JD, Calamante F, Connelly A (2007) Robust determination of the fibre orientation distribution in diffusion MRI: non-negativity constrained super-resolved spherical deconvolution. Neuroimage 35:1459–1472. CrossRefPubMedGoogle Scholar
  86. Tournier JD, Yeh CH, Calamante F, Cho KH, Connelly A, Lin CP (2008) Resolving crossing fibres using constrained spherical deconvolution: validation using diffusion-weighted imaging phantom data. Neuroimage 42:617–625. CrossRefPubMedGoogle Scholar
  87. Tournier JD, Mori S, Leemans A (2011) Diffusion tensor imaging and beyond. Magn Reson Med 65:1532–1556. CrossRefPubMedPubMedCentralGoogle Scholar
  88. Tournier JD, Calamante F, Connelly A (2012) MRtrix: diffusion tractography in crossing fiber regions. Int J Imaging Syst Technol 22:53–66CrossRefGoogle Scholar
  89. Viano DC, Casson IR, Pellman EJ, Zhang L, King AI, Yang KH (2005) Concussion in professional football: brain responses by finite element analysis: part 9. Neurosurgery 57:891–916 (discussion 891–916) CrossRefGoogle Scholar
  90. Ware JB, Hart T, Whyte J, Rabinowitz A, Detre JA, Kim J (2017) Inter-subject variability of axonal injury in diffuse traumatic brain injury. J Neurotrauma 34:2243–2253. CrossRefPubMedPubMedCentralGoogle Scholar
  91. Werner C, Engelhard K (2007) Pathophysiology of traumatic brain injury. Br J Anaesth 99:4–9. CrossRefPubMedGoogle Scholar
  92. Westfall DR, West JD, Bailey JN, Arnold TW, Kersey PA, Saykin AJ, McDonald BC (2015) Increased brain activation during working memory processing after pediatric mild traumatic brain injury (mTBI). J Pediatr Rehabil Med 8:297–308. CrossRefPubMedPubMedCentralGoogle Scholar
  93. Wood DM, Bigler ED (1995) Diencephalic changes in traumatic brain injury: relationship to sensory perceptual function. Brain Res Bull 38:545–549CrossRefGoogle Scholar
  94. Woolrich MW et al (2009) Bayesian analysis of neuroimaging data in FSL. Neuroimage 45:S173–S186. CrossRefPubMedGoogle Scholar
  95. Yeatman JD, Dougherty RF, Myall NJ, Wandell BA, Feldman HM (2012) Tract profiles of white matter properties: automating fiber-tract quantification. PLoS ONE 7:e49790. CrossRefPubMedPubMedCentralGoogle Scholar
  96. You Y et al (2019) Demyelination precedes axonal loss in the transneuronal spread of human neurodegenerative disease. Brain 142:426–442. CrossRefPubMedGoogle Scholar
  97. Yuh EL et al (2013) Magnetic resonance imaging improves 3-month outcome prediction in mild traumatic brain injury. Ann Neurol 73:224–235. CrossRefPubMedGoogle Scholar
  98. Zhang Y, Brady M, Smith S (2001) Segmentation of brain MR images through a hidden Markov random field model and the expectation-maximization algorithm. IEEE Trans Med Imaging 20:45–57. CrossRefPubMedGoogle Scholar
  99. Zhang L, Yang KH, King AI (2004) A proposed injury threshold for mild traumatic brain injury. J Biomech Eng 126:226–236CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2020

Authors and Affiliations

  1. 1.Department of Neurology and Neurosurgery, Faculty of MedicineMcGill UniversityMontrealCanada
  2. 2.Department of Computer ScienceSherbrooke UniversitySherbrookeCanada
  3. 3.Department of Pediatrics, Faculty of Medicine, Montreal Children’s HospitalMcGill UniversityQuebecCanada
  4. 4.Montreal Neurological InstituteMontrealCanada

Personalised recommendations