Repeated mild traumatic brain injuries is not associated with volumetric differences in former high school football players

Original Research

Abstract

We investigated potential brain volumetric differences in a sample of former high school football players many years after these injuries. Forty community-dwelling males ages 40–65 who played high school football, but not college or professional sports, were recruited. The experimental group (n = 20) endorsed experiencing two or more mTBIs on an empirically validated mTBI assessment tool (median = 3, range = 2–15). The control group (n = 20) denied ever experiencing an mTBI. Participants completed a self-report index of current mTBI symptomatology and underwent high-resolution T1-weighted MRI scanning, which were analyzed using the Freesurfer software package. A priori regions of interest (ROIs) included total intracranial volume (ICV), total gray matter, total white matter, bilateral anterior cingulate cortex, bilateral hippocampi, and lateral ventricles. ROIs were corrected for head size using a normalization method that took ICV into account. Despite an adequate sample size and being matched on age, education, estimated premorbid IQ, current concussive symptomatology, there were no statistically significant volumetric group differences across all of the ROIs. These data suggest that multiple mTBIs from high school football may not be associated with measurable brain atrophy later in life. Accounting for the severity of injury and chronicity of sport exposure may be especially important when measuring long-term neuroanatomical differences.

Keywords

Concussion Mild traumatic brain injury MRI Brain volume Atrophy Cognition 

Notes

Acknowledgements

This research was made possible by the charitable contributions of the John & Mary Franklin Foundation and the BioImaging Research Center at the University of Georgia. There are no other funding agencies or conflicts of interest to declare.

Compliance with ethical standards

Funding

This study was funded by partial support to D.P. Terry by the John and Mary Franklin Foundation and the University of Georgia BioImaging Research Center.

Conflict of interest

D.P. Terry and L.S. Miller declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the University of Georgia Institutional Review Board and with the 1964 Helsinki declaration and its later amendments.

References

  1. American Congress of Rehabilitation Medicine. (1993). Definition of mild traumatic brain injury. Journal of Head Trauma Rehabilitation, 8, 86–87.CrossRefGoogle Scholar
  2. Arciniegas, D., Olincy, A., Topkoff, J., McRae, K., Cawthra, E., Filley, C., et al. (2000). Impaired auditory gating and P50 Nonsuppression following traumatic brain injury. The Journal of Neuropsychiatry and Clinical Neurosciences, 12, 77–85.CrossRefPubMedGoogle Scholar
  3. Bazarian, J. J., Zhong, J., Blyth, B., Zhu, T., Kavcic, V., & Peterson, D. (2007). DTI detects clinically important axonal damage after mild TBI: A pilot study. Journal of Neurotrauma, 24, 1447–1459. doi: 10.1089/neu.2007.0241.CrossRefPubMedGoogle Scholar
  4. Bigler, E. D. (2004). Neuropsychological results and neuropathological findings at autopsy in a case of mild traumatic brain injury. Journal of the International Neuropsychological Society, 10, 794–800. doi: 10.1017/S1355617704105146.PubMedGoogle Scholar
  5. Blennow, K., Hardy, J., Zetterberg, H. (2012). The neuropathology and neurobiology of traumatic brain injury. Neuron, 6,(76), 886–899.Google Scholar
  6. Blumbergs, P. C., Scott, G., Manavis, J., Wainwright, H., Simpson, D. A., & McLean, A. J. (1994). Staining of amyloid precursor protein to study axonal damage in mild head injury. Lancet, 344, 1055–1056. doi: 10.1016/S0140-6736(94)91712-4.CrossRefPubMedGoogle Scholar
  7. Broglio, S. P., Macciocchi, S. N., & Ferrara, M. S. (2007). Neurocognitive performance of concussed athletes when symptom free. Journal of Athletic Training, 42, 504–508.PubMedPubMedCentralGoogle Scholar
  8. Broglio, S. P., Eckner, J. T., Paulson, H. L., & Kutcher, J. S. (2012). Cognitive decline and aging: The role of concussive and subconcussive impacts. Exercise and Sport Sciences Reviews, 40, 138–144. doi: 10.1097/JES.0b013e3182524273.PubMedPubMedCentralGoogle Scholar
  9. Buckner, R. L., Head, D., Parker, J., Fotenos, A. F., Marcus, D., Morris, J. C., & Synder, A. Z. (2004). A unified approach for morphometric and functional data analysis in young, old, and demented adults using automated atlas-based head size normalization: Reliability and validation against manual of total intracranial volume. NeuroImage, 23, 724–738. doi: 10.1016/j.neuroimage.2004.06.018.CrossRefPubMedGoogle Scholar
  10. Canu, E., McLaren, D. G., Fitzgerald, M. E., Bendlin, B. B., Zoccatelli, G., Alessandrini, F., et al. (2010). Microstructural diffusion changes are independent of macrostructural volume loss in moderate to severe Alzheimer’s disease. Journal of Alzheimer’s Disease, 19, 963–976. doi: 10.3233/JAD-2010-1295.CrossRefPubMedPubMedCentralGoogle Scholar
  11. Cassidy, J. D., Carroll, L. J., Peloso, P. M., Borg, J., von Holst, H., Holm, L., Kraus, J., Coronado, VG.; WHO Collaborating Centre Task Force on Mild Traumatic Brain Injury. (2004). Incidence, risk factors and prevention of mild traumatic brain injury: results of the WHO Collaborating Centre Task Force on Mild Traumatic Brain Injury. Journal of Rehabilitation Medicine, 43(suppl), 28–60.Google Scholar
  12. CDC (2010). Injury, prevention, & control: Traumatic brain injury. Center for Disease Control and Prevention. Retrieved from http://www.cdc.gov/traumaticbraininjury/statistics.html.
  13. De Beaumont, L., Théoret, H., Mongeon, D., Messier, J., Leclerc, S., Tremblay, S., et al. (2009). Brain function decline in healthy retired athletes who sustained their last sports concussion in early adulthood. Brain, 132, 695–708. doi: 10.1093/brain/awn347.CrossRefPubMedGoogle Scholar
  14. Du, A.-T., Schuff, N., Chao, L. L., Kornak, J., Jagust, W. J., Kramer, J. H., et al. (2006). Age effects on atrophy rates of entorhinal cortex and hippocampus. Neurobiology of Aging, 27, 733–740. doi: 10.1016/j.neurobiolaging.2005.03.021.CrossRefPubMedGoogle Scholar
  15. Erickson, K. I., Prakash, R. S., Voss, M. W., Chaddock, L., Hu, L., Morris, K. S., et al. (2009). Aerobic fitness is associated with hippocampal volume in elderly humans. Hippocampus, 19, 1030–1039. doi: 10.1002/hipo.20547.CrossRefPubMedPubMedCentralGoogle Scholar
  16. Faul, M. D., Xu, L., Wald, M. M., & Coronado, V. G., (2010). Traumatic brain injury in the United States: Emergency department visits, hospitalizations, and deaths 2002–2006. Atlanta: Centers for Disease Control and Prevention, National Center for Injury Prevention and Control, pp. 2–70.Google Scholar
  17. Fischl, B., Salat, D., Busa, E., Albert, M., Dieterich, M., Haselgrove, C., et al. (2002). Whole brain segmentation: Automated labeling of neuroanatomical structures in the human brain. Neuron, 33(3), 341–355. doi: 10.1016/S0896-6273(02)00569-X.CrossRefPubMedGoogle Scholar
  18. Fischl, B., van der Kouwe, A., Destrieux, C., Halgren, E., Ségonne, F., Salat, D. H., et al. (2004a). Automatically parcellating the human cerebral cortex. Cerebral Cortex, 14(1), 11–22. doi: 10.1093/cercor/bhg087.CrossRefPubMedGoogle Scholar
  19. Fischl, B., Salat, D. H., van der Kouwe, A. J., Makris, N., Ségonne, F., Quinn, B. T., & Dale, A. (2004b). Sequence-independent segmentation of magnetic resonance images. NeuroImage, 23, S69–S84. doi: 10.1016/j.neuroimage.2004.07.016.CrossRefPubMedGoogle Scholar
  20. Gale, S. D., Johnson, S. C., Bigler, E. D., & Blatter, D. D. (1995). Trauma-induced degenerative changes in brain injury: A morphometric analysis of three patients with preinjury and postinjury MR scans. Journal of Neurotrauma, 12(2), 151–158. doi: 10.1089/neu.1995.12.151.CrossRefPubMedGoogle Scholar
  21. Gioia, G. A., & Collins, M. W. (2006) Acute concussion evaluation (ace): physician/clinician version. Available at: http://ww.cdc.gov/ncipc/tbi/PhysiciansToolKit.htm.
  22. Gioia, G. A., Collins, M. W., & Isquith, P. K. (2008). Improving identification and diagnosis of mild traumatic brain injury with evidence: Psychometric support for the acute concussion evaluation. The Journal of Head Trauma Rehabilitation, 23, 230–242. doi: 10.1097/01.HTR.0000327255.38881.ca.CrossRefPubMedGoogle Scholar
  23. Hall, R. C., Hall, R. C., & Chapman, M. J. (2005). Definition, diagnosis, and forensic implications of postconcussional syndrome. Psychosomatics, 46(3), 195–202. doi: 10.1176/appi.psy.46.3.195.CrossRefPubMedGoogle Scholar
  24. Hart Jr., J., Kraut, M. A., Womack, K. B., Strain, J., Didehbani, N., Bartz, E., et al. (2013). Neuroimaging of cognitive dysfunction and depression in aging retired National Football League players: A cross-sectional study. JAMA Neurology, 70, 326–335. doi: 10.1001/2013.jamaneurol.340.CrossRefPubMedPubMedCentralGoogle Scholar
  25. Head, D., Rodrigue, K. M., Kennedy, K. M., & Raz, N. (2008). Neuroanatomical and cognitive mediators of age-related differences in episodic memory. Neuropsychology, 22(4), 491–507. doi: 10.1037/0894-4105.22.4.491.CrossRefPubMedPubMedCentralGoogle Scholar
  26. Henry, L. C., Tremblay, S., & De Beaumont, L. (2016). Long-term effects of sports Concussions: Bridging the Neurocognitive Repercussions of the Injury with the Newest Neuroimaging Data. Neuroscientist. doi: 10.1177/1073858416651034
  27. Hofman, P. A., Stapert, S. Z., van Kroonenburgh, M. J., Jolles, J., de Kruijk, J., & Wilmink, J. T. (2001). MR imaging, single-photon emission CT, and neurocognitive performance after mild traumatic brain injury. American. Journal of Neuroradiology, 22(3), 441–449.PubMedGoogle Scholar
  28. Hughes, D. G., Jackson, A., Mason, D. L., Berry, E., Hollis, S., & Yates, D. W. (2004). Abnormalities on magnetic resonance imaging seen acutely following mild traumatic brain injury: Correlation with neuropsychological tests and delayed recovery. Neuroradiology, 46(7), 550–558. doi: 10.1007/s00234-004-1227-x.CrossRefPubMedGoogle Scholar
  29. Iverson, G. L., Lovell, M. R., Smith, S., & Franzen, M. D. (2000). Prevalence of abnormal CT- scans following mild head injury. Brain Injury, 14(12), 1057–1061. doi: 10.1080/02699050050203559.CrossRefPubMedGoogle Scholar
  30. Jarrett, M., Tam, R., Hernández-Torres, E., Martin, N., Perera, W., Zhao, Y., et al. (2016). A prospective pilot investigation of brain volume, white matter Hyperintensities, and hemorrhagic lesions after mild traumatic brain injury. Frontiers in Neurology, 7, 11. doi: 10.3389/fneur.2016.00011.CrossRefPubMedPubMedCentralGoogle Scholar
  31. Johnston, K. M., Ptito, A., et al. (2001). New frontiers in diagnostic imaging in concussive head injury. Clinical Journal of Sport Medicine, 11(3), 166–175. doi: 10.1097/00042752-200107000-00007.CrossRefPubMedGoogle Scholar
  32. Kendler, K. S., Jacobson, K., Myers, J. M., & Eaves, L. J. (2008). A genetically informative developmental study of the relationship between conduct disorder and peer deviance in males. Psychological Medicine, 38, 1001–1011. doi: 10.1017/S0033291707001821.PubMedGoogle Scholar
  33. Kramer, J. H., Mungas, D., Reed, B. R., Wetzel, M. E., Burnett, M. M., Miller, B. L., et al. (2007). Longitudinal MRI and cognitive change in healthy elderly. Neuropsychology, 21(4), 412–418. doi: 10.1037/0894-4105.21.4.412.CrossRefPubMedPubMedCentralGoogle Scholar
  34. Ling, J. M., Kilmaj, S., Toulouse, T., & Mayer, A. R. (2013). A prospective study of gray matter abnormalities in mild traumatic brain injury. Neurology, 81, 2121–2127. doi: 10.1212/01.wnl.0000437302.36064.b1.CrossRefPubMedPubMedCentralGoogle Scholar
  35. List, J., Ott, S., Bukowski, M., Lindenberg, R., & Flöel, A. (2015). Cognitive function and brain structure after recurrent mild traumatic brain injuries in young-to-middle-aged adults. Frontiers in Human Neuroscience, 9, 228. doi: 10.3389/fnhum.2015.00228.CrossRefPubMedPubMedCentralGoogle Scholar
  36. MacKenzie, J. D., Siddiqi, F., Babb, J. S., Bagley, L. J., Mannon, L. J., Sinson, G. P., & Grossman, R. I. (2002). Brain atrophy in mild or moderate traumatic brain injury: A longitudinal quantitative analysis. American Journal of Neuroradiology, 23(9), 1509–1515.PubMedGoogle Scholar
  37. McCrory, P., Meeuwisse, W., Johnston, K., Dvorak, J., Aubry, M., Molloy, M., & Cantu, R. (2009). Consensus statement on concussion in sport - the 3rd international conference on concussion in sport held in Zurich. PM R, 1, 406–420. doi: 10.1016/j.pmrj.2009.03.010.CrossRefPubMedGoogle Scholar
  38. Moffitt, T. E., Harrington, H., Caspi, A., Kim-Cohen, J., Goldberg, D., Gregory, A. M., & Poulton, R. (2007). Depression and generalized anxiety disorder: Cumulative and sequential comorbidity in a birth cohort followed prospectively to age 32 years. Archives of General Psychiatry, 64, 651–660. doi: 10.1001/archpsyc.64.6.651.CrossRefPubMedGoogle Scholar
  39. Monti, J. M., Voss, M. W., Pence, A., McAuley, E., Kramer, A. F., & Cohen, N. J. (2013). History of mild traumatic brain injury is associated with deficits in relational memory, reduced hippocampal volume, and less neural activity later in life. Frontiers in Aging Neuroscience, 5, 41. doi: 10.3389/fnagi.2013.00041.CrossRefPubMedPubMedCentralGoogle Scholar
  40. Morey, R. A., Petty, C. M., Xu, Y., Hayes, J. P., Wagner, H. R., Lewis, D. V., et al. (2009). A comparison of automated seg- mentation and manual tracing for quantifying hippocampal and amygdala volumes. NeuroImage, 45, 855–866. doi: 10.1016/j.neuroimage.2008.12.033.CrossRefPubMedGoogle Scholar
  41. Niogi, S. N., & Mukherjee, P. (2010). Diffusion tensor imaging of mild TBI. The Journal of Head Trauma Rehabilitation, 25(4), 241–255. doi: 10.1097/HTR.0b013e3181e52c2a.CrossRefPubMedGoogle Scholar
  42. Piland, S. G., Ferrara, M. S., Macciocchi, S. N., Broglio, S. P., & Gould, T. E. (2010). Investigation of baseline self-report concussion symptom scores. Journal of Athletic Training, 45(3), 273–278. doi: 10.4085/1062-6050-45.3.273.CrossRefPubMedPubMedCentralGoogle Scholar
  43. Randolph, C., Tierney, M., Mohr, E., & Chase, T. (1998). The Repeatable Battery for the assessment of neuropsychological status (RBANS): Preliminary clinical validity. Journal of Clinical and Experimental Neuropsychology, 20, 310–319. doi: 10.1076/jcen.20.3.310.823.CrossRefPubMedGoogle Scholar
  44. Ross, D. E., Ochs, A. L., Seabaugh, J. M., DeMark, M. F., Shrader, C. R., Marwitz, J. H., & Havranek, M. D. (2012). Progressive brain atrophy in patients with chronic neuropsychiatric symptoms after mild traumatic brain injury: A preliminary study. Brain Injury, 26, 1500–1509. doi: 10.3109/02699052.2012.694570.CrossRefPubMedGoogle Scholar
  45. Ross, D. E., Ochs, A. L., DeSmit, M. E., & Seabaugh, J. M. (2014). Back to the future estimating pre-injury brain volume in patients with traumatic brain injury. NeuroImage. doi: 10.1016/j.neuroimage.2014.07.043.PubMedGoogle Scholar
  46. Sanfilipo, M. P., Benedict, R. H., Zivadinov, R., & Bakshi, R. (2004). Correction for intracranial volume in analysis of whole brain atrophy in multiple sclerosis: The proportion vs. residual method. NeuroImage, 22, 1732–1743.CrossRefPubMedGoogle Scholar
  47. Singh, R., Meier, T. B., Kuplicki, R., Savitz, J., Mukai, I., Cavanagh, L., Allen, T., Teague, T. K., et al. (2014). Relationship of collegiate football experience and concussion with hippocampal volume and cognitive outcomes. JAMA, 311, 1883–1888. doi: 10.1001/jama.2014.3313.CrossRefPubMedGoogle Scholar
  48. Stein, M. B., & McAllister, T. W. (2009). Exploring the convergence of posttraumatic stress disorder and mild TBI. The American Journal of Psychiatry, 166(7), 768–776. doi: 10.1176/appi.ajp.2009.08101604.CrossRefPubMedGoogle Scholar
  49. Tate, D. F., York, G. E., Reid, M. W., Cooper, D. B., Jones, L., Robin, D. A., Kennedy, J. E., & Lewis, J. (2014). Preliminary findings of cortical thickness abnormalities in blast injured service members and their relationship to clinical findings. Brain, Imaging, and Behavior, 8, 102–109. doi: 10.1007/s11682-013-9257-9.CrossRefGoogle Scholar
  50. Terribilli, D., Schaufelberger, M. S., Duran, F. L. S., Zanetti, M. V., Curiati, P. K., Menezes, P. R., et al. (2011). Age-related gray matter volume changes in the brain during non-elderly adulthood. Neurobiology of Aging, 32(2–6), 354–368. doi: 10.1016/j.neurobiolaging.2009.02.008.CrossRefPubMedPubMedCentralGoogle Scholar
  51. Terry, D. P., & Miller, L. S. (2016). Microstructural white matter differences in former high school football players with a history of multiple concussions. In Paper presented at the National Academy of Neuropsychology annual conference, October 2016. Seattle, WA.Google Scholar
  52. Terry, D. P., Adams, T. E., Ferrara, M. S., & Miller, L. S. (2015). FMRI hypoactivation during verbal learning and memory in former high school football players with multiple concussions. Archives of Clinical Neuropsychology, 30, 341–355. doi: 10.1093/arclin/acv020.CrossRefPubMedGoogle Scholar
  53. Tremblay, S., De Beaumont, L., Henry, L. C., Boulanger, Y., Evans, A. C., Bourgouin, P., et al. (2013). Sports concussions and aging: A neuroimaging investigation. Cerebral Cortex, 23, 1159–1166. doi: 10.1093/cercor/bhs102.CrossRefPubMedGoogle Scholar
  54. Tremblay, S., Henry, L. C., Bedetti, C., Larson-Dupuis, C., Gagnon, J. F., Evans, A. C., et al. (2014). Diffuse white matter tract abnormalities in clinically normal ageing retired athletes with a history of sports-related concussions. Brain, 137, 2997–3011. doi: 10.1093/brain/awu236.CrossRefPubMedPubMedCentralGoogle Scholar
  55. Wierenga, C. E., & Bondi, M. W. (2007). Use of functional magnetic resonance imaging in the early identification of Alzheimer’s disease. Neuropsychology Review, 17(2), 127–143. doi: 10.1007/s11065-007-9025-y.CrossRefPubMedPubMedCentralGoogle Scholar
  56. Wilde, E. A., Bigler, E. D., Huff, T., Wang, H., Black, G. M., Christensen, Z. P., et al. (2016). Quantitative structural neuroimaging of mild traumatic brain injury in the chronic effects of Neurotrauma consortium (CENC): Comparison of volumetric data within and across scanners. Brain Injury, 30, 1442–1451. doi: 10.1080/02699052.2016.1219063.CrossRefPubMedGoogle Scholar
  57. Zhou, Y., Kierans, A., Kenul, D., Ge, Y., Rath, J., Reaume, J., Grossman, R. I., & Lui, Y. W. (2013). Mild traumatic brain injury: Longitudinal regional brain volume changes. Radiology, 267, 880–890. doi: 10.1148/radiol.13122542.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  1. 1.Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation NetworkHarvard Medical SchoolBostonUSA
  2. 2.Department of Psychiatry, Massachusetts General HospitalHarvard Medical SchoolBostonUSA
  3. 3.Department of PsychologyUniversity of GeorgiaAthensUSA
  4. 4.BioImaging Research Center, Biomedical & Health Science InstituteUniversity of GeorgiaAthensUSA

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