Skip to main content Accessibility help
×
Home

Repeated Sport-Related Concussion Shows Only Minimal White Matter Differences Many Years After Playing High School Football

  • Douglas P. Terry (a1), Catherine M. Mewborn (a2) and L. Stephen Miller (a2)

Abstract

Objective: Multiple concussions sustained in youth sport may be associated with later-life brain changes and worse cognitive outcomes. We examined the association between two or more concussions during high school football and later-life white matter (WM) microstructure (i.e., 22–47 years following football retirement) using diffusion tensor imaging (DTI). Method: Forty former high school football players aged 40–65 who received 2+ concussions during high school football (N = 20), or denied concussive events (N = 20) were recruited. Participants underwent neurocognitive testing and DTI scanning. Results: Groups did not statistically differ on age, education, or estimated pre-morbid intelligence. Tract-based Spatial Statistics (TBSS) correcting for Family-Wise Error (FWE)(p < .05) did not yield differences between groups at the whole-brain level. Region of interest analyses showed higher mean diffusivity (MD) in the anterior limb of the internal capsule (ALIC) in the concussed group compared to the non-concussed former players. More liberal analyses (i.e., p < .001, uncorrected for multiple comparisons, ≥8 voxels) also revealed that former players endorsing 2+ concussions had higher MD in the ALIC. Analyses that covaried for age did not reveal differences at either threshold. Concussive histories were not associated with worse cognitive functioning, nor did it impact the relationship between neuropsychological scores and DTI metrics. Discussion: Results suggest only minimal neuroanatomical brain differences in former athletes many years following original concussive injuries compared to controls.

Copyright

Corresponding author

Correspondence and reprint requests to: L. Stephen Miller, 125 Baldwin Street, Psychology Bldg Rm 202, University of Georgia, Athens, GA 30602. E-mail: lsmiller@uga.edu

References

Hide All
Alexander, A.L., Lee, J.E., Lazar, M., & Field, A.S. (2007). Diffusion tensor imaging of the brain. Neurotherapeutics, 4, 316329. doi:10.1016/j.nurt.2007.05.011
American Congress of Rehabilitation Medicine. (1993). Definition of mild traumatic brain injury. Journal of Head Trauma Rehabilitation, 8, 8687.
Andersson, J.L.R., Jenkinson, M., & Smith, S. (2007a). Non-linear optimisation. FMRIB technical report TR07JA1, Retrieved from www.fmrib.ox.ac.uk/analysis/techrep
Andersson, J.L.R., Jenkinson, M., & Smith, S. (2007b). Non-linear registration, aka Spatial normalisation FMRIB technical report TR07JA2, Retrieved from www.fmrib.ox.ac.uk/analysis/techrep
Aoki, Y., Inokuchi, R., Gunshin, M., Yahagi, N., & Suwa, H. (2012). Diffusion tensor imaging studies of mild traumatic brain injury: a meta-analysis. Journal of Neurology, Neurosurgery, and Psychiatry, 83, 870876. doi:10.1136/jnnp-2012-302742
Arfanakis, K., Haughton, V.M., Carew, J.D., Rogers, B.P., Dempsey, R.J., & Meyerand, M.E. (2002). Diffusion tensor MR imaging in diffuse axonal injury. American Journal of Neuroradiology, 23, 794802.
Astafiev, S.V., Shulman, G.L., Metcalf, N.V., Rengachary, J., MacDonald, C.L., Harrington, D.L., Maruta, J., Shimony, J.S., Ghajar, J., Diwakar, M., Huang, M.X., Lee, R.R., & Corbetta, M. (2015). Abnormal white matter blood-oxygen-level-dependent signals in chronic mild traumatic brain injury. Journal of Neurotrauma, 32(16), 12541271. doi:10.1089/neu.2014.3547
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, 14471459. doi:10.1089/neu.2007.0241
Bazarian, J.J., Zhu, T., Zhong, J., Janigro, D., Rozen, E., Roberts, A., Javien, H., Merchant-Borna, K., Abar, B., & Blackman, E.G. (2014). Persistent, long-term cerebral white matter changes after sports-related repetitive head impacts. PLOS ONE, 9, e94734. doi:10.1371/journal.pone.0094734
Beaulieu, C. & Allen, P.S., (1994). Determinants of anisotropic water diffusion in nerves. Magnetic Resonance in Medicine, 31, 394400. doi:10.1002/mrm.1910310408
Behrens, T.E., Woolrich, M.W., Jenkinson, M., Johansen-Berg, H., Nunes, R.G., Clare, S., Matthews, P.M., Brady, J.M., & Smith, S.M. (2003). Characterization and propagation of uncertainty in diffusion-weighted MR imaging. Magnetic Resonance in Medicine , 50, 1077–88. doi:10.1002/mrm.10609
Benson, R.R., Meda, S.A., Vasudevan, S., Kou, Z., Govindarajan, K.A., Hanks, R.A., Millis, S.R., Makki, M., Latif, Z., Coplin, W., Meythaler, J., & Haacke, E.M. (2007). Global white matter analysis of diffusion tensor images is predictive of injury severity in traumatic brain injury. Journal of Neurotrauma, 24, 446–459. doi:10.1089/neu.2006.0153
Bigler, E.D. (2013). Neuroimaging biomarkers of mild traumatic brain injury (mTBI). Neuropsychology Review, 23, 169209. doi:10.1007/s11065-013-9237-2
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.
Cassidy, J.D., Carroll, L.J., Peloso, P.M., Borg, J., von Holst, H., Holm, L., Kraus, J., Coronado, V.G., & 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, Supplement 43, 2860.
Cubon, V.A. & Putukian, M. (2011). A diffusion tensor imaging study on the white matter skeleton in individuals with sports-related concussion. Journal of Neurotrauma, 28, 189201. doi:10.1089/neu.2010.1430
Davenport, E.M., Whitlow, C.T., Urban, J.E., Espeland, M.A., Jung, Y., Rosenbaum, D.A., Gioia, G.A., Powers, A.K., Stitzel, J.D., & Maldjian, J.A. (2014). Abnormal white matter integrity related to head impact exposure in a season of high school varsity football. Journal of Neurotrauma, 31, 16171624. doi:10.1089/neu.2013.3233
Dean, P.J., Sato, J.R., Vieira, G., McNamara, A., & Sterr, A. (2015). Long-term structural changes after mTBI and their relation to postconcussion symptoms. Brain Injury, 29(10), 12111218. doi:10.3109/02699052.2015.1035334
Dettwiler, A., Murugavel, M., Cubon, V., Putukian, M., Echemendia, R., Cabrera, J., & Osherson, D. (2014). A longitudinal diffusion tensor imaging study assessing white matter fiber tracts after sports related concussion. Journal of Neurotrauma, 31, 18601871. doi:10.1089/neu.2014.3368
Dykiert, D. & Deary, I.J. (2013). Retrospective validation of WTAR and NART scores as estimators of prior cognitive ability using the Lothian Birth Cohort 1936. Psychological Assessment, 25(4), 13611366. doi:10.1037/a0033623
Glenn, O.A., Henry, R.G., Berman, J.I., Chang, P.C., Miller, S.P., Vigneron, D.B., & Barkovich, A.J. (2003). DTI-based three-dimensional tractography detects differences in the pyramidal tracts of infants and children with congenital hemiparesis. Journal of Magnetic Resonance Imaging, 18(6), 641648. doi:10.1002/jmri.10420
Green, P. (2004). Medical Symptom Validity Test (MSVT) for Microsoft Windows: User’s manual. Edmonton: Paul Green Publishing.
Green, R.E., Melo, B., Christensen, B., Ngo, L.A., Monette, G., & Bradbury, C. (2008). Measuring premorbid IQ in traumatic brain injury: an examination of the validity of the Wechsler Test of Adult Reading (WTAR). Journal of Clinical and Experimental Neuropsychology, 30(2), 163172. doi:10.1080/13803390701300524
Hart, J., Kraut, M.A., Womack, K.B., Strain, J., Didehbani, N., Bartz, E., Conover, H., Mansinghani, S., Lu, H., & Cullum, C.M. (2013). Neuroimaging of cognitive dysfunction and depression in aging retired National Football League players: a cross-sectional study. JAMA Neurology, 70(3), 326335. doi:10.1001/2013.jamaneurol.340
Hayes, A.F. (2013). Methodology in the social sciences. Introduction to mediation, moderation, and conditional process analysis: A regression-based approach, New York, NY: The Guilford Press.
Howe, L.L., Anderson, A.M., Kaufman, D.A., Sachs, B.C., & Loring, D.W. (2007). Characterization of the Medical Symptom Validity Test in evaluation of clinically referred memory disorders clinic patients. Archives of Clinical Neuropsychology, 22, 753–61. doi: 10.1016/j.acn.2007.06.003
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), 550558. doi:10.1007/s00234-004-1227-x
Inglese, M., Makani, S., Johnson, G., Cohen, B.A., Silver, J.A., Gonen, O., & Grossman, R.I. (2005). Diffuse axonal injury in mildtraumatic brain injury: a diffusion tensor imaging study. Journal of Neurosurgery, 103(2), 298303. 10.3171/jns.2005.103.2.0298
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), 10571061. doi:10.1080/02699050050203559
Jones, D.K., Catani, M., Pierpaoli, C., Reeves, S.J., Shergill, S.S., & O’sullivan, M. (2006). Age effects on diffusion tensor magnetic resonance imaging tractography measures of frontal cortex connections in schizophrenia. Human Brain Mapping, 27, 230238. doi:10.1002/hbm.20179
Kou, Z., Wu, Z., Tong, K.A., Holshouser, B., Benson, R.R., Hu, J., & Haacke, E.M. (2010). The role of advanced MR imaging findings as biomarkers of TBI. The Journal of Head Trauma Rehabilitation, 25(4), 267282. doi:10.1097/HTR.0b013e3181e54793
Kumar, R., Gupta, R.K., Husain, M., Chaudhry, C., Srivastava, A., Saksena, S., & Rathore, R.K. (2009). Comparative evaluation of corpus callosum DTI metrics in acute mild and moderate traumatic brain injury: its correlation with neuropsychometric tests. Brain Injury, 23(7), 675685. doi:10.1080/02699050903014915
Lange, R.T., Iverson, G.L., Brubacher, J.R., Madler, B., & Heran, M.K. (2012). Diffusion tensor imaging findings are not strongly associated with postconcussional disorder 2 months following mild traumatic brain injury. Journal of Head Trauma Rehabilitation, 27, 188198. doi:10.1097/HTR.0b013e318217f0ad
Lipton, M.L., Gellella, E., Lo, C., Gold, T., Ardekani, B.A., Shifteh, K., Bello, J.A., & Branch, C.A. (2008). Multifocal white matter ultrastructural abnormalities in mild traumatic brain injury with cognitive disability: a voxel-wise analysis of diffusion tensor imaging. Journal of Neurotrauma, 25, 13351342. doi:10.1089/neu.2008.0547
Lipton, M.L., Gulko, E., Zimmerman, M.E., Friedman, B.W., Kim, M., Gellella, E., Gold, T., Shifteh, K., Ardekani, B.A., & Branch, C.A. (2009). Diffusion-tensor imaging implicates prefrontal axonal injury in executive function impairment following very mild traumatic brain injury. Radiology, 252(3), 816824. doi:10.1148/radiol.2523081584
Lipton, M.L., Kim, N., Park, Y.K., Hulkower, M.B., Gardin, T.M., Shifteh, K., … Branch, C.A. (2012). Robust detection of traumatic axonal injury in individual mild traumatic brain injury patients: intersubject variation, change over time and bidirectional changes in anisotropy. Brain Imaging and Behavior, 6(2), 329–342. doi:10.1007/s11682-012-9175-2
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
Lo, C., Shifteh, K., Gold, T., Bello, J.A., & Lipton, M.L. (2009). Diffusion tensor imaging abnormalities in patients with mild traumatic brain injury and neurocognitive impairment. Journal of Computer Assisted Tomography, 33(2), 293297. doi:10.1097/RCT.0b013e31817579d1
Maruta, J., Palacios, E.M., Zimmerman, R.D., Ghajar, J., & Mukherjee, P. (2016). Chronic post-concussion neurocognitive deficits. I. Relationship with white matter integrity. Frontiers in Human Neuroscience, 10, 35. doi:10.3389/fnhum.2016.00035
McAllister, T.W., Ford, J.C., Flashman, L.A., Maerlender, A., Greenwald, R.M., Beckwith, J.G., Bolander, R.P., Tosteson, T.D., Turco, J.H., Raman, R., & Jain, S. (2014). Effects of head impact measures in a cohort of collegiate contact sport athletes. Neurology, 82, 6369. doi:10.1212/01.wnl.0000438220.16190.42
McKay, C., Wertheimer, J.C., Fichtenberg, N.L., & Casey, J.E. (2008). The repeatable battery for the assessment of neuropsychological status (RBANS): clinical utility in a traumatic brain injury sample. The Clinical Neuropsychologist, 22, 228241. doi:10.1080/13854040701260370
Miles, L., Grossman, R. I., Johnson, G., Babb, J.S., Diller, L., &Inglese, M. (2008). Short-term DTI predictors of cognitive dysfunction in mild traumatic brain injury. Brain Injury, 22(2), 115122. doi:10.1080/02699050801888816
Mori, S., Oishi, K., Jiang, H., Jiang, L., Li, X., Akhter, K., Hua, K., Faria, A.V., Mahmood, A., Woods, R., Toga, A.W., Pike, G.B., Neto, P.R., Evans, A., Zhang, J., Huang, H., Miller, M.I., van Zijl, P., & Mazziotta, J. (2008). Stereotaxic white matter atlas based on diffusion tensor imaging in an ICBM template. NeuroImage, 40, 570582. doi:10.1016/j.neuroimage.2007.12.035
Neil, J., Miller, J., Mukherjee, P., & Huppi, P.S. (2002). Diffusion tensor imaging of normal and injured developing human brain: A technical review. NMR in Biomedicine, 15, 543552. doi:10.1002/nbm.784
Niogi, S.N., Mukherjee, P., Ghajar, J., Johnson, C., Kolster, R.A., Sarkar, R., Lee, H., Meeker, M., Zimmerman, R.D., Manley, G.T., & McCandliss, B.D. (2008). Extent of microstructural white matter injury in postconcussive syndrome correlates with impaired cognitive reaction time: a 3T diffusion tensor imaging study of mild traumatic brain injury. American Journal of Neuroradiology, 29(5), 967973. doi:10.3174/ajnr.A0970
Niogi, S.N., Mukherjee, P., Ghajar, J., Johnson, C.E., Kolster, R., Lee, H., Suh, M., Zimmerman, R.D., Manley, G.T., & McCandliss, B.D. (2008). Structural dissociation of attentional control and memory in adults with and without mild traumatic brain injury. Brain, 131(12), 32093221. doi:10.1093/brain/awn247
Psychological Corporation. (2001). Wechsler Test of Adult Reading. San Antonio, TX: The Psychological Corporation.
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, 310319. doi:10.1076/jcen.20.3.310.823
Rueckert, D., Sonoda, L.I., Hayes, C., Hill, D.L.G., Leach, M.O., & Hawkes, D.J. (1999) Non-rigid registration using free-form deformations: Application to breast MR images. IEEE Transactions on Medical Imaging, 18(8), 712721.
Shenton, M.E., Hamoda, H.M., Schneiderman, J.S., Bouix, S., Pasternak, O., Rathi, Y., Vu, M.A., Purohit, M.P., Helmer, K., Koerte, I., Lin, A.P., Westin, C.F., Kikinis, R., Kubicki, M., Stern, R.A., & Zafonte, R. (2012). A review of magnetic resonance imaging and diffusiontensor imaging findings in mild traumatic brain injury. Brain Imaging Behavior, 6, 137192. doi:10.1007/s11682-012-9156-5
Smith, S.M., Jenkinson, M., Johansen-Berg, H., Rueckert, D., Nichols, T.E., Mackay, C.E., Watkins, K.E., Ciccarelli, O., Cader, M.Z., Matthews, P.M., & Behrens, T.E.J. (2006). Tract-based spatial statistics: Voxelwise analysis of multi- subject diffusion data. NeuroImage, 31, 14871505. doi:10.1016/j.neuroimage.2006.02.024
Smith, S.M., Jenkinson, M., Woolrich, M.W., Beckmann, C.F., Behrens, T.E.J., Johansen-Berg, H., Bannister, P.R., De Luca, M., Drobnjak, I., Flitney, D.E., Niazy, R.K.., Saunders, J., Vickers, J., Zhang, Y., De Stefano, N., Brady, J.M., & Matthews, P.M. (2004). Advances in functional and structural MR image analysis and implementation as FSL. NeuroImage, 23(S1), 208219. doi:10.1016/j.neuroimage.2004.07.051
Smith, S.M. & Nichols, T.E. (2009). Threshold-free cluster enhancement: addressing problems of smoothing, threshold dependence and localisation in cluster inference. Neuroimage, 44, 8398. doi: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, 17141722. doi:10.1016/j.neuroimage.2003.07.005
Song, S.K., Sun, S.W., Ramsbottom, M.J., Chang, C., Russell, J., & Cross, A.H. (2002). Dysmyelination revealed through MRI as increased radial (but unchanged axial) diffusion of water. Neuroimage, 17, 14291436. doi:10.1006/nimg.2002.1267
Song, S.K., Yoshino, J., Le, T.Q., Lin, S.J., Sun, S.W., Cross, A.H., & Armstrong, R.C. (2005). Demyelination increases radial diffusivity in corpus callosum of mouse brain. Neuroimage, 26, 132140. doi:10.1016/j.neuroimage.2005.01.028
Strain, J., Didehbani, N., Cullum, C.M., Mansinghani, S., Conover, H., Kraut, M. A., Hart, J. Jr, & Womack, K.B. (2013). Depressive symptoms and white matter dysfunction in retired NFL players with concussion history. Neurology, 81(1), 2532. doi:10.1212/WNL.0b013e318299ccf8
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, 341355. doi:10.1093/arclin/acv020
Tremblay, S., Henry, L.C., Bedetti, C., Larson-Dupuis, C., Gagnon, J.F., Evans, A.C., Théoret, H., Lassonde, M., & De Beaumont, L. (2014). Diffuse white matter tract abnormalities in clinically normal ageing retired athletes with a history of sports-related concussions. Brain, 137(Pt 11), 29973011. doi:10.1093/brain/awu236
Vos, S.B., Jones, D.K., Jeurissen, B., Viergever, M.A., &Leemans, A. (2012). The influence of complex white matter architecture on the mean diffusivity in diffusion tensor MRI of the human brain. Neuroimage, 59, 22082216. doi:10.1016/j.neuroimage.2011.09.086
Wada, T., Asano, Y., & Shinoda, J. (2012). Decreased fractional anisotropy evaluated using tract-based spatial statistics and correlated with cognitive dysfunction in patients with mild traumatic brain injury in the chronic stage. American Journal of Neuroradiology, 33, 21172122. doi:10.3174/ajnr.A3141
Weinberger, D.R. & Radulescu, E. (2015). Finding the elusive psychiatric “Lesion” with 21st centure neuroanatomy: A note of caution. The American Journal of Psychiatry, 173, 2733. doi:10.1176/appi.ajp.2015.15060753
Winkler, A.M., Ridgway, G.R., Webster, M.A., Smith, S.M., & Nichols, T.E. (2014). Permutation inference for the general linear model. Neuroimage, 92, 381397 (2014). doi:10.1016/j.neuroimage.2014.01.060
Zhang, K., Johnson, B., Pennell, D., Ray, W., Sebastianelli, W., & Slobounov, S. (2010). Are functional deficits in concussed individuals consistent with white matter structural alterations: combined FMRI & DTI study. Experimental Brain Research, 204, 5770. doi:10.1007/s00221-010-2294-3
Zuckerman, S.L., Apple, R.P., Odom, M.J., Lee, Y.M., Solomon, G.S., & Sills, A.K. (2014). Effect of sex on symptoms and return to baseline in sport-related concussion. Journal of Neurosurgery, Pediatrics, 13, 7281. doi:10.3171/2013.9.PEDS13257

Keywords

Metrics

Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed