Published Online:

Whole-brain automated volumetric analysis of longitudinal changes in brain volume in a well-defined cohort of patients with mild traumatic brain injury (MTBI) demonstrated atrophy within the anterior cingulate white matter (WM) bilaterally, the left cingulate gyrus isthmus WM, and the precuneal gray matter 1 year after MTBI.


To investigate longitudinal changes in global and regional brain volume in patients 1 year after mild traumatic brain injury (MTBI) and to correlate such changes with clinical and neurocognitive metrics.

Materials and Methods

This institutional review board–approved study was HIPAA compliant. Twenty-eight patients with MTBI (with 19 followed up at 1 year) with posttraumatic symptoms after injury and 22 matched control subjects (with 12 followed up at 1 year) were enrolled. Automated segmentation of brain regions to compute regional gray matter (GM) and white matter (WM) volumes was performed by using three-dimensional T1-weighted 3.0-T magnetic resonance imaging, and results were correlated with clinical metrics. Pearson and Spearman rank correlation coefficients were computed between longitudinal brain volume and neurocognitive scores, as well as clinical metrics, over the course of the follow-up period.


One year after MTBI, there was measurable global brain atrophy, larger than that in control subjects. The anterior cingulate WM bilaterally and the left cingulate gyrus isthmus WM, as well as the right precuneal GM, showed significant decreases in regional volume in patients with MTBI over the 1st year after injury (corrected P < .05); this was confirmed by means of cross-sectional comparison with data in control subjects (corrected P < .05). Left and right rostral anterior cingulum WM volume loss correlated with changes in neurocognitive measures of memory (r = 0.65, P = .005) and attention (r = 0.60, P = .01). At 1-year follow-up, WM volume in the left cingulate gyrus isthmus correlated with clinical scores of anxiety (Spearman rank correlation r = −0.68, P = .007) and postconcussive symptoms (Spearman rank correlation r = −0.65, P = .01).


These observations demonstrate structural changes to the brain 1 year after injury after a single concussive episode. Regional brain atrophy is not exclusive to moderate and severe traumatic brain injury but may be seen after mild injury. In particular, the anterior part of the cingulum and the cingulate gyrus isthmus, as well as the precuneal GM, may be distinctively vulnerable 1 year after MTBI.

© RSNA, 2013


  • 1 Rutland-Brown W, Langlois JA, Thomas KE, Xi YL. Incidence of traumatic brain injury in the United States, 2003. J Head Trauma Rehabil 2006;21(6):544–548. Crossref, MedlineGoogle Scholar
  • 2 Sosin DM, Sniezek JE, Thurman DJ. Incidence of mild and moderate brain injury in the United States, 1991. Brain Inj 1996;10(1):47–54. Crossref, MedlineGoogle Scholar
  • 3 Smits M, Hunink MG, van Rijssel DA, et al.. Outcome after complicated minor head injury. AJNR Am J Neuroradiol 2008;29(3):506–513. Crossref, MedlineGoogle Scholar
  • 4 Kraus JF, McArthur DL. Epidemiologic aspects of brain injury. Neurol Clin 1996;14(2):435–450. Crossref, MedlineGoogle Scholar
  • 5 Sorenson SB, Kraus JF. Occurrence, severity and outcomes of brain injury. J Head Trauma Rehabil 1991;6(2):1–12. CrossrefGoogle Scholar
  • 6 Barth JT, Macciocchi SN, Giordani B, Rimel R, Jane JA, Boll TJ. Neuropsychological sequelae of minor head injury. Neurosurgery 1983;13(5):529–533. Crossref, MedlineGoogle Scholar
  • 7 McAllister TW. Neuropsychiatric sequelae of head injuries. Psychiatr Clin North Am 1992;15(2):395–413. Crossref, MedlineGoogle Scholar
  • 8 Alexander MP. Minor traumatic brain injury: a review of physiogenesis and psychogenesis. Semin Clin Neuropsychiatry 1997;2(3):177–187. MedlineGoogle Scholar
  • 9 Dikmen S, McLean A, Temkin N. Neuropsychological and psychosocial consequences of minor head injury. J Neurol Neurosurg Psychiatry 1986;49(11):1227–1232. Crossref, MedlineGoogle Scholar
  • 10 Anderson CV, Bigler ED. The role of caudate nucleus and corpus callosum atrophy in trauma-induced anterior horn dilation. Brain Inj 1994;8(6):565–569. Crossref, MedlineGoogle Scholar
  • 11 Anderson CV, Wood DM, Bigler ED, Blatter DD. Lesion volume, injury severity, and thalamic integrity following head injury. J Neurotrauma 1996;13(1):35–40. Crossref, MedlineGoogle Scholar
  • 12 Bigler ED, Blatter DD, Anderson CV, et al.. Hippocampal volume in normal aging and traumatic brain injury. AJNR Am J Neuroradiol 1997;18(1):11–23. MedlineGoogle Scholar
  • 13 Gale SD, Burr RB, Bigler ED, Blatter D. Fornix degeneration and memory in traumatic brain injury. Brain Res Bull 1993;32(4):345–349. Crossref, MedlineGoogle Scholar
  • 14 Yount R, Raschke KA, Biru M, et al.. Traumatic brain injury and atrophy of the cingulate gyrus. J Neuropsychiatry Clin Neurosci 2002;14(4):416–423. Crossref, MedlineGoogle Scholar
  • 15 McKee AC, Cantu RC, Nowinski CJ, et al.. Chronic traumatic encephalopathy in athletes: progressive tauopathy after repetitive head injury. J Neuropathol Exp Neurol 2009;68(7):709–735. Crossref, MedlineGoogle Scholar
  • 16 Stern RA, Riley DO, Daneshvar DH, Nowinski CJ, Cantu RC, McKee AC. Long-term consequences of repetitive brain trauma: chronic traumatic encephalopathy. PM R 2011;3(10 Suppl 2):S460–S467. Crossref, MedlineGoogle Scholar
  • 17 Grossman EJ, Ge Y, Jensen JH, et al.. Thalamus and cognitive impairment in mild traumatic brain injury: a diffusional kurtosis imaging study. J Neurotrauma 2012;29(13):2318–2327. Crossref, MedlineGoogle Scholar
  • 18 Raz E, Jensen JH, Ge Y, et al.. Brain iron quantification in mild traumatic brain injury: a magnetic field correlation study. AJNR Am J Neuroradiol 2011;32(10):1851–1856. Crossref, MedlineGoogle Scholar
  • 19 Tang L, Ge Y, Sodickson DK, et al.. Thalamic resting-state functional networks: disruption in patients with mild traumatic brain injury. Radiology 2011;260(3):831–840. LinkGoogle Scholar
  • 20 Zhou Y, Milham MP, Lui YW, et al.. Default-mode network disruption in mild traumatic brain injury. Radiology 2012;265(3):882–892. LinkGoogle Scholar
  • 21 Kay T, Harrington DE, Adams R. Definition of mild traumatic brain injury. J Head Trauma Rehabil 1993;8(3):86–87. CrossrefGoogle Scholar
  • 22 Petchprapai N, Winkelman C. Mild traumatic brain injury: determinants and subsequent quality of life: a review of the literature. J Neurosci Nurs 2007;39(5):260–272. Crossref, MedlineGoogle Scholar
  • 23 Freeborough PA, Fox NC. The boundary shift integral: an accurate and robust measure of cerebral volume changes from registered repeat MRI. IEEE Trans Med Imaging 1997;16(5):623–629. Crossref, MedlineGoogle Scholar
  • 24 Leung KK, Clarkson MJ, Bartlett JW, et al.. Robust atrophy rate measurement in Alzheimer’s disease using multi-site serial MRI: tissue-specific intensity normalization and parameter selection. Neuroimage 2010;50(2):516–523. Crossref, MedlineGoogle Scholar
  • 25 Fischl B, Salat DH, Busa E, et al.. Whole brain segmentation: automated labeling of neuroanatomical structures in the human brain. Neuron 2002;33(3):341–355. Crossref, MedlineGoogle Scholar
  • 26 Destrieux C, Fischl B, Dale A, Halgren E. Automatic parcellation of human cortical gyri and sulci using standard anatomical nomenclature. Neuroimage 2010;53(1):1–15. Crossref, MedlineGoogle Scholar
  • 27 Fischl B, van der Kouwe A, Destrieux C, et al.. Automatically parcellating the human cerebral cortex. Cereb Cortex 2004;14(1):11–22. Crossref, MedlineGoogle Scholar
  • 28 Salat DH, Greve DN, Pacheco JL, et al.. Regional white matter volume differences in nondemented aging and Alzheimer’s disease. Neuroimage 2009;44(4):1247–1258. Crossref, MedlineGoogle Scholar
  • 29 Reuter M, Schmansky NJ, Rosas HD, Fischl B. Within-subject template estimation for unbiased longitudinal image analysis. Neuroimage 2012;61(4):1402–1418. Crossref, MedlineGoogle Scholar
  • 30 Reuter M, Fischl B. Avoiding asymmetry-induced bias in longitudinal image processing. Neuroimage 2011;57(1):19–21. Crossref, MedlineGoogle Scholar
  • 31 Reuter M, Rosas HD, Fischl B. Highly accurate inverse consistent registration: a robust approach. Neuroimage 2010;53(4):1181–1196. Crossref, MedlineGoogle Scholar
  • 32 Smith A. Symbol Digit Modalities Test manual. Los Angeles, Calif: Western Psychological Services, 1973. Google Scholar
  • 33 Wechsler D. Wechsler Adult Intelligence Scale-III. New York, NY: The Psychological Corporation, 1985. Google Scholar
  • 34 Reitan R. Trail Making Test: manual for administration and scoring. Tucson, Ariz: Reitan Neuropsychology Laboratory, 1992. Google Scholar
  • 35 Delis DC, Kramer JH, Kaplan E, Ober BA. California Verbal Learning Test. Adult Version. Manual. 2nd ed. San Antonio, Tex: The Psychological Corporation, 2000. Google Scholar
  • 36 Meyers JE, Meyers KR. Rey Complex Figure Test and Recognition Trial: professional manual. Odessa, Fla: Psychological Assessment Resources, 1995. Google Scholar
  • 37 Gronwall D, Wrightson P. Delayed recovery of intellectual function after minor head injury. Lancet 1974;2(7881):605–609. Crossref, MedlineGoogle Scholar
  • 38 Beck AT, Epstein N, Brown G, Steer RA. An inventory for measuring clinical anxiety: psychometric properties. J Consult Clin Psychol 1988;56(6):893–897. Crossref, MedlineGoogle Scholar
  • 39 Beck AT, Ward CH, Mendelson M, Mock J, Erbaugh J. An inventory for measuring depression. Arch Gen Psychiatry 1961;4:561–571. Crossref, MedlineGoogle Scholar
  • 40 Krupp LB, LaRocca NG, Muir-Nash J, Steinberg AD. The fatigue severity scale: application to patients with multiple sclerosis and systemic lupus erythematosus. Arch Neurol 1989;46(10):1121–1123. Crossref, MedlineGoogle Scholar
  • 41 Aubry M, Cantu R, Dvorak J, et al.. Summary and agreement statement of the First International Conference on Concussion in Sport, Vienna 2001: recommendations for the improvement of safety and health of athletes who may suffer concussive injuries. Br J Sports Med 2002;36(1):6–10. Crossref, MedlineGoogle Scholar
  • 42 Chen JK, Johnston KM, Collie A, McCrory P, Ptito A. A validation of the post concussion symptom scale in the assessment of complex concussion using cognitive testing and functional MRI. J Neurol Neurosurg Psychiatry 2007;78(11):1231–1238. Crossref, MedlineGoogle Scholar
  • 43 Smith SM, Nichols TE. Threshold-free cluster enhancement: addressing problems of smoothing, threshold dependence and localisation in cluster inference. Neuroimage 2009;44(1):83–98. Crossref, MedlineGoogle Scholar
  • 44 Ruff RM, Camenzuli L, Mueller J. Miserable minority: emotional risk factors that influence the outcome of a mild traumatic brain injury. Brain Inj 1996;10(8):551–565. Crossref, MedlineGoogle Scholar
  • 45 Rutherford WH, Merrett JD, McDonald JR. Symptoms at one year following concussion from minor head injuries. Injury 1979;10(3):225–230. Crossref, MedlineGoogle Scholar
  • 46 Hudak A, Warner M, Marquez de la Plata C, Moore C, Harper C, Diaz-Arrastia R. Brain morphometry changes and depressive symptoms after traumatic brain injury. Psychiatry Res 2011;191(3):160–165. Crossref, MedlineGoogle Scholar
  • 47 Levine B, Kovacevic N, Nica EI, et al.. The Toronto traumatic brain injury study: injury severity and quantified MRI. Neurology 2008;70(10):771–778. Crossref, MedlineGoogle Scholar
  • 48 Bush G, Whalen PJ, Rosen BR, Jenike MA, McInerney SC, Rauch SL. The counting Stroop: an interference task specialized for functional neuroimaging—validation study with functional MRI. Hum Brain Mapp 1998;6(4):270–282. Crossref, MedlineGoogle Scholar
  • 49 Egner T, Hirsch J. The neural correlates and functional integration of cognitive control in a Stroop task. Neuroimage 2005;24(2):539–547. Crossref, MedlineGoogle Scholar
  • 50 Kolassa IT, Wienbruch C, Neuner F, et al.. Altered oscillatory brain dynamics after repeated traumatic stress. BMC Psychiatry 2007;7:56. Crossref, MedlineGoogle Scholar
  • 51 Lanius RA, Bluhm R, Lanius U, Pain C. A review of neuroimaging studies in PTSD: heterogeneity of response to symptom provocation. J Psychiatr Res 2006;40(8):709–729. Crossref, MedlineGoogle Scholar
  • 52 Haupt S, Axmacher N, Cohen MX, Elger CE, Fell J. Activation of the caudal anterior cingulate cortex due to task-related interference in an auditory Stroop paradigm. Hum Brain Mapp 2009;30(9):3043–3056. Crossref, MedlineGoogle Scholar
  • 53 Polli FE, Barton JJS, Cain MS, Thakkar KN, Rauch SL, Manoach DS. Rostral and dorsal anterior cingulate cortex make dissociable contributions during antisaccade error commission. Proc Natl Acad Sci U S A 2005;102(43):15700–15705. Crossref, MedlineGoogle Scholar
  • 54 Kiehl KA, Liddle PF, Hopfinger JB. Error processing and the rostral anterior cingulate: an event-related fMRI study. Psychophysiology 2000;37(2):216–223. Crossref, MedlineGoogle Scholar
  • 55 Chen JK, Johnston KM, Petrides M, Ptito A. Neural substrates of symptoms of depression following concussion in male athletes with persisting postconcussion symptoms. Arch Gen Psychiatry 2008;65(1):81–89. Crossref, MedlineGoogle Scholar
  • 56 di Pellegrino G, Ciaramelli E, Làdavas E. The regulation of cognitive control following rostral anterior cingulate cortex lesion in humans. J Cogn Neurosci 2007;19(2):275–286. Crossref, MedlineGoogle Scholar
  • 57 Bohnen N, Jolles J. Neurobehavioral aspects of postconcussive symptoms after mild head injury. J Nerv Ment Dis 1992;180(11):683–692. Crossref, MedlineGoogle Scholar
  • 58 Cicerone KD, Azulay J. Diagnostic utility of attention measures in postconcussion syndrome. Clin Neuropsychol 2002;16(3):280–289. Crossref, MedlineGoogle Scholar
  • 59 Vogt BA, Laureys S. Posterior cingulate, precuneal and retrosplenial cortices: cytology and components of the neural network correlates of consciousness. Prog Brain Res 2005;150:205–217. Crossref, MedlineGoogle Scholar
  • 60 Silver JM, McAllister TW, Yudofsky SC. Textbook of traumatic brain injury. 2nd ed. Arlington, Va: American Psychiatric Publishing, 2011. CrossrefGoogle Scholar
  • 61 Bendlin BB, Ries ML, Lazar M, et al.. Longitudinal changes in patients with traumatic brain injury assessed with diffusion-tensor and volumetric imaging. Neuroimage 2008;42(2):503–514. Crossref, MedlineGoogle Scholar
  • 62 Gultekin SH, Smith TW. Diffuse axonal injury in craniocerebral trauma: a comparative histologic and immunohistochemical study. Arch Pathol Lab Med 1994;118(2):168–171. MedlineGoogle Scholar
  • 63 Haznedar MM, Buchsbaum MS, Hazlett EA, Shihabuddin L, New A, Siever LJ. Cingulate gyrus volume and metabolism in the schizophrenia spectrum. Schizophr Res 2004;71(2-3):249–262. Crossref, MedlineGoogle Scholar
  • 64 Max JE, Keatley E, Wilde EA, et al.. Depression in children and adolescents in the first 6 months after traumatic brain injury. Int J Dev Neurosci 2012;30(3):239–245. Crossref, MedlineGoogle Scholar

Article History

Received December 6, 2012; revision requested January 29, 2013; revision received February 8; accepted February 14; final version accepted February 15.
Published online: June 2013
Published in print: June 2013