Brain Imaging and Behavior

, Volume 7, Issue 3, pp 307–315 | Cite as

Early metabolic crisis-related brain atrophy and cognition in traumatic brain injury

  • Matthew J. WrightEmail author
  • David L. McArthur
  • Jeffry R. Alger
  • Jack Van Horn
  • Andrei Irimia
  • Maria Filippou
  • Thomas C. Glenn
  • David A. Hovda
  • Paul Vespa
Original Research


Traumatic brain injury often results in acute metabolic crisis. We recently demonstrated that this is associated with chronic brain atrophy, which is most prominent in the frontal and temporal lobes. Interestingly, the neuropsychological profile of traumatic brain injury is often characterized as ‘frontal-temporal’ in nature, suggesting a possible link between acute metabolic crisis-related brain atrophy and neurocognitive impairment in this population. While focal lesions and diffuse axonal injury have a well-established role in the neuropsychological deficits observed following traumatic brain injury, no studies to date have examined the possible contribution of acute metabolic crisis-related atrophy in the neuropsychological sequelae of traumatic brain injury. In the current study we employed positron emission tomography, magnetic resonance imaging, and neuropsychological assessments to ascertain the relationship between acute metabolic crisis-related brain atrophy and neurocognitive outcome in a sample of 14 right-handed traumatic brain injury survivors. We found that acute metabolic crisis‐related atrophy in the frontal and temporal lobes was associated with poorer attention, executive functioning, and psychomotor abilities at 12 months post-injury. Furthermore, participants with gross frontal and/or temporal lobe atrophy exhibited numerous clinically significant neuropsychological deficits in contrast to participants with other patterns of brain atrophy. Our findings suggest that interventions that reduce acute metabolic crisis may lead to improved functional outcomes for traumatic brain injury survivors.


Traumatic brain injury Metabolic crisis Neuropsychology Brain atrophy Neuroimaging 



This research was supported by NS049471, NS02089, P01-NS058489 and the California State Neurotrauma Initiative.


  1. Adams, J. H., & Jennett, D. I. G. (2001). The structural basis of moderate disability after traumatic brain injury. Journal of Neurology, Neurosurgery, and Psychiatry, 71, 521–524. doi: 10.1136/jnnp.71.4.521.PubMedCrossRefGoogle Scholar
  2. Adams, J. H., Doyle, D., Graham, D. I., Parker, L., & Scott, G. (1980). Brain damage in fatal non-missile head injury. Journal of Clinical Pathology, 33, 1132–1145. doi: 10.1136/jcp.33.12.1132.PubMedCrossRefGoogle Scholar
  3. Adams, J. H., Doyle, D., Ford, I., Gennarelli, T. A., Graham, D. I., & McLellan, D. R. (1989). Diffuse axonal injury in head injury: definition, diagnosis, and grading. Histopathology, 15, 49–59. doi: 10.1111/j.1365-2559.1989.tb03040.x.PubMedCrossRefGoogle Scholar
  4. Army Individual Test Battery. (1944). Manual of directions and scoring. Washington, D.C: War Department, Adjutant General’s Office.Google Scholar
  5. Auerbach, S. H. (1986). Neuroanatomical correlates of attention and memory in traumatic brain injury: an application of neurobehavioral subtypes. The Journal of Head Trauma Rehabilitation, 1, 1–12. doi: 10.1097/00001199-198609000-00004.CrossRefGoogle Scholar
  6. Benton, A. L., Hamsher, K., Varney, N. R., & Spreen, O. (1983). Contributions to neuropsychological assessment. Oxford: New York.Google Scholar
  7. Bentourkia, M., Bol, A., Ivanoiu, A., Labar, D., Sibomana, M., Coppens, A., & De Volder, A. G. (2000). Comparison of regional cerebral blood flow and glucose metabolism in the normal brain: effect of aging. Journal of Neurological Science, 181, 19–28. doi: 10.1016/S0022-510X(00)00396-8.CrossRefGoogle Scholar
  8. Bigler, E. D. (2001). Quantitative magnetic resonance imaging in traumatic brain injury. The Journal of Head Trauma Rehabilitation, 16, 117–134.PubMedCrossRefGoogle Scholar
  9. Bohlman, L., & Knight, R. T. (1994). Electrophysiological dissociation of rapid memory mechanisms in humans. NeuroReport, 5, 1517–1521. doi: 10.1097/00001756-199407000-00027.CrossRefGoogle Scholar
  10. Bor, D., Cumming, N., Scott, C. E. L., & Owen, A. M. (2004). Prefrontal cortical involvement in verbal encoding strategies. European Journal of Neuroscience, 19, 3365–3370. doi: 10.1111/j.1460-9568.2004.03438.x.PubMedCrossRefGoogle Scholar
  11. Clifton, G. L., Hayes, R. L., Levin, H. S., Michel, M. E., & Choi, S. C. (1992). Outcome measures for clinical trials involving traumatically brain-injured patients: report of a conference. Neurosurgery, 31, 975–978.PubMedCrossRefGoogle Scholar
  12. Corwin, J., & Bylsma, F. W. (1993). Psychological examination of traumatic encephalopathyby A. Rey and The Complex Figure Copy Test by P. A. Osterrieth. The Clinical Neuropsychologist, 7, 3–21.CrossRefGoogle Scholar
  13. Dinov, I. D., Van Horn, J. D., Lozev, K. M., Magsipoc, R., Petrosyan, P., Liu, Z., MacKenzie-Graham, A., & Toga, A. W. (2009). Efficient, distributed and interactive neuroimaging data analysis using the LONI pipeline. Frontiers in Neuroinformation, 3, 1–10. doi: 10.3389/neuro.11.022.2009.Google Scholar
  14. Fork, M., Bartels, C., Ebert, A. D., Grubich, C., Synowitz, H., & Wallesch, C. (2005). Neuropsychological sequelae of diffuse traumatic brain injury. Brain Injury, 19, 101–108. doi: 10.1080/02699050410001726086.PubMedCrossRefGoogle Scholar
  15. Gleissner, U., Helmstaedter, C., Kurthen, M., & Elger, C. E. (1997). Evidence of very fast memory consolidation: an intracarotid amytal study. NeuroReporter, 8, 2893–2896. doi: 10.1097/00001756-199709080-00018.CrossRefGoogle Scholar
  16. Glenn, T. C., Kelly, D. F., Boscardin, W. J., McArthur, D. L., Vespa, P., Oertel, M., & Martin, N. A. (2003). Energy dysfunction as a predictor of outcome after moderate or severe head injury: indices of oxygen, glucose, and lactate metabolism. Journal of Cerebral Blood Flow and Metabolism, 23, 1239–1250. doi: 10.1097/01.WCB.0000089833.23606.7.PubMedGoogle Scholar
  17. Habib, R., Nyberg, L., & Tulving, E. (2003). Hemispheric asymmetries of memory: the HERA model revisited. Trends in Cognitive Science, 7, 241–245. doi: 10.1016/S1364-6613(03)00110-4.CrossRefGoogle Scholar
  18. Hannay, H. J., & Levin, H. S. (1985). Selective reminding test: an examination of the equivalence of four forms. Journal of Clinical and Experimental Neuropsychology, 7, 251–263. doi: 10.1080/01688638508401258.PubMedCrossRefGoogle Scholar
  19. Hattori, N., Hung, S. C., Wu, H. M., Yeh, E., Glenn, T. C., Vespa, P. M., & Bergsneider, M. (2003). Correlation of regional metabolic rates of glucose with Glasgow Coma Scale after traumatic brain injury. Journal of Nuclear Medicine, 44, 1709–1716.PubMedGoogle Scholar
  20. Hayman, L. A. (1992). Adult cerebrum. In L. A. Hayman & V. Hinck (Eds.), Clinical brain imaging: normal structure and functional anatomy (pp. 130–137). St Louis: Mosby Year book.Google Scholar
  21. Head, D., Buckner, R. L., Shimony, J. S., Williams, L. E., Akbudak, E., Conturo, T. E., & Snyder, A. Z. (2004). Differential vulnerability of anterior white matter in nondemented aging with minimal acceleration in dementia of the Alzheimer type: evidence from diffusion tensor imaging. Cerebral Cortex, 14, 410–423. doi: 10.1093/cercor/bhh003.PubMedCrossRefGoogle Scholar
  22. Kraus, M. F., Susmaras, T., Caughlin, B. P., Walker, C. J., Sweeney, J. A., & Little, D. M. (2007). White matter integrity and cognition in chronic traumatic brain injury: a diffusion tensor imaging study. Brain, 130, 2508–2519. doi: 10.1093/brain/awm216.PubMedCrossRefGoogle Scholar
  23. Larrabee, G. J., Trahan, D. E., & Levin, H. S. (2000). Normative data for a six-trial administration of the verbal selective reminding test. Clinical Neuropsycholgy, 14, 110–118. doi: 10.1076/1385-4046(200002)14:1;1-8;FT110.CrossRefGoogle Scholar
  24. Lehtonen, S., Stringer, A. Y., Millis, S., Boake, C., Englander, J., Hart, T., & Whyte, J. (2005). Neuropsychological outcome and community re-integration following traumatic brain injury: the impact of frontal and non-frontal lesions. Brain Injury, 19, 239–256. doi: 10.1080/0269905040004310.PubMedCrossRefGoogle Scholar
  25. Levine, B., Cabeza, R., McIntosh, A. R., Black, S. E., Grady, C. L., & Stuss, D. T. (2002). Functional reorganization of memory after traumatic brain injury: a study with H2 15O positron emission topography. Journal of Neurology, Neurosurgery & Psychiatry, 73, 173–181. doi: 10.1136/jnnp.73.2.173.CrossRefGoogle Scholar
  26. Lezak, M. D., Howieson, D. B., Loring, D. W., Hannay, H. J., & Fischer, J. S. (2004). Neuropsychological assessment (4th ed., pp. 158–194). New York: Oxford University Press.Google Scholar
  27. Lin, K., Huang, S., Baxter, L., & Phelps, M. (1994). A general technique for inter-study registration of multi-function and multimodality images. IEEE Transactions on Nuclear Science, 41, 2850–2855.CrossRefGoogle Scholar
  28. Marcoux, J., McArthur, D. A., Miller, C., Glenn, T. C., Villablanca, P., Martin, N. A., & Vespa, P. M. (2008). Persistent metabolic crisis as measured by elevated cerebral microdialysis lactate-pyruvate ratio predicts chronic frontal lobe brain atrophy after traumatic brain injury. Critical Care Medicine, 36, 2871–2877.PubMedCrossRefGoogle Scholar
  29. Matthews, C. G., & Klǿve, K. (1964). [Instruction manual] for the adult neuropsychology test battery. Madison: University of Wisconsin Medical School.Google Scholar
  30. Mitrushina, M., Boone, K. B., Razani, J., & D’Elia, L. F. (2005). Handbook of normative data for neuropsychological assessment (2nd ed.) (pp. 648, 760, 782, 969). New York: Oxford University Press.Google Scholar
  31. National Institutes of Health. (1999). NIH consensus development panel on rehabilitation of persons with traumatic brain injury. Journal of the American Medical Association, 282, 974–983.CrossRefGoogle Scholar
  32. Ohta, S., Meyer, E., Thompson, C. J., & Gjedde, A. (1992). Oxygen consumption of the living human brain measured after a single inhalation of positron emitting oxygen. Journal of Cerebral Blood Flow and Metabolism, 12, 179–192.PubMedCrossRefGoogle Scholar
  33. Raz, N. (2000). Aging of the brain and its impact on cognitive performance: Integration of structural and functional findings. In F. I. M. Craik & T. A. Salthouse (Eds.), The handbook of aging and cognition (2nd ed., pp. 1–90). Mahwah: Lawrence Erlbaum Associates Publishers.Google Scholar
  34. Schmitter-Edgecombe, M., & Wright, M. J. (2003). Content memory and temporal order memory for performed activities after severe closed-head injury. Journal of Clinical and Experimental Neuropsychology, 25, 933–948. doi: 10.1076/jcen.25.7.933.16493.PubMedCrossRefGoogle Scholar
  35. Schmitter-Edgecombe, M., & Wright, M. J. (2004). Event-based prospective memory following severe closed-head injury. Neuropsychology, 18, 353–361. doi: 10.1037/0894-4105.18.2.353.PubMedCrossRefGoogle Scholar
  36. Schmitter-Edgecombe, M., Marks, W., & Fahy, J. F. (1993). Semantic priming after severe closed head trauma: automatic and attentional processes. Neuropsychology, 7, 136–148. doi: 10.1037/0894-4105.7.2.136.CrossRefGoogle Scholar
  37. Schmitter-Edgecombe, M., Marks, W., Wright, M. J., & Ventura, M. (2004). Retrieval inhibition in directed forgetting following severe closed-head injury. Neuropsychology, 18, 104–114. doi: 10.1037/0894-4105.18.1.104.PubMedCrossRefGoogle Scholar
  38. Shattuck, D. W., & Leahy, R. M. (2002). BrainSuite: an automated cortical surface identification tool. Medical Image Analysis, 6, 129–142. doi: 10.1007/978-3-540-40889-4_6.PubMedCrossRefGoogle Scholar
  39. Smith, A. (1991). Symbol digit modalities test. Los Angeles, CA: Western Psychological Services.Google Scholar
  40. Squire, L. R. (1980). Specifying the defect in human amnesia: storage, retrieval, and semantics. Neuropsychology, 18, 369–372. doi: 10.1016/0028-3932(80)90134-7.CrossRefGoogle Scholar
  41. Squire, L. R. (1994). Memory and forgetting: Long-term and gradual changes in memory storage. In O. Sporns & G. Tononi (Eds.), Selectionism and the brain (pp. 243–269). San Diego: Academic.CrossRefGoogle Scholar
  42. Squire, L. R., & Zola, S. M. (1998). Episodic memory, semantic memory, and amnesia. Hippocampus, 8, 205–211.PubMedCrossRefGoogle Scholar
  43. Storey, J. D. (2002). A direct approach to false discovery rates. Journal of the Royal Statistical Society, 64, 479–498.CrossRefGoogle Scholar
  44. Stuss, D. T., & Gow, C. A. (1992). Frontal dysfunction after traumatic brain injury. Neuropsychiatry, Neuropsychology, Behavior & Neurology, 5, 272–282.Google Scholar
  45. Takaoka, M., Tabuse, H., Kumura, E., Nakajima, S., Tsuzuki, T., Nakamura, K., Okada, A., & Sugimoto, H. (2002). Semi-quantitative analysis of corpus callosum injury using magnetic resonance imaging indicates clinical severity in patients with diffuse axonal injury. Journal of Neurology, Neurosurgery & Psychiatry, 73, 289–293. doi: 10.1136/jnnp.73.3.289.CrossRefGoogle Scholar
  46. Vakil, E. (2005). The effect of moderate to severe traumatic brain injury (TBI) on different aspects of memory: a selective review. Journal of Clinical and Experimental Neuropsychology, 27, 977–1021. doi: 10.1080/13803390490919245.PubMedCrossRefGoogle Scholar
  47. Vespa, P., McArthur, D., Alger, J., O’Phelan, K., Glenn, T., Bergsneider, B., & Hovda, D. A. (2004). Regional heterogeneity of brain metabolism using cerebral microdialysis: concordance with magnetic resonance spectroscopy and positron emission tomography. Brain Pathology, 14, 210–214.PubMedCrossRefGoogle Scholar
  48. Vespa, P., Bergsneider, M., Hattori, N., Wu, H. M., Huang, S. C., Martin, N. A., & Hovda, D. A. (2005). Metabolic crisis without brain ischemia is common after traumatic brain injury: a combined microdialysis and positron emission tomography study. Journal of Cerebral Blood Flow and Metabolism, 25, 763–774. doi: 10.1038/sj.jcbfm.9600073.PubMedCrossRefGoogle Scholar
  49. Vespa, P. M., Miller, C., McArthur, D., Eliseo, M., Etchepare, M., Hirt, D., & Hovda, D. A. (2007). Non-convulsive electrographic seizures after traumatic brain injury result in a delayed, prolonged increase in intracranial pressure and metabolic crisis. Critical Care Medicine, 35, 2830–2836. doi: 10.1097/01.CCM.0000295667.66853.BC.PubMedCrossRefGoogle Scholar
  50. Wallesch, C., Curio, N., Kutz, S., Jost, S., Bartels, C., & Synowitz, H. (2001). Outcome after mild-to-moderate blunt head injury: effects of focal lesions and diffuse axonal injury. Brain Injury, 15, 401–412. doi: 10.1080/02699050116886.PubMedCrossRefGoogle Scholar
  51. Williamson, D. J. G., Scott, J. G., & Adams, R. L. (1996). Traumatic brain injury. In R. L. Adams, O. A. Parsons, J. L. Culbertson, & S. J. Nixon (Eds.), Neuropsychology for clinical practice: etiology, assessment, and treatment of common neurological disorders (pp. 9–64). Washington, DC: American Psychological Association.CrossRefGoogle Scholar
  52. Wilson, J. T. L., Hadley, D. M., Wiedmann, K. D., & Teasdale, G. M. (1995). Neuropsychological consequences of two patterns of brain damage shown by MRI in survivors of severe head injury. Journal of Neurology, Neurosurgery, and Psychiatry, 59, 328–331. doi: 10.1136/jnnp.59.3.328.PubMedCrossRefGoogle Scholar
  53. Wright, M. J., & Schmitter-Edgecombe, M. (2011). The impact of verbal memory encoding and consolidation deficits during recovery from moderate-to-severe traumatic brain injury. The Journal of Head Trauma Rehabilitation, 26, 182–191. doi: 10.1097/HTR.0b013e318218dcf9.PubMedCrossRefGoogle Scholar
  54. Wright, M. J., Woo, E., Schmitter-Edgecombe, M., Hinkin, C. H., Miller, E. N., & Gooding, A. L. (2009). The Item-Specific Deficit Approach (ISDA) to evaluating verbal memory dysfunction: rationale, psychometrics, and application. Journal of Clinical and Experimental Neuropsychology, 31, 790–802. doi: 10.1080/13803390802508918.PubMedCrossRefGoogle Scholar
  55. Wright, M. J., Schmitter-Edgecombe, M., & Woo, E. (2010). Verbal memory impairment in severe closed-head injury: the role of encoding and consolidation. Journal of Clinical and Experimental Neuropsychology, 32, 728–736. doi: 10.1080/13803390903512652.PubMedCrossRefGoogle Scholar
  56. Xu, Y., McArthur, D. L., Alger, J. R., Etchepare, M., Hovda, D. A., Glenn, T. C., & Vespa, P. M. (2010). Early nonischemic oxidative metabolic dysfunction leads to chronic brain atrophy in traumatic brain injury. Journal of Cerebral Blood Flow and Metabolism, 30, 883–894. doi: 10.1038/jcbfm.2009.263.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Matthew J. Wright
    • 1
    • 2
    Email author
  • David L. McArthur
    • 3
  • Jeffry R. Alger
    • 4
  • Jack Van Horn
    • 4
  • Andrei Irimia
    • 4
  • Maria Filippou
    • 3
  • Thomas C. Glenn
    • 3
  • David A. Hovda
    • 3
  • Paul Vespa
    • 3
    • 4
  1. 1.Los Angeles Biomedical Research Institute, Psychology Division, Department of PsychiatryHarbor-University of California, Los Angeles Medical CenterTorranceUSA
  2. 2.Department of Psychiatry and Biobehavioral SciencesUniversity of CaliforniaLos AngelesUSA
  3. 3.Department of Neurosurgery, David Geffen School of MedicineUniversity of CaliforniaLos AngelesUSA
  4. 4.Department of Neurology, David Geffen School of MedicineUniversity of CaliforniaLos AngelesUSA

Personalised recommendations