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Network dysfunction after traumatic brain injury

Nature Reviews Neurology volume 10, pages 156–166 (2014)Cite this article

Subjects

Key Points

  • Diffuse axonal injury after traumatic brain injury (TBI) disconnects large-scale brain networks, leading to network dysfunction and cognitive impairment

  • Interactions between the salience network and the default mode network are disrupted by TBI, producing impairments of cognitive control

  • TBI shifts the brain away from the small-world architecture that is optimal for information processing, and particularly affects highly connected network hubs

  • TBI can trigger neurodegenerative processes that can lead to conditions such as Alzheimer disease and chronic traumatic encephalopathy, which might result from the diffusion of misfolded proteins along damaged white matter tracts

  • Network diagnostics can provide individual measures of the structural and functional integrity of intrinsic connectivity networks, and are likely to have clinical utility for predicting outcomes and guiding treatment development

Abstract

Diffuse axonal injury after traumatic brain injury (TBI) produces neurological impairment by disconnecting brain networks. This structural damage can be mapped using diffusion MRI, and its functional effects can be investigated in large-scale intrinsic connectivity networks (ICNs). Here, we review evidence that TBI substantially disrupts ICN function, and that this disruption predicts cognitive impairment. We focus on two ICNs—the salience network and the default mode network. The activity of these ICNs is normally tightly coupled, which is important for attentional control. Damage to the structural connectivity of these networks produces predictable abnormalities of network function and cognitive control. For example, the brain normally shows a 'small-world architecture' that is optimized for information processing, but TBI shifts network function away from this organization. The effects of TBI on network function are likely to be complex, and we discuss how advanced approaches to modelling brain dynamics can provide insights into the network dysfunction. We highlight how structural network damage caused by axonal injury might interact with neuroinflammation and neurodegeneration in the pathogenesis of Alzheimer disease and chronic traumatic encephalopathy, which are late complications of TBI. Finally, we discuss how network-level diagnostics could inform diagnosis, prognosis and treatment development following TBI.

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Figure 1: Levels of brain network investigation.
Figure 2: Effects of TBI across spatial scales.
Figure 3: Network diagnostics in the assessment and management of traumatic brain injury.

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References

  1. Mesulam, M. M. From sensation to cognition. Brain 121, 1013–1052 (1998).

    Article  PubMed  Google Scholar 

  2. Hagmann, P. et al. Mapping the structural core of human cerebral cortex. PLoS Biol. 6, e159 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Bullmore, E. & Sporns, O. Complex brain networks: graph theoretical analysis of structural and functional systems. Nat. Rev. Neurosci. 10, 186–198 (2009).

    Article  CAS  PubMed  Google Scholar 

  4. Zhang, D. & Raichle, M. E. Disease and the brain's dark energy. Nat. Rev. Neurol. 6, 15–28 (2010).

    Article  PubMed  Google Scholar 

  5. Smith, D. H., Meaney, D. F. & Shull, W. H. Diffuse axonal injury in head trauma. J. Head Trauma Rehabil. 18, 307–316 (2003).

    Article  PubMed  Google Scholar 

  6. Gentleman, S. M. et al. Axonal injury: a universal consequence of fatal closed head injury? Acta Neuropath. 89, 537–543 (1995).

    Article  CAS  PubMed  Google Scholar 

  7. Kinnunen, K. M. et al. White matter damage and cognitive impairment after traumatic brain injury. Brain 134, 449–463 (2011).

    Article  PubMed  Google Scholar 

  8. Bonnelle, V. et al. Default mode network connectivity predicts sustained attention deficits after traumatic brain injury. J. Neurosci. 31, 13442–13451 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Beckmann, C. F., DeLuca, M., Devlin, J. T. & Smith, S. M. Investigations into resting-state connectivity using independent component analysis. Philos. Trans. R. Soc. Lond. B Biol. Sci. 360, 1001–1013 (2005).

    Article  PubMed  PubMed Central  Google Scholar 

  10. Smith, S. M. et al. Correspondence of the brain's functional architecture during activation and rest. Proc. Natl Acad. Sci. USA 106, 13040–13045 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  11. Bonnelle, V. et al. Salience network integrity predicts default mode network function after traumatic brain injury. Proc. Natl Acad. Sci. USA 109, 4690–4695 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  12. Graham, D. I., McIntosh, T. K., Maxwell, W. L. & Nicoll, J. A. Recent advances in neurotrauma. J. Neuropathol. Exp. Neurol. 59, 641–651 (2000).

    Article  CAS  PubMed  Google Scholar 

  13. Gurdjian, E. S. Re-evaluation of the biomechanics of blunt impact injury of the head. Surg. Gynecol. Obstet. 140, 845–850 (1975).

    CAS  PubMed  Google Scholar 

  14. Adams, J. H. et al. Diffuse axonal injury in head injury: definition, diagnosis and grading. Histopathology 15, 49–59 (1989).

    Article  CAS  PubMed  Google Scholar 

  15. Werner, C. & Engelhard, K. Pathophysiology of traumatic brain injury. Brit. J. Anaesth. 99, 4–9 (2007).

    Article  CAS  PubMed  Google Scholar 

  16. Bigler, E. D. Anterior and middle cranial fossa in traumatic brain injury: relevant neuroanatomy and neuropathology in the study of neuropsychological outcome. Neuropsychology 21, 515–531 (2007).

    Article  PubMed  Google Scholar 

  17. Blumbergs, P. C. et al. Staining of amyloid precursor protein to study axonal damage in mild head injury. Lancet 344, 1055–1056 (1994).

    Article  CAS  PubMed  Google Scholar 

  18. Adams, J. H., Graham, D. I. & Jennett, B. The neuropathology of the vegetative state after an acute brain insult. Brain 123, 1327–1338 (2000).

    Article  PubMed  Google Scholar 

  19. Hellyer, P. J., Leech, R., Ham, T. E., Bonnelle, V. & Sharp, D. J. Individual prediction of white matter injury following traumatic brain injury. Ann. Neurol. 73, 489–499 (2012).

    Article  Google Scholar 

  20. Scheid, R., Preul, C., Gruber, O., Wiggins, C. & von Cramon, D. Y. Diffuse axonal injury associated with chronic traumatic brain injury: evidence from T2*-weighted gradient-echo imaging at 3 T. Am. J. Neuroradiol. 24, 1049–1056 (2003).

    PubMed  PubMed Central  Google Scholar 

  21. Basser, P. J. & Pierpaoli, C. Microstructural and physiological features of tissues elucidated by quantitative-diffusion-tensor MRI. J. Magn. Reson. B 111, 209–219 (1996).

    Article  CAS  PubMed  Google Scholar 

  22. Mac Donald, C. L., Dikranian, K., Bayly, P., Holtzman, D. & Brody, D. Diffusion tensor imaging reliably detects experimental traumatic axonal injury and indicates approximate time of injury. J. Neurosci. 27, 11869–11876 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Sidaros, A. et al. Diffusion tensor imaging during recovery from severe traumatic brain injury and relation to clinical outcome: a longitudinal study. Brain 131, 559–572 (2008).

    Article  PubMed  Google Scholar 

  24. Mac Donald, C. L. et al. Detection of blast-related traumatic brain injury in U. S. military personnel. N. Engl. J. Med. 364, 2091–2100 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Kim, Y. H. et al. Plasticity of the attentional network after brain injury and cognitive rehabilitation. Neurorehabil. Neural Repair 23, 468–477 (2009).

    Article  PubMed  Google Scholar 

  26. McAllister, T. W. et al. Brain activation during working memory 1 month after mild traumatic brain injury: a functional MRI study. Neurology 53, 1300–1308 (1999).

    Article  CAS  PubMed  Google Scholar 

  27. Buckner, R. L., Andrews-Hanna, J. R. & Schacter, D. L. The brain's default network: anatomy, function, and relevance to disease. Ann. N. Y. Acad. Sci. 1124, 1–38 (2008).

    Article  PubMed  Google Scholar 

  28. Seeley, W. W. et al. Dissociable intrinsic connectivity networks for salience processing and executive control. J. Neurosci. 27, 2349–2356 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Raichle, M. E. et al. A default mode of brain function. Proc. Natl Acad. Sci. USA 98, 676–682 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Leech, R. & Sharp, D. J. The role of the posterior cingulate cortex in cognition and disease. Brain 137, 12–32 (2014).

    Article  PubMed  Google Scholar 

  31. Greicius, M. D., Supekar, K., Menon, V. & Dougherty, R. F. Resting-state functional connectivity reflects structural connectivity in the default mode network. Cereb. Cortex 19, 72–78 (2009).

    Article  PubMed  Google Scholar 

  32. Singh, K. D. & Fawcett, I. P. Transient and linearly graded deactivation of the human default-mode network by a visual detection task. NeuroImage 41, 100–112 (2008).

    Article  CAS  PubMed  Google Scholar 

  33. Weissman, D. H., Roberts, K. C., Visscher, K. M. & Woldorff, M. G. The neural bases of momentary lapses in attention. Nat. Neurosci. 9, 971–978 (2006).

    Article  CAS  PubMed  Google Scholar 

  34. Sonuga-Barke, E. J. & Castellanos, F. X. Spontaneous attentional fluctuations in impaired states and pathological conditions: a neurobiological hypothesis. Neurosci. Biobehav. Rev. 31, 977–986 (2007).

    Article  PubMed  Google Scholar 

  35. Nakashima, T. et al. Focal brain glucose hypometabolism in patients with neuropsychologic deficits after diffuse axonal injury. Am. J. Neuroradiol. 28, 236–242 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Kato, T. et al. Statistical image analysis of cerebral glucose metabolism in patients with cognitive impairment following diffuse traumatic brain injury. J. Neurotrauma 24, 919–926 (2007).

    Article  PubMed  Google Scholar 

  37. Garcia-Panach, J. et al. A voxel-based analysis of FDG-PET in traumatic brain injury: regional metabolism and relationship between the thalamus and cortical areas. J. Neurotrauma 28, 1707–1717 (2011).

    Article  PubMed  Google Scholar 

  38. Sharp, D. J. et al. Distinct frontal systems for response inhibition, attentional capture, and error processing. Proc. Natl Acad. Sci. USA 107, 6106–6111 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  39. Sridharan, D., Levitin, D. J. & Menon, V. A critical role for the right fronto-insular cortex in switching between central-executive and default-mode networks. Proc. Natl Acad. Sci. USA 105, 12569–12574 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  40. Stevens, M. C. et al. Multiple resting state network functional connectivity abnormalities in mild traumatic brain injury. Brain Imaging Behav. 6, 293–318 (2012).

    Article  PubMed  Google Scholar 

  41. Hillary, F. G. et al. Changes in resting connectivity during recovery from severe traumatic brain injury. Int. J. Psychophys. 82, 115–123 (2011).

    Article  CAS  Google Scholar 

  42. Mayer, A. R., Mannell, M. V., Ling, J., Gasparovic, C. & Yeo, R. A. Functional connectivity in mild traumatic brain injury. Hum. Brain Mapp. 32, 1825–1835 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  43. Shumskaya, E., Andriessen, T. M., Norris, D. G. & Vos, P. E. Abnormal whole-brain functional networks in homogeneous acute mild traumatic brain injury. Neurology 79, 175–182 (2012).

    Article  PubMed  Google Scholar 

  44. Sharp, D. J. et al. Default mode network functional and structural connectivity after traumatic brain injury. Brain 134, 2233–2247 (2011).

    Article  PubMed  Google Scholar 

  45. Tang, L. et al. Thalamic resting-state functional networks: disruption in patients with mild traumatic brain injury. Radiology 260, 831–840 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  46. Messe, A. et al. Specific and evolving resting-state network alterations in post-concussion syndrome following mild traumatic brain injury. PLoS ONE 8, e65470 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Caeyenberghs, K. et al. Altered structural networks and executive deficits in traumatic brain injury patients. Brain Struct. Funct. 219, 193–209 (2014).

    Article  CAS  PubMed  Google Scholar 

  48. Sponheim, S. R. et al. Evidence of disrupted functional connectivity in the brain after combat-related blast injury. NeuroImage 54, (Suppl. 1), S21–S29 (2011).

    Article  PubMed  Google Scholar 

  49. Cao, C. & Slobounov, S. Alteration of cortical functional connectivity as a result of traumatic brain injury revealed by graph theory, ICA, and sLORETA analyses of EEG signals. IEEE Trans. Neural Syst. Rehabil. Eng. 18, 11–19 (2010).

    Article  CAS  PubMed  Google Scholar 

  50. Castellanos, N. P. et al. Reorganization of functional connectivity as a correlate of cognitive recovery in acquired brain injury. Brain 133, 2365–2381 (2010).

    Article  PubMed  Google Scholar 

  51. Tarapore, P. E. et al. Resting state magnetoencephalography functional connectivity in traumatic brain injury. J. Neurosurg. 118, 1306–1316 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  52. Kasahara, M. et al. Traumatic brain injury alters the functional brain network mediating working memory. Brain Inj. 25, 1170–1187 (2011).

    Article  PubMed  Google Scholar 

  53. Rasmussen, I. A. et al. Simple dual tasking recruits prefrontal cortices in chronic severe traumatic brain injury patients, but not in controls. J. Neurotrauma 25, 1057–1070 (2008).

    Article  PubMed  Google Scholar 

  54. Turner, G. R. & Levine, B. Augmented neural activity during executive control processing following diffuse axonal injury. Neurology 71, 812–818 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  55. Turner, G. R., McIntosh, A. R. & Levine, B. Prefrontal compensatory engagement in TBI is due to altered functional engagement of existing networks and not functional reorganization. Front. Syst. Neurosci. 5, 9 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  56. Kasahara, M. et al. Altered functional connectivity in the motor network after traumatic brain injury. Neurology 75, 168–176 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Vanhaudenhuyse, A. et al. Default network connectivity reflects the level of consciousness in non-communicative brain-damaged patients. Brain 133, 161–171 (2010).

    Article  PubMed  Google Scholar 

  58. Cauda, F. et al. Disrupted intrinsic functional connectivity in the vegetative state. J. Neurol. Neurosurg. Psychiatry 80, 429–431 (2009).

    Article  CAS  PubMed  Google Scholar 

  59. Greicius, M. D. et al. Persistent default-mode network connectivity during light sedation. Hum. Brain Mapp. 29, 839–847 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  60. Boly, M. et al. Functional connectivity in the default network during resting state is preserved in a vegetative but not in a brain dead patient. Hum. Brain Mapp. 30, 2393–2400 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Norton, L. et al. Disruptions of functional connectivity in the default mode network of comatose patients. Neurology 78, 175–181 (2012).

    Article  CAS  PubMed  Google Scholar 

  62. Laureys, S. et al. Impaired effective cortical connectivity in vegetative state: preliminary investigation using PET. NeuroImage 9, 377–382 (1999).

    Article  CAS  PubMed  Google Scholar 

  63. Ham, T. E. et al. The neural basis of impaired self-awareness after traumatic brain injury. Brain http://dx.doi.org/10.1093/brain/awt350.

  64. van den Heuvel, M. P. & Sporns, O. Rich-club organization of the human connectome. J. Neurosci. 31, 15775–15786 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. van den Heuvel, M. P. & Sporns, O. An anatomical substrate for integration among functional networks in human cortex. J. Neurosci. 33, 14489–14500 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Achard, S., Salvador, R., Whitcher, B., Suckling, J. & Bullmore, E. A resilient, low-frequency, small-world human brain functional network with highly connected association cortical hubs. J. Neurosci. 26, 63–72 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Pandit, A. S. et al. Traumatic brain injury impairs small-world topology. Neurology 80, 1826–1833 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  68. Achard, S. et al. Hubs of brain functional networks are radically reorganized in comatose patients. Proc. Natl Acad. Sci. USA 109, 20608–20613 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  69. Honey, C. J. et al. Predicting human resting-state functional connectivity from structural connectivity. Proc. Natl Acad. Sci. USA 106, 2035–2040 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  70. O'Reilly, J. X. et al. Causal effect of disconnection lesions on interhemispheric functional connectivity in rhesus monkeys. Proc. Natl Acad. Sci. USA 110, 13982–13987 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  71. Deco, G., Jirsa, V., McIntosh, A. R., Sporns, O. & Kotter, R. Key role of coupling, delay, and noise in resting brain fluctuations. Proc. Natl Acad. Sci. USA 106, 10302–10307 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  72. Chialvo, D. R. Emergent complex neural dynamics. Nat. Phys. 6, 744–750 (2010).

    Article  CAS  Google Scholar 

  73. Cabral, J., Hughes, E., Sporns, O. & Deca, G. Role of local network oscillations in resting-state functional connectivity. Neuroimage 57, 130–139 (2011).

    Article  PubMed  Google Scholar 

  74. Hellyer, P. J. et al. The control of global brain dynamics: opposing actions of fronto-parietal control and default mode networks on attention. J. Neurosci. 34, 451–461 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. McMillan, T. M., Teasdale, G. M. & Stewart, E. Disability in young people and adults after head injury: 12–14 year follow-up of a prospective cohort. J. Neurol. Neurosurg. Psychiatry 83, 1086–1091 (2012).

    Article  PubMed  Google Scholar 

  76. Mayeux, R. et al. Synergistic effects of traumatic head injury and apolipoprotein-epsilon 4 in patients with Alzheimer's disease. Neurology 45, 555–557 (1995).

    Article  CAS  PubMed  Google Scholar 

  77. Smith, D. H., Johnson, V. E. & Stewart, W. Chronic neuropathologies of single and repetitive TBI: substrates of dementia? Nat. Rev. Neurol. 9, 211–221 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Nemetz, P. N. et al. Traumatic brain injury and time to onset of Alzheimer's disease: a population-based study. Am. J. Epidemiol. 149, 32–40 (1999).

    Article  CAS  PubMed  Google Scholar 

  79. Lye, T. C. & Shores, E. A. Traumatic brain injury as a risk factor for Alzheimer's disease: a review. Neuropsychol. Rev. 10, 115–129 (2000).

    Article  CAS  PubMed  Google Scholar 

  80. Goldstein, L. E. et al. Chronic traumatic encephalopathy in blast-exposed military veterans and a blast neurotrauma mouse model. Sci. Transl. Med. 4, 134ra60 (2012).

    PubMed  PubMed Central  Google Scholar 

  81. Sayed, N., Culver, C., Dams-O'Connor, K., Hammond, F. & Diaz-Arrastia, R. Clinical phenotype of dementia after traumatic brain injury. J. Neurotrauma 30, 1117–1122 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  82. Ramlackhansingh, A. F. et al. Inflammation after trauma: Microglial activation and traumatic brain injury. Ann. Neurol. 70, 374–383 (2011).

    Article  PubMed  Google Scholar 

  83. Johnson, V. E., Stewart, W. & Smith, D. H. Axonal pathology in traumatic brain injury. Exp. Neurol. 246, 35–43 (2013).

    Article  CAS  PubMed  Google Scholar 

  84. McKee, A. C. et al. The spectrum of disease in chronic traumatic encephalopathy. Brain 136, 43–64 (2013).

    Article  PubMed  Google Scholar 

  85. Polymenidou, M. & Cleveland, D. W. Prion-like spread of protein aggregates in neurodegeneration. J. Exp. Med. 209, 889–893 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. de Calignon, A. et al. Propagation of tau pathology in a model of early Alzheimer's disease. Neuron 73, 685–697 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Warner, M. A. et al. Regionally selective atrophy after traumatic axonal injury. Arch. Neurol. 67, 1336–1344 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  88. Buckner, R. L. et al. Molecular, structural, and functional characterization of Alzheimer's disease: evidence for a relationship between default activity, amyloid, and memory. J. Neurosci. 25, 7709–7717 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Seeley, W. W., Crawford, R. K., Zhou, J., Miller, B. L. & Greicius, M. D. Neurodegenerative diseases target large-scale human brain networks. Neuron 62, 42–52 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Raj, A., Kuceyeski, A. & Weiner, M. A network diffusion model of disease progression in dementia. Neuron 73, 1204–1215 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Shitaka, Y. et al. Repetitive closed-skull traumatic brain injury in mice causes persistent multifocal axonal injury and microglial reactivity. J. Neuropath. Exp. Neurol. 70, 551–567 (2011).

    Article  PubMed  Google Scholar 

  92. Johnson, V. E. et al. Inflammation and white matter degeneration persist for years after a single traumatic brain injury. Brain 136, 28–42 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  93. Gentleman, S. M. Review: microglia in protein aggregation disorders: friend or foe? Neuropathol. Appl. Neurobiol. 39, 45–50 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Holmin, S. & Mathiesen, T. Long-term intracerebral inflammatory response after experimental focal brain injury in rat. Neuroreport 10, 1889–1891 (1999).

    Article  CAS  PubMed  Google Scholar 

  95. Irimia, A. et al. Patient-tailored connectomics visualization for the assessment of white matter atrophy in traumatic brain injury. Front. Neurol. 3, 10 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  96. Van Horn, J. D. et al. Mapping connectivity damage in the case of Phineas Gage. PLoS ONE 7, e37454 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Hellyer, P. J., Leech, R., Ham, T. E., Bonnelle, V. & Sharp, D. J. Individual prediction of white matter injury following traumatic brain injury. Ann. Neurol. 73, 489–499 (2013).

    Article  PubMed  Google Scholar 

  98. Schiff, N. D. et al. Behavioural improvements with thalamic stimulation after severe traumatic brain injury. Nature 448, 600–603 (2007).

    Article  CAS  PubMed  Google Scholar 

  99. Bales, J. W., Wagner, A. K., Kline, A. E. & Dixon, C. E. Persistent cognitive dysfunction after traumatic brain injury: a dopamine hypothesis. Neurosci. Biobehav. Rev. 33, 981–1003 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Whyte, J. et al. Effects of methylphenidate on attention deficits after traumatic brain injury: a multidimensional, randomized, controlled trial. Am. J. Phys. Med. Rehabil. 83, 401–420 (2004).

    Article  PubMed  Google Scholar 

  101. Smith, S. M. et al. Functional connectomics from resting-state fMRI. Trends Cogn. Sci. 17, 666–682 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  102. Vincent, J. L. et al. Intrinsic functional architecture in the anaesthetized monkey brain. Nature 447, 83–86 (2007).

    Article  CAS  PubMed  Google Scholar 

  103. Squarcina, L., Bertoldo, A., Ham, T. E., Heckemann, R. & Sharp, D. J. A robust method for investigating thalamic white matter tracts after traumatic brain injury. Neuroimage 63, 779–788 (2012).

    Article  PubMed  Google Scholar 

  104. Friston, K. J., Harrison, L. & Penny, W. Dynamic causal modelling. Neuroimage 19, 1273–1302 (2003).

    Article  CAS  PubMed  Google Scholar 

  105. Spitz, G., Maller, J., O'Sullivan, R. & Ponsford, J. White matter integrity following traumatic brain injury: the association with severity of injury and cognitive functioning. Brain Topogr. 26, 648–660 (2013).

    Article  PubMed  Google Scholar 

  106. Strangman, G. E. et al. Fractional anisotropy helps predicts memory rehabilitation outcome after traumatic brain injury. NeuroRehabilitation 31, 295–310 (2012).

    PubMed  Google Scholar 

  107. Messé, A. et al. Structural integrity and postconcussion syndrome in mild traumatic brain injury patients. Brain Imaging Behav. 6, 283–292 (2012).

    Article  PubMed  Google Scholar 

  108. Newsome, M. R. et al. Effects of traumatic brain injury on working memory-related brain activation in adolescents. Neuropsychology 22, 419–425 (2008).

    Article  PubMed  Google Scholar 

  109. Christodoulou, C. et al. Functional magnetic resonance imaging of working memory impairment after traumatic brain injury. J. Neurol. Neurosurg. Psychiatr. 71, 161–168 (2001).

    Article  CAS  Google Scholar 

  110. Raja Beharelle, A., Tisserand, D., Stuss, D. T., McIntosh, A. R. & Levine, B. Brain activity patterns uniquely supporting visual feature integration after traumatic brain injury. Front. Hum. Neurosci. 5, 164 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  111. Scheibel, R. S. et al. Effects of severity of traumatic brain injury and brain reserve on cognitive-control related brain activation. J. Neurotrauma 26, 1447–1461 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  112. Levine, B. et al. Functional reorganisation of memory after traumatic brain injury: a study with H2150 positron emission tomography. J. Neurol. Neurosurg. Psychiatr. 73, 173–181 (2002).

    Article  CAS  Google Scholar 

  113. Witt, S., Lovejoy, D., Pearlson, G. & Stevens, M. Decreased prefrontal cortex activity in mild traumatic brain injury during performance of an auditory oddball task. Brain Imaging Behav. 4, 232–247 (2010).

    Article  PubMed  Google Scholar 

  114. Kim, J. et al. Resting cerebral blood flow alterations in chronic traumatic brain injury: an arterial spin labeling perfusion FMRI study. J. Neurotrauma 27, 1399–1411 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  115. Palacios, E. M. et al. Resting-state functional magnetic resonance imaging activity and connectivity and cognitive outcome in traumatic brain injury. JAMA Neurol. 70, 845–851 (2013).

    Article  PubMed  Google Scholar 

  116. Zhou, Y. et al. Default-mode network disruption in mild traumatic brain injury. Radiology 265, 882–892 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  117. Mayer, A. R., Mannell, M. V., Ling, J., Gasparovic, C. & Yeo, R. A. Functional connectivity in mild traumatic brain injury. Hum. Brain Mapp. 32, 1825–1835 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  118. Marquez de la Plata, C. D. et al. Deficits in functional connectivity of hippocampal and frontal lobe circuits after traumatic axonal injury. Arch. Neurol. 68, 74–84 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  119. Slobounov, S. M. et al. Alteration of brain functional network at rest and in response to YMCA physical stress test in concussed athletes: RsFMRI study. Neuroimage 55, 1716–1727 (2011).

    Article  CAS  PubMed  Google Scholar 

  120. Stevens, M. et al. Multiple resting state network functional connectivity abnormalities in mild traumatic brain injury. Brain Imaging Behav. 6, 293–318 (2012).

    Article  PubMed  Google Scholar 

  121. Pandit, A. S. et al. Traumatic brain injury impairs small-world topology. Neurology 80, 1826–1833 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  122. Zhang, J. et al. Statistical parametric mapping and cluster counting analysis of [18F] FDG-PET imaging in traumatic brain injury. J. Neurotrauma 27, 35–49 (2010).

    Article  PubMed  Google Scholar 

  123. van den Heuvel, M. P., Mandl, R. C., Kahn, R. S. & Hulshoff Pol, H. E. Functionally linked resting-state networks reflect the underlying structural connectivity architecture of the human brain. Hum. Brain Mapp. 30, 3127–3141 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The work of the authors has been supported by a National Institute of Health Research Professorship (to D.J.S.) and a GlaxoSmithKline/Wellcome Clinical Research Fellowship (G.S.). The authors thank M. O'Sullivan for comments on the manuscript before submission.

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Authors and Affiliations

  1. Division of Experimental Medicine, Computational, Cognitive and Clinical Neuroimaging Laboratory, Centre for Neuroscience, Imperial College London, Hammersmith Hospital Campus, Du Cane Road, London, W12 0NN, UK

    David J. Sharp, Gregory Scott & Robert Leech

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  1. David J. Sharp
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  2. Gregory Scott
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  3. Robert Leech
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Contributions

D.J.S., G.S. and R.L. provided equal contributions to researching data for review, developing the discussion of content, and writing and reviewing the manuscript before submission.

Corresponding author

Correspondence to David J. Sharp.

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Competing interests

D.J.S. has received a research grant from Pfizer. G.S. receives research funding from GlaxoSmithKline via a Wellcome Trust grant. R.L. declares no competing interests.

Supplementary information

Supplementary Video 1

Interactions between two intrinsic connectivity networks—the default mode network (DMN) and salience network (SN). Red/yellow represents increasing activity, and blue/light blue represents decreasing activity within these networks. The nodes of the DMN include the posterior cingulate cortex, the ventromedial prefrontal cortex and the inferior parietal lobules. The DMN shows increased activity during internally directed thought ('mind wandering'). The anterior insulae and the dorsal anterior cingulate cortex form the main nodes of the SN, which activates when salient or unexpected events occur. The activity of intrinsic connectivity networks is modulated by changes in behavioural state, and the activities of the DMN and SN are often 'anti-correlated'; that is, with correlated but opposed patterns of activation and deactivation. The appearance of a salient external stimulus, in this case a car, is associated with rapid SN activation with corresponding DMN deactivation. This interaction can be impaired following damage to the structural connectivity of the SN after traumatic brain injury. (MOV 43490 kb)

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Sharp, D., Scott, G. & Leech, R. Network dysfunction after traumatic brain injury. Nat Rev Neurol 10, 156–166 (2014). https://doi.org/10.1038/nrneurol.2014.15

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