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Articles
April 17, 2013

Traumatic brain injury impairs small-world topology

May 14, 2013 issue
80 (20) 1826-1833

Abstract

Objective:

We test the hypothesis that brain networks associated with cognitive function shift away from a "small-world" organization following traumatic brain injury (TBI).

Methods:

We investigated 20 TBI patients and 21 age-matched controls. Resting-state functional MRI was used to study functional connectivity. Graph theoretical analysis was then applied to partial correlation matrices derived from these data. The presence of white matter damage was quantified using diffusion tensor imaging.

Results:

Patients showed characteristic cognitive impairments as well as evidence of damage to white matter tracts. Compared to controls, the graph analysis showed reduced overall connectivity, longer average path lengths, and reduced network efficiency. A particular impact of TBI is seen on a major network hub, the posterior cingulate cortex. Taken together, these results confirm that a network critical to cognitive function shows a shift away from small-world characteristics.

Conclusions:

We provide evidence that key brain networks involved in supporting cognitive function become less small-world in their organization after TBI. This is likely to be the result of diffuse white matter damage, and may be an important factor in producing cognitive impairment after TBI.

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REFERENCES

1.
Whitnall L, McMillan TM, Murray GD, Teasdale GM. Disability in young people and adults after head injury: 5-7 year follow up of a prospective cohort study. J Neurol Neurosurg Psychiatry 2006;77:640-645.
2.
Arciniegas DB, Held K, Wagner P. Cognitive impairment following traumatic brain injury. Curr Treat Options Neurol 2002;4:43-57.
3.
Ghajar J, Ivry RB. The predictive brain state: timing deficiency in traumatic brain injury? Neurorehabil Neural Repair 2008;22:217-227.
4.
Lowenstein DH. Traumatic brain injury: a glimpse of order among the chaos? Ann Neurol 2009;66:A7-A8.
5.
Bonnelle V, Ham TE, Leech R, et al. Salience network integrity predicts default mode network function after traumatic brain injury. Proc Natl Acad Sci USA 2012;109:4690-4695.
6.
Bonnelle V, Leech R, Kinnunen KM, et al. Default mode network connectivity predicts sustained attention deficits after traumatic brain injury. J Neurosci 2011;31:13442-13451.
7.
Kinnunen KM, Greenwood R, Powell JH, et al. White matter damage and cognitive impairment after traumatic brain injury. Brain 2011;134:449-463.
8.
Scheid R, Walther K, Guthke T, Preul C, Cramon von DY. Cognitive sequelae of diffuse axonal injury. Arch Neurol. JAMA 2006;63:418.
9.
Povlishock JT, Katz DI. Update of neuropathology and neurological recovery after traumatic brain injury. J Head Trauma Rehabil 2005;20:76.
10.
Büki A, Povlishock JT. All roads lead to disconnection? Traumatic axonal injury revisited. Acta Neurochir 2006;148:181-193; discussion 193-194.
11.
Sharp DJ, Beckmann CF, Greenwood R, et al. Default mode network functional and structural connectivity after traumatic brain injury. Brain 2011;134:2233-2247.
12.
Bullmore E, Sporns O. Complex brain networks: graph theoretical analysis of structural and functional systems. Nat Rev Neurosci 2009;10:186-198.
13.
Bassett DS, Bullmore ET. Human brain networks in health and disease. Curr Opin Neurol 2009;22:340-347.
14.
Stam CJ, Jones BF, Nolte G, Breakspear M, Scheltens P. Small-world networks and functional connectivity in Alzheimer's disease. Cereb Cortex 2007;17:92-99.
15.
Liu Y, Liang M, Zhou Y, et al. Disrupted small-world networks in schizophrenia. Brain 2008;131:945-961.
16.
Mac Donald CL, 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 2007;27:11869-11876.
17.
Beckmann CF, DeLuca M, Devlin JT, Smith SM. Investigations into resting-state connectivity using independent component analysis. Philosophical Trans R Soc Lon B Biol Sci 2005;360:1001-1013.
18.
Smith SM, Miller KL, Salimi-Khorshidi G, et al. Network modelling methods for FMRI. Neuroimage 2011;54:875-891.
19.
Andrews-Hanna JR, Reidler JS, Sepulcre J, Poulin R, Buckner RL. Functional-anatomic fractionation of the brain's default network. Neuron 2010;65:550-562.
20.
Dikmen SS, Corrigan JD, Levin HS, Machamer J, Stiers W, Weisskopf MG. Cognitive outcome following traumatic brain injury. J Head Trauma Rehabil 2009;24:430-438.
21.
Marrelec G, Krainik A, Duffau H, et al. Partial correlation for functional brain interactivity investigation in functional MRI. Neuroimage 2006;32:228-237.
22.
Rubinov M, Sporns O. Complex network measures of brain connectivity: uses and interpretations. Neuroimage 2010;52:1059-1069.
23.
Stuss DT, Stethem LL, Hugenholtz H, Picton T, Pivik J, Richard MT. Reaction time after head injury: fatigue, divided and focused attention, and consistency of performance. J Neurol Neurosurg Psychiatry 1989;52:742-748.
24.
Stuss DT. Staying on the job: the frontal lobes control individual performance variability. Brain 2003;126:2363-2380.
25.
Hagmann P, Cammoun L, Gigandet X, et al. Mapping the structural core of human cerebral cortex. PLoS Biol 2008;6:e159.
26.
Tomasi D, Volkow ND. Functional connectivity density mapping. Proc Natl Acad Sci USA 2010;107:9885-9890.
27.
Sidaros A, Engberg AW, Sidaros K, et al. Diffusion tensor imaging during recovery from severe traumatic brain injury and relation to clinical outcome: a longitudinal study. Brain 2008;131:559-572.
28.
Kaiser M, Hilgetag CC. Nonoptimal component placement, but short processing paths, due to long-distance projections in neural systems. PLoS Comput Biol 2006;2:e95.
29.
Supekar K, Menon V, Rubin D, Musen M, Greicius MD. Network analysis of intrinsic functional brain connectivity in Alzheimer's disease. PLoS Comput Biol 2008;4:e1000100.
30.
Andrews-Hanna JR, Snyder AZ, Vincent JL, et al. Disruption of large-scale brain systems in advanced aging. Neuron 2007;56:924-935.
31.
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 2006;26:63-72.
32.
Gratton C, Nomura EM, Pérez F, D'Esposito M. Focal brain lesions to critical locations cause widespread disruption of the modular organization of the brain. J Cogn Neurosci 2012;24:1275-1285.
33.
Buckner RL, Andrews-Hanna JR, Schacter DL. The brain's default network: anatomy, function, and relevance to disease. Ann NY Acad Sci 2008;1124:1-38.
34.
Greicius MD, Supekar K, Menon V, Dougherty RF. Resting-state functional connectivity reflects structural connectivity in the default mode network. Cereb Cortex 2009;19:72-78.
35.
Leech R, Braga R, Sharp DJ. Echoes of the brain within the posterior cingulate cortex. J Neurosci 2012;32:215-222.
36.
Leech R, Kamourieh S, Beckmann CF, Sharp DJ. Fractionating the default mode network: distinct contributions of the ventral and dorsal posterior cingulate cortex to cognitive control. J Neurosci 2011;31:3217-3224.
37.
Mesulam M. From sensation to cognition. Brain 1998;121:1013-1052.
38.
Nakamura T, Hillary FG, Biswal BB. Resting network plasticity following brain injury. PLoS One 2009;4:e8220.
39.
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 2010;18:11-19.

Information & Authors

Information

Published In

Neurology®
Volume 80Number 20May 14, 2013
Pages: 1826-1833
PubMed: 23596068

Publication History

Received: July 14, 2012
Accepted: January 18, 2013
Published online: April 17, 2013
Published in print: May 14, 2013

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Disclosure

The authors report no disclosures relevant to the manuscript. Go to Neurology.org for full disclosures.

Study Funding

Supported by The Medical Research Council (UK) (to D.J.S., F.E.T., and P.E.), The Imperial College Healthcare Charity (to D.J.S.), a fellowship from the RCUK (to R.L.), and EPSRC grant EP/E049451/1.

Authors

Affiliations & Disclosures

Anand S. Pandit, BSc
From The Computational, Cognitive and Clinical Neuroimaging Laboratory (A.S.P., V.B., R.L., D.J.S.), The Division of Experimental Medicine, Imperial College London, Hammersmith Hospital Campus, London; Centre for Neuroimaging Sciences (P.E., F.E.T.), Institute of Psychiatry, London, UK; and Department of Mathematics/Naxys (R.L.), University of Namur, Namur, Belgium.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Paul Expert, PhD
From The Computational, Cognitive and Clinical Neuroimaging Laboratory (A.S.P., V.B., R.L., D.J.S.), The Division of Experimental Medicine, Imperial College London, Hammersmith Hospital Campus, London; Centre for Neuroimaging Sciences (P.E., F.E.T.), Institute of Psychiatry, London, UK; and Department of Mathematics/Naxys (R.L.), University of Namur, Namur, Belgium.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Renaud Lambiotte, PhD
From The Computational, Cognitive and Clinical Neuroimaging Laboratory (A.S.P., V.B., R.L., D.J.S.), The Division of Experimental Medicine, Imperial College London, Hammersmith Hospital Campus, London; Centre for Neuroimaging Sciences (P.E., F.E.T.), Institute of Psychiatry, London, UK; and Department of Mathematics/Naxys (R.L.), University of Namur, Namur, Belgium.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Valerie Bonnelle, PhD
From The Computational, Cognitive and Clinical Neuroimaging Laboratory (A.S.P., V.B., R.L., D.J.S.), The Division of Experimental Medicine, Imperial College London, Hammersmith Hospital Campus, London; Centre for Neuroimaging Sciences (P.E., F.E.T.), Institute of Psychiatry, London, UK; and Department of Mathematics/Naxys (R.L.), University of Namur, Namur, Belgium.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Robert Leech, PhD
From The Computational, Cognitive and Clinical Neuroimaging Laboratory (A.S.P., V.B., R.L., D.J.S.), The Division of Experimental Medicine, Imperial College London, Hammersmith Hospital Campus, London; Centre for Neuroimaging Sciences (P.E., F.E.T.), Institute of Psychiatry, London, UK; and Department of Mathematics/Naxys (R.L.), University of Namur, Namur, Belgium.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Federico E. Turkheimer, PhD
From The Computational, Cognitive and Clinical Neuroimaging Laboratory (A.S.P., V.B., R.L., D.J.S.), The Division of Experimental Medicine, Imperial College London, Hammersmith Hospital Campus, London; Centre for Neuroimaging Sciences (P.E., F.E.T.), Institute of Psychiatry, London, UK; and Department of Mathematics/Naxys (R.L.), University of Namur, Namur, Belgium.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
(1) 2010 - 2014, DECIDE, The European Commission, 7th Framework Programme; (2) 2010 - 2014, Medical Research Council, Project Grant no. G0900891; (3) 2009 - 2011, The Royal Society; (4) 2008 - 2013 CRUK-EPSRC Imaging Centre; (5) 2007 - 2010 EPSRC; (6) 2006 - 2012, Core funding-PET Methodology, Grant no. U1200.04.004.000001.01, MRC
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
David J. Sharp, PhD
From The Computational, Cognitive and Clinical Neuroimaging Laboratory (A.S.P., V.B., R.L., D.J.S.), The Division of Experimental Medicine, Imperial College London, Hammersmith Hospital Campus, London; Centre for Neuroimaging Sciences (P.E., F.E.T.), Institute of Psychiatry, London, UK; and Department of Mathematics/Naxys (R.L.), University of Namur, Namur, Belgium.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
1) Medical Research Council (UK) Clinician Scientist Fellowship for Prof. David Sharp. 09-13. 2) Medical Research Council (UK)- Co-Investigator. Cortical Function in Visual Dependency in Patients with Chronic Dizziness. PI Prof Bronstein. 12-15. 3) EU FP7 grant. Co-morbidity in relation to Aids (COBRA). Principle Investigator on neuroimaging section. Co-investigator Dr Robert Leech & Dr Alan Winston. 13-17. 4) National Institute for Health Research Professorship (UK). Translational traumatic brain injury research 12-17.
Research Support, Academic Entities:
1.
1) Wellcome Trust Network of Excellence Award - Co-Investigator Optogenetic manipulation of injured neural circuits. PI Dr Simon Schultz (Bioengineering).12-13. 2) The Imperial College Charitable Trustee's Research Fellowship - PI. What is the Impact of Early Growth Hormone Deficiency on Brain Function after Traumatic Brain Injury?
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE

Notes

Correspondence to Dr. Sharp: [email protected]
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

Author Contributions

A.S.P., F.E.T., R. Leech, and D.J.S. designed and conceptualized the study. A.S.P., P.E., V.B., R. Lambiotte, R. Leech, F.E.T., and D.J.S. were involved in analysis or interpretation of the data (including contribution of tools and reagents). A.S.P., F.E.T., and D.J.S. were involved in drafting and revising the manuscript for intellectual content.

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