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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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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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