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Disconnection, network dysfunction and cognitive impairment after traumatic brain injury

It is now widely accepted that cognitive functions depend on the integrated operation of large-scale distributed brain networks. Recent methodological advances allow both structural and functional connectivity within these networks to be studied non-invasively in vivo. These approaches hold the promise of dramatically extending our understanding of the impact of traumatic brain injury (TBI) on cognition, which should help determine strategic targets for the rehabilitation of individuals with TBI. In this thesis, I present three studies that combine structural and functional magnetic resonance imaging to test the general hypothesis that cognitive deficits after TBI arise from structural disconnection within brain networks that mediate cognitive functions. In the first study, I demonstrate that sustained attention deficits in TBI patients are related to a failure to regulate activity within a ‘default-mode’ network (DMN) thought to be involved, among others, in internally directed processes such as self-referential thought. In addition, these deficits can be predicted by the functional and structural connectivity within the DMN. Next, I present a study investigating the neural basis for inhibitory control in healthy subjects using a modified version of the Stop Signal Task (SST). This study allows a clear distinction between attentional and response inhibition processes, and paves the way for my last study, which investigates inhibitory deficits after TBI. In this study, I demonstrate that a failure of DMN deactivation during response inhibition is associated with impaired inhibitory performance in TBI patients. The ability to efficiently regulate the DMN can be predicted by the structural integrity within a remote brain network previously proposed to be involved in switching between internally and externally directed attention. This work identifies DMN dysfunction as underlying various cognitive deficits after TBI, and confirms the relevance of white matter damage in the development of brain dysfunctions after TBI.

Identiferoai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:560650
Date January 2012
CreatorsBonnelle, Valerie
ContributorsSharp, David ; de Boissezon, Xavier ; Wise, Richard
PublisherImperial College London
Source SetsEthos UK
Detected LanguageEnglish
TypeElectronic Thesis or Dissertation
Sourcehttp://hdl.handle.net/10044/1/9782

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