Distinct patterns of structural damage underlie working memory and reasoning deficits after traumatic brain injury
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Author(s)
Jolly, Amy
Scott, Gregory
Sharp, David
Hampshire, Adam
Type
Journal Article
Abstract
It is well established that chronic cognitive problems after traumatic brain injury (TBI) relate to diffuse axonal injury (DAI) and the consequent widespread disruption of brain connectivity. However, the pattern of DAI varies between patients and they have a correspondingly heterogeneous profile of cognitive deficits. This heterogeneity is poorly understood, presenting a non-trivial challenge for prognostication and treatment.
Prominent amongst cognitive problems are deficits in working memory and reasoning. Previous functional magnetic resonance imaging (fMRI) in controls has associated these aspects of cognition with distinct, but partially overlapping, networks of brain regions. Based on this, a logical prediction is that differences in the integrity of the white matter tracts that connect these networks should predict variability in the type and severity of cognitive deficits after TBI.
We use diffusion-weighted imaging, cognitive testing and network analyses to test this prediction. We define functionally distinct sub-networks of the structural connectome by intersecting previously published fMRI maps of the brain regions that are activated during our working memory and reasoning tasks, with a library of the white-matter tracts that connect them. We examine how graph theoretic measures within these sub-networks relate to the performance of the same tasks in a cohort of 92 moderate-severe TBI patients. Finally, we use machine learning to determine whether cognitive performance in patients can be predicted using graph theoretic measures from each sub-network.
Principal component analysis of behavioural scores confirm that reasoning and working memory form distinct components of cognitive ability, both of which are vulnerable to TBI. Critically, impairments in these abilities after TBI correlate in a dissociable manner with the information-processing architecture of the sub-networks that they are associated with. This dissociation is confirmed when examining degree centrality measures of the sub-networks using a canonical correlation analysis. Notably, the dissociation is prevelant across a number of node-centric measures and is asymmetrical: disruption to the working memory sub-network relates to both working memory and reasoning performance whereas disruption to the reasoning sub-network relates to reasoning performance selectively. Machine learning analysis further supports this finding by demonstrating that network measures predict cognitive performance in patients in the same asymmetrical manner. These results accord with hierarchical models of working memory, where reasoning is dependent on the ability to first hold task relevant information in working memory.
We propose that this finer grained information may be useful for future applications that attempt to predict long-term outcomes or develop tailored therapies.
Prominent amongst cognitive problems are deficits in working memory and reasoning. Previous functional magnetic resonance imaging (fMRI) in controls has associated these aspects of cognition with distinct, but partially overlapping, networks of brain regions. Based on this, a logical prediction is that differences in the integrity of the white matter tracts that connect these networks should predict variability in the type and severity of cognitive deficits after TBI.
We use diffusion-weighted imaging, cognitive testing and network analyses to test this prediction. We define functionally distinct sub-networks of the structural connectome by intersecting previously published fMRI maps of the brain regions that are activated during our working memory and reasoning tasks, with a library of the white-matter tracts that connect them. We examine how graph theoretic measures within these sub-networks relate to the performance of the same tasks in a cohort of 92 moderate-severe TBI patients. Finally, we use machine learning to determine whether cognitive performance in patients can be predicted using graph theoretic measures from each sub-network.
Principal component analysis of behavioural scores confirm that reasoning and working memory form distinct components of cognitive ability, both of which are vulnerable to TBI. Critically, impairments in these abilities after TBI correlate in a dissociable manner with the information-processing architecture of the sub-networks that they are associated with. This dissociation is confirmed when examining degree centrality measures of the sub-networks using a canonical correlation analysis. Notably, the dissociation is prevelant across a number of node-centric measures and is asymmetrical: disruption to the working memory sub-network relates to both working memory and reasoning performance whereas disruption to the reasoning sub-network relates to reasoning performance selectively. Machine learning analysis further supports this finding by demonstrating that network measures predict cognitive performance in patients in the same asymmetrical manner. These results accord with hierarchical models of working memory, where reasoning is dependent on the ability to first hold task relevant information in working memory.
We propose that this finer grained information may be useful for future applications that attempt to predict long-term outcomes or develop tailored therapies.
Date Issued
2020-04-03
Date Acceptance
2020-01-25
Citation
Brain: a journal of neurology, 2020, 143 (4), pp.1158-1176
ISSN
0006-8950
Publisher
Oxford University Press (OUP)
Start Page
1158
End Page
1176
Journal / Book Title
Brain: a journal of neurology
Volume
143
Issue
4
Copyright Statement
© The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Sponsor
Imperial College Healthcare NHS Trust- BRC Funding
Imperial Health Charity
Imperial College Healthcare NHS Trust- BRC Funding
The Royal British Legion
Imperial College Healthcare NHS Trust- BRC Funding
National Institute for Health Research
Identifier
https://academic.oup.com/brain/article/143/4/1158/5815602
Grant Number
RDA03_79560
7006/R21U
RDC04 79560
BMPF_P60304
RDC04
NIHR-RP-011-048
Subjects
graph theory
reasoning
structural connectome
traumatic brain injury
working memory
Neurology & Neurosurgery
11 Medical and Health Sciences
17 Psychology and Cognitive Sciences
Publication Status
Published
Date Publish Online
2020-04-03