Default mode network functional and structural connectivity after traumatic brain injury

The Hammersmith Hospital, London, W12 0NN, UK.
Brain (Impact Factor: 9.2). 08/2011; 134(Pt 8):2233-47. DOI: 10.1093/brain/awr175
Source: PubMed


Traumatic brain injury often results in cognitive impairments that limit recovery. The underlying pathophysiology of these impairments is uncertain, which restricts clinical assessment and management. Here, we use magnetic resonance imaging to test the hypotheses that: (i) traumatic brain injury results in abnormalities of functional connectivity within key cognitive networks; (ii) these changes are correlated with cognitive performance; and (iii) functional connectivity within these networks is influenced by underlying changes in structural connectivity produced by diffuse axonal injury. We studied 20 patients in the chronic phase after traumatic brain injury compared with age-matched controls. Network function was investigated in detail using functional magnetic resonance imaging to analyse both regional brain activation, and the interaction of brain regions within a network (functional connectivity). We studied patients during performance of a simple choice-reaction task and at 'rest'. Since functional connectivity reflects underlying structural connectivity, diffusion tensor imaging was used to quantify axonal injury, and test whether structural damage correlated with functional change. The patient group showed typical impairments in information processing and attention, when compared with age-matched controls. Patients were able to perform the task accurately, but showed slow and variable responses. Brain regions activated by the task were similar between the groups, but patients showed greater deactivation within the default mode network, in keeping with an increased cognitive load. A multivariate analysis of 'resting' state functional magnetic resonance imaging was then used to investigate whether changes in network function were present in the absence of explicit task performance. Overall, default mode network functional connectivity was increased in the patient group. Patients with the highest functional connectivity had the least cognitive impairment. In addition, functional connectivity at rest also predicted patterns of brain activation during later performance of the task. As expected, patients showed widespread white matter damage compared with controls. Lower default mode network functional connectivity was seen in those patients with more evidence of diffuse axonal injury within the adjacent corpus callosum. Taken together, our results demonstrate altered patterns of functional connectivity in cognitive networks following injury. The results support a direct relationship between white matter organization within the brain's structural core, functional connectivity within the default mode network and cognitive function following brain injury. They can be explained by two related changes: a compensatory increase in functional connectivity within the default mode network; and a variable degree of structural disconnection that modulates this change in network function.

Download full-text


Available from: Robert Leech, Feb 19, 2014
    • "ated with task - positive networks , it has been suggested that upregulation of DMN connectivity might tune the network so as to allow rapid deactivation required for task performance ( Sharp et al . , 2011 ) . Consistent with this view are findings of a positive correlation between DMN connectivity and cognitive outcome ( Bonelle et al . , 2011 ; Sharp et al . , 2011 ) ."
    [Show abstract] [Hide abstract]
    ABSTRACT: Recent advances in neuroimaging methodologies sensitive to axonal injury have made it possible to assess in vivo the extent of traumatic brain injury (TBI) -related disruption in neural structures and their connections. The objective of this paper is to review studies examining connectivity in TBI with an emphasis on structural and functional MRI methods that have proven to be valuable in uncovering neural abnormalities associated with this condition. We review studies that have examined white matter integrity in TBI of varying etiology and levels of severity, and consider how findings at different times post-injury may inform underlying mechanisms of post-injury progression and recovery. Moreover, in light of recent advances in neuroimaging methods to study the functional connectivity among brain regions that form integrated networks, we review TBI studies that use resting-state functional connectivity MRI methodology to examine neural networks disrupted by putative axonal injury. The findings suggest that TBI is associated with altered structural and functional connectivity, characterized by decreased integrity of white matter pathways and imbalance and inefficiency of functional networks. These structural and functional alterations are often associated with neurocognitive dysfunction and poor functional outcomes. TBI has a negative impact on distributed brain networks that lead to behavioral disturbance.
    Journal of the International Neuropsychological Society 11/2015; in press. · 2.96 Impact Factor
  • Source
    • "A meta-analytic comparison of DMN to task-based activation maps (Smith et al., 2009) reported substantial overlap with tasks that encompassed theory of mind, social cognition, episodic recall and imagined scenes (Laird et al., 2011). Furthermore, many task-free studies have all revealed alterations in this network's properties in different patient populations such as Alzheimer's disease (Buckner et al., 2009) and traumatic brain injury (Sharp et al., 2011), following pharmacological interventions such as propofol (Stamatakis et al., 2010), and with normal ageing (Damoiseaux et al., 2008). Overall, existing evidence advocates for a NeuroImage 122 (2015) 96–104 ⁎ Corresponding author at: Department of Clinical Neurosciences, Division of Anaesthesia, University of Cambridge, Box 93, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, UK. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Initially described as task-induced deactivations during goal-directed paradigms of high attentional load, the unresolved functionality of default mode regions has long been assumed to interfere with task performance. However, recent evidence suggests a potential default mode network involvement in fulfilling cognitive demands. We tested this hypothesis in a finger opposition paradigm with task and fixation periods which we compared with an independent resting state scan using functional magnetic resonance imaging and a comprehensive analysis pipeline including activation, functional connectivity, behavioural and graph theoretical assessments. The results indicate task specific changes in the default mode network topography. Behaviourally, we show that increased connectivity of the posterior cingulate cortex with the left superior frontal gyrus predicts faster reaction times. Moreover, interactive and dynamic reconfiguration of the default mode network regions' functional connections illustrate their involvement with the task at hand with higher-level global parallel processing power, yet preserved small-world architecture in comparison with rest. These findings demonstrate that the default mode network does not disengage during this paradigm, but instead may be involved in task relevant processing. Copyright © 2015. Published by Elsevier Inc.
    NeuroImage 07/2015; 122. DOI:10.1016/j.neuroimage.2015.07.053 · 6.36 Impact Factor
  • Source
    • "Though TBI is acquired rather than developmental, it has some shared characteristics with ADHD and has been associated with measures of cognitive inefficiency. Specifically, both have been associated with slower processing speed (Hervey et al., 2004; Holdnack et al., 1995; Katz et al., 2011; Sharp et al., 2011); reduced white matter tract integrity according to diffusion tensor imaging with structural magnetic resonance imaging MRI (Hellyer et al., 2013; Konrad et al., 2010; Konrad and Eickhoff, 2010; Silk et al., 2009); and abnormal functional network connectivity using functional MRI (Castellanos and Proal, 2012; Sharp et al., 2011). Given these similarities and the reliance that allocentric memory has on multiple structures, it certainly seemed reasonable to expect that this type of visual memory may be lower among ADHD subjects. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Attention Deficit Hyperactivity Disorder (ADHD) has often been conceptualized as arising executive dysfunctions (e.g., inattention, defective inhibition). However, recent studies suggested that cognitive inefficiency may underlie many ADHD symptoms, according to reaction time and processing speed abnormalities. This study explored whether a non-timed measure of cognitive inefficiency would also be abnormal. A sample of 23 ADHD subjects was compared to 23 controls on a test that included both egocentric and allocentric visual memory subtests. A factor analysis was used to determine which cognitive variables contributed to allocentric visual memory. The ADHD sample performed significantly lower on the allocentric but not egocentric conditions. Allocentric visual memory was not associated with timed, working memory, visual perception, or mental rotation variables. This paper concluded by discussing how these results supported a cognitive inefficiency explanation for some ADHD symptoms, and discussed future research directions. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    06/2015; 228(3). DOI:10.1016/j.psychres.2015.04.051
Show more