Article

Default mode network functional and structural connectivity after traumatic brain injury

The Hammersmith Hospital, London, W12 0NN, UK.
Brain (Impact Factor: 10.23). 08/2011; 134(Pt 8):2233-47. DOI: 10.1093/brain/awr175
Source: PubMed

ABSTRACT 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.

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Available from: Robert Leech, Feb 19, 2014
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    • "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. "
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    • "Conflicting results have been obtained by previous studies on DMN alterations after mTBI, with reduced DMN connectivity seen at rest (Mayer et al. 2011; Johnson et al. 2012; Zhang et al. 2012), but both lower (Bonnelle et al. 2012; Mayer et al. 2012) and higher task-induced DMN deactivation (Sharp et al. 2011). However, only the study which found greater task-induced deactivation investigated performance in chronic TBI (Sharp et al. 2011). Furthermore, a negative association between PCS symptom report and lower BOLD response in DMN-related areas has been found previously in participants performing the n-Back task (Pardini et al. 2010). "
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