Default mode network functional and structural connectivity after traumatic brain injury

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.

Altered cross-frequency coupling in resting-state MEG after mild traumatic brain injury

“…This linkage supports the assumption that ICN function is vulnerable to the effects of mTBI, considering that diffuse axonal injury (DAI) usually damages long-distance white-matter tracts that connect key brain areas (known as hubs) in these networks (Smith et al, 2003;Gentleman et al, 1995). ICN abnormalities after TBI have been widely observed in resting-state fMRI, demonstrating both increase and decrease of connectivity in a number of networks, including the default mode network (DMN) and salience network (SN) (Sharp et al, 2011;Stevens et al, 2012). Several studies have also reported that these abnormalities correlate with cognitive impairment or post-concussive symptoms (Messe et al, 2013;Caeyenberghs et al, 2014).…”

Hyperconnectivity is a fundamental response to neurological disruption.

“…Articles were also excluded when the primary goal was to examine the influence of an intervention or drug and no initial group comparison was made affording the opportunity to examine relative group connectivity (e.g., Solé-Padullés et al, 2013). Finally, articles were excluded if no baseline comparison of connectivity was made between the clinical sample and healthy control sample (e.g., Bonnelle et al, 2012;Bonnelle et al, 2011) or the comparison was made but only based upon a specific contrast or manipulation (e.g., Palacios et al, 2012). Study inclusion was determined by thorough review of the study design and methods.…”

Strategy‐based reasoning training modulates cortical thickness and resting‐state functional connectivity in adults with chronic traumatic brain injury

“…Diffuse axonal injury (DAI) (Smith, Meaney, & Shull, 2003) is a primary injury mechanism of TBI, and rsFC has been a promising technique to identify DAI‐induced higher‐order cognitive impairments (e.g., reasoning, decision making, and selective attention) among individuals with TBI (Sharp, Scott, & Leech, 2014). Notably, large‐scale network approaches using rsFC in TBI have effectively revealed the complex patterns of the injured brain (Han, Chapman, & Krawczyk, 2016; Mayer, Mannell, Ling, Gasparovic, & Yeo, 2011; Sharp et al., 2011). The large established literature in large‐scale networks in healthy individuals facilitates the interpretation of study findings as applied to individuals after a TBI.…”