White matter abnormalities are associated with overall cognitive status in blast-related mTBI

Abstract

Blast-related mild traumatic brain injury (mTBI) is a common injury of the Iraq and Afghanistan Wars. Research has suggested that blast-related mTBI is associated with chronic white matter abnormalities, which in turn are associated with impairment in neurocognitive function. However, findings are inconsistent as to which domains of cognition are affected by TBI-related white matter disruption. Recent evidence that white matter abnormalities associated with blast-related mTBI are spatially variable raises the possibility that the associated cognitive impairment is also heterogeneous. Thus, the goals of this study were to examine (1) whether mTBI-related white matter abnormalities are associated with overall cognitive status and (2) whether white matter abnormalities provide a mechanism by which mTBI influences cognition. Ninety-six Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) veterans were assigned to one of three groups: no-TBI, mTBI without loss of consciousness (LOC) (mTBI−LOC), and mTBI with LOC (mTBI+LOC). Participants were given a battery of neuropsychological tests that were selected for their sensitivity to mTBI. Results showed that number of white matter abnormalities was associated with the odds of having clinically significant cognitive impairment. A mediation analysis revealed that mTBI+LOC was indirectly associated with cognitive impairment through its effect on white matter integrity. These results suggest that cognitive difficulties in blast-related mTBI can be linked to injury-induced neural changes when taking into account the variability of injury as well as the heterogeneity in cognitive deficits across individuals.

Functional and Structural Neuroimaging Correlates of Repetitive Low-Level Blast Exposure in Career Breachers

“…increased, decreased, or bidirectional values in the acute to subacute phase post-TBI, 72 chronic white matter injury largely presents with decreased FA and increased RD, 68,69,73 consistent with our findings.…”

“…Earlier work exploring DTI-based measures in TBI is extensive. [67][68][69][70][71] Whereas FA and RD may demonstrate Along the x-axis are the controls and breacher groups with raw p values in the upper left of the plots. Connectivity between default mode network and other networks is increased in breachers whereas resting-state activity, largely within the default mode regions, is higher in controls.…”

Theta-Band Functional Connectivity and Single-Trial Cognitive Control in Sports-Related Concussion: Demonstration of Proof-of-Concept for a Potential Biomarker of Concussion

“…There were also trends for diminished modulation of brain activity following errors (i.e., error-minus-correct difference score), and altered relationships between brain activity and response inhibition (i.e., single-trial relationships between connectivity and PES). These group differences in connectivity and cognitive control emerged late in the time series (>300 ms) and may indicate that complex cognitive processes such as error awareness (Nieuwenhuis, Ridderinkhof, Blom, Band, & Kok, 2001) and learning from errors (Cavanagh, Frank, Klein, & Allen, 2010; Cohen and van Gaal, 2013) may be especially vulnerable to concussion and functioning of cortical-cortical pathways (e.g., Miller, Hayes, Lafleche, Salat, & Verfaellie, 2017;Orr et al, 2016). Moreover, FCz-F6 connectivity demonstrated some specificity with regard to prediction of mTBI (e.g., Supplementary Figures 3 and 4), suggestive that FCz-F6 connectivity assesses functioning of a vulnerable right-lateralized frontal lobe network that is important for behavioral inhibition (Aron et al, 2014).…”

Neuroimaging of deployment-associated traumatic brain injury (TBI) with a focus on mild TBI (mTBI) since 2009

“…Since Davenport et al's original publication, several other studies investigating white matter in blast-related mTBI have found similar results, suggesting that the injury is associated with diffuse white matter abnormalities, particularly in those who experienced a LOC [47][48][49]. Additionally, these diffuse white matter disruptions have been associated with both neurocognitive [47,49] and behavioral [48] outcomes in blast-related mTBI, with more recent work suggesting that the associated cognitive impairment of these global disruptions is also heterogeneous [50]. This heterogeneity may be to blame for studies that did not find differences in DTI imaging associated with military mTBI, some of which found that other contributing factors, such as cognitive impairment [51] or co-occurring PTSD [52] (but see [47,48]) could account for variability among individuals with mTBI.…”