Compromised Neurocircuitry in Chronic Blast‐Related Mild Traumatic Brain Injury

Abstract

The aim of this study was to apply recently developed automated fiber segmentation and quantification methods using diffusion tensor imaging (DTI) and DTI-based deterministic and probabilistic tractography to access local and global diffusion changes in blast-induced mild traumatic brain injury (bmTBI). Two hundred and two (202) male active US service members who reported persistent post-concussion symptoms for more than 6 months after injury were recruited. An additional forty (40) male military controls were included for comparison. DTI results were examined in relation to post-concussion and post-traumatic stress disorder (PTSD) symptoms. No significant group difference in DTI metrics was found using voxel-wise analysis. However, group comparison using tract profile analysis and tract specific analysis, as well as single subject analysis using tract profile analysis revealed the most prominent white matter microstructural injury in chronic bmTBI patients over the frontal fiber tracts, that is, the front-limbic projection fibers (cingulum bundle, uncinate fasciculus), the fronto-parieto-temporal association fibers (superior longitudinal fasciculus), and the fronto-striatal pathways (anterior thalamic radiation). Effects were noted to be sensitive to the number of previous blast exposures, with a negative association between fractional anisotropy (FA) and time since most severe blast exposure in a subset of the multiple blast-exposed group. However, these patterns were not observed in the subgroups classified using macrostructural changes (T2 white matter hyperintensities). Moreover, post-concussion symptoms and PTSD symptoms, as well as neuropsychological function were associated with low FA in the major nodes of compromised neurocircuitry. Hum Brain Mapp 38:352-369, 2017. © 2016 Wiley Periodicals, Inc.

Compromised hippocampus‐striatum pathway as a potential imaging biomarker of mild‐traumatic brain injury and posttraumatic stress disorder

“…First, complementary to the connectivity findings, DTI results confirmed greater diversity (more diffuse, hence less integrity) of white‐matter tracts between hippocampus and striatum in the PCS + PTSD group compared to both the control and PTSD groups, suggesting a strong structural basis for PCS. Prior work shows affected white‐matter integrity with left striatum in subjects sustaining an mTBI (Yeh et al, ). This structural specificity implies that it is unlikely that the PCS + PTSD group is an extreme subset of PTSD.…”

Fear learning alterations after traumatic brain injury and their role in development of posttraumatic stress symptoms

“…Chronic traumatic encephalopathy (Gavett, Stern, & McKee, ; Stern et al., ) resulting from multiple concussions is associated with abnormal cortical and limbic circuit activation and morphology as well as symptoms of depression and emotional instability (Stern et al., ; ). In military samples, multiple blast exposures are associated with reduced cortical‐limbic white matter integrity (Yeh et al., ), suggesting that “multiple hits” may particularly predispose subjects to abnormalities in fear circuit integrity and function.…”

“…Prevalence rates for veterans of these conflicts are estimated at 23% for PTSD (Fulton et al, 2015) and 10-23% for TBI (Hoge et al, 2008;O'Neil et al, (Acheson et al, 2015;Briscione, Jovanovic, & Norrholm, 2014;Craske & Mystkowski, 2006;Grillon et al, 2009;Hermans, CRASKE, Mineka, & Lovibond, 2006;Lissek & van Meurs, 2015;Milad et al, 2009;Mineka & Zinbarg, 2006;Norrholm et al, 2011;Risbrough, Glenn, & Baker, 2016;VanElzakker, Dahlgren, Davis, Dubois, & Shin, 2014). Thus, head injuries affecting circuits involved with regulation of learned fear processes may increase risk for developing and maintaining PTSD symptoms (Yeh et al, 2016). In animals, brain injury is associated with enhanced fear acquisition (Reger et al, 2012;Schneider et al, 2016), impaired fear extinction (Schneider et al, 2016), and altered fear circuitry (Palmer, Metheny, Elkind, & Cohen, 2016) (but see (Sierra-Mercado et al, 2015)).…”

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

“…This has been the topic of several recent discussions in the literature [105,106] with a range of epidemiological and clinical studies suggesting that TBI increases later life cognitive risk to some degree [107][108][109]. Brain imaging has demonstrated the potential modification of aging trajectories, at least cross-sectionally, in Veterans with blast exposure compared to unexposed Veterans [91,110] and for Veterans with symptomatic blast-related mTBI compared to pre-deployed military personnel [91]. Moreover, recent imaging work demonstrates that genetic risk for Alzheimer's disease and exposure to TBI have a potentially interactive effect on cortical thickness [111], which may suggest some enhanced risk for degenerative processes that have long term consequences.…”