title: The nature of white matter abnormalities in blast-related mild traumatic brain injury.
abstract: Blast-related traumatic brain injury (TBI) has been a common injury among returning troops due to the widespread use of improvised explosive devices in the Iraq and Afghanistan Wars. As most of the TBIs sustained are in the mild range, brain changes may not be detected by standard clinical imaging techniques such as CT. Furthermore, the functional significance of these types of injuries is currently being debated. However, accumulating evidence suggests that diffusion tensor imaging (DTI) is sensitive to subtle white matter abnormalities and may be especially useful in detecting mild TBI (mTBI). The primary aim of this study was to use DTI to characterize the nature of white matter abnormalities following blast-related mTBI, and in particular, examine the extent to which mTBI-related white matter abnormalities are region-specific or spatially heterogeneous. In addition, we examined whether mTBI with loss of consciousness (LOC) was associated with more extensive white matter abnormality than mTBI without LOC, as well as the potential moderating effect of number of blast exposures. A second aim was to examine the relationship between white matter integrity and neurocognitive function. Finally, a third aim was to examine the contribution of PTSD symptom severity to observed white matter alterations. One hundred fourteen OEF/OIF veterans underwent DTI and neuropsychological examination and were divided into three groups including a control group, blast-related mTBI without LOC (mTBI - LOC) group, and blast-related mTBI with LOC (mTBI + LOC) group. Hierarchical regression models were used to examine the extent to which mTBI and PTSD predicted white matter abnormalities using two approaches: 1) a region-specific analysis and 2) a measure of spatial heterogeneity. Neurocognitive composite scores were calculated for executive functions, attention, memory, and psychomotor speed. Results showed that blast-related mTBI + LOC was associated with greater odds of having spatially heterogeneous white matter abnormalities. Region-specific reduction in fractional anisotropy (FA) in the left retrolenticular part of the internal capsule was observed in the mTBI + LOC group as the number of blast exposures increased. A mediation analysis revealed that mTBI + LOC indirectly influenced verbal memory performance through its effect on white matter integrity. PTSD was not associated with spatially heterogeneous white matter abnormalities. However, there was a suggestion that at higher levels of PTSD symptom severity, LOC was associated with reduced FA in the left retrolenticular part of the internal capsule. These results support postmortem reports of diffuse axonal injury following mTBI and suggest that injuries with LOC involvement may be particularly detrimental to white matter integrity. Furthermore, these results suggest that LOC-associated white matter abnormalities in turn influence neurocognitive function.
authors.affiliation: National Center for PTSD, VA Boston Healthcare System, Boston, MA, USA ; Department of Psychiatry, Boston University School of Medicine, Boston, MA, USA ; Neuroimaging Research for Veterans Center, VA Boston Healthcare System, Boston, MA, USA.
authors.forename: Jasmeet P
authors.initials: JP
authors.lastname: Hayes
authors.affiliation: Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston, MA, USA ; Memory Disorders Research Center, VA Boston Healthcare System, Boston, MA, USA.
authors.forename: Danielle R
authors.initials: DR
authors.lastname: Miller
authors.affiliation: Department of Psychiatry, Boston University School of Medicine, Boston, MA, USA ; Memory Disorders Research Center, VA Boston Healthcare System, Boston, MA, USA.
authors.forename: Ginette
authors.initials: G
authors.lastname: Lafleche
authors.affiliation: Neuroimaging Research for Veterans Center, VA Boston Healthcare System, Boston, MA, USA ; Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard University, Boston, USA ; Harvard Medical School, Harvard University, Boston, USA.
authors.forename: David H
authors.initials: DH
authors.lastname: Salat
authors.affiliation: Memory Disorders Research Center, VA Boston Healthcare System, Boston, MA, USA ; Department of Psychiatry, Boston University School of Medicine, Boston, MA, USA.
authors.forename: Mieke
authors.initials: M
authors.lastname: Verfaellie
mesh_terms: D000328:Adult; D055826:Afghan Campaign 2001-; D001753:Blast Injuries / Q000150:complications*; D001930:Brain Injuries / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D056324:Diffusion Tensor Imaging; D005260:Female; D006801:Humans; D020772:Internal Capsule / Q000473:pathology; D054542:Iraq War, 2003-2011; D008297:Male; D008569:Memory Disorders / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D012720:Severity of Illness Index; D013313:Stress Disorders, Post-Traumatic / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D014474:Unconsciousness / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D014728:Veterans; D066127:White Matter / Q000473:pathology*; D055815:Young Adult
keywords: Diffusion tensor imaging; Fractional anisotropy; Loss of consciousness; OEF/OIF; PTSD