White Matter Abnormalities in Veterans With Mild Traumatic Brain Injury

Department of Child and Adolescent Psychiatry, Erasmus Universiteit Rotterdam, Rotterdam, South Holland, Netherlands
American Journal of Psychiatry (Impact Factor: 12.3). 12/2012; 169(12):1284-91. DOI: 10.1176/appi.ajp.2012.12050600
Source: PubMed


It has been estimated that 10%-20% of U.S. veterans of the wars in Iraq and Afghanistan experienced mild traumatic brain injury (TBI), mostly secondary to blast exposure. Diffusion tensor imaging (DTI) may detect subtle white matter changes in both the acute and chronic stages of mild TBI and thus has the potential to detect white matter damage in patients with TBI. The authors used DTI to examine white matter integrity in a relatively large group of veterans with a history of mild TBI.

DTI images from 72 veterans of the wars in Iraq and Afghanistan who had mild TBI were compared with DTI images from 21 veterans with no exposure to TBI during deployment. Conventional voxel-based analysis as well as a method of identifying spatially heterogeneous areas of decreased fractional anisotropy ("potholes") were used. Veterans also underwent psychiatric and neuropsychological assessments.

Voxel-based analysis did not reveal differences in DTI parameters between the veterans with mild TBI and those with no TBI. However, the veterans with mild TBI had a significantly higher number of potholes than those without TBI. The difference in the number of potholes was not influenced by age, time since trauma, a history of mild TBI unrelated to deployment, or coexisting psychopathology. The number of potholes was correlated with the severity of TBI and with performance in executive functioning tasks.

Veterans who had blast-related mild TBI showed evidence of multifocal white matter abnormalities that were associated with severity of the injury and with relevant functional measures. Overall, white matter potholes may constitute a sensitive biomarker of axonal injury that can be identified in mild TBI at acute and chronic stages of its clinical course.

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Available from: Ricardo E. Jorge, Aug 14, 2015
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    • "However, PTSD symptom severity was not associated with white matter alterations. Several other studies have reported similar negative findings [Jorge et al., 2012; Morey et al., 2012; Taber et al., 2015] although two studies using different diffusion metrics suggest white matter involvement in PTSD [Bazarian et al., 2012; Davenport et al., 2015]. Nonetheless, PTSD-related neuropathology appears to be associated primarily with changes in gray matter volume [Bremner et al., 1995; Corbo et al., 2005; Kasai et al., 2008; O'Doherty et al., 2015; Smith, 2005] and functional alterations [Bremner et al., 1999; Daniels et al., 2010; Hayes et al., 2011; Milad et al., 2009; Sadeh et al., 2015; Shin and Liberzon , 2010; Shin et al., 2004; St Jacques et al., 2013; van Wingen et al., 2012]. "
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    ABSTRACT: Blast-related mild traumatic brain injury (mTBI) is a common injury among Iraq and Afghanistan military veterans due to the frequent use of improvised explosive devices. A significant minority of individuals with mTBI report chronic postconcussion symptoms (PCS), which include physical, emotional, and cognitive complaints. However, chronic PCS are non-specific and are also associated with mental health disorders such as posttraumatic stress disorder (PTSD). Identifying the mechanisms that contribute to chronic PCS is particularly challenging in blast-related mTBI, where the incidence of co-morbid PTSD is high. In this study, we examined whether blast-related mTBI is associated with diffuse white matter changes, and whether these neural changes are associated with chronic PCS. Ninety OEF/OIF Veterans were assigned to one of three groups including a blast-exposed no-TBI group, a blast-related mTBI without loss of consciousness (LOC) group (mTBI-LOC), and a blast-related mTBI with LOC group (mTBI+LOC). PCS were measured with the Rivermead Postconcussion Questionnaire. Results showed that participants in the mTBI+LOC group had more spatially heterogeneous white matter abnormalities than those in the no-TBI group. These white matter abnormalities were significantly associated with physical PCS severity even after accounting for PTSD symptoms, but not with cognitive or emotional PCS severity. A mediation analysis revealed that mTBI+LOC significantly influenced physical PCS severity through its effect on white matter integrity. These results suggest that white matter abnormalities are associated with chronic PCS independent of PTSD symptom severity and that these abnormalities are an important mechanism explaining the relationship between mTBI and chronic physical PCS.
    Full-text · Article · Jan 2016 · Human Brain Mapping
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    • "(combat mTBI, not specifically blast) Possible connection between combat-related mTBI damage to posterior cingulum/PCC white matter, DMN, and presence of PTSD symptoms. Jorge et al. 2012 29 probable mTBI; 43 possible mTBI (all combat related mTBI; not differentiated by mechanism) "
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    ABSTRACT: Mild traumatic brain injury (mTBI) has been labeled the “signature injury” of the wars in Iraq and Afghanistan, and approximately half of mTBIs that occur in combat are due to explosive blasts. The rapid change in pressure that results from an explosion may make blast injury distinct from mTBI due to other causes. Persistent symptoms following blast mTBI may be related to white matter damage that has recently been identified using innovative neuroimaging techniques, such as diffusion tensor imaging (DTI). By comparing the DTI findings in blast mTBI to studies of the effects of white matter structure on functional performance, hypotheses can be developed about the implications of the injury for engagement in occupation. Incorporation of neuroscience evidence about the effects of blast mTBI may provide objective evidence of underlying damage that correlates with deficits in occupational engagement of military service members and veterans who are affected by these injuries.
    Full-text · Article · Dec 2015 · Journal of Occupational Science
    • "the bulk of studies examining military blast mTBI have included individuals with both primary blast exposure and additional secondary and tertiary injuries . These studies have generally shown decreases in white matter integrity both in the subacute ( Mac Donald et al . , 2011 ) and chronic phase ( Davenport et al . , 2012 ; Hayes et al . , 2015 ; Jorge et al . , 2012 ; Mac Donald et al . , 2011 ; Morey et al . , 2013 ) , similar to the civilian mTBI literature ( but see Bazarian et al . , 2013 ; Levin et al . , 2010 ; Watts et al . , 2014 ) . However , findings of greater neurologic deficits in individuals exposed to combat - related mTBI than civilian mTBI ( Ruff et al . , 2012 ) provide some evide"
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    ABSTRACT: Recent advances in neuroimaging methodologies sensitive to axonal injury have made it possible to assess in vivo the extent of traumatic brain injury (TBI) -related disruption in neural structures and their connections. The objective of this paper is to review studies examining connectivity in TBI with an emphasis on structural and functional MRI methods that have proven to be valuable in uncovering neural abnormalities associated with this condition. We review studies that have examined white matter integrity in TBI of varying etiology and levels of severity, and consider how findings at different times post-injury may inform underlying mechanisms of post-injury progression and recovery. Moreover, in light of recent advances in neuroimaging methods to study the functional connectivity among brain regions that form integrated networks, we review TBI studies that use resting-state functional connectivity MRI methodology to examine neural networks disrupted by putative axonal injury. The findings suggest that TBI is associated with altered structural and functional connectivity, characterized by decreased integrity of white matter pathways and imbalance and inefficiency of functional networks. These structural and functional alterations are often associated with neurocognitive dysfunction and poor functional outcomes. TBI has a negative impact on distributed brain networks that lead to behavioral disturbance.
    No preview · Article · Nov 2015 · Journal of the International Neuropsychological Society
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