Diffusion tensor imaging evidence of white matter disruption associated with loss versus alteration of consciousness in warfighters exposed to combat in Operations Enduring and Iraqi Freedom

doi:10.1016/j.pscychresns.2012.04.018

Psychiatry Research: Neuroimaging

Volume 204, Issues 2–3, 30 November 2012, Pages 149-154

https://doi.org/10.1016/j.pscychresns.2012.04.018 Get rights and content

Abstract

The effects on the human brain of mild traumatic brain injury (mTBI), which is defined as a brief alteration (AOC) or loss of consciousness (LOC), are incompletely understood. Major psychiatric illnesses such as major depressive disorder (MDD) and posttraumatic stress disorder (PTSD) are common after mTBI. Prior research suggests that individuals who develop MDD after blast-related mTBI versus those who do not show significant white matter disruption and higher rates of LOC, suggesting that LOC might be uniquely associated with brain changes that increase the risk of developing mental illness after neurotrauma. Therefore, the objective of this study was to examine the effects of LOC, MDD, and PTSD on white matter integrity in individuals who reported experiencing mTBI during combat in Operations Enduring and Iraqi Freedom. We hypothesized that LOC would be associated with significant disruption of white matter, above and beyond putative effects of MDD and PTSD. To test this hypothesis, 46 individuals who experienced blast-related mTBI underwent a detailed clinical assessment and diffusion tensor imaging. As hypothesized, LOC versus AOC individuals displayed significantly lower fractional anisotropy (FA) in 14 regions, which included the superior longitudinal fasciculus and corpus callosum. No regions of significant FA difference were identified between individuals with and without PTSD, or between individuals with and without MDD. These preliminary results show that LOC is associated with detectable alterations in brain microstructure and may suggest a brain basis for psychiatric symptoms and mental illness after mTBI.

Introduction

The majority of combat injuries sustained by warfighters in Operations Enduring (OEF) and Iraqi (OIF) Freedom are caused by improvised explosive devices, blasts, landmines, and explosive fragments (Warden, 2006). These blast injuries result commonly in neurotrauma, such as mild traumatic brain injury (mTBI), which is defined as a blow or jolt to the head that disrupts brain function (Warden, 2006, Finkel, 2006) resulting in a brief (i.e., maximum of 20 min) loss (LOC) or alteration (AOC) of consciousness. It has been estimated that approximately 196,000 cases of blast-related TBI occurred among OIF-OEF warriors between 2000 and 2010, approximately 150,000 of which were of mild severity (Schneiderman et al., 2008, Terrio et al., 2009). Although neurotrauma that results in LOC >20 min (i.e., moderate/severe TBI) often produces brain damage that is detectable with clinical neuroimaging techniques (Povlishock and Katz, 2005), individuals who have experienced mTBI often have normal scans. Little is known about the neuroanatomical effects of blast-related mTBI on the human brain.

Although the mechanism is unknown, individuals who sustain mTBI frequently develop major psychiatric illnesses, such as major depressive disorder (MDD) and posttraumatic stress disorder (PTSD) (Warden, 2006, Koponen et al., 2002, Hoge et al., 2008). Prior research has shown that 30% of a brigade of warriors exposed to OIF combat subsequently experienced MDD and/or PTSD (Hoge et al., 2008). Related evidence from a group of individuals who sustained blunt force neurotrauma showed that depression severity was related to structural changes in brain regions involved in emotion processing (Mollica et al., 2009). Functional neuroimaging research has revealed that among OIF-OEF veterans who experienced blast-related mTBI, functional activation of emotion-processing circuitry was dependent on whether or not the subjects had experienced LOC (Matthews et al., 2011). Additionally, individuals who developed MDD after blast-related mTBI versus those who did not reported higher rates of LOC and appeared to show disruption in white matter tracts such as the superior longitudinal fasciculus (SLF), (Matthews et al., 2011). Taken together, this evidence suggests the possibility that LOC may be uniquely associated with brain changes that may increase risk of developing psychiatric symptoms or mental illness after neurotrauma.

The primary aim of the current study was to build on prior work suggesting that LOC may be associated with maladaptive brain changes that may increase risk of psychiatric symptoms and mental illness (Matthews et al., 2011, Matthews et al., 2011), by using diffusion tensor imaging (DTI) to examine the effect of LOC, MDD and PTSD on white matter integrity in OEF-OIF veterans who sustained blast-related mTBI. We hypothesized that LOC would be associated with significant disruption, above and beyond putative effects of MDD and PTSD, of white matter tracts such as the SLF and corpus callosum. Support for this hypothesis would increase understanding of the effects of LOC on the human brain and suggest a brain basis for psychiatric symptoms and mental illness after mTBI.

Section snippets

Study design

Forty-six male subjects with a reported history of blast-related mTBI during OEF-OIF combat completed this cross sectional study, which was approved by the local Human Research Protection Program. During session 1, subjects: (a) provided written informed consent; (b) completed a semi-structured interview based on the DSM-IV (First et al., 1997); (c) completed the Combat Exposure Scale (CES) (Blake et al., 1995), the Beck Depression Inventory-2 (BDI-2) (Beck et al., 1996), the Patient Health

Clinical findings

All subjects reported a history of concussion (i.e., LOC or AOC for a maximum of 20 min) related to blast exposure. Within the total sample (n=46), 23 subjects met DSM-IV criteria for current MDD, 28 subjects met DSM-IV criteria for current PTSD and 22 reported a history of LOC (Table 1). Because several regions of FA difference were observed between the LOC and AOC subgroups, we compared these subgroups on demographic and clinical characteristics (Table 1). LOC versus AOC individuals had a

Discussion

The main goal of this study was to examine the effects of LOC, MDD and PTSD on white matter integrity in OEF-OIF warfighters with a history of mTBI. Three main findings were observed. First, LOC versus AOC individuals showed significant disruption of white matter, as indicated by lower FA in several regions, which included the bilateral brainstem, inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, body of the corpus callosum, cingulum, superior longitudinal fasciculus

Acknowledgments

We thank Ryan O'Connell, Elena Kosheleva, Martin Paulus, Dean Delis, and Larry Frank for their contributions to this research, which was funded by grants from the Veterans Administration and the Congressionally Directed Medical Research Program and was supported by the VA Mental Illness Research, Education and Clinical Center and the VA Center of Excellence for Stress and Mental Health. Dr. Matthews' VA salary is supported by a CDA-2 from VA Clinical Science Research and Development.

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Published by Elsevier Ltd.

Diffusion tensor imaging evidence of white matter disruption associated with loss versus alteration of consciousness in warfighters exposed to combat in Operations Enduring and Iraqi Freedom

Abstract

Introduction

Section snippets

Study design

Clinical findings

Discussion

Acknowledgments

Psychiatry Research: Neuroimaging

Neuroimage

Biological Psychiatry

Brain Research

Neurobiology of Aging

Journal of Neurological Sciences

Neuroimage

General Hospital Psychiatry

Neuroimage

Neuroimage

Comparison of Beck Depression Inventories -IA and -II in psychiatric outpatients

Journal of Personality Assessment

The development of a clinician-administered PTSD scale

Journal of Traumatic Stress

Diagnostic procedures in mild traumatic brain injury: results of the WHO Collaborating Centre Task Force On Mild Traumatic Brain Injury

Journal of Rehabilitation Medicine

Methodological issues and research recommendations for mild traumatic brain injury: the WHO Collaborating Centre Task Force on Mild Traumatic Brain Injury

Journal of Rehabilitation Medicine

Topography of the human corpus callosum

Journal of Neuropathology and Experimental Neurology

Anisotropy in high angular resolution diffusion-weighted MRI

Magnetic Resonance in Medicine

Combat duty in Iraq and Afghanistan, mental health problems and barriers to care

U.S. Army Medical Department Journal

Mild traumatic brain injury in U.S. soldiers returning from Iraq

The New England Journal of Medicine

Summary of the WHO Collaborating Centre for Neurotrauma Task Force on Mild Traumatic Brain Injury

Journal of Rehabilitation Medicine

Correction for geometric distortion in echo planar images from B0 field variations

Magnetic Resonance in Medicine