Elevated Intraindividual Variability in Executive Functions and Associations with White Matter Microstructure in Veterans with Mild Traumatic Brain Injury

Abstract Objective: We examined whether intraindividual variability (IIV) across tests of executive functions (EF-IIV) is elevated in Veterans with a history of mild traumatic brain injury (mTBI) relative to military controls (MCs) without a history of mTBI. We also explored relationships among EF-IIV, white matter microstructure, and posttraumatic stress disorder (PTSD) symptoms. Method: A total of 77 Veterans (mTBI = 43, MCs = 34) completed neuropsychological testing, diffusion tensor imaging (DTI), and PTSD symptom ratings. EF-IIV was calculated as the standard deviation across six tests of EF, along with an EF-Mean composite. DSI Studio connectometry analysis identified white matter tracts significantly associated with EF-IIV according to generalized fractional anisotropy (GFA). Results: After adjusting for EF-Mean and PTSD symptoms, the mTBI group showed significantly higher EF-IIV than MCs. Groups did not differ on EF-Mean after adjusting for PTSD symptoms. Across groups, PTSD symptoms significantly negatively correlated with EF-Mean, but not with EF-IIV. EF-IIV significantly negatively correlated with GFA in multiple white matter pathways connecting frontal and more posterior regions. Conclusions: Veterans with mTBI demonstrated significantly greater IIV across EF tests compared to MCs, even after adjusting for mean group differences on those measures as well as PTSD severity. Findings suggest that, in contrast to analyses that explore effects of mean performance across tests, discrepancy analyses may capture unique variance in neuropsychological performance and more sensitively capture cognitive disruption in Veterans with mTBI histories. Importantly, findings show that EF-IIV is negatively associated with the microstructure of white matter pathways interconnecting cortical regions that mediate executive function and attentional processes.

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Examining Microstructural White Matter in Active Duty Soldiers with a History of Mild Traumatic Brain Injury and Traumatic Stress

The Open Neuroimaging Journal ◽

10.2174/1874440001711010046 ◽

2017 ◽

Vol 11 (1) ◽

pp. 46-57 ◽

Cited By ~ 7

Author(s):

Michael N. Dretsch ◽

Rael T. Lange ◽

Jeffery S. Katz ◽

Adam Goodman ◽

Thomas A. Daniel ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

White Matter ◽

Mild Traumatic Brain Injury ◽

Psychological Health ◽

Traumatic Stress ◽

Diffusion Tensor ◽

Active Duty ◽

Control Group ◽

History Of

Background:There is a high comorbidity of posttraumatic stress (PTS) and mild traumatic brain injury (mTBI), with largely overlapping symptomatology, in military service members.Objective:To examine white matter integrity associated with PTS and mTBI as assessed using diffusion tensor imaging (DTI).Method:Seventy-four active-duty U.S. soldiers with PTS (n = 16) and PTS with co-morbid history of mTBI (PTS/mTBI; n = 28) were compared to a military control group (n = 30). Participants received a battery of neurocognitive and clinical symptom measures. The number of abnormal DTI values was determined (>2 SDs from the mean of the control group) for fractional anisotropy (FA) and mean diffusivity (MD), and then compared between groups. In addition, mean DTI values from white matter tracts falling into three categories were compared between groups: (i) projection tracts: superior, middle, and inferior cerebellar peduncles, pontine crossing tract, and corticospinal tract; (ii) association tracts: superior longitudinal fasciculus; and (iii) commissure tracts: cingulum bundle (cingulum-cingulate gyrus and cingulum-hippocampus), and corpus callosum.Results:The comorbid PTS/mTBI group had significantly greater traumatic stress, depression, anxiety, and post-concussive symptoms, and they performed worse on neurocognitive testing than those with PTS alone and controls. The groups differed greatly on several clinical variables, but contrary to what we hypothesized, they did not differ greatly on primary and exploratory analytic approaches of hetero-spatial whole brain DTI analyses.Conclusion:The findings suggest that psychological health conditions rather than pathoanatomical changes may be contributing to symptom presentation in this population.

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Brain white matter after pediatric mild traumatic brain injury: a diffusion tensor and neurite orientation and dispersion imaging study

10.1101/2021.09.09.21263356 ◽

2021 ◽

Author(s):

Ayushi Shukla ◽

Ashley L Ware ◽

Sunny Guo ◽

Bradley Gooodyear ◽

Miriam H Beauchamp ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

White Matter ◽

Mild Traumatic Brain Injury ◽

Diffusion Tensor ◽

Univariate Analysis ◽

Significant Group ◽

Brain White Matter ◽

Orthopedic Injury ◽

White Matter Microstructure

Background: Pediatric mild traumatic brain injury (mTBI) affects millions of children annually. Diffusion tensor imaging (DTI) is sensitive to axonal injuries and white matter microstructure and has been used to characterize the brain changes associated with mild traumatic brain injury (mTBI). Neurite orientation dispersion and density imaging (NODDI) is a diffusion model that can provide additional insight beyond traditional DTI metrics, but has not been examined in pediatric mTBI. The goal of this study was to employ DTI and NODDI to gain added insight into white matter alterations in children with mTBI compared to children with mild orthopedic injury (OI). Methods: Children (mTBI n=320, OI n=176) aged 8-16.99 years (12.39 ± 2.32 years) were recruited from emergency departments at five hospitals across Canada and underwent 3T MRI on average 11 days post-injury. DTI and NODDI metrics were calculated for seven major white matter tracts and compared between groups using univariate analysis of covariance controlling for age, sex, and scanner type. False discovery rate (FDR) was used to correct for multiple comparisons. Results: Univariate analysis revealed no significant group main effects or interactions in DTI or NODDI metrics. Fractional anisotropy and neurite density index in all tracts exhibited a significant positive association with age and mean diffusivity in all tracts exhibited a significant negative association with age in the whole sample. Conclusions: Overall, there were no differences between mTBI and OI groups in brain white matter microstructure from either DTI or NODDI in the seven tracts. This indicates that mTBI is associated with only relatively minor white matter differences, if any, at the post-acute stage. Brain differences may evolve at later stages of injury, so longitudinal studies with long-term follow-up are needed.

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Acute mild traumatic brain injury is not associated with white matter change on diffusion tensor imaging

Brain ◽

10.1093/brain/awu095 ◽

2014 ◽

Vol 137 (7) ◽

pp. 1876-1882 ◽

Cited By ~ 47

Author(s):

Tero Ilvesmäki ◽

Teemu M. Luoto ◽

Ullamari Hakulinen ◽

Antti Brander ◽

Pertti Ryymin ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Diffusion Tensor Imaging ◽

Brain Injury ◽

White Matter ◽

Mild Traumatic Brain Injury ◽

Diffusion Tensor ◽

White Matter Change

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Corpus Callosum Vasculature Predicts White Matter Microstructure Abnormalities after Pediatric Mild Traumatic Brain Injury

Journal of Neurotrauma ◽

10.1089/neu.2018.5670 ◽

2019 ◽

Vol 36 (1) ◽

pp. 152-164 ◽

Cited By ~ 8

Author(s):

Kara M. Wendel ◽

Jeong Bin Lee ◽

Bethann M. Affeldt ◽

Mary Hamer ◽

Indira S. Harahap-Carrillo ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

White Matter ◽

Corpus Callosum ◽

Mild Traumatic Brain Injury ◽

White Matter Microstructure

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Pilot investigation of a novel white matter imaging technique in Veterans with and without history of mild traumatic brain injury

Brain Injury ◽

10.1080/02699052.2018.1493225 ◽

2018 ◽

Vol 32 (10) ◽

pp. 1255-1264 ◽

Cited By ~ 5

Author(s):

Sarah M. Jurick ◽

Samantha N. Hoffman ◽

Scott Sorg ◽

Amber V. Keller ◽

Nicole D. Evangelista ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

White Matter ◽

Mild Traumatic Brain Injury ◽

Imaging Technique ◽

Pilot Investigation ◽

History Of

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A-108 Psychological and Sociodemographic Challenges, but Not History of Mild Traumatic Brain Injury, Is Associated with Criminal Justice Involvement among Veterans and Service Members

Archives of Clinical Neuropsychology ◽

10.1093/arclin/acab062.126 ◽

2021 ◽

Vol 36 (6) ◽

pp. 1157-1157

Author(s):

Becky Gius ◽

Lauren F Fournier ◽

Tea Reljic ◽

Terri Pogoda ◽

John Corrigan ◽

...

Keyword(s):

Social Support ◽

Traumatic Brain Injury ◽

Brain Injury ◽

Criminal Justice ◽

Alcohol Consumption ◽

Mild Traumatic Brain Injury ◽

Ptsd Symptoms ◽

Criminal Justice Involvement ◽

Lifetime History ◽

History Of

Abstract Objective Examine factors associated with history of arrests and felony incarceration among Veterans and Service Members (V/SM) with combat exposure. Method Participants were V/SM who completed a baseline assessment for the multicenter Chronic Effects of Neurotrauma Consortium study (N = 1555). Most were male (87%), white (72%), with a mean age of 40 years (SD = 9.71). The majority (83%) reported a history of ≥1 mild traumatic brain injury (mTBI), with thirty-five present of those experiencing 3+ mTBIs. Results Three groups were composed based on self-reported level of involvement with the criminal justice system: 1.) No history of arrests or incarcerations (65%), 2.) A lifetime history of arrest but no felony incarceration (32%), and 3.) A lifetime history of felony incarceration (3%). Chi-square and Kruskal-Wallis H tests revealed statistically significant differences between the groups in demographic factors including the incarcerated group having younger age, greater percentage of men, lower education, and greater percentage of never being married, followed by the arrest group and then the no arrest group (all p < 0.05). The incarcerated group also had the highest level of posttraumatic stress disorder (PTSD) symptoms, lowest social support, and greatest percentage of hazardous alcohol consumption, followed by the arrest and then the no arrest groups (all p < 0.05). No differences were found between groups for mTBI history or neuropsychological testing results. Conclusions Correlates of legal involvement among V/SM span demographic and psychological dimensions. Some correlates are modifiable, including social support, PTSD symptoms, and alcohol consumption. Addressing these modifiable risk factors is critical to lower the risk of future criminal justice involvement.

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Diffusion Tensor Imaging of the Evolving Response to Mild Traumatic Brain Injury in Rats

Journal of Experimental Neuroscience ◽

10.1177/1179069519858627 ◽

2019 ◽

Vol 13 ◽

pp. 117906951985862 ◽

Cited By ~ 5

Author(s):

Wouter S Hoogenboom ◽

Todd G Rubin ◽

Kenny Ye ◽

Min-Hui Cui ◽

Kelsey C Branch ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Diffusion Tensor Imaging ◽

Brain Injury ◽

White Matter ◽

Mild Traumatic Brain Injury ◽

Diffusion Tensor ◽

Axonal Injury ◽

Mean Diffusivity ◽

Multiple Time ◽

Post Injury

Mild traumatic brain injury (mTBI), also known as concussion, is a serious public health challenge. Although most patients recover, a substantial minority suffers chronic disability. The mechanisms underlying mTBI-related detrimental effects remain poorly understood. Although animal models contribute valuable preclinical information and improve our understanding of the underlying mechanisms following mTBI, only few studies have used diffusion tensor imaging (DTI) to study the evolution of axonal injury following mTBI in rodents. It is known that DTI shows changes after human concussion and the role of delineating imaging findings in animals is therefore to facilitate understanding of related mechanisms. In this work, we used a rodent model of mTBI to investigate longitudinal indices of axonal injury. We present the results of 45 animals that received magnetic resonance imaging (MRI) at multiple time points over a 2-week period following concussive or sham injury yielding 109 serial observations. Overall, the evolution of DTI metrics following concussive or sham injury differed by group. Diffusion tensor imaging changes within the white matter were most noticeable 1 week following injury and returned to baseline values after 2 weeks. More specifically, we observed increased fractional anisotropy in combination with decreased radial diffusivity and mean diffusivity, in the absence of changes in axial diffusivity, within the white matter of the genu corpus callosum at 1 week post-injury. Our study shows that DTI can detect microstructural white matter changes in the absence of gross abnormalities as indicated by visual screening of anatomical MRI and hematoxylin and eosin (H&E)-stained sections in a clinically relevant animal model of mTBI. Whereas additional histopathologic characterization is required to better understand the neurobiological correlates of DTI measures, our findings highlight the evolving nature of the brain’s response to injury following concussion.

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Repeated Mild Traumatic Brain Injury Results in Long-Term White-Matter Disruption

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2014.6 ◽

2014 ◽

Vol 34 (4) ◽

pp. 715-723 ◽

Cited By ~ 58

Author(s):

Virginia Donovan ◽

Claudia Kim ◽

Ariana K Anugerah ◽

Jacqueline S Coats ◽

Udochuwku Oyoyo ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

White Matter ◽

Mild Traumatic Brain Injury ◽

Diffusion Tensor ◽

Ex Vivo ◽

Health Concern ◽

Sprague Dawley ◽

G Ratio

Mild traumatic brain injury (mTBI) is an increasing public health concern as repetitive injuries can exacerbate existing neuropathology and result in increased neurologic deficits. In contrast to other models of repeated mTBI (rmTBI), our study focused on long-term white-matter abnormalities after bilateral mTBIs induced 7 days apart. A controlled cortical impact (CCI) was used to induce an initial mTBI to the right cortex of Single and rmTBI Sprague Dawley rats, followed by a second injury to the left cortex of rmTBI animals. Shams received only a craniectomy. Ex vivo diffusion tensor imaging (DTI), transmission electron microscopy (TEM), and histology were performed on the anterior corpus callosum at 60 days after injury. The rmTBI animals showed a significant bilateral increase in radial diffusivity (myelin), while only modest changes in axial diffusivity (axonal) were seen between the groups. Further, the rmTBI group showed an increased g-ratio and axon caliber in addition to myelin sheath abnormalities using TEM. Our DTI results indicate ongoing myelin changes, while the TEM data show continuing axonal changes at 60 days after rmTBI. These data suggest that bilateral rmTBI induced 7 days apart leads to progressive alterations in white matter that are not observed after a single mTBI.

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