Alterations in the Topology of Functional Connectomes Are Associated with Post-Traumatic Stress Disorder and Blast-Related Mild Traumatic Brain Injury in Combat Veterans

Rowland, Jared A.; Stapleton-Kotloski, Jennifer R.; Martindale, Sarah L.; Rogers, Emily; Ord, Anna S.; Godwin, Dwayne W.; Taber, Katherine H.

doi:10.1089/neu.2020.7450

Cited by 13 publications

(10 citation statements)

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“…To illustrate these points and the broad issue of variability in measurement, we present new analyses of previous work ( 35 , 37 ) that provide a side-by-side comparison of results when using different definitions of blast exposure identified in published human studies, including: blast TBI ( 34 , 58 ), primary blast TBI ( 28 ), pressure severity ( 4 , 37 ), distance from the blast ( 32 , 43 ), and frequency of exposure ( 49–51 ). These analyses utilize data from the Chronic Effects of Neurotrauma Consortium Study 34 (CENC-34) that has been described previously ( 35 , 37 ).…”

Section: Demonstration Of Pitfalls Due To Measurement Inconsistencymentioning

confidence: 99%

Considerations for the assessment of blast exposure in service members and veterans

Rowland,

Martindale

2024

Front. Neurol.

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IntroductionBlast exposure is an increasingly present occupational hazard for military service members, particularly in modern warfare scenarios. The study of blast exposure in humans is limited by the lack of a consensus definition for blast exposure and considerable variability in measurement. Research has clearly demonstrated a robust and reliable effect of blast exposure on brain structure and function in the absence of other injury mechanisms. However, the exact mechanisms underlying these outcomes remain unclear. Despite clear contributions from preclinical studies, this knowledge has been slow to translate to clinical applications. The present manuscript empirically demonstrates the consequences of variability in measurement and definition across studies through a re-analysis of previously published data from the Chronic Effects of Neurotrauma Study 34.MethodsDefinitions of blast exposure used in prior work were examined including Blast TBI, Primary Blast TBI, Pressure Severity, Distance, and Frequency of Exposure. Outcomes included both symptom report and cognitive testing.ResultsResults demonstrate significant differences in outcomes based on the definition of blast exposure used. In some cases the same definition was strongly related to one type of outcome, but unrelated to another.DiscussionThe implications of these results for the study of blast exposure are discussed and potential actions to address the major limitations in the field are recommended. These include the development of a consensus definition of blast exposure, further refinement of the assessment of blast exposure, continued work to identify relevant mechanisms leading to long-term negative outcomes in humans, and improved education efforts.

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Section: Demonstration Of Pitfalls Due To Measurement Inconsistencymentioning

confidence: 99%

Considerations for the assessment of blast exposure in service members and veterans

Rowland,

Martindale

2024

Front. Neurol.

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“…The interview produces a rich dataset about these experiences and can provide critical, contextual information about key blast exposure characteristics. This tool has been used to understand risk for psychiatric and cognitive symptoms as well as neuroimaging alterations in combat veterans across the full spectrum of blast exposures ( 11 – 14 ). However, the time and administration requirements may make the measure more challenging to include in large-scale research studies in comparison to self-report questionnaires.…”

Section: Self-report Measures Of Career Blastmentioning

confidence: 99%

Perspectives on Development of Measures to Estimate Career Blast Exposure History in Service Members and Veterans

et al. 2022

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The Department of Defense (DOD) has recently prioritized the investigation of the acute and chronic adverse brain health and performance effects of low-level blast (LLB) generated by the use of weapons systems. While acute exposure can be quantified by sensor technology, career exposure has no widely accepted and validated measure for characterization. Currently, distinct research groups are developing and validating four promising measures to estimate career blast exposure history: the Salisbury Blast Interview, Blast Exposure Threshold Survey, Blast Ordnance and Occupational Exposure Measure, and the Blast Frequency and Symptom Severity. Each measure offers an assessment of blast history that is uniquely beneficial to addressing specific research questions. However, use of divergent strategies is not efficient to accelerate the field's understanding of the impact of career exposure and Service-connected health outcomes. As a DOD-wide solution, collaboration across these groups is required to develop a tool(s) that can be standardized across research studies and, ultimately, pared down to be implemented in clinical settings. Here, we overview the current four measures and provide a perspective on the way forward for optimization and/or combination in support of this solution.

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“…24 Although fewer studies of brain volume have been published, volumetric changes have been noted in the hippocampus. 3,25 bTBI has also been shown to alter brain function, 26 the structure of whole-brain functional connectomes, 27 functional connectivity throughout the brain, 28 and functional connectivity within specific circuits. 29,30 Further, these functional brain imaging changes have also been associated with changes in cognitive performance, specifically working memory.…”

Section: Introductionmentioning

confidence: 99%

Brain volume changes following blast-related mild TBI in service members and veterans: a LIMBIC-CENC study

Dennis,

Rowland,

Esopenko

et al. 2024

Preprint

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ImportanceBlast-related mild traumatic brain injuries (bTBI), the “signature injury” of post-9/11 conflicts, are associated with clinically-relevant long-term cognitive, psychological, and behavioral dysfunction and disability; however, the underlying neural mechanisms remain unclear.ObjectiveTo investigate associations between a history of remote bTBI and regional brain volume in a sample of United States (U.S.) Veterans and Active Duty Service Members (VADSM).DesignProspective case-control study of U.S. VADSM of participants from the Long-term Impact of Military-relevant Brain Injury Consortium - Chronic Effects of Neurotrauma Consortium (LIMBIC-CENC), which enrolled over 1,500 participants at five sites used in this analysis between 2014-2023.SettingParticipants were recruited from Veterans Affairs medical centers across the U.S.ParticipantsSeven hundred and seventy-four VADSM of the U.S. military met eligibility criteria for this analysis.ExposureAll participants had combat exposure, and 82% had one or more lifetime mild TBIs with variable injury mechanisms.Main Outcomes and MeasuresRegional brain volume was calculated using tensor-based morphometry on 3D T1-weighted magnetic resonance imaging scans. TBI history, including history of blast-related injury (bTBI), was assessed by structured clinical interview. Cognitive performance and psychiatric symptoms were assessed with a battery of validated instruments. We hypothesized that regional volume would be smaller in the bTBI group, and that this would be associated with cognitive performance.ResultsIndividuals with a history of bTBI had smaller brain volumes in several clusters, with the largest centered bilaterally in the superior corona radiata and globus pallidus. Greater volume deficits were associated with a larger number of lifetime bTBIs. Additionally, causal mediation analysis revealed that these volume differences significantly mediated the association between bTBI and performance on measures of working memory and processing speed.Conclusions and RelevanceOur results reveal robust volume differences associated with bTBI. Magnetic resonance elastography atlases reveal that the specific regions affected include the stiffest tissues in the brain, which may underlie their vulnerability to pressure waves from blast exposures. Furthermore, these volume differences significantly mediated the association between bTBI and cognitive function, indicating that this may be a helpful biomarker in tracking outcome after bTBI and suggesting potential treatment targets to prevent or limit chronic dysfunction.

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Alterations in the Topology of Functional Connectomes Are Associated with Post-Traumatic Stress Disorder and Blast-Related Mild Traumatic Brain Injury in Combat Veterans

Cited by 13 publications

References 77 publications

Considerations for the assessment of blast exposure in service members and veterans

Considerations for the assessment of blast exposure in service members and veterans

Perspectives on Development of Measures to Estimate Career Blast Exposure History in Service Members and Veterans

Brain volume changes following blast-related mild TBI in service members and veterans: a LIMBIC-CENC study

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