Central Executive Dysfunction and Deferred Prefrontal Processing in Veterans With Gulf War Illness

Hubbard, Nicholas A.; Hutchison, Joanna L.; Motes, Michael A.; Shokri‐Kojori, Ehsan; Bennett, Ilana J.; Brigante, Ryan; Haley, Robert W.

doi:10.1177/2167702613506580

Cited by 39 publications

(40 citation statements)

References 50 publications

(113 reference statements)

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“…Recent work examining brain changes in GWI support an underlying neurobiological underpinning to these problems. Results show that participants with GWI perform significantly slower and less accurately on working memory tasks than matched healthy veterans, and that this decrease correlates with lower levels of activity in prefrontal brain regions [ 35 ]. Fatigue and pain, other commonly reported symptoms associated with GWI have been linked to alterations in the brain’s white matter in GWI subjects [ 36 , 37 ].…”

Section: Discussionmentioning

confidence: 99%

Using gene expression signatures to identify novel treatment strategies in gulf war illness

et al. 2015

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BackgroundGulf War Illness (GWI) is a complex multi-symptom disorder that affects up to one in three veterans of this 1991 conflict and for which no effective treatment has been found. Discovering novel treatment strategies for such a complex chronic illness is extremely expensive, carries a high probability of failure and a lengthy cycle time. Repurposing Food and Drug Administration approved drugs offers a cost-effective solution with a significantly abbreviated timeline.MethodsHere, we explore drug re-purposing opportunities in GWI by combining systems biology and bioinformatics techniques with pharmacogenomic information to find overlapping elements in gene expression linking GWI to successfully treated diseases. Gene modules were defined based on cellular function and their activation estimated from the differential expression of each module’s constituent genes. These gene modules were then cross-referenced with drug atlas and pharmacogenomic databases to identify agents currently used successfully for treatment in other diseases. To explore the clinical use of these drugs in illnesses similar to GWI we compared gene expression patterns in modules that were significantly expressed in GWI with expression patterns in those same modules in other illnesses.ResultsWe found 19 functional modules with significantly altered gene expression patterns in GWI. Within these modules, 45 genes were documented drug targets. Illnesses with highly correlated gene expression patterns overlapping considerably with GWI were found in 18 of the disease conditions studied. Brain, muscular and autoimmune disorders composed the bulk of these.ConclusionOf the associated drugs, immunosuppressants currently used in treating rheumatoid arthritis, and hormone based therapies were identified as the best available candidates for treating GWI symptoms.Electronic supplementary materialThe online version of this article (doi:10.1186/s12920-015-0111-3) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Using gene expression signatures to identify novel treatment strategies in gulf war illness

et al. 2015

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“…Both human (Gulf War veteran populations) and animal studies have reported neurological outcomes associated with the exposures present during Gulf War deployment, including neuro-inflammation [16], changes in brain volume [17], hippocampal dysfunction [18,19], decreased white matter [7,9,20] and alterations in executive function and cognition [21,22]. …”

Section: Introductionmentioning

confidence: 99%

Trends in brain cancer mortality among U.S. Gulf War veterans: 21 year follow-up

Barth

Dursa

Bossarte

et al. 2017

Cancer Epidemiology

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Objective Previous mortality studies of U.S. Gulf War veterans through 2000 and 2004 have shown an increased risk of brain cancer mortality among some deployed individuals. When veterans possibly exposed to environmental contaminants associated with demolition of the Khamisiyah Ammunition Storage Facility at Khamisiyah, Iraq, have been compared to contemporaneously deployed unexposed veterans, the results have suggested increased risk for mortality from brain cancer among the exposed. Brain cancer mortality risk in this cohort has not been updated since 2004. Methods This study analyzes the risk for brain cancer mortality between 1991–2011 through two series of comparisons: U.S. Gulf War deployed and non-deployed veterans from the same era; and veterans possibly exposed to environmental contaminants at Khamisiyah compared to contemporaneously deployed but unexposed U.S. Gulf War veterans. Risk of brain cancer mortality was determined using logistic regression. Life test hazard models were created to plot comparisons of annual hazard rates. Joinpoint regression models were applied to assess trends in hazard rates for brain cancer mortality. Results U.S. Army veterans possibly exposed at Khamisiyah had similar rates of brain cancer mortality compared to those not possibly exposed; however, veterans possibly exposed had a higher risk of brain cancer in the time period immediately following the Gulf War. Conclusion Results from these analyses suggest that veterans possibly exposed at Khamisiyah experienced different patterns of brain cancer mortality risk compared to the other groups.

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“…Forty-seven participants (ages 40-73, M =58±8 years, 0 female) were recruited from a group of military-veterans formerly deployed to the 1991 Persian Gulf War; military-veterans’ participation was included as part of a larger study. Approximately half of the military-veterans were diagnosed with Gulf War Illnesses (GWI; n=23; for neural sequelae of GWI see Hubbard et al, 2013), whereas the remainder of the military-veterans reported being healthy (n=24). All participants gave written informed consent.…”

Section: Methodsmentioning

confidence: 99%

The efficiency of fMRI region of interest analysis methods for detecting group differences

Hutchison

Hubbard

Brigante

et al. 2014

Journal of Neuroscience Methods

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Background Using a standard space brain template is an efficient way of determining region-of-interest (ROI) boundaries for functional magnetic resonance imaging (fMRI) data analyses. However, ROIs based on landmarks on subject-specific (i.e., native space) brain surfaces are anatomically accurate and probably best reflect the regional blood oxygen level dependent (BOLD) response for the individual. Unfortunately, accurate native space ROIs are often time-intensive to delineate even when using automated methods. New Method We compared analyses of group differences when using standard versus native space ROIs using both volume and surface-based analyses. Collegiate and military-veteran participants completed a button press task and a digit-symbol verification task during fMRI acquisition. Data were analyzed within ROIs representing left and right motor and prefrontal cortices, in native and standard space. Volume and surface-based analysis results were also compared using both functional (i.e., percent signal change) and structural (i.e., voxel or node count) approaches. Results and Comparison with Existing Method(s) Results suggest that transformation into standard space can affect the outcome of structural and functional analyses (inflating/minimizing differences, based on cortical geography), and these transformations can affect conclusions regarding group differences with volumetric data. Conclusions Caution is advised when applying standard space ROIs to volumetric fMRI data. However, volumetric analyses show group differences and are appropriate in circumstances when time is limited. Surface-based analyses using functional ROIs generated the greatest group differences and were less susceptible to differences between native and standard space. We conclude that surface-based analyses are preferable with adequate time and computing resources.

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Central Executive Dysfunction and Deferred Prefrontal Processing in Veterans With Gulf War Illness

Cited by 39 publications

References 50 publications

Using gene expression signatures to identify novel treatment strategies in gulf war illness

Using gene expression signatures to identify novel treatment strategies in gulf war illness

Trends in brain cancer mortality among U.S. Gulf War veterans: 21 year follow-up

The efficiency of fMRI region of interest analysis methods for detecting group differences

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