Research Reports from the Brain Sciences Center

BSC Researchers awarded Grant from Department of Defense for Gulf War Illness research

The Department of Defense, as part of the US Army Medical Research and Material Command Congressionally Directed Medical Research Programs, has awarded Lisa James, Apostolos Georgopoulos, Brian Engdahl, and Adam Carpenter with a 36 month grant for the project "Human Leukocyte Antigen in Gulf War Veterans: Association with Symptoms and Inflammatory Makers"

This grant will help to fund important research for Veterans, especially those veterans who suffer from Gufl War Illness.


Subcortical brain atrophy in Gulf War Illness

More than a quarter of the veterans who served in the 1990-1991 Persian Gulf War experience chronic unexplained health problems collectively referred to as Gulf War Illness. GWI is characterized by multiple symptoms. Although characteristic symptoms span multiple systems, several involve the brain. These symptoms and others are among the most commonly reported symptoms in veterans who deployed during the Gulf War, strongly suggesting brain involvement.

We suspect that the limited evidence of cerebellar and other subcortical anomalies in GWI in not a reflection of "normality" but is instead attributable to a tendency in neuroimaging research to focus on particular regions of interest at the exclusion of other brain difference. We aim to further explore cerebellar and other subcortical abnormalities associated with GWI by comparing subcortical volumes in veterans with GWI to healthy veterans.

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HLA and Gulf War Illness: HLA-DRB1*13:02 Spares Subcortical Atrophy in Gulf War Veterans

For over 25 years, veterans of the 1990-1991 Gulf War have been affected by chronic health problems that are presumed to be sequelae of service related exposures to toxins such as pyridostigmine bromide, pesticides, multiple vaccinations, and//or stress. Many symptoms involve the central nervous system; consequently, several studies have investigated brain structure and function with mixed findings.

We have recently identified function and structure brain anomalies, both of which prominently involved subcortical regions. We investigated the effect of DRB1*13:02 on the volumes of subcortical brain regions found to be reduced in affected veterans to test the hypothesis that HLA BRB1*13:02 prevents subcortical brain atrophy.

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Gulf War Illness as a Neuroimmune Disease

by Apostolos Georgopoulos, et al.

GWI is a chronic disease characterized by the involvement of several organs, including the brain. Previously, the BSC had identified six protective alleles from the HLA genes, and have investigated the correlates of the protection with this gene. Those and other studies suggested an involvement of the immune system in GWI. Here we focused on the Synchronous Neural Interactions itself, as a basic measure of neural communication and compared in between GWI and seven other diseases that cover a broad spectrum of etiology and pathophysiology.

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Researchers pinpoint reductions in brain volume of ill Gulf War Vets

by Mike Richman, VA Research Communications

The Brain Sciences Center at the Minneapolis VA Health Care System has evolved into one of the leading facilities in the country for researching Gulf War illness (GWI), a condition that is of major concern to the Veteran community.
Researchers at the center have made what they believe to be key breakthroughs with GWI.

read more here - read full study here


Commentary: Supporting a Neuroimmune Basis of Gulf War Illness

EBioMedicine - 2016 - James P. O'Callaghan, et al

Gulf War Illness (GWI) is a complex multi-symptom disorder that has proven elusive to understand and treat. No specific st of exposures can explain the persistent symptoms, and the pathophysiology of GWI has remained unclear.

There have been several studies suggesting that this illness is the result of an interaction between exposures and genetics. A prior report by Georgopoulos and colleagues provided insight into a basis for a genetic/immune role in GWI.

read full commentary here

Brain Correlates of Human Leukocyte Antigen (HLA) Protection in Gulf War Illness (GWI)

EBioMedicine - 2016 - L.M. James, et al

We recently reported that six alleles from class II genes of the HLA confer protection from GWI. Here we tested the hypothesis that this effect is exerted by modulating the strength of neural synchronicity.

Participants underwent a mangetoencephalography (MEG) scan to assess the strength of brain synchronicity by computing zero-lag crosscorrelations between prewhitened MEG time series.

We found significant, graded HLA- and non-HLA-related effects. These effects had widespread but distinct distributions in seensor space that allowed for orderly separation of the 6 terms in the multidimensional plot.

These findings demonstrate the presence of substantial, widespread, distinct and orderly HLA- and non-HLA-related neural influences on symptom severity in GWI

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Reduced Human Leukocyte Antigen (HLA) Protection in Gulf War Illness (GWI)

EBioMedicine 3 - 2016 - Apostolos P. Georgopoulos, et al

Gulf War Illness (GWI) is a disease of unknown etiology with symptoms suggesting the involvement of an immune process. Here we tested the hypothesis that Human Leukocyte Antigen (HLA) composition might differ between veterans with and without GWI.

We identified 144 unique alleles of Class I and II HLA genes in 82 veterans (66 with and 16 without GWI). We tested the hypothesis that a subset of HLA alleles may classify veterans in their respective group using a stepwise linear discriminant analysis. In addition, each participant rated symptom severity in 6 domains according to established GWI criteria, and an overall symptom severity was calculated.

We found 6 Class II alleles that classified participants 84.1% correctly (13/16 control and 56/66 GWI). The number of copies of the 6 alleles was significantly higher in the control group, suggesting a protective role.

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A Magnetoencephalographic (MEG) Study of Gulf War Illness (GWI)

EBioMedicine - 2016 - Brian E. Engdahl, et al

Gulf War Illness (GWI) has affected many Gulf War veterans. It involves several organs, most notably the brain. Neurological-cognitive-mood-related symptoms frequently dominate and are at the root of chronic illhealth and disability in GWI. Here we investigated the neural mechanisms underlying brain dysfunction in GWI in the absence of mental health disorders.

Eighty-six veterans completed diagnostic interviews to establish the presence of GWI and assess mental health status. Participants diagnosed with GWI met both Center for Disease Control and Kansas criteria. We studied 46 healthy controls and 40 veterans with GWI without mental illness. They all underwent a resting-state magnetoencephalographic (MEG) scan to assess brain communication based on synchronous neural interactions (SNI; Georgopoulos et al., 2007).

We found substantial differences in SNI between control and GWI groups centered on the cerebellum and frontal cortex. In addition, using the maxima and minima of SNI per sensor as predictors, we successfully classified 94.2% of the 86 participants (95% sensitivity, 93.5% specificity).

These findings document distinct differences in brain function between control and GWI in the absence of mental health comorbidities, differences that are excellent predictors of GWI.

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Updated April 30, 2018