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

Engdahl, Brian; James, Lisa M.; Miller, Ryan D.; Leuthold, Arthur C.; Lewis, Scott M.; Carpenter, Adam F.; Georgopoulos, Apostolos P.

doi:10.1016/j.ebiom.2016.08.030

Cited by 32 publications

(30 citation statements)

References 18 publications

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“…These correlations have proved powerful in successfully discriminating various brain diseases (Georgopoulos et al, 2007), including posttraumatic stress disorder (PTSD) (Georgopoulos et al, 2010, Engdahl et al, 2010), and in identifying neural correlates of resilience to trauma (James et al, 2013), of posttraumatic growth (Anders et al, 2015), and of measures of psychopathology (James et al, 2015). More importantly, in a recent study of MEG patterns in GWI (Engdahl et al, 2016) we found synchronous crosscorrelations differed significantly between controls and GWI patients and could classify successfully (> 93% correctly) control and GWI participants. These findings provided the framework for this study, which investigated more specifically the relations between these correlations and specific GWI symptomatology.…”

Section: Introductionmentioning

confidence: 59%

“…Cognitively healthy individuals display remarkably similar patterns of neural synchronicity (Langheim, 2006), whereas alterations in neural synchrony have been associated with several neuropsychiatric disorders (Engdahl et al, 2010, Georgopoulos et al, 2007, Georgopoulos et al, 2010, James et al, 2013, 2015; Uhlhaas and Singer, 2006). We have recently demonstrated that GWI is also associated with aberrant synchronicity affecting cortical areas and the cerebellum (Engdahl et al, 2016). Our working hypothesis (Fig.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2016

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BackgroundWe recently reported that six alleles from class II genes of the Human Leukocyte Antigen (HLA) confer protection from Gulf War Illness (GWI) (Georgopoulos et al., 2015). The most significant effect is exerted on Neurological-Cognitive-Mood (NCM), Pain, and Fatigue symptoms, such that higher number of copies of the protective alleles are associated with lower symptom severity. Here we tested the hypothesis that this effect is exerted by modulating the strength of neural synchronicity.MethodsEighty-one Gulf War veterans (65 with GWI and 16 healthy controls) underwent a magnetoencephalography (MEG) scan to assess the strength of brain synchronicity by computing zero-lag crosscorrelations (and their Fisher z transforms) between prewhitened MEG time series. A high-resolution HLA genotyping determined the number of copies, k, of the 6 protective alleles above in each participant. We tested the hypothesis above by regressing NCM, Pain and Fatigue symptom severity against the interaction term, k × z (HLA-related effect), while including z (non-HLA-related effect), gender and age as covariates. The k × z and z terms assessed HLA- and non-HLA-related effects, respectively, of neural synchronicity on symptom severity. The distributions of these effects in sensor space were visualized using statistical heatmaps.FindingsWe found significant, graded HLA- and non-HLA-related effects: (a) NCM > Pain > Fatigue for HLA-related effects, (b) NCM > Fatigue > Pain for non-HLA-related effects, and (c) HLA-related > non-HLA-related effects for all symptoms. These effects had widespread but distinct distributions in sensor space that allowed the orderly separation of the 6 terms (3 symptom domains × 2 HLA factors) in a multidimensional plot, where one dimension separated the symptoms and the other the HLA relation.InterpretationThese findings demonstrate the presence of substantial, widespread, distinct and orderly HLA- and non-HLA-related neural influences on NCM, Pain and Fatigue symptom severity in GWI.FundingU.S. Department of Veterans Affairs and University of Minnesota.

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Section: Introductionmentioning

confidence: 59%

Section: Discussionmentioning

confidence: 99%

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

et al. 2016

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“…Many symptoms of GWI involve the central nervous system; consequently, several studies have investigated brain structure and function as it relates to GWI, with mixed findings ( White et al, 2016 ). We have recently identified functional ( Engdahl et al, 2016 ) and structural ( Christova et al, 2017 ) brain anomalies in GWI, both of which prominently involved subcortical regions. For example, compared to healthy control veterans, veterans with GWI showed an average of 10.4% reduction in cerebellar volume and 2 × the rate of reduction of cerebellar gray matter volume with age (− 14%/decade in GWI vs. − 6.9%/decade in controls).…”

Section: Introductionmentioning

confidence: 99%

Human Leukocyte Antigen (HLA) and Gulf War Illness (GWI): HLA-DRB1*13:02 Spares Subcortical Atrophy in Gulf War Veterans

James¹,

Christova

Engdahl³

et al. 2017

EBioMedicine

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BackgroundGulf War Illness (GWI) is a multisystem disorder that has affected a substantial number of veterans who served in the 1990–91 Gulf War. The brain is prominently affected, as manifested by the presence of neurological, cognitive and mood symptoms. We reported previously on the protective role of six Human Leukocyte Antigen (HLA) alleles in GWI (Georgopoulos et al., 2016) and their association with regional brain function (James et al., 2016). More recently, we reported on the presence of subcortical brain atrophy in GWI (Christova et al., 2017) and discussed its possible relation to immune mechanisms. Here we focused on one of the six HLA GWI-protective HLA alleles, DRB1*13:02, which has been found to have a protective role in a broad range of autoimmune diseases (Furukawa et al., 2017), and tested its effects on brain volumes.MethodsSeventy-six Gulf War veterans (55 with GWI and 21 healthy controls) underwent a structural Magnetic Resonance Imaging (sMRI) scan to measure the volumes of 9 subcortical brain regions to assess differences between participants with (N = 11) and without (N = 65) HLA class II allele DRB1*13:02.FindingsWe found that DRB1*13:02 spared subcortical brain atrophy in Gulf War veterans; overall subcortical volume was 6.6% higher in carriers of DRB1*13:02 (P = 0.007). The strongest effect was observed in the volume of cerebellar gray matter which was 9.6% higher (P = 0.007) in carriers of DRB1*13:02 than in non-carriers. By contrast, DRB1*13:01 had no effect.InterpretationThese findings document the protective effect of DRB1*13:02 on brain atrophy in Gulf War veterans and are in keeping with recent results documenting sharing of brain mechanisms between GWI and other immune-related diseases (Georgopoulos et al., 2017). We hypothesize that the protective role of DRB1*13:02 is due to its successful elimination of external antigens to which Gulf War veterans were exposed, antigens that otherwise would persist causing low-grade inflammation and possibly leading to autoimmunity.Funding source (W81XWH-15-1-0520), , and .

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“…A prior report in EBioMedicine by Georgopoulos and colleagues (Georgopoulos et al, 2015) provided insight into a basis for a genetic/immune role in GWI by showing that higher counts for six Class II human leukocyte antigen (HLA) alleles conferred protective effects in GW veterans based on lowered symptom severity. In a recent follow-up from this group (Engdahl et al, 2016), a difference in neural synchrony was found between ill and healthy GW veterans. In an important extension of these findings in the current issue, James et al (2016) integrate these “neuro” and immune components.…”

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confidence: 74%