FMRI reveals abnormal central processing of sensory and pain stimuli in ill Gulf War veterans

Gopinath, Kaundinya; Gandhi, Parina; Goyal, Arun; Jiang, Lei; Fang, Yan; Ouyang, Luo; Ganji, Sandeepkumar; Buhner, David M.; Ringe, Wendy K; Spence, Jeffrey S.; Biggs, Melanie M.; Briggs, Richard W.; Haley, Robert W.

doi:10.1016/j.neuro.2012.01.014

Cited by 31 publications

(17 citation statements)

References 46 publications

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“…To our knowledge, this is one of very few fMRI studies to evaluate GWIPs (see Calley et al, 2010; Gopinath et al, 2012; and Odegard et al, 2012). Consistent with our hypotheses, we observed WM performance deficits in GWIPs as well as group-differential BOLD activation in right DLPFC and VLPFC during WM.…”

Section: Discussionmentioning

confidence: 99%

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

Hubbard

Hutchison

Motes

et al. 2013

Clinical Psychological Science

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Gulf War Illness is associated with toxic exposure to cholinergic disruptive chemicals. The cholinergic system has been shown to mediate the central executive of working memory (WM). The current work proposes that impairment of the cholinergic system in Gulf War Illness patients (GWIPs) leads to behavioral and neural deficits of the central executive of WM. A large sample of GWIPs and matched controls (MCs) underwent functional magnetic resonance imaging during a varied-load working memory task. Compared to MCs, GWIPs showed a greater decline in performance as WM-demand increased. Functional imaging suggested that GWIPs evinced separate processing strategies, deferring prefrontal cortex activity from encoding to retrieval for high demand conditions. Greater activity during high-demand encoding predicted greater WM performance. Behavioral data suggest that WM executive strategies are impaired in GWIPs. Functional data further support this hypothesis and suggest that GWIPs utilize less effective strategies during high-demand WM.

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Section: Discussionmentioning

confidence: 99%

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

Hubbard

Hutchison

Motes

et al. 2013

Clinical Psychological Science

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“…This could be due to the relatively more mature population of oligodendrocytes in the corpus callosum as well as differences in ACh availability in the two regions. The importance of regional differences is highlighted by the reported abundance of cognitive rather than sensory symptoms in the younger GW veterans (Gopinath et al, ), implicating the involvement of PFC, a region where myelination continues into the third decade of life (Miller et al, ). The decrease in mature oligodendrocytes identified in the PFC suggests that the PFC is especially vulnerable to GW agents; a finding that is consistent with the neuropsychological impairments presented by GW veterans (Janulewicz et al, ; Sullivan et al, ; Sullivan et al, ).…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, there is a reserve pool of proliferative NG2+ cells in the adult brain, which have the potential to generate oligodendrocyte lineage cells throughout life (Nishiyama, Suzuki, & Zhu, ; Kang, Fukaya, Yang, Rothstein, & Bergles, ). Epidemiological data indicate that GW veterans who report impaired cognition as their prominent symptom were significantly younger than their GW veteran counterparts with no‐symptoms or who experience primarily sensory symptoms (Gopinath et al, ). This pattern is consistent with possible involvement of disrupted PFC myelination in GWI and presents a compelling hypothesis for the neurological and cognitive impairments of GWI.…”

Section: Introductionmentioning

confidence: 99%

Oligodendrocyte involvement in Gulf War Illness

Belgrad

Dutta

Bromley-Coolidge

et al. 2019

Glia

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Low level sarin nerve gas and other anti‐cholinesterase agents have been implicated in Gulf War illness (GWI), a chronic multi‐symptom disorder characterized by cognitive, pain and fatigue symptoms that continues to afflict roughly 32% of veterans from the 1990–1991 Gulf War. How disrupting cholinergic synaptic transmission could produce chronic illness is unclear, but recent research indicates that acetylcholine also mediates communication between axons and oligodendrocytes. Here we investigated the hypothesis that oligodendrocyte development is disrupted by Gulf War agents, by experiments using the sarin‐surrogate acetylcholinesterase inhibitor, diisopropyl fluorophosphate (DFP). The effects of corticosterone, which is used in some GWI animal models, were also investigated. The data show that DFP decreased both the number of mature and dividing oligodendrocytes in the rat prefrontal cortex (PFC), but differences were found between PFC and corpus callosum. The differences seen between the PFC and corpus callosum likely reflect the higher percentage of proliferating oligodendroglia in the adult PFC. In cell culture, DFP also decreased oligodendrocyte survival through a non‐cholinergic mechanism. Corticosterone promoted maturation of oligodendrocytes, and when used in combination with DFP it had protective effects by increasing the pool of mature oligodendrocytes and decreasing proliferation. Cell culture studies indicate direct effects of both DFP and corticosterone on OPCs, and by comparison with in vivo results, we conclude that in addition to direct effects, systemic effects and interruption of neuron–glia interactions contribute to the detrimental effects of GW agents on oligodendrocytes. Our results demonstrate that oligodendrocytes are an important component of the pathophysiology of GWI.

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“…Using magnetic resonance imaging, Rayhan et al (2013) reported reduced cerebellar volume and functional anomalies in a small sample of GWI veterans. Others have identified enhanced cerebellar activation to noxious heat, presumably reflecting increased pain perception, in some GWI veterans relative to controls (Gopinath et al, 2012). In contrast, researchers using magnetic resonance spectroscopy found no significant differences in metabolites in various brain regions when comparing veterans with GWI to controls (Weiner et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2016

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BackgroundGulf 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 ill-health and disability in GWI. Here we investigated the neural mechanisms underlying brain dysfunction in GWI in the absence of mental health disorders.MethodsEighty-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).FindingsWe 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).InterpretationThese 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.FundingU.S. Department of Veterans Affairs and University of Minnesota.

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FMRI reveals abnormal central processing of sensory and pain stimuli in ill Gulf War veterans

Cited by 31 publications

References 46 publications

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

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

Oligodendrocyte involvement in Gulf War Illness

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

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