Effects of low-level sarin and cyclosarin exposure and Gulf War Illness on Brain Structure and Function: A study at 4T

Chao, Li-Lian; Abadjian, Linda; Hlavin, Jennifer; Meyerhoff, Dieter J.; Weiner, Michael W.

doi:10.1016/j.neuro.2011.06.006

Cited by 80 publications

(95 citation statements)

References 34 publications

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“…This second post hoc analysis revealed a positive correlation between axial diffusivity in the posterior limb of the internal capsule, which maps to the posterior limb of the internal capsule to motor and premotor cortices (Zarei et al, 2007), and response time on the Grooved Pegboard test in veterans with predicted GB/GF exposure. Although there have been reports of psychomotor slowing in GW veterans with predicted GB/GF exposure (Proctor et al, 2006) and in victims of the Tokyo subway sarin attack (Miyaki et al, 2005;Yokoyama et al, 1998), it is noteworthy that we did not find any evidence of psychomotor slowing in the current cohort of GW veterans with predicted GB/GF exposure (Chao et al, 2011). Instead, this cohort of GW veterans with predicted GB/GF exposure actually performed faster than unexposed GW veterans on the Trail Making Test A and the Grooved Pegboard test with the non-dominant hand.…”

Section: Va Author Manuscriptcontrasting

confidence: 78%

“…Instead, this cohort of GW veterans with predicted GB/GF exposure actually performed faster than unexposed GW veterans on the Trail Making Test A and the Grooved Pegboard test with the non-dominant hand. Moreover, compared to unexposed GW veterans, there were no major neurobehavioral impairments in this cohort of GW veterans with predicted GB/GF exposure other than subtle attention deficits (i.e., more omission errors on the Continuous Performance Test; Chao et al, 2011). We similarly found no evidence of significant neurobehavioral deficits in an earlier study of a different cohort of GW veterans with predicted GB/GF exposure compared to unexposed veterans.…”

Section: Va Author Manuscriptsupporting

confidence: 63%

“…On the other hand, if higher axial diffusivity in GW veterans with predicted GB/GF exposure were associated with better neurobehavioral performance, it may be related to white matter reorganization after exposure to GB/GF. We correlated the DTI data with the neurobehavioral measures that we previously reported in our 4 T study of GW veterans (Chao et al, 2011), of which the current cohort is a subset. These included: the Continuous Performance Test (Letz, 1991), the Digit Span subtest of the Wechsler Adult Intelligence Scale-III (Wechsler, 1997), and the Trail-Making Test, Parts A and B (Reitan and Wolfson, 1985), the Short Category Test (Wetzel and Boll, 1987), the California Verbal Learning Test-II (Delis et al, 2000), and the Grooved Pegboard test (Lafayette Instrument, Lafayette, IN).…”

Section: Post Hoc Analysesmentioning

confidence: 99%

“…After the plume model analyses were made public, we and other investigators have reported evidence that GW veterans with predicted GB/GF exposure have reduced gray (Chao et al, 2010(Chao et al, , 2011 and white (Heaton et al, 2007;Chao et al, 2011) matter volume compared to unexposed GW veterans. Because loss of tissue integrity in regions of normal-appearing white matter has been associated with atrophy in both gray (Agosta et al, 2011;Steenwijk et al, 2014) and white (Vernooij et al, 2008) matter, the present study sought to test the hypothesis that GW veterans with predicted GB/GF exposure evidence of have disrupted white matter microstructure integrity compared to unexposed GW veterans.…”

Section: Introductionmentioning

confidence: 99%

“…Because we previously found evidence of whole brain gray and white atrophy in GW veterans with predicted GB/GF exposure (Chao et al, 2010(Chao et al, , 2011, the third aim of the study was to investigate the effects of predicted GB/GF exposure on DTI measures from major white matter fiber systems through the brain. Finally Rayhan et al (2013) recently proposed that axial diffusivity in the right inferior fronto-occipital fasciculus may be a biomarker for Gulf War Illness (or Chronic Multisymptom Illness, CMI).…”

Section: Introductionmentioning

confidence: 99%

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Effects of low-level sarin and cyclosarin exposure on white matter integrity in Gulf War Veterans

Chao

Buckley

2015

NeuroToxicology

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Background-We previously found evidence of reduced gray and white matter volume in Gulf War (GW) veterans with predicted low-level exposure to sarin (GB) and cyclosarin (GF). Because loss of white matter tissue integrity has been linked to both gray and white matter atrophy, the current study sought to test the hypothesis that GW veterans with predicted GB/GF exposure have evidence of disrupted white matter microstructural integrity.Methods-Measures of fractional anisotropy and directional (i.e., axial and radial) diffusivity were assessed from the 4 T diffusion tensor images (DTI) of 59 GW veterans with predicted GB/GF exposure and 59 "matched" unexposed GW veterans (mean age: 48 ± 7 years). The DTI data were analyzed using regions of interest (ROI) analyses that accounted for age, sex, total brain gray and white matter volume, trauma exposure, posttraumatic stress disorder, current major depression, and chronic multisymptom illness status.Results-There were no significant group differences in fractional anisotropy or radial diffusivity. However, there was increased axial diffusivity in GW veterans with predicted GB/GF exposure compared to matched, unexposed veterans throughout the brain, including the temporal stem, corona radiata, superior and inferior (hippocampal) cingulum, inferior and superior frontooccipital fasciculus, internal and external capsule, and superficial cortical white matter blades. Post hoc analysis revealed significant correlations between higher fractional anisotropy and lower radial diffusivity with better neurobehavioral performance in unexposed GW veterans. In contrast, only Conflict of interestThe authors declare that there are no conflicts of interest. Transparency documentThe Transparency document associated with this article can be found in the online version. U.S. Department of Veterans Affairs VA Author ManuscriptVA Author Manuscript VA Author Manuscript increased axial diffusivity in posterior limb of the internal capsule was associated with better psychomotor function in GW veterans with predicted GB/GF exposure.Conclusions-The finding that increased axial diffusivity in a region of the brain that contains descending corticospinal fibers was associated with better psychomotor function and the lack of significant neurobehavioral deficits in veterans with predicted GB/GF exposure hint at the possibility that the widespread increases in axial diffusivity that we observed in GW veterans with predicted GB/GF exposure relative to unexposed controls may reflect white matter reorganization after brain injury (i.e., exposure to GB/GF).

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