Abnormal brain response to cholinergic challenge in chronic encephalopathy from the 1991 Gulf War

Robert W. Haley, Jeffrey S. Spence, Patrick S. Carmack, Richard F. Gunst, William R. Schucany, Frederick Petty, Michael D. Devous, Frederick J. Bonte, Madhukar H. Trivedi

Research output: Contribution to journalArticlepeer-review

39 Scopus citations


Several case definitions of chronic illness in veterans of the 1991 Persian Gulf War have been linked epidemiologically with environmental exposure to cholinesterase-inhibiting chemicals, which cause chronic changes in cholinergic receptors in animal models. Twenty-one chronically ill Gulf War veterans (5 with symptom complex 1, 11 with complex 2, and 5 with complex 3) and 17 age-, sex- and education-matched controls, underwent an 99mTc-HMPAO-SPECT brain scan following infusion of saline and > 48 h later a second scan following infusion of physostigmine in saline. From each SPECT image mean normalized regional cerebral blood flow (nrCBF) from 39 small blocks of correlated voxels were extracted with geostatistical spatial modeling from eight deep gray matter structures in each hemisphere. Baseline nrCBF in symptom complex 2 was lower than controls throughout deep structures. The change in nrCBF after physostigmine (challenge minus baseline) was negative in complexes 1 and 3 and controls but positive in complex 2 in some structures. Since effects were opposite in different groups, no finding typified the entire patient sample. A hold-out discriminant model of nrCBF from 17 deep brain blocks predicted membership in the clinical groups with sensitivity of 0.95 and specificity of 0.82. Gulf War-associated chronic encephalopathy in a subset of veterans may be due to neuronal dysfunction, including abnormal cholinergic response, in deep brain structures.

Original languageEnglish (US)
Pages (from-to)207-220
Number of pages14
JournalPsychiatry Research - Neuroimaging
Issue number3
StatePublished - Mar 31 2009


  • Brain diseases
  • Persian Gulf syndrome
  • Physostigmine
  • Regional blood flow
  • Tomography, emission-computed, single-photon
  • Veterans

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Radiology Nuclear Medicine and imaging
  • Psychiatry and Mental health


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