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Am J Transl Res 2013;5(2):212-223

Original Article
Prefrontal lactate predicts exercise-induced cognitive dysfunction in
Gulf War Illness

Rakib U Rayhan, Megna P Raksit, Christian R Timbol, Oluwatoyin Adewuyi, John W VanMeter, James N Baraniuk
Division of Rheumatology, Immunology and Allergy; Department of Medicine, Georgetown University Medical
Center Room 3004F, 3rd Floor PHC Building, 3800 Reservoir Road, NW, Washington, DC 20007, USA;
Department of Neurology, Center for Functional and Molecular Imag-ing; Georgetown University Medical Center
Suite LM14, Preclinical Sciences Building, 3900 Reservoir Road, NW Washington, DC 20057, USA; Georgetown
University Department of Psychology; Cognitive Neurogenetics Laboratory, 305 White-Gravenor Hall, 3700 O
Street, NW, Washington, DC 20057, USA

Received January 4, 2013; Accepted March 2, 2013; Epub March 28, 2013; Published April 8, 2013

Abstract: Background: 25% to 30% of Veterans deployed to the 1990 to 1991 Persian Gulf War exhibit an
idiopathic syndrome of chronic fatigue, exertional exhaustion, pain, hyperalgesia, cognitive and affective
dysfunction known as Gulf War Illness (GWI). Methods: Gulf War veterans (n=15) and sedentary veteran and
civilian controls (n=11) completed a 2-back working memory test in an fMRI before and after two bicycle exercise
stress test. We performed single voxel 1H MRS to evaluate brain metabolic differences in the left anterior
cingulate cortex and the changes associated with exercise. Results: Eight GWI subjects increased their 2-back
scores after exercise (labelled increasers) and seven GWI subjects decreased their 2-back scores after exercise
(labelled decreasers). These phenotypic responses were absent for controls. Decreasers had significantly
elevated prefrontal lactate levels compared to Increasers prior to completion of the exercise stress tests.
Evaluation of prefrontal lactate levels prior to exercise demonstrated predictability (ROC analysis) of the two
diametrically opposed subgroups. Conclusion: Prefrontal lactate levels may be a potential biomarker for
exercise-induced subgroups in GWI. The alterations in brain energetics may be in part responsible for a
subgroup of GWI and underlie some of the symptoms present in the patient population (AJTR1302004).

Keywords: Gulf War Illness (GWI), pre-frontal lactate, exercise-induced cognitive dysfunction, biomarker

Address correspondence to: Mr. Rakib U. Rayhan, or Dr. James N Baraniuk, Division of Rheumatology,
Immunology and Allergy; Department of Medicine, Georgetown University Medical Center Room 3004F, 3rd Floor
PHC Building, 3800 Reservoir Road, NW, Washington, DC 20007-2197, USA. E-mail: rur@georgetown.edu
(RUR), baraniuj@georgetown.edu (JNB).