Visual event-related potentials as markers of hyperarousal in Gulf War illness: evidence against a stress-related etiology

Abstract

An exaggerated response to emotional stimuli is among the many symptoms widely reported by veterans of the 1991 Persian Gulf War. These symptomologies have been attributed to damage and dysfunction associated with deployment-related exposures. We collected event-related potential data from 22 veterans meeting Haley criteria for Gulf War (GW) Syndromes 1-3 and from 8 matched GW veteran controls, who were deployed but not symptomatic, while they performed a visual three-condition oddball task where images authenticated to be associated with the 1991 Persian Gulf War were the distractor stimuli. Hyperarousal reported by ill veterans was significantly greater than that by control veterans, but this was not paralleled by higher amplitude P3a in their ERP responses to GW-related distractor stimuli. Whereas previous studies of PTSD patients have shown higher amplitude P3b responses to target stimuli that are placed amid trauma-related nontarget stimuli, ill veterans in this study showed P3b amplitudes to target stimuli - placed amid GW-related nontarget stimuli - that were significantly lower than those of the control group. Hyperarousal scores reliably predicted P3b, but not P3a, amplitudes. Although many factors may contribute to P3b amplitude differences - most notably depression and poor sleep quality, symptoms that are prevalent in the GW syndrome groups - our findings in context of previous studies on this population are consistent with the contention that dysfunction in cholinergic and dopaminergic neurotransmitter systems, and in white matter and basal ganglia may be contributing to impairments in GW veterans.

Figure 1

Gulf War veterans were classified as either controls, Syndrome 1, Syndrome 2, or Syndrome 3 based on Haley et al. (1997, 2000a) criteria, and underwent a week-long multi-modal neuropsychological, neuroimaging, and biomarker study, which included electroencephalography and measurement of hyperarousal using the Mississippi Scale for Combat-Related PTSD (Keane et al., 1988).

Figure 2

Schematic diagram of the three-condition oddball paradigm used. After instructions, stimuli were presented for 1 sec followed by a 1-sec fixation. Participants responded with a button push that was different for target stimuli (animals) than for nonthreatening nontarget stimuli and threatening nontarget distractor stimuli.

Figure 3

A prevalent anterior N300 was present for all conditions, preventing the measure of an anterior P3a. There were no significant effects of group or condition on the N300 amplitude or latency.

Figure 4

P3a response to threatening distractor stimuli

Figure 5

P3b response to target stimuli

Figure 6

P3a component to distractor threatening stimuli at midline occipitoparietal electrode site POZ for all four Gulf War Illness syndrome groups.

Figure 7

P3b component to target stimuli at midline centroparietal electrode site CPZ for all four Gulf War Illness syndrome groups.