Event-related potential patterns associated with hyperarousal in Gulf War illness syndrome groups

Abstract

An exaggerated response to emotional stimuli is one of the several symptoms widely reported by veterans of the 1991 Persian Gulf War. Many have attributed these symptoms to post-war stress; others have attributed the symptoms to deployment-related exposures and associated damage to cholinergic, dopaminergic, and white matter systems. We collected event-related potential (ERP) data from 20 veterans meeting Haley criteria for Gulf War Syndromes 1-3 and from 8 matched Gulf War veteran controls, who were deployed but not symptomatic, while they performed an auditory three-condition oddball task with gunshot and lion roar sounds as the distractor stimuli. Reports of hyperarousal from the ill veterans were significantly greater than those from the control veterans; different ERP profiles emerged to account for their hyperarousability. Syndromes 2 and 3, who have previously shown brainstem abnormalities, show significantly stronger auditory P1 amplitudes, purported to indicate compromised cholinergic inhibitory gating in the reticular activating system. Syndromes 1 and 2, who have previously shown basal ganglia dysfunction, show significantly weaker P3a response to distractor stimuli, purported to indicate dysfunction of the dopaminergic contribution to their ability to inhibit distraction by irrelevant stimuli. All three syndrome groups showed an attenuated P3b to target stimuli, which could be secondary to both cholinergic and dopaminergic contributions or disruption of white matter integrity.

Figure 1

Mean hyperarousal scores of each of the ill veterans (Syndromes 1–3) were significantly higher than the scores of the control veterans (p< .0007). Error bars indicate standard deviation.

Figure 2

P1 amplitudes showed a main effect of syndrome group, p=.0154. Syndromes 2 and 3 P1 amplitudes were significantly higher, p=.004 (p = .012, Bonferroni-corrected). A strong trend toward an interaction between syndrome group and stimulus condition (p=.050) was due to Syndromes 2 and 3 showing a stronger response to the threatening stimuli whereas Syndrome 1 showed a stronger response to the task-relevant stimuli (p=.035, Bonferroni-corrected). Error bars indicate standard deviation.

Figure 3

P1 peak latencies showed an effect of syndrome group, p = .001. Syndromes 2 and 3 were significantly longer than those of controls and Syndrome 1, p= .0001 (p =.0003, Bonferroni-corrected). Error bars indicate standard deviation.

Figure 4

P3a mean amplitudes to distractor stimuli showed an effect of syndrome group, p = .011. Mean amplitudes of Syndromes 1 and 2 were significantly lower than those of controls and Syndrome 3, p = .003 (p = .009, Bonferroni-corrected). Error bars indicate standard deviation.

Figure 5

P3b mean amplitudes to target stimuli showed an effect of syndrome group, p = .006. Mean amplitudes of the ill veteran groups were significantly lower than those of controls, p = .001 (p = .003, Bonferroni-corrected). Error bars indicate standard deviation.

Figure 6

Mean reaction times grouped by syndrome group. There was a significant main effect of syndrome group on reaction time, p = .0367. Syndromes 1 and 2 mean reaction time was longer than those of controls and Syndrome 3, p = .005 (p = .015, Bonferroni-corrected). Stimulus condition also had a main effect on reaction times, p < .0001. Responses to both the gun shot and the nontarget tone were faster than responses to mountain lion and target tone stimuli, p < .003 (p<.018, Bonferroni-corrected). An interaction between syndrome group and stimulus condition was also indicated, p = .0242. Mean reaction times for distractor stimuli (gunshot, mountain lion) are longer than those for task-related tones for Syndromes 2 and 3, whereas the opposite is seen in Syndrome 1, p=.011 (p=.034, Bonferroni-corrected). Error bars indicate standard deviation.

Figure 7

Accuracy rates grouped by stimulus condition. There was a significant effect of stimulus condition on accuracy (p = .0045) due solely to the difference between the percent correct responses to the lion stimulus and percent correct response to the nontarget stimulus, p = .0004 (p = .0012, Bonferroni-corrected). Error bars indicate standard deviation.