Abstract
One quarter of veterans returning from the 1990–1991 Persian Gulf War have developed Gulf War Illness (GWI) with chronic pain, fatigue, cognitive and gastrointestinal dysfunction. Exertion leads to characteristic, delayed onset exacerbations that are not relieved by sleep. We have modeled exertional exhaustion by comparing magnetic resonance images from before and after submaximal exercise. One third of the 27 GWI participants had brain stem atrophy and developed postural tachycardia after exercise (START: Stress Test Activated Reversible Tachycardia). The remainder activated basal ganglia and anterior insulae during a cognitive task (STOPP: Stress Test Originated Phantom Perception). Here, the role of attention in cognitive dysfunction was assessed by seed region correlations during a simple 0-back stimulus matching task (“see a letter, push a button”) performed before exercise. Analysis was analogous to resting state, but different from psychophysiological interactions (PPI). The patterns of correlations between nodes in task and default networks were significantly different for START (n = 9), STOPP (n = 18) and control (n = 8) subjects. Edges shared by the 3 groups may represent co-activation caused by the 0-back task. Controls had a task network of right dorsolateral and left ventrolateral prefrontal cortex, dorsal anterior cingulate cortex, posterior insulae and frontal eye fields (dorsal attention network). START had a large task module centered on the dorsal anterior cingulate cortex with direct links to basal ganglia, anterior insulae, and right dorsolateral prefrontal cortex nodes, and through dorsal attention network (intraparietal sulci and frontal eye fields) nodes to a default module. STOPP had 2 task submodules of basal ganglia–anterior insulae, and dorsolateral prefrontal executive control regions. Dorsal attention and posterior insulae nodes were embedded in the default module and were distant from the task networks. These three unique connectivity patterns during an attention task support the concept of Gulf War Disease with recognizable, objective patterns of cognitive dysfunction.
Highlights
Between 25% and 32% of veterans from the 1990–1991 Persian Gulf War have developed chronic pain, fatigue, cognitive and gastrointestinal dysfunction, a cluster of symptoms that has been called Gulf War Illness (GWI) [1]
START and Stress Test Originated Phantom Perception (STOPP) were significantly more tender to pressure measured by dolorimetry than sedentary control (SC) [54]
This group of START had more impairment than STOPP subjects based on McGill Pain [51], Mental Fatigue [44], Center for Epidemiological Studies–Depression (CESD) [45,46], Beck Depression Inventory (BDI) [46], Catastrophizing (Rumination, Magnification, Helplessness) [49], The Irritability Questionnaire [48], and Global Interoceptive Score (Sum52) [50] (Table 2)
Summary
Between 25% and 32% of veterans from the 1990–1991 Persian Gulf War have developed chronic pain, fatigue, cognitive and gastrointestinal dysfunction, a cluster of symptoms that has been called Gulf War Illness (GWI) [1]. An important clinical finding in GWI is that physical, emotional, cognitive, or other exertion can trigger symptom exacerbations (post-exertional malaise or exertional exhaustion) [3]. This phenomenon was studied by having subjects perform 2 submaximal bicycle exercise stress tests on 2 consecutive days with functional magnetic resonance imaging (fMRI) before and after exercise [4]. This report discusses brain connectivity during the simple 0-back stimulus–response task performed before exercise as a measure of dysfunctional attention in GWI veterans compared to control subjects
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