Central Executive Dysfunction and Deferred Prefrontal Processing in Veterans with Gulf War Illness

Abstract

Gulf War Illness is associated with toxic exposure to cholinergic disruptive chemicals. The cholinergic system has been shown to mediate the central executive of working memory (WM). The current work proposes that impairment of the cholinergic system in Gulf War Illness patients (GWIPs) leads to behavioral and neural deficits of the central executive of WM. A large sample of GWIPs and matched controls (MCs) underwent functional magnetic resonance imaging during a varied-load working memory task. Compared to MCs, GWIPs showed a greater decline in performance as WM-demand increased. Functional imaging suggested that GWIPs evinced separate processing strategies, deferring prefrontal cortex activity from encoding to retrieval for high demand conditions. Greater activity during high-demand encoding predicted greater WM performance. Behavioral data suggest that WM executive strategies are impaired in GWIPs. Functional data further support this hypothesis and suggest that GWIPs utilize less effective strategies during high-demand WM.

Conflict of interest statement

Financial Disclosures

NAH, JLH, MAM, IJB, RMB, ES-K, and BR declare no biomedical financial interests or potential conflicts of interest. RWH received an honorarium from Targeted Medical Pharma, Inc. for a review of a Food and Drug Administration application for a nonpharmaceutical medication to treat fatigue, with possible benefit to Gulf War Illness patients.

Figures

Figure 1

Repeated measures analyses of WM-phase by group interactions. (a) Right DLPFC percent signal change during encoding, maintenance, and retrieval, at WM-load 2 and 4 (top left) and at WM-load 6 (bottom left). (b) Right VLPFC percent signal change during encoding, maintenance, and retrieval, at WM-load 2 and 4 (top right), and at WM-load 6 (bottom right). p-values represent mixed-model, repeated measures ANOVAs. * = p < .05. Error bars represent standard error of the mean.

Figure 2

Group differences in encoding and retrieval processing strategies across WM-loads. (a) Bar graph of right DLPFC percent signal change difference between encoding and retrieval across WM-loads (top), MC – GWIP contrast of percent signal change difference in encoding and retrieval strategies at WM-load 6 (bottom). (b) Bar graph of right VLPFC percent signal change difference between encoding and retrieval across WM-loads (top), MC – GWIP contrast of percent signal change difference in encoding and retrieval strategies at WM-load 6 (bottom). * = p < .05. Error bars represent standard error of the mean.