Exercise challenge alters Default Mode Network dynamics in Gulf War Illness

Abstract

Background: Gulf War Illness (GWI) affects 30% of veterans from the 1991 Gulf War and has no known cause. Everyday symptoms include pain, fatigue, migraines, and dyscognition. A striking syndromic feature is post-exertional malaise (PEM). This is recognized as an exacerbation of everyday symptoms following a physically stressful or cognitively demanding activity. The underlying mechanism of PEM is unknown. We previously reported a novel paradigm that possibly captured evidence of PEM by utilizing fMRI scans taken before and after sub-maximal exercises. We hypothesized that A) exercise would be a sufficient physically stressful activity to induce PEM and B) Comparison of brain activity before and after exercise would provide evidence of PEM's effect on cognition. We reported two-exercise induced GWI phenotypes with distinct changes in brain activation patterns during the completion of a 2-back working memory task (also known as two-back > zero-back).

Results: Here we report unanticipated findings from the reverse contrast (zero-back > two-back), which allowed for the identification of task-related deactivation patterns. Following exercise, patients developed a significant increase in deactivation patterns within the Default Mode Network (DMN) that was not seen in controls. The DMN is comprised of regions that are consistently down regulated during external goal-directed activities and is often altered within many neurological disease states.

Conclusions: Exercise-induced alterations within the DMN provides novel evidence of GWI pathophysiology. More broadly, results suggest that task-related deactivation patterns may have biomarker potential in Gulf War Illness.

Keywords: Default Mode Network; Exercise; GWI; PEM; fMRI.

Figures

Fig. 1

Protocol setup and accuracy. a Schematic of fMRI-exercise protocol. b Experimental N-back task design and timing intervals. c 0-back accuracy. There was no significant difference between HC, STOPP, or START subjects before and after exercise. Bicycle images were generated by staff of the actual bicycle used during the protocol

Fig. 2

Significant deactivation during the 0-back condition (0 > 2-back contrast) before exercise. Prior to exercise controls and GWI subgroups demonstrated similar deactivation patterns within the medial prefrontal cortex (P < 0.05, clusterwise corrected threshold)

Fig. 3

Significant deactivation during the 0-back condition (0 > 2-back contrast) after exercise. Following exercise controls did not have any significant BOLD activity. In contrast, GWI subgroups demonstrated similar and robust deactivation patterns in DMN regions such as the precuneus and medial prefrontal cortex (P < 0.05, clusterwise corrected threshold)