Submaximal Exercise Provokes Increased Activation of the Anterior Default Mode Network During the Resting State as a Biomarker of Postexertional Malaise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Rakib U Rayhan,James N Baraniuk

doi:10.3389/fnins.2021.748426

Abstract

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by disabling fatigue and postexertional malaise. We developed a provocation paradigm with two submaximal bicycle exercise stress tests on consecutive days bracketed by magnetic resonance imaging, orthostatic intolerance, and symptom assessments before and after exercise in order to induce objective changes of exercise induced symptom exacerbation and cognitive dysfunction.Method: Blood oxygenation level dependent (BOLD) scans were performed while at rest on the preexercise and postexercise days in 34 ME/CFS and 24 control subjects. Seed regions from the FSL data library with significant BOLD signals were nodes that clustered into networks using independent component analysis. Differences in signal amplitudes between groups on pre- and post-exercise days were determined by general linear model and ANOVA.Results: The most striking exercise-induced effect in ME/CFS was the increased spontaneous activity in the medial prefrontal cortex that is the anterior node of the Default Mode Network (DMN). In contrast, this region had decreased activation for controls. Overall, controls had higher BOLD signals suggesting reduced global cerebral blood flow in ME/CFS.Conclusion: The dynamic increase in activation of the anterior DMN node after exercise may be a biomarker of postexertional malaise and symptom exacerbation in CFS. The specificity of this postexertional finding in ME/CFS can now be assessed by comparison to post-COVID fatigue, Gulf War Illness, fibromyalgia, chronic idiopathic fatigue, and fatigue in systemic medical and psychiatric diseases.

Highlights

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS, abbreviated here as CFS) has been defined by subjective symptom criteria
We discovered the novel finding that submaximal exercise induced transient postural tachycardia in about 25% of study participants (Rayhan et al, 2013; Garner et al, 2018; Garner and Baraniuk, 2019) and as a result investigated exercise-induced orthostatic tachycardia as a potential contributor to cognitive dysfunction and postexertional malaise (PEM)
No significant differences were found for the Center for Epidemiological Studies-Depression (CESD) domains (Vilagut et al, 2016)

Summary

Introduction

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS, abbreviated here as CFS) has been defined by subjective symptom criteria. The emphasis shifted to fatigue, PEM, and unrefreshing sleep with either cognitive dysfunction or orthostatic intolerance in the 2015 Institute of Medicine criteria for Systemic Exercise Intolerance Disease (SEID)(Institute of Medicine, 2015). Performing modestly greater than usual physical, cognitive, emotional or other effort leads to a “collapse” and relapse of dysfunctional impairment with fatigue, flu-like malaise, widespread pain, tenderness, orthostatic intolerance, and cognitive dysfunction of attention and working memory. Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by disabling fatigue and postexertional malaise. We developed a provocation paradigm with two submaximal bicycle exercise stress tests on consecutive days bracketed by magnetic resonance imaging, orthostatic intolerance, and symptom assessments before and after exercise in order to induce objective changes of exercise induced symptom exacerbation and cognitive dysfunction

Methods

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Discussion

Conclusion