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

• Published in: Frontiers in neuroscience Vol. 15; p. 748426
• Main Authors: Rayhan, Rakib U., Baraniuk, James N.
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Research Foundation 15.12.2021; Frontiers Media S.A
• Subjects: Anaerobic threshold; Biomarkers; Blood flow; blood oxygenation level dependent; BOLD; Brain; Cardiac arrhythmia; Cardiac stress tests; Cerebral blood flow; Chronic fatigue syndrome; Cognition & reasoning; Cognitive ability; Data imaging; default mode network; DMN; Encephalomyelitis; Exercise; Fatigue; Fibromyalgia; Functional magnetic resonance imaging; Gulf War; Gulf War syndrome; Hypotheses; Intolerance; Memory; Mental disorders; Neuroimaging; Neuroscience; Post traumatic stress disorder; postexertional malaise; Prefrontal cortex; Sleep; submaximal exercise; chronic idiopathic fatigue; DMN; fibromyalgia; blood oxygenation level dependent; postexertional malaise; BOLD; default mode network
• ISSN: 1662-453X; 1662-4548; 1662-453X
• DOI: 10.3389/fnins.2021.748426

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.