Journal
BRAIN SCIENCES
Volume 12, Issue 2, Pages -Publisher
MDPI
DOI: 10.3390/brainsci12020132
Keywords
postexertional malaise; arousal; fatigue; threat assessment; anxiety; posttraumatic stress disorder; inferior colliculus; periaqueductal gray; midbrain reticular formation; parabrachial complex; locus coeruleus
Categories
Funding
- Sergeant Sullivan Circle
- Barbara Cottone
- Dean Clarke Bridge Prize
- Department of Defense Congressionally Directed Medical Research Program (CDMRP) [W81XWH-15-1-0679, W81-XWH-09-1-0526]
- National Institute of Neurological Disorders and Stroke [R21NS088138, RO1NS085131]
- National Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH), through the Clinical and Translational Science Awards Program (CTSA), a trademark of DHHS, part of the Roadmap Initiative, Re-Engineering the Clinical Resear [UL1TR000101]
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The study found differential responses and pathological mechanisms of post-exertional malaise in ME/CFS and GWI. The dorsal midbrain and isthmus nuclei play important roles in threat assessment, awareness, attention, mood, cognition, pain, tenderness, sleep, thermoregulation, light and sound sensitivity, orthostatic symptoms, and autonomic dysfunction, which may contribute to post-exertional malaise symptoms in ME/CFS and GWI.
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS and Gulf War Illness (GWI) share features of post-exertional malaise (PEM), exertional exhaustion, or postexertional symptom exacerbation. In a two-day model of PEM, submaximal exercise induced significant changes in activation of the dorsal midbrain during a high cognitive load working memory task (Washington 2020) (Baraniuk this issue). Controls had no net change. However, ME/CFS had increased activity after exercise, while GWI had significantly reduced activity indicating differential responses to exercise and pathological mechanisms. These data plus findings of the midbrain and brainstem atrophy in GWI inspired a review of the anatomy and physiology of the dorsal midbrain and isthmus nuclei in order to infer dysfunctional mechanisms that may contribute to disease pathogenesis and postexertional malaise. The nuclei of the ascending arousal network were addressed. Midbrain and isthmus nuclei participate in threat assessment, awareness, attention, mood, cognition, pain, tenderness, sleep, thermoregulation, light and sound sensitivity, orthostatic symptoms, and autonomic dysfunction and are likely to contribute to the symptoms of postexertional malaise in ME/CFS and GWI.
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