scholarly journals Differential Effects of Exercise on fMRI of the Midbrain Ascending Arousal Network Nuclei in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Gulf War Illness (GWI) in a Model of Postexertional Malaise (PEM)

2022 ◽  
Vol 12 (1) ◽  
pp. 78
Author(s):  
James N. Baraniuk ◽  
Alison Amar ◽  
Haris Pepermitwala ◽  
Stuart D. Washington
Keyword(s):  
Chronic Fatigue Syndrome ◽  
Threat Assessment ◽  
Chronic Fatigue ◽  
Gulf War ◽  
Myalgic Encephalomyelitis ◽  
Seed Region ◽  
Gulf War Illness ◽  
Fatigue Syndrome ◽  
Before And After ◽  
And Control

Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), Gulf War Illness (GWI) and control subjects underwent fMRI during difficult cognitive tests performed before and after submaximal exercise provocation (Washington 2020). Exercise caused increased activation in ME/CFS but decreased activation for GWI in the dorsal midbrain, left Rolandic operculum and right middle insula. Midbrain and isthmus nuclei participate in threat assessment, attention, cognition, mood, pain, sleep, and autonomic dysfunction. Methods: Activated midbrain nuclei were inferred by a re-analysis of data from 31 control, 36 ME/CFS and 78 GWI subjects using a seed region approach and the Harvard Ascending Arousal Network. Results: Before exercise, control and GWI subjects showed greater activation during cognition than ME/CFS in the left pedunculotegmental nucleus. Post exercise, ME/CFS subjects showed greater activation than GWI ones for midline periaqueductal gray, dorsal and median raphe, and right midbrain reticular formation, parabrachial complex and locus coeruleus. The change between days (delta) was positive for ME/CFS but negative for GWI, indicating reciprocal patterns of activation. The controls had no changes. Conclusions: Exercise caused the opposite effects with increased activation in ME/CFS but decreased activation in GWI, indicating different pathophysiological responses to exertion and mechanisms of disease. Midbrain and isthmus nuclei contribute to postexertional malaise in ME/CFS and GWI.

scholarly journals Differential Effects of Exercise on fMRI of the Midbrain Ascending Arousal Network Nuclei in Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS) and Gulf War Illness (GWI) in a Model of Postexertional Malaise (PEM)

2021 ◽  
Author(s):  
James N Baraniuk ◽  
Alison Amar ◽  
Haris Pepermintwala ◽  
Stuart D Washington
Keyword(s):  
Chronic Fatigue Syndrome ◽  
Threat Assessment ◽  
Chronic Fatigue ◽  
Gulf War ◽  
Myalgic Encephalomyelitis ◽  
Seed Region ◽  
Fatigue Syndrome ◽  
Before And After ◽  
And Control ◽  
Region Approach

Background: Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS), Gulf War Ill-ness (GWI) and control subjects had fMRI during difficult cognitive tests performed before and after submaximal exercise provocation (Washington 2020). Exercise caused increased activation in ME/CFS but decreased activation for GWI in the dorsal midbrain, left Rolandic operculum and right middle insula. Midbrain and isthmus nuclei participate in threat assessment, attention, cognition, mood, pain, sleep, and autonomic dysfunction Methods: Activated midbrain nuclei were inferred by re-analysis of data from 31 control, 36 ME/CFS and 78 GWI subjects using a seed region approach and the Harvard Ascending Arousal Network. Results: Before exercise, control and GWI had greater activation during cognition than ME/CFS in left pedunculotegmental nucleus. Postexercise ME/CFS had greater activation than GWI for midline periaqueductal gray, dorsal and median raphe, and right midbrain reticular formation, parabrachial complex and locus coeruleus. The change between days (delta) was positive for ME/CFS but negative for GWI indicating reciprocal patterns of activation. Controls had no changes. Conclusions: Exercise caused opposite effects with increased activation in ME/CFS but decreased activation in GWI indicating different pathophysiological responses to exertion and mechanisms of disease. Midbrain and isthmus nuclei contribute to postexertional malaise in ME/CFS and GWI.

scholarly journals Exercise modifies glutamate and other metabolic biomarkers in cerebrospinal fluid from Gulf War Illness and Myalgic encephalomyelitis / Chronic Fatigue Syndrome

PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0244116
Author(s):  
James N. Baraniuk ◽  
Grant Kern ◽  
Vaishnavi Narayan ◽  
Amrita Cheema
Keyword(s):  
Cerebrospinal Fluid ◽  
Lipid Metabolism ◽  
Chronic Fatigue Syndrome ◽  
Chronic Fatigue ◽  
Gulf War ◽  
Myalgic Encephalomyelitis ◽  
Exercise Stress ◽  
Gulf War Illness ◽  
Fatigue Syndrome ◽  
Postural Tachycardia

Myalgic encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS) and Gulf War Illness (GWI) share many symptoms of fatigue, pain, and cognitive dysfunction that are not relieved by rest. Patterns of serum metabolites in ME/CFS and GWI are different from control groups and suggest potential dysfunction of energy and lipid metabolism. The metabolomics of cerebrospinal fluid was contrasted between ME/CFS, GWI and sedentary controls in 2 sets of subjects who had lumbar punctures after either (a) rest or (b) submaximal exercise stress tests. Postexercise GWI and control subjects were subdivided according to acquired transient postexertional postural tachycardia. Banked cerebrospinal fluid specimens were assayed using Biocrates AbsoluteIDQ® p180 kits for quantitative targeted metabolomics studies of amino acids, amines, acylcarnitines, sphingolipids, lysophospholipids, alkyl and ether phosphocholines. Glutamate was significantly higher in the subgroup of postexercise GWI subjects who did not develop postural tachycardia after exercise compared to nonexercise and other postexercise groups. The only difference between nonexercise groups was higher lysoPC a C28:0 in GWI than ME/CFS suggesting this biochemical or phospholipase activities may have potential as a biomarker to distinguish between the 2 diseases. Exercise effects were suggested by elevation of short chain acylcarnitine C5-OH (C3-DC-M) in postexercise controls compared to nonexercise ME/CFS. Limitations include small subgroup sample sizes and absence of postexercise ME/CFS specimens. Mechanisms of glutamate neuroexcitotoxicity may contribute to neuropathology and “neuroinflammation” in the GWI subset who did not develop postural tachycardia after exercise. Dysfunctional lipid metabolism may distinguish the predominantly female ME/CFS group from predominantly male GWI subjects.

scholarly journals Subcortical brain segment volumes in Gulf War Illness and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Life Sciences ◽  
2021 ◽  
pp. 119749
Author(s):  
Florencia Martinez Addiego ◽  
Kristina Zajur ◽  
Sarah Knack ◽  
Jessie Jamieson ◽  
Rakib U. Rayhan ◽  
...  
Keyword(s):  
Chronic Fatigue Syndrome ◽  
Chronic Fatigue ◽  
Gulf War ◽  
Myalgic Encephalomyelitis ◽  
Gulf War Illness ◽  
Fatigue Syndrome ◽  
Subcortical Brain

scholarly journals Exercise alters brain activation in Gulf War Illness and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

2020 ◽  
Vol 2 (2) ◽  
Author(s):  
Stuart D Washington ◽  
Rakib U Rayhan ◽  
Richard Garner ◽  
Destie Provenzano ◽  
Kristina Zajur ◽  
...  
Keyword(s):  
Working Memory ◽  
Chronic Fatigue Syndrome ◽  
Neural Activity ◽  
Chronic Fatigue ◽  
Neural Substrates ◽  
Gulf War ◽  
Myalgic Encephalomyelitis ◽  
Healthy Controls ◽  
Gulf War Illness ◽  
Fatigue Syndrome

Abstract Gulf War Illness affects 25–30% of American veterans deployed to the 1990–91 Persian Gulf War and is characterized by cognitive post-exertional malaise following physical effort. Gulf War Illness remains controversial since cognitive post-exertional malaise is also present in the more common Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. An objective dissociation between neural substrates for cognitive post-exertional malaise in Gulf War Illness and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome would represent a biological basis for diagnostically distinguishing these two illnesses. Here, we used functional magnetic resonance imaging to measure neural activity in healthy controls and patients with Gulf War Illness and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome during an N-back working memory task both before and after exercise. Whole brain activation during working memory (2-Back > 0-Back) was equal between groups prior to exercise. Exercise had no effect on neural activity in healthy controls yet caused deactivation within dorsal midbrain and cerebellar vermis in Gulf War Illness relative to Myalgic Encephalomyelitis/Chronic Fatigue Syndrome patients. Further, exercise caused increased activation among Myalgic Encephalomyelitis/Chronic Fatigue Syndrome patients within the dorsal midbrain, left operculo-insular cortex (Rolandic operculum) and right middle insula. These regions-of-interest underlie threat assessment, pain, interoception, negative emotion and vigilant attention. As they only emerge post-exercise, these regional differences likely represent neural substrates of cognitive post-exertional malaise useful for developing distinct diagnostic criteria for Gulf War Illness and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

scholarly journals Machine Learning Detects Pattern of Differences in Functional Magnetic Resonance Imaging (fMRI) Data between Chronic Fatigue Syndrome (CFS) and Gulf War Illness (GWI)

2020 ◽  
Vol 10 (7) ◽  
pp. 456
Author(s):  
Destie Provenzano ◽  
Stuart D. Washington ◽  
Yuan J. Rao ◽  
Murray Loew ◽  
James Baraniuk
Keyword(s):  
Machine Learning ◽  
Logistic Regression ◽  
Random Forest ◽  
Chronic Fatigue Syndrome ◽  
Chronic Fatigue ◽  
Gulf War ◽  
Gulf War Illness ◽  
Fatigue Syndrome ◽  
Before And After ◽  
The Right

Background: Gulf War Illness (GWI) and Chronic Fatigue Syndrome (CFS) are two debilitating disorders that share similar symptoms of chronic pain, fatigue, and exertional exhaustion after exercise. Many physicians continue to believe that both are psychosomatic disorders and to date no underlying etiology has been discovered. As such, uncovering objective biomarkers is important to lend credibility to criteria for diagnosis and to help differentiate the two disorders. Methods: We assessed cognitive differences in 80 subjects with GWI and 38 with CFS by comparing corresponding fMRI scans during 2-back working memory tasks before and after exercise to model brain activation during normal activity and after exertional exhaustion, respectively. Voxels were grouped by the count of total activity into the Automated Anatomical Labeling (AAL) atlas and used in an “ensemble” series of machine learning algorithms to assess if a multi-regional pattern of differences in the fMRI scans could be detected. Results: A K-Nearest Neighbor (70%/81%), Linear Support Vector Machine (SVM) (70%/77%), Decision Tree (82%/82%), Random Forest (77%/78%), AdaBoost (69%/81%), Naïve Bayes (74%/78%), Quadratic Discriminant Analysis (QDA) (73%/75%), Logistic Regression model (82%/82%), and Neural Net (76%/77%) were able to differentiate CFS from GWI before and after exercise with an average of 75% accuracy in predictions across all models before exercise and 79% after exercise. An iterative feature selection and removal process based on Recursive Feature Elimination (RFE) and Random Forest importance selected 30 regions before exercise and 33 regions after exercise that differentiated CFS from GWI across all models, and produced the ultimate best accuracies of 82% before exercise and 82% after exercise by Logistic Regression or Decision Tree by a single model, and 100% before and after exercise when selected by any six or more models. Differential activation on both days included the right anterior insula, left putamen, and bilateral orbital frontal, ventrolateral prefrontal cortex, superior, inferior, and precuneus (medial) parietal, and lateral temporal regions. Day 2 had the cerebellum, left supplementary motor area and bilateral pre- and post-central gyri. Changes between days included the right Rolandic operculum switching to the left on Day 2, and the bilateral midcingulum switching to the left anterior cingulum. Conclusion: We concluded that CFS and GWI are significantly differentiable using a pattern of fMRI activity based on an ensemble machine learning model.

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