Post-exertional malaise was modeled by having Chronic Fatigue Syndrome (CFS) and sedentary control subjects perform submaximal exercise on 2 consecutive days with objective changes in brain function measured by magnetic resonance imaging (MRI) during cognitive tests before and after the 2 exercise sessions.

Chronic Fatigue Syndrome (CFS) and sedentary control subjects answered on-line advertisements and word-of-mouth communications. Candidates gave verbal informed consent to discuss their medical history during a telephone interview. If the met inclusion and exclusion criteria, they were assigned an log-in code and password to complete an extensive on-line questionnaire, and were scheduled for the 3 day in-patient study.

On the Screening Day subjects completed written informed consent, history and physical, screening blood work, mental status exam, heart rate variability for orthostasis, and dolorimetry for systemic hyperalgesia.

On Exercise Day 1, subjects had magnetic resonance imaging (MRI) for structure (MPRAGE), white matter integrity (diffusion tensor imaging, DTI), and blood oxygenation level dependent (BOLD) analysis during working memory tasks. The tasks were the simple stimulus-response 0-back "see a letter, push a button" task, and the difficult continuous 2-back task "see a string of letters, remember the letters in order, press the button for the letter seen 2 previously ("2-back)".

The submaximal exercise test was performed in identical fashion on day 1 and day 2. Subjects rested on a bicycle ergometer for 5 minutes for baseline cardiopulmonary (VO2) measurements. They began pedalling with resistance increased in step wise fashion until their heart rate reached 70% of predicted maximum heart rate (pHR = 220 - age). They pedaled 25 minutes at 70% or until they felt they had their personal maximum effort (e.g. Borg Exertional Scale 19/20). If they reached 25 minutes, then resistance was increased until they reached 85% of pHR. Continuous EKG, symptoms and VO2 were followed from rest until 5 minutes after peak exercise.

Heart rate variability and symptoms were assessed during recumbent and standing posture to assess orthostatic intolerance.

On Exercise Day 2, the same methods were used, but the order was reversed with the submaximal exercise test first, followed by the identical MRI protocol.

Inclusion Criteria:

CFS and healthy subjects

Exclusion Criteria:

• HIV / AIDS subjects
• Pregnant women
• Lactation
• Cognitive impairment, mental retardation, severe head injury, stroke, proven multiple sclerosis, "melancholic" suicidal major depression, schizophrenia, Alzheimer's disease, "mild cognitive impairment" (MCI), other dementia, or other serious neurological diseases
• Brain injury. stroke, severe head injury (concussion, severe motor vehicle accidents), bleeding into brain, have been unconscious for more than 1 day (in a coma), seizures, brain inflammation such as multiple sclerosis or lupus.
• Metal implants such as prostheses, wires, plates, or screws that may heat up in the magnetic resonance imaging scanner and cause harm.
• Claustrophobia.
• Abnormal laboratory and questionnaire results.
• Heart, lung, kidney, arthritis, autoimmune, cancer, and other chronic illnesses, leg amputations heart attacks (myocardial infarction), coronary artery disease, abnormal heart rhythms, congestive heart failure, heart valve disease, uncontrolled high blood pressure or strokes, lung disease from smoking or other causes, painful, swollen or deformed joints related to arthritis or autoimmune diseases, weakness from nerve damage, kidney disease on dialysis, liver disease (alcoholic cirrhosis, hepatitis B, hepatitis C), inflammatory bowel disease (Crohn's disease, ulcerative colitis), or cancer Subjects may participate if they have well-controlled diabetes or thyroid disease.

Any other chronic disease with chronic pain, fatigue and thinking problems (cognitive impairment) that would limit the ability to complete the questionnaires and other tests.

• Amputation that would prevent bicycle exercise.
• Medications. Drugs that interfere with heart, lung, brain and nerve function
• Drinking and Smoking. You will have to stop caffeine (coffee, tea, soft drinks), alcohol, cannabis and nicotine products (smoking) for 3 days before the study, and the full period of the testing.
• Difficulties Drawing Blood.
• Children under the age of 18 years
• Incarcerated people (in jail)
• Alcohol or substance abuse in the past 6 months.
• English: Subjects must be able to speak and understand English to be able to understand the tests and other instructions during the study.
• Disruptive: Subjects who are disruptive or may reveal medical information about other subjects will be excluded.

RedCap

2019

open

All control and Chronic Fatigue Syndrome subjects were treated in identical fashion.