Functional Neuroimaging to Detect the Neural Signatures of the Unpleasantness of Pain and Effort

* INCLUSION CRITERIA: Healthy Controls: In order to be eligible to participate in this study as a healthy control, an individual must meet all the following criteria: 1. Ability of subject to understand and the willingness to sign a written informed consent document. 2. Stated willingness to comply with all study procedures and availability for the duration of the study. 3. Male or female, aged 18-50 (inclusive). 4. Good general health as evidenced by medical history and/or physical examination. ME/CFS Patients: In order to be eligible to participate in this study as an ME/CFS patient, an individual must meet all the following criteria: 1. Ability of subject to understand and the willingness to sign a written informed consent document. 2. Stated willingness to comply with all study procedures and availability for the duration of the study. 3. Male or female, aged 18-50 (inclusive). 4. Has a diagnosis of ME/CFS, meeting at least one of three ME/CFS criteria: the 1994 Fukuda Criteria, the 2003 Canadian Consensus Criteria for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, or the Institute of Medicine Diagnostic Criteria. EXCLUSION CRITERIA: Healthy Controls: 1. Any current major neurological or psychiatric disorder such as (but not limited to) stroke, Parkinson s disease, Alzheimer s disease, schizophrenia, or major depressive disorder. 2. Any other current major medical disorder, such as a kidney disease, liver disease, cardiovascular disease, chronic pain condition, or any other disorder which, in the opinion of the PI would make participation risky for the individual or negatively affect the individual s ability to cooperate with study procedures. 3. Current use of medications acting primarily on the central nervous system, such as antidepressants, stimulants, etc. 4. Use of opioid medications for more than two weeks within the last two years or any use in the last month. 5. Current or history of substance use disorder, binge drinking, illegal drug use, or excessive tobacco use (defined as more than 10 cigarettes of nicotine per week). 6. Any more than occasional use of cannabis, defined as a score \>1 (indicating use on more than one or two days in the last two weeks) on the marijuana use item of the DSM-5 Level 2-Substance Use-Adult questionnaire. 7. Any use of other illicit drugs or misuse of prescription medications, defined as a score \>0 on any of the other items of the DSM-5 Level 2-Substance Use-Adult questionnaire. 8. Condition or injury affecting grip. 9. Condition or injury affecting extremities that would alter peripheral sensitivity to painful thermal stimuli or would otherwise cause such stimuli to be contraindicated. 10. Contraindications to MRI, including ferromagnetic metal in the cranial cavity or eye, implanted neural stimulator, cochlear implant, or ocular foreign body, implanted cardiac pacemaker, auto-defibrillator, or pump, non-removable body piercing, claustrophobia, inability to lie supine for 90 minutes, known pregnancy, or plans to become pregnant during the study. 11. Members of the NINDS BNU and their family members. 12. Non-English speakers will be excluded from the study as several study instruments do not have validated translations. ME/CFS Patients: 1. Any current major neurological or psychiatric disorder, other than ME/CFS, such as (but not limited to) stroke, Parkinson s disease, Alzheimer s disease, schizophrenia, or major depressive disorder. 2. Any other current major medical disorder, other than ME/CFS, such as a kidney disease, liver disease, cardiovascular disease, chronic pain condition, or any other disorder which, in the opinion of the PI would make participation risky for the individual or negatively affect the individual s ability to cooperate with study procedures. 3. Current use of psychomotor stimulants, antipsychotics, or benzodiazepines. 4. Use of opioid medications for more than two weeks within the last two years or any use in the last month. 5. Current or history of substance use disorder, binge drinking, illegal drug use, or excessive tobacco use (defined as more than 10 cigarettes of nicotine per week). 6. Any more than occasional use of cannabis, defined as a score \>1 (indicating use on more than one or two days in the last two weeks) on the marijuana use item of the DSM-5 Level 2-Substance Use-Adult questionnaire. 7. Any use of other illicit drugs or misuse of prescription medications, defined as a score \>0 on any of the other items of the DSM-5 Level 2-Substance Use-Adult questionnaire. 8. Condition or injury affecting grip. 9. Condition or injury affecting extremities that would alter peripheral sensitivity to painful thermal stimuli or would otherwise cause such stimuli to be contraindicated. 10. Contraindications to MRI, including ferromagnetic metal in the cranial cavity or eye, implanted neural stimulator, cochlear implant, or ocular foreign body, implanted cardiac pacemaker, auto-defibrillator, or pump, non-removable body piercing, claustrophobia, inability to lie supine for 90 minutes, known pregnancy, or plans to become pregnant during the study. 11. Members of the NINDS BNU and their family members. 12. Non-English speakers will be excluded from the study as several study instruments do not have validated translations.