This research is studying whether mental functions take place during different levels of anesthesia, using a commonly used drug (either dexmedetomidine [with propofol in some participants] or ketamine), which shows areas in the brain involved in thinking at different depths of anesthesia. As a result of this study, the researchers expect to gain a deeper understanding of mental function during different levels of anesthesia.

Dexmedetomidine is an FDA-approved sedative agent and is used off-label in this study for controlled experimental modulation of consciousness under direct anesthesiology supervision. Ketamine is a FDA-approved anesthetic and analgesic agent and is used off-label in this study for controlled experimental modulation of consciousness under direct anesthesiology supervision.

Using fMRI and established cognitive paradigms, the proposed study will directly examine residual conscious processing under dexmedetomidine and ketamine and compare these findings with our existing propofol dataset from NCT03361605.

Inclusion Criteria:

• Healthy study subjects with American Society of Anesthesiologists (ASA)-1 status
• Right-handed
• Body mass index (BMI) less than 30
• Participants will have the experience of playing tennis (or other racquet sport) at least 30 times in their lifetime
• English speaking

Exclusion Criteria:

• Medical contraindication to MRI scanning; are unable to undergo MRI scanning because of possible pregnancy or currently breastfeeding
• BMI greater than or equal to 30
• Metallic substances in the body
• claustrophobia, anxiety, or cardiopulmonary disease; or have an intracranial structural abnormality on T1-weighted MRI scans
• history of allergy to dexmedetomidine, ketamine, propofol, or any components of these medications, eggs or egg products, soybean or soybean products
• neurological, cardiovascular, or pulmonary illness
• significant head injury with loss of consciousness; learning disability or other developmental disorder
• sleep apnea or any severe snoring history
• gastroesophageal reflux disease (GERD) or heartburn; pancreatitis or a history of pancreatitis,
• sensory/motor loss sufficient to interfere with performance of the study
• epilepsy/seizure disorder (including a history of seizures) or stroke (including a history of stroke).
• history of schizophrenia spectrum disorder, bipolar disorder, other psychotic disorder, or any prior adverse psychiatric reaction to ketamine or similar drugs
• Participants taking medications that, in the judgment of the investigators or attending anesthesiologist, may interact with the study drugs or increase the risk of participation will also be excluded
• participants with hypertension or diabetes mellitus
• tattoos in the head or neck region will be excluded from study; other tattoos are subject to determination by investigators based on their assessment regarding participant safety
• recent food or liquid intake (within 8 hours)
• history of drug use, have a positive drug screen, are unwilling to abstain from alcohol for 24 hours prior to dosing, or have a current history of nicotine use.
• Potential participants who have participated in a clinical trial using an investigational drug or device within 30 days will be considered for enrollment after 30 days.
• History of a difficult airway with a previous anesthetic

Data collected in the proposed experiments will be shared at the OpenNeuro. Preprocessed, curated, artifact-free data will be preserved and shared. Detailed documentation for reproducing the specific analyses will be provided in publications and in open sharing. In addition to the fMRI imaging data, task related paradigm designs and experiment definitions will be shared in OpenNeuro.

The data will be deposited after the after the analysis have been completed and accepted for scientific publication. Access to the data deposited to OpenNeuro will not be controlled. Data will remain accessible as long as OpenNeuro hosts the data.

All research participants will be consented for sharing their de-identified data.