UNderstanding CONSciousness Connectedness and Intraoperative Unresponsiveness Study

This study will be a single-site, controlled, unblinded study at the University of Wisconsin to examine changes in the electroencephalogram during anesthesia and waking.

\* 20 subjects will be recruited per drug, and subjects can be recruited to undergo multiple sedation protocols.

Screening:

Subjects will respond to the volunteer posts for the study by calling into a study specific phone number. They will complete a phone screening to determine basic eligibility for the study. At the beginning of the sedation session, participants will affirm that in the interval since their baseline visit, they have not acquired any of the cited exclusion criteria that would preclude participation. A review of these exclusion criteria will be completed by the Anesthesiologist. A standard pre-anesthetic assessment will be performed, including confirmation of NPO status, and documented using the standard Department of Anesthesiology pre-operative evaluation form.

The first sedative will be dexmedetomidine followed by ketamine, propofol and then midazolam (dependent on the availability of the drugs). Total enrollment in the study will be up to 80 subjects. Each sedation experiment will occur on separate days at least 28 days apart, if the subject chooses to participate in more than one session.

Eligibility Criteria:
Inclusion Criteria:

* Age 18-40
* In good health, determined by the PI on the basis of medical history and a standard assessment for anesthesia to be documented as part of the study record
* Right handed, to standardize for asymmetry in brain functions

Exclusion Criteria:

* Adults \<18 years old or \>40 years old
* Pregnancy confirmed on pregnancy test on day of sedation
* Contraindication to anesthesia or allergy to study drug
* Difficult anesthesia: American Society of Anesthesiologists Physical Status greater than 1, per the discretion of the PI. Examples of ASA status include, but are not limited to:

  * Any systemic disease present, such as diabetes, cardiac, pulmonary, or other acute or chronic disorder, or history of smoking
  * Narrow angle glaucoma
  * Abnormal airway examination
  * Any abnormality on medical history and physical examination
  * Snoring or sleep disorders including apnea
  * Antecedent pulmonary aspiration risk (e.g., history GI reflux, heartburn, hiatal hernia)
  * Adverse reaction or allergy with anesthesia or other sedatives
  * Chronic medication use
  * History of difficult anesthesia, laryngoscopy or intubation
  * Family history of difficulty with anesthesia or sedation
  * History of vertigo, nausea or vomiting after anesthesia
* BMI \> 35
* Contraindication to HD-EEG, TMS or MRI for relative parts of the procedures. MRI exclusion criteria: presence of metallic or electronic implants; history of claustrophobia. TMS exclusion criteria: Presence or history of medical conditions that could increase the chance of seizures (e.g. - stroke, aneurysm, brain surgery, structural brain lesion) cranial metal implants; structural brain lesion; devices that may be affected by TMS (pacemaker, medication pump, cochlear implant, implanted brain stimulator); history of head trauma with loss of consciousness for greater than 5 minutes; family history of seizures; history of antecedent mood disorder.
* Exclusion from Dexmedetomidine:

  o Resting heart Rate\<60 bpm
* Exclusion from Propofol:

  o Reported egg allergy
* Exclusion from Ketamine:

  * History of post-operative nausea and vomiting
  * History of motion sickness

Additional exclusion criteria on the day of sedation:

* Anything to eat or drink for the preceding 8 hours
* Any use of over-the-counter or recreational drugs (including alcohol or tobacco) within the preceding 24 hours
* Any use of sedative or sleep agents within the preceding 24 hours
* Recent change in health, including cough, cold, or fever
* Exposure to anesthesia or sedation in the last 6 days