Assessing Covert Consciousness During Dexmedetomidine and Ketamine Sedation: An fMRI Study

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Healthy; Covert Consciousness
• Intervention / Treatment: Drug: Dexmedetomidine (+propofol as indicated); Drug: Ketamine

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Aaron Ellis; Phone Number: 734-647-8129; Email: aaronel@umich.edu

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
      • Contact: Aaron Ellis; Phone Number: 734-647-8129; Email: aaronel@umich.edu
      • Principal Investigator: Zirui Huang, Ph.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dexmedetomidine during fMRI; About 30 healthy participants will be randomized to this arm.	Drug: Dexmedetomidine (+propofol as indicated); Dexmedetomidine dosing will follow FDA-labeled parameters for procedural sedation, with a loading dose of 1 mcg/kg administered intravenously over 10 minutes, followed by maintenance infusion within the range of 0.2 to 1.0 mcg/kg/hr, titrated to clinical effect under anesthesiologist supervision. Sedation depth will be assessed behaviorally using standardized squeeze-response testing to determine lost responsiveness (LOR). If LOR is not achieved within labeled dexmedetomidine dosing limits, low-dose propofol will be conditionally added using a target-controlled infusion at an effect-site concentration of 0.5-1.5 μg/ml, which is below typical induction levels and intended to provide supplemental sedation while preserving spontaneous ventilation. Once LOR is achieved, sedation will be maintained within the approved dexmedetomidine range, with adjunct propofol continued only as clinically indicated.
Experimental: Ketamine during fMRI; About 30 healthy participants will be randomized to this arm.	Drug: Ketamine; participants will first receive a subanesthetic ketamine infusion of 0.5 mg/kg administered intravenously over 40 minutes. After that, 1.5 mg/kg ketamine will be administered slowly as a bolus over 60 seconds. Based on prior experience with this paradigm, most subjects who lose responsiveness do so for approximately 10 minutes following the bolus dose. For a 70 kg healthy subject, the total ketamine dose in this paradigm is approximately 140 mg. This dosing remains within the range of standard anesthetic induction dosing, which is typically 1.5 to 2 mg/kg in clinical practice.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood Oxygen Level Dependent (BOLD) response to mental imagery tasks	Three mental imagery tasks will be used: tennis imagery, navigation imagery, and hand-squeeze imagery	Up to approximately 130 minutes

Secondary Outcome Measures

Outcome Measure	Time Frame
Grip force (in mmHg) of participants' hand squeezing on a rubber ball in response to squeeze instructions	Up to approximately 130 minutes

Collaborators and Investigators

• Sponsor: University of Michigan
• Collaborators: National Institute of General Medical Sciences (NIGMS)
• Investigators: Principal Investigator: Zirui Huang, PhD, University of Michigan

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2028

Study Registration Dates

• First Submitted: July 10, 2026
• First Submitted That Met QC Criteria: July 10, 2026
• First Posted (Actual): July 15, 2026

Study Record Updates

• Last Update Posted (Actual): July 15, 2026
• Last Update Submitted That Met QC Criteria: July 10, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Anesthesia; Functional magnetic resonance imaging (fMRI)
• Additional Relevant MeSH Terms: Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Azoles; Hydrocarbons; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Imidazoles; Phenols; Benzene Derivatives; Dexmedetomidine; Propofol; Ketamine
• Other Study ID Numbers: HUM00285398; R01GM103894 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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.
• IPD Sharing Time Frame: 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.
• IPD Sharing Access Criteria: All research participants will be consented for sharing their de-identified data.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No