Ultrasonic Deep Brain Stimulation During Anesthetic Sedation

The purpose of this study is to see if mental functions take place during different levels of anesthesia. The researchers expect to gain a deeper understanding of mental function during different levels of anesthesia, and to evaluate if the use of ultrasonic brain stimulation accelerates return to consciousness.

Study Overview

• Status: Completed
• Conditions: Mental Function
• Intervention / Treatment: Device: Low-intensity focused ultrasound pulsation (LIFUP); Combination product: Functional Magnetic Resonance Imaging (fMRI) using Propofol

Detailed Description

The decision was made in 2023 to focus on the Central Thalmus arm only for this trial. Participants were only randomized to this arm.

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• The participants will be right-handed adults
• Body mass index (BMI) less than 30.
• All subjects will be English speakers.

Exclusion Criteria:

• Participants will be excluded if they have any medical contraindication to MRI scanning
• Unable to undergo MRI scanning because of possible pregnancy or currently breastfeeding,
• BMI>30
• Metallic substances in the body, claustrophobia, anxiety, or cardiopulmonary disease;
• Intracranial structural abnormality on T1-weighted MRI scans.
• Potential subjects will be excluded if they have a history of allergy to propofol, eggs or egg products, soybean or soybean products,
• Neurological, cardiovascular, or pulmonary illness;
• 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, or sensory/motor loss sufficient to interfere with performance of the study. Participants with 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. To eliminate aspiration risk subjects will also be excluded if they have had recent food or liquid intake (within 8 hours). Subjects will be excluded if they have a 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. Women will be required to take a pregnancy test prior to participation to ensure a negative result. The pre-scan drug screen and pregnancy test will be paid for by the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dorsolateral prefrontal cortex (DLPFC)	Device: Low-intensity focused ultrasound pulsation (LIFUP); LIFUP will be used to stimulate specific brain regions and assess their causal involvement in the control of conscious state and contents.; Combination product: Functional Magnetic Resonance Imaging (fMRI) using Propofol; Propofol will be administered by intravenous infusion. All anesthesia equipment, supplies, and drugs will be provided by anesthesiologists from the University of Michigan Health System. The researchers will manually control the infusion of propofol to achieve target effect-site concentrations; Other Names: Diprivan
Experimental: Anterior insula cortex (AIC)	Device: Low-intensity focused ultrasound pulsation (LIFUP); LIFUP will be used to stimulate specific brain regions and assess their causal involvement in the control of conscious state and contents.; Combination product: Functional Magnetic Resonance Imaging (fMRI) using Propofol; Propofol will be administered by intravenous infusion. All anesthesia equipment, supplies, and drugs will be provided by anesthesiologists from the University of Michigan Health System. The researchers will manually control the infusion of propofol to achieve target effect-site concentrations; Other Names: Diprivan
Experimental: Central thalamus (CT)	Device: Low-intensity focused ultrasound pulsation (LIFUP); LIFUP will be used to stimulate specific brain regions and assess their causal involvement in the control of conscious state and contents.; Combination product: Functional Magnetic Resonance Imaging (fMRI) using Propofol; Propofol will be administered by intravenous infusion. All anesthesia equipment, supplies, and drugs will be provided by anesthesiologists from the University of Michigan Health System. The researchers will manually control the infusion of propofol to achieve target effect-site concentrations; Other Names: Diprivan
Active Comparator: Sham control	Combination product: Functional Magnetic Resonance Imaging (fMRI) using Propofol; Propofol will be administered by intravenous infusion. All anesthesia equipment, supplies, and drugs will be provided by anesthesiologists from the University of Michigan Health System. The researchers will manually control the infusion of propofol to achieve target effect-site concentrations; Other Names: Diprivan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood Oxygen Level Dependent (BOLD) Response to Visual Stimuli	BOLD signal was measured by Magnetic Resonance Imaging (MRI) scanning of the brain in response to a visual stimuli. This method reflected changes in oxygenation of blood in the brain during a scene-processing task.	Up to 90 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Perceptual Criterion Derived From the Signal Detection Theory (SDT)	SDT was a means of measuring participants' ability to differentiate between information-bearing patterns and random patterns that distract from the information. Perceptual criterion measured a participant's tendency to say "yes" or "no" when the participant was unsure if a signal was present. Perceptual criterion was measured on a scale from -1.0 to 1.0, with a score of 0 indicating no bias towards "yes" or "no". Negative scores meant a bias towards "yes" (more likely to say a signal was present), while positive scores meant a bias towards "no" (more likely to say a signal was absent).	Up to 90 minutes
Sensitivity Derived From the Signal Detection Theory (SDT)	SDT was a means of measuring participants' ability to differentiate between information-bearing patterns and random patterns that distract from the information. Sensitivity measured a participant's ability to differentiate between real and scrambled images on a scale from 0.0 to 1.0, with higher scores indicating better accuracy in detecting a signal when it was present and lower scores indicating more missed signals. A score of 1.0 was perfect sensitivity (i.e., never missing a real signal).	Up to 90 minutes
Grip Force	Participants' grip force of hand squeezing on a rubber ball in response to instructions was measured.	Up to 90 minutes

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): August 26, 2022
• Primary Completion (Actual): October 7, 2023
• Study Completion (Actual): October 7, 2023

Study Registration Dates

• First Submitted: August 8, 2022
• First Submitted That Met QC Criteria: August 8, 2022
• First Posted (Actual): August 10, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 19, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Ultrasound; fMRI; Propofol; Anesthesia
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Anesthetics; Central Nervous System Depressants; Hypnotics and Sedatives; Anesthetics, Intravenous; Anesthetics, General; Propofol
• Other Study ID Numbers: HUM00213014; 2R01GM103894-10A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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