Mental Function
Conditions
Keywords
Propofol, Anesthesia, Ultrasound, fMRI
Brief summary
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.
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.
Interventions
LIFUP will be used to stimulate specific brain regions and assess their causal involvement in the control of conscious state and contents.
COMBINATION_PRODUCTFunctional 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
Sponsors
National Institute of General Medical Sciences (NIGMS)
University of Michigan
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 40 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Blood Oxygen Level Dependent (BOLD) Response to Visual Stimuli | Up to 90 minutes | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Perceptual Criterion Derived From the Signal Detection Theory (SDT) | Up to 90 minutes | 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). |
| Sensitivity Derived From the Signal Detection Theory (SDT) | Up to 90 minutes | 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). |
| Grip Force | Up to 90 minutes | Participants' grip force of hand squeezing on a rubber ball in response to instructions was measured. |
Countries
United States
Participant flow
Pre-assignment details
4 participants were consented but did not receive sedation, as they were used as dry runs to test behavioral responses without sedation. 1 participant was consented but was a screen fail, so was not randomized. Participants for this trial were only randomized to the central thalamus arm.
Participants by arm
| Arm | Count |
|---|---|
| Dorsolateral Prefrontal Cortex (DLPFC) 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.
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 | 0 |
| Anterior Insula Cortex (AIC) 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.
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 | 0 |
| Central Thalamus (CT) 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.
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 | 8 |
| Sham Control 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 | 0 |
| Total | 8 |
Baseline characteristics
| Characteristic | Central Thalamus (CT) | Total |
|---|---|---|
| Age, Continuous | 25.1 years STANDARD_DEVIATION 6.6 | 25.1 years STANDARD_DEVIATION 6.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 7 Participants | 7 Participants |
| Region of Enrollment United States | 8 Participants | 8 Participants |
| Sex: Female, Male Female | 7 Participants | 7 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 0 | 0 / 8 | 0 / 0 |
| other Total, other adverse events | 0 / 0 | 0 / 0 | 4 / 8 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 | 0 / 8 | 0 / 0 |
Outcome results
Primary
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.
Time frame: Up to 90 minutes
Population: 4 participants were consented but did not receive sedation, as they were used as dry runs to test behavioral responses without sedation.~1 participant was consented but was a screen fail, so was not randomized. Participants for this trial were only randomized to the central thalamus arm.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Central Thalamus (CT) | Blood Oxygen Level Dependent (BOLD) Response to Visual Stimuli | Baseline | 0.56 percentage of BOLD signal | Standard Deviation 0.03 |
| Central Thalamus (CT) | Blood Oxygen Level Dependent (BOLD) Response to Visual Stimuli | Following Intervention | 0.51 percentage of BOLD signal | Standard Deviation 0.06 |
p-value: 0.62Wilcoxon (Mann-Whitney)
Secondary
Grip Force
Participants' grip force of hand squeezing on a rubber ball in response to instructions was measured.
Time frame: Up to 90 minutes
Population: 4 participants were consented but did not receive sedation, as they were used as dry runs to test behavioral responses without sedation.~1 participant was consented but was a screen fail, so was not randomized. Participants for this trial were only randomized to the central thalamus arm.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Central Thalamus (CT) | Grip Force | Baseline | 13.8 mmHg | Standard Deviation 5.3 |
| Central Thalamus (CT) | Grip Force | Following Intervention | 11.9 mmHg | Standard Deviation 3.8 |
p-value: 0.02Wilcoxon (Mann-Whitney)
Secondary
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).
Time frame: Up to 90 minutes
Population: 4 participants were consented but did not receive sedation, as they were used as dry runs to test behavioral responses without sedation.~1 participant was consented but was a screen fail, so was not randomized. Participants for this trial were only randomized to the central thalamus arm.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Central Thalamus (CT) | Perceptual Criterion Derived From the Signal Detection Theory (SDT) | Baseline | 0.56 score on a scale | Standard Deviation 0.89 |
| Central Thalamus (CT) | Perceptual Criterion Derived From the Signal Detection Theory (SDT) | Following Intervention | 0.80 score on a scale | Standard Deviation 1.05 |
p-value: 0.18Wilcoxon (Mann-Whitney)
Secondary
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).
Time frame: Up to 90 minutes
Population: 4 participants were consented but did not receive sedation, as they were used as dry runs to test behavioral responses without sedation.~1 participant was consented but was a screen fail, so was not randomized. Participants for this trial were only randomized to the central thalamus arm.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Central Thalamus (CT) | Sensitivity Derived From the Signal Detection Theory (SDT) | Baseline | 0.72 score on a scale | Standard Deviation 0.5 |
| Central Thalamus (CT) | Sensitivity Derived From the Signal Detection Theory (SDT) | Following Intervention | 0.39 score on a scale | Standard Deviation 0.58 |
p-value: 0.2Wilcoxon (Mann-Whitney)