Healthy
Conditions
Keywords
Music, Propofol
Brief summary
This study is to better understand the systems-level neuronal mechanisms by which general anesthetics produce loss of consciousness.The researchers believe that anesthetics suppress consciousness by disrupting the functioning of large-scale brain networks that support information integration in the brain.
Interventions
OTHERFunctional Magnetic Resonance Imaging (fMRI)
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 which will be maintained for 4 minutes each. Four types of music, including Jazz, Rock, Pop and Country, will be presented in a pseudo-randomized order. During the behavioral test period, participants will be asked to squeeze an Magnetic Resonance Imaging (MRI) compatible grip dynamometer (a rubber ball) for every 10-second periods (96 cycles in total). The beginning of each cycle will be cued with the spoken word squeeze.
Sponsors
National Institute of General Medical Sciences (NIGMS)
University of Michigan
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
* American Society of Anesthesiologist physical status of 1 (ASA-1), Healthy, non-smoking, no or minimal alcohol use * Right-handed * Body mass index (BMI) of less than 30 * English speakers
Exclusion criteria
* Medical contraindication to Magnetic Resonance Imaging (MRI) scanning * Unable to undergo MRI scanning because of possible pregnancy * BMI over 30 * Tattoos in the head or neck region * Unwilling to abstain from alcohol for 24 hours prior to dosing
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Blood Oxygen Level Dependent (BOLD) Response to Sensory Stimuli During Sedation | 60 minutes | Music evoked activity was quantified by measurements of the fMRI BOLD signal. Neural response to a natural auditory stimulus, music, was assessed during both conscious and anesthetized states. Measurements were taken at baseline (30 minutes) and during anesthesia (60 minutes). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Average Squeeze Pressure Over 60 Minutes | 60 minutes | Measurement of force of participants' hand squeezing on a rubber ball in response to instructions. This will be measured in millimeters of mercury (mmHg) of air pressure during squeezing the rubber ball. Measurements are provided for the 30-minute means based on measurements taken every 10 seconds for 30 minutes prior to intervention (baseline) and every 10 seconds for 30 minutes during intervention (intervention), using BIOPAC (https://www.biopac.com) MP160 system with AcqKnowledge software (V5.0). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Functional Magnetic Resonance Imaging While music is played Noninvasive functional magnetic resonance (fMRI) imaging will be performed at the University of Michigan Health System, University Hospital, Department of Radiology.
The fMRI is done under anesthesia using propofol. The researchers will manually control the infusion of propofol to achieve target effect-site concentrations of 1.2, 1.6, 2.0, and 2.4 μg/ml in a stepwise fashion.
Functional Magnetic Resonance Imaging (fMRI): 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 which will be maintained for 4 minutes each.
Four types of music, including Jazz, Rock, Pop and Country, will be presented in a pseudo-randomized order. During the behavioral test period, participants will be asked to squeeze an Magnetic Resonance Imaging (MRI) compatible grip dynamometer (a rubber ball) for every 10-second periods (96 cycles in total). The beginning of each cycle will be cued with the spoken word squeeze. | 32 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Physician Decision | 2 |
Baseline characteristics
| Characteristic | Functional Magnetic Resonance Imaging |
|---|---|
| Age, Continuous | 24 years STANDARD_DEVIATION 0.01 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 31 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 10 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 21 Participants |
| Sex: Female, Male Female | 21 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 30 |
| other Total, other adverse events | 1 / 30 |
| serious Total, serious adverse events | 0 / 30 |
Outcome results
Primary
Blood Oxygen Level Dependent (BOLD) Response to Sensory Stimuli During Sedation
Music evoked activity was quantified by measurements of the fMRI BOLD signal. Neural response to a natural auditory stimulus, music, was assessed during both conscious and anesthetized states. Measurements were taken at baseline (30 minutes) and during anesthesia (60 minutes).
Time frame: 60 minutes
Population: Reason of excluding 3 subjects: there were large head motions during fMRI so that the results were not analyzed or pooled in the whole study group. Two additional subjects were excluded, as they withdrew due to physician discretion.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Functional Magnetic Resonance Imaging | Blood Oxygen Level Dependent (BOLD) Response to Sensory Stimuli During Sedation | Baseline (at 30 minutes) | 0.04 arbitrary units | Standard Deviation 0.02 |
| Functional Magnetic Resonance Imaging | Blood Oxygen Level Dependent (BOLD) Response to Sensory Stimuli During Sedation | During Anesthesia (at 60 Minutes) | 0.01 arbitrary units | Standard Deviation 0.01 |
Comparison: The null hypothesis is no difference in BOLD response between sedated state and baseline. For an fMRI study of cognitive function, Desmond and Glover (J. Neurosci. Methods., 2002) reported that about 25 subjects are necessary to achieve 80% power for a 0.5% increase of activity. We analyzed 27 subjects that fulfilled the suggested optimal group size for reliable statistics in functional MRI studies (also see Thirion et al., Neuroimage, 2007).p-value: <0.001t-test, 2 sided
Secondary
Average Squeeze Pressure Over 60 Minutes
Measurement of force of participants' hand squeezing on a rubber ball in response to instructions. This will be measured in millimeters of mercury (mmHg) of air pressure during squeezing the rubber ball. Measurements are provided for the 30-minute means based on measurements taken every 10 seconds for 30 minutes prior to intervention (baseline) and every 10 seconds for 30 minutes during intervention (intervention), using BIOPAC (https://www.biopac.com) MP160 system with AcqKnowledge software (V5.0).
Time frame: 60 minutes
Population: Two subjects were excluded, as they withdrew due to physician discretion.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Functional Magnetic Resonance Imaging | Average Squeeze Pressure Over 60 Minutes | Baseline (at 30 minutes) | 11.64 mmHg | Standard Deviation 4.01 |
| Functional Magnetic Resonance Imaging | Average Squeeze Pressure Over 60 Minutes | Intervention (at 60 minutes) | 8.92 mmHg | Standard Deviation 4.11 |
p-value: <0.001t-test, 2 sided