Ultrasonic Deep Brain Stimulation During Anesthetic Sedation

Study Overview
=================
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.

Official Title
-----------------
Ultrasonic Deep Brain Stimulation During Anesthetic Sedation

Conditions
-----------------
Mental Function

Intervention / Treatment
-----------------
* Device: Low-intensity focused ultrasound pulsation (LIFUP)
* Combination Product: Functional Magnetic Resonance Imaging (fMRI) using Propofol


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dorsolateral prefrontal cortex (DLPFC)<br> | Device: Low-intensity focused ultrasound pulsation (LIFUP)<br>* LIFUP will be used to stimulate specific brain regions and assess their causal involvement in the control of conscious state and contents.<br>Combination Product: Functional Magnetic Resonance Imaging (fMRI) using Propofol<br>* 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<br>* Other names: Diprivan;|
| Experimental: Anterior insula cortex (AIC)<br> | Device: Low-intensity focused ultrasound pulsation (LIFUP)<br>* LIFUP will be used to stimulate specific brain regions and assess their causal involvement in the control of conscious state and contents.<br>Combination Product: Functional Magnetic Resonance Imaging (fMRI) using Propofol<br>* 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<br>* Other names: Diprivan;|
| Experimental: Central thalamus (CT)<br> | Device: Low-intensity focused ultrasound pulsation (LIFUP)<br>* LIFUP will be used to stimulate specific brain regions and assess their causal involvement in the control of conscious state and contents.<br>Combination Product: Functional Magnetic Resonance Imaging (fMRI) using Propofol<br>* 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<br>* Other names: Diprivan;|
| Active Comparator: Sham control<br> | Combination Product: Functional Magnetic Resonance Imaging (fMRI) using Propofol<br>* 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<br>* 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 | Measured by fMRI | Up to 90 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Perceptual criterion derived from the Signal Detection Theory (SDT) | Measured by subjective reports of recognition | Up to 90 minutes | 
| Sensitivity derived from the Signal Detection Theory (SDT) | Measured by subjective reports of recognition | Up to 90 minutes | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Propofol, Anesthesia, Ultrasound, fMRI