Clinical trial NCT03361605
Conditions: Healthy
Sponsor: University of Michigan
Start date: 2017-04-12; Completion date: 2019-07-12
Enrollment: 30 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This study's purpose is to see if mental functions take place during different levels of anesthesia, using a commonly used drug (Propofol). fMRI (functional Magnetic Resonance Imaging, or "brain imaging") shows areas in the brain involved in thinking at different depths of anesthesia.

Detailed description:
Administering anesthetic drugs to suppress consciousness is an imperatively important step in major surgical operations. Yet the neurobiological mechanisms that underlie loss of consciousness under general anesthesia remain elusive. Despite advancements in understanding the molecular, synaptic, and cellular effects of anesthetics, the large-scale, systems-level modulation of neuronal processes that support conscious cognitive functions is incompletely understood. While profound decreases in global and regional brain metabolism, blood flow, and functional connectivity have been reported, these changes often fail to correlate with the loss and return of consciousness. To date, there is no "consciousness meter" or "gold standard" to objectively assess and monitor the level of consciousness under general anesthesia. Several studies suggest that residual cognitive functions may not completely vanish under general anesthesia; however, the level and complexity of residual information processing in the anesthetized brain remains unknown. Finally, the neurobiological mechanisms that govern anesthesia induction and emergence appear to be partially different, but the relevance of these differences to the modulation of the state of consciousness is unclear.

Arms: arm 1: None
Interventions: intervention 1: Propofol
Intervention descriptions: intervention 1: Propofol administration

Protocol documents:
Prot_SAP_000.pdf: 
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Neuroimaging of Anesthetic Modulation of Human Consciousness  
NCT #:03361605 
Document date: 03/10/2020 
 
 


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Neuroimaging of Anesthetic Modulation of Human Consciousness 
Dr. Anthony G. Hudetz, Dr. George A. Mashour, and Dr. Richard E. Harris 
 
Specific Aims 
Administering anesthetic drugs to suppress consciousness is an imperatively important step in 
major surgical operations. Yet the neurobiological mechanisms that underlie loss of 
consciousness under general anesthesia remain elusive. Despite advancements in 
understanding the molecular, synaptic, and cellular effects of anesthetics, the large-scale, 
systems-level modulation of neuronal processes that support conscious cognitive functions is 
incompletely understood. While profound decreases in global and regional brain metabolism, 
blood flow, and functional connectivity have been reported, these changes often fail to correlate 
with the loss and return of consciousness. To date, we have no “consciousness meter” or “gold 
standard” to objectively assess and monitor the level of consciousness under general 
anesthesia. Several studies suggest that residual cognitive functions may not completely vanish 
under general anesthesia; however, the level and complexity of residual information processing 
in the anesthetized brain remains unknown. Finally, the neurobiological mechanisms that 
govern anesthesia induction and emergence appear to be partially different, but the relevance of 
these differences to the modulation of the state of consciousness is unclear. 
Our fundamental hypothesis has been that consciousness emerges from brain function as a 
network phenomenon, and that loss of consciousness during general anesthesia results from a 
disruption of communication in networks that support information integration. Our findings 
suggest that anesthetic unconsciousness correlates with a decrease of functional connectivity in 
the thalamocortical systems, particularly in the “nonspecific” thalamocortical division. Our recent 
data also suggest that anesthetics modulate additional intrinsic networks involved in information 
integration in specialized cognitive subsystems. 
During the last decade, we have been developing novel blood-oxygen level-dependent (BOLD) 
functional MRI (fMRI) and resting-state functional connectivity MRI (R-fcMRI) methods with high 
spatial and temporal resolution to test specific hypotheses about the anesthetic modulation of 
cognitive functioning, network organization, and information integration in the human brain. 
Accordingly, our general plan of work includes both task-dependent and task-free (resting state) 
imaging of brain networks. We focus on determining the brain’s ability for integrative functioning 
under wakefulness and graded levels of suppressed consciousness achieved with propofol. Our 
specific Aims are: 
Specific Aim 1. To determine the order and neural correlates of the loss of cognitive and motor 
functions of the brain in time and space during deepening of anesthesia up to a complete loss of 
consciousness. Hypotheses: 1) Anesthetics suppress consciousness by diminishing 
integrative functional networks of the brain in a graded, top-down manner, suppressing 
the most complex systems first and the simplest systems last. 2) These changes can be 
characterized by assessing the anesthetics’ effect on the behavioral response and neural 
activity to a series of tasks that depend on different levels of information integration. 
Specifically, we focus on anesthetic modulation of sensory reaction, attention, semantic 
processing, motor execution, and the associated state of awareness, up to a total 
unconsciousness. 
Specific Aim 2. To determine the resting-state anesthetic modulation of functional connectivity, 
integration, and reconfiguration of brain networks at four conditions: wakeful baseline, mild 
sedation, deep sedation, and recovery. Our hypotheses are: (1) anesthetic-induced loss of 
consciousness correlates with specific changes of functional connectivity and network 
integration in thalamocortical and frontoparietal networks, (2) some intrinsic networks, 
particularly the attention, executive control, and salience networks, are significantly 


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affected by anesthetics, while others, such as the default mode network (DMN) and 
sensory networks, are not, and (3) significant modular network reconfiguration occurs in 
response to anesthetic intervention, reflecting the changes in resource distribution and 
integrative processing. 
Specific Aim 3. To determine the different neural mechanisms of recovery of consciousness 
from anesthesia as opposed to loss of consciousness during deepening anesthesia. This aim 
seeks a deeper understanding of how the brain responds to anesthetic modulation in network 
interaction and self-reorganization as a function of its prior state. Based on the “neural inertia” 
theory and our preliminary findings, we hypothesize that (1) anesthetic-modulated loss and 
return of consciousness are mediated in part by different neural processes that show a 
prior state dependency, as reflected by various brain network interaction measures (e.g., 
connectivity, mutual information, etc.), and (2) the restoration of consciousness from 
anesthesia requires additional neural resources over those for maintaining 
consciousness at wakeful baseline, reflecting a reconfiguration capability of the healthy 
brain as a self-organizing system for resource management and functional resilience. 
 
Number of Subjects, Recruitment and Informed Consent. Statistical power analysis (see 
below) requires a group of 30 subjects for each of the proposed Specific Aims. As such, a total 
of 30 subjects (ages between 18-40 years old) will be required to complete the study. Healthy 
participants will be recruited by listing on UMClinicalStudies.org and by postings at area 
colleges and community groups in Ann Arbor. Interested volunteers will call the phone number 
of a designated recruiter for an initial phone screening. The initial phone screening will consist of 
questionnaires related to medical history, demographic information, handedness, inclusion and 
exclusion criteria and procedure standard MRI screening questionnaire. If interested, the 
participant will complete the questionnaires, which will be reviewed by the study team. The 
health status will be confirmed by the attending anesthesiologist before the study on site. Once 
eligibility is confirmed by the study team, the one-time research study session will be scheduled. 
 
All participants will give written informed consent according to institutional guidelines prior to any 
testing. The Principal Investigators or their designee will obtain consent using a written consent 
form approved by the Institutional Review Boards of the University of Michigan Medical School 
(IRBMED). It will contain detailed information regarding the purpose, risks and benefits of 
participating. Copies of the signed consent form will be given to the subjects; the original 
consent will remain with the study team. Subjects will be compensated for their involvement.  
 
Inclusion and exclusion criteria. Volunteers are screened using a medical history and 
demographics questionnaire.  
Inclusion Criteria: The subject population will consist of healthy study subjects with ASA-1 
status. The participants’ health status will be assessed by the attending anesthesiologist prior to 
inclusion in the study. The participants will be right-handed adults between the ages of 18 and 
40 with a 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. All subjects will be English 
speakers.  
 
Exclusion Criteria: Participants will be excluded if they have any medical contraindication to 
MRI scanning; are unable to undergo MRI scanning because of possible pregnancy, extreme 
obesity, metallic substances in the body, claustrophobia, anxiety, or cardiopulmonary disease; 
or have an intracranial structural abnormality on T1-weighted MRI scans. Potential subjects will 
be excluded if they have a history of allergic reaction to eggs, neurological, cardiovascular, or 
pulmonary illness; significant head injury with loss of consciousness; learning disability or other 


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developmental disorder; sleep apnea or any severe snoring history; gastroesophageal reflux 
disease (GERD) or heartburn; 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 nicotine use. Women will be required to take a pregnancy test 
prior to participation to ensure a negative result. 
 
Procedures 
Imaging. Noninvasive functional magnetic resonance imaging will be performed in the Philips 
3T (MR2) Research MRI at the University of Michigan Health System, University Hospital, 
Department of Radiology.  
 1) SPGR high-resolution images. Acquire T1 weighted spoiled gradient recalled echo 
(SPGR) images for high spatial resolution of anatomical images. The SPGR images can be 
employed for tissue segmentation and volumetric analysis using FreeSurfer, and image 
registration for functional neural network. The localized T1-weighted axial and sagittal plane 
slices will be acquired to provide structural information and to define the number of slices and 
location. Three-D high-spatial resolution anatomical images (T1-weighted SPGR sequence) will 
be acquired with parameters: 124 axial slices with 1.0 mm thickness, TR = 24 ms, TE = 5 ms, 
flip angle = 45o, image matrix 256 ´ 256, and one excitation-per-phase encoding step for 7 min.  
 2) fMRI images. A gradient-echo EPI pulse sequence will be employed to acquire functional 
images over the whole brain. Imaging parameters will be first optimized by comparing the data 
quality among three different sampling rates in TR of 2 sec, TR of 1 sec or TR of 800 ms (based 
on multiband fMRI acquisition). The TE will be adjusted according to the TR setting to yield 
optimized signal to noise ratio (e.g. 25 ms). FOV of 22 cm, in-plane resolution with 64 ´ 64 
matrix, bandwidth of 125 kHz, slice thickness of 6 mm, sagittal image orientation. There will be 
120 min of data (continuous scanning) including the 15 dummy scans to avoid T1 effects. The 
number of slices per TR will be 21 image slices obtained with voxel resolution of 6 ´ 3.4375 ´ 
3.4375 mm3. Note, the residue respiratory signal will be filtered by low-pass filter. The cardiac 
aliasing and variation of respiratory signal will be minimized with RETROICOR. In addition, we 
have recently added real-time on-site fMRI acquisition, so we can identify subject movement during 
experiments and immediately determine if scan repetition is necessary in order to increase the rate 
of successful scans. There will be a 5-10 minute break in between the first resting-state (10 min), 
the first task-state (15 min), sedation period (60 min) with task, the second task-state (15 min), 
and the second resting-state (10 min).  
 3) Quality control (FBURN). Apply FBURN imaging protocols for control imaging quality, 
including acquiring field map. All these imaging protocols and data acquisition will be completed 
within a singular two-hour scanning session for each subject.  
Anesthesia. Sedation will be achieved by target-controlled IV infusion of propofol. The IV line 
will be placed after application of a local anesthetic. 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.  
We will manually control the infusion of propofol to achieve target effect-site concentrations of 0, 
0.4, 0.8, 1.2, 1.6, 2.0, and 2.4 μg/ml in a stepwise fashion. A maximum target concentration 
between 1.2 and 2.4 ug/ml will be chosen at the anesthesiologists’ discretion for each 
participant. The intermediate target concentrations will be maintained for 5 minutes. Depending 
on the highest target concentration chosen, the last level could be held for 5-30 minutes before 


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the infusion is terminated and the propofol concentration is allowed to gradually decrease. The 
figure below illustrates the case of propofol dosing to the highest level. Participants will be 
instructed to perform cognitive and motor tasks as described below. 
 
Tasks and testing. Participants will be asked to simply lay at rest in the scanner for the first 10 
min and last 10 min scan. They will be asked to not move and to not fall asleep. Verbal 
instructions will be presented through earphones.  
During the task period, participants will be asked to perform three imagery tasks (tennis, 
navigation and hand squeeze or finger tapping) plus a motor response task (actual hand 
squeeze or press a button). In the tennis imagery task, they will be instructed to imagine 
standing still on a tennis court and to swing an arm to “hit the ball” back and forth to an imagined 
instructor. In the navigation imagery task, participants will be instructed to imagine navigating 
the streets of a familiar city or to imagine walking from room to room in their home and to 
visualize all that they would “see” if they were there. In the squeeze imagery or finger tapping 
imagery task, participants will be instructed to imagine squeezing an MRI compatible device for 
measuring gripping (https://www.biopac.com/product/responsehand-force-for-mri/) or imagine 
tapping a button intensively and successively. In the motor response task (hand squeeze or 
press a button), participants will be instructed to actually grip the device or press a button. This 
motor response task always follows the squeeze (or tapping) imagery task. A pseudo-
randomized (Latin square design) event-related design will be applied, in which the participants 
will be instructed to alternate between 15-second periods of mental imagery (except for a 5-
second motor response period after squeeze or tapping imagery) and 15-second periods of rest. 
The whole scan will include 180 rest–imagery cycles or trials (60 trials per condition). The 
beginning of each trial will be cued with the spoken word “tennis imagery”, “navigation imagery”, 
“squeeze imagery (or tapping imagery)”, or “action”, and the rest periods will be cued with the 
word “relax”. In addition, 10-minute resting-state fMRI scans will be applied at the beginning of 
the scan (wakefulness) and at the end of the task performance scan (recovery). A continuous 
scan will be performed. The complete scanning session will last for approximately 120 minutes. 


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To help prepare participants for the study tasks, they will be provided with a brief summary of 
the tasks the day before the study visit. This will help them be more prepared for the fMRI study 
tasks once they arrive. Additionally, we will have participants complete a short survey for both 
before and after the scan to receive some feedback. 
 
All testing will be performed by the attending anesthesiologist. Spontaneous respiration, end-
tidal CO2, heart rate, and electrocardiogram will be continuously monitored. Noninvasive arterial 
pressure will be measured with magnetic resonance (MR)-compatible automatic monitor 
(BIOPAC). Oxygen will be available and used if needed. Post anesthesia care will consist of 
checking vital signs for 1 hour by the nursing staff. A wheelchair will be provided to assist the 
participant if needed. An anesthesiologist will be present during the entire duration of the study. 
 
Primary outcome measure:  Blood Oxygen Level Dependent (BOLD) Response to sensory 
stimuli during sedation (timeframe: baseline to 90 minutes). 
 
Secondary outcome measure: Squeeze Pressure, defined as measurement of force of 
participants’ hand squeezing on a rubber ball in response to instructions (timeframe: baseline to 
90 minutes). 
 
 
Data Analysis. Image analysis will be conducted using AFNI (http://afni.nimh.nih.gov/afni) and 
Matlab (The MathWorks, Natick, MA) software. Preprocessing includes despiking, detrending, 
and motion correction. Potential contaminating signals from the white matter (WM) and the 
cerebral spinal fluid (CSF) are extracted for each subject using the WM and CSF segments of 
the anatomical image. A general linear model fitting (3dDeconvolve in AFNI) is performed using 
regressors constructed from motion correction, WM, and CSF signals to minimize potential 
contaminations. As we did previously (1), the voxel-wise task-related hemodynamic responses 
during each run will be evaluated using the area under the curve of the estimated hemodynamic 
response functions (HRFs) for each voxel (2). Spatial smoothing of the response magnitude 
across voxels will be performed using a Gaussian kernel filter to compensate for intersubject 
variability. Lastly, in the group analysis, activation maps for each run are derived by applying 
voxel-wise one-sample t-tests followed by transformation to z-scores and correction for multiple 
comparisons (e.g., AlphaSim in AFNI). 
 
Experimental contrasts and functional regions of interest (ROIs). The following activation maps 
will be computed for each anesthesia condition: 
 
1. All stimuli vs. silent baseline: Identifies auditory sensory, attention, and action processing 
common to verbal instructions. 
 
2. Tennis imagery vs. silent baseline: Identifies supplementary motor area. 
 
3. Navigation imagery vs. silent baseline: Identifies parahippocampal gyrus. 
 
4. Squeeze (or tapping) imagery vs. silent baseline: Identifies supplementary motor area. 
 
5. Squeeze (or press a button) action vs. squeeze (or tapping) imagery: Identifies M1 and 
sensorimotor cortex.  
 
The results of these contrasts obtained in the fully awake state will be thresholded (whole-brain 
corrected p <0.05) to define ROIs representing each functional network. In some cases – 
particularly contrast #1 – the networks will be subdivided using anatomical information. For 
example, the activated areas for contrast #1 will be divided into a superior temporal auditory 


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ROI, a dorsal attention network (including intraparietal sulcus, frontal eye field, and anterior 
cingulate gyrus), and a sensorimotor action network (including primary sensorimotor and 
premotor cortex). These ROIs will then be overlaid on the activation maps for each anesthesia 
condition to measure the extent of activation (number of activated voxels) and magnitude of 
activation (mean beta coefficient) in each ROI across the levels of anesthesia. 
 
For Aim 1, dynamic brain activation maps will be calculated as a function of anesthetics dose 
and behavioral responses. Similarly, for Aim 2 and 3, dynamic functional connectivity matrices 
will be calculated as a function of anesthetics dose and behavioral responses from the first 
10min resting-state data, the residual data (after regressing out task component) of the 60 min 
task period, and the last 10 min resting-state data.  
 
Power Analysis. For an fMRI study of cognitive function, Desmond and Glover (2002) reported 
that about 30 subjects are necessary to achieve 80% power for a 0.5% increase of activity (3). 
We also conducted power analysis based on nonspecific thalamocortical connectivity changes 
in deep sedation as compared with wakefulness (4, 5). We used Cohen’s d (6) as a measure of 
the effect size (ES) of connectivity difference. The computation yields averaged ES=0.56, and 
for power=80% and alpha=0.05, N=22 human subjects will be needed. The obtained subject 
number is also very close to the suggested optimal group size for reliable statistics in functional 
MRI studies (7). Considering the potential failure rate estimated from our previous study (1), 30 
human participants will be recruited for the study. 
 
Potential Risks. There are no known risks associated with magnetic resonance imaging, as 
long as technical parameters remain within FDA guidelines. A licensed MR technologist is 
instructed in these guidelines and performs all machine manipulations. Complete histories, 
physical examinations and stringent medical guidelines exclude many potential subjects before 
they enter the study, thereby further minimizing risks. A crash cart is always present and regular 
safety drills are performed by the medical and experimental staff to prepare for any untoward 
effects. 
Risks related to MRI scanning: 
MRI Static Magnetic Fields: FDA guidelines for clinical product scanners limit the main magnetic 
field to 3 Tesla. Our studies will be performed on a standard, clinical 3 T Philips scanner. A 
substantial body of literature exits that supports the safety of field strengths up to 7 T. There are 
no known risks of exposure to 3 or 7 T fields for MR imaging. 
Among the reported biological effects of exposure to strong static magnetic fields are the 
following: 1) Dizziness (with nausea) or stimulation of the sensory nerves in the soft palate has 
been reported as a result of the subject’s head being moved while in the magnet. 2) Rapid eye 
movement has been reported (at 4 and 7 T) to cause magnetophosphene effects. First 
described in 1896, these flickering light sensations are similar to visual phenomena caused by 
direct electric current passage across the head or retina. 
Radiofrequency (rf) Magnetic Fields: Radiofrequency energy burns are the result of high electric 
fluxes in the immediate vicinity of the patient. All MRI systems create some rf electric fields 
incidental to the production of the intended rf magnetic fields. The potential causes are 
malfunctions in the rf coil switching circuitry, improper use of the surface coils, design flaws in 
some clinical MRI system surface coils or cardiac gating patient connection leads. Nationally, 60 
burn incidents have been reported to the FDA in the course of approximately 11 million exams. 
Our site has never experienced any difficulty in this regard. 


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Acoustic Noise: The sound generated by an MR system usually consists of a series of repetitive 
pulses. The relevant safety parameters required to characterize such a noise are the peak 
impulse sound pressure level (Lpeak) and the time integral of the A-weighted sound pressure 
level (Leq). In MR applications, the peak impulse sound pressure level is dependent upon the 
peak amplitude of the individual pulses, while the time integral of the A-weighted sound 
pressure level is dependent upon the continuous exposure to a series of such pulses. Acoustic 
noise is a result of the mechanical vibration produced by the gradient coils when the nominally 
large currents are applied to them to create time varying imaging gradient fields. The sound 
produced can be loud enough to produce temporary deafness (up to 95 dB). Foam earplugs will 
attenuate this noise by up to 30 dB. They are in routine use at the 3T systems, and have been 
proven effective. 
Claustrophobia: While inside the magnet, subjects may experience an acute panic attack due to 
claustrophobia. Subjects are all prescreened for fear of tight places. Once inside the magnet, 
the subject will be given a squeeze ball to signal the MR operator if he or she is under acute 
distress. 
 
Risks related to anesthesia: 
Risks associated with intravenous catheter placement include brief, local discomfort and 
possible bruising, which can occur at the site of the IV line. There is also a possible (rare) 
chance of infection, but every precaution will be taken to reduce this risk by keeping the IV site 
clean and dry. Although rare, there is a risk of nerve damage at the arterial line insertion site. 
Risks associated with propofol administration include: pain at the site of injection, possible 
allergic reaction to the drug, depression of respiration which may necessitate placement of an 
endotracheal tube to assist breathing, and mechanical ventilation, or a decrease in blood 
pressure which may necessitate giving a drug or IV fluids to bring the subject's blood pressure 
up. These effects disappear when propofol is discontinued. 
 
Justification for the risks involved: The risks of the proposed procedure are minimal, and the 
importance to mankind of the potential knowledge gains is substantial, making the risk/benefit 
ratio very low. We combine the state-of-the-art brain imaging facility currently in place in the 
University of Michigan Health System with the experience of the imaging staff and clinic 
anesthesiologists in the Department of Anesthesiology. These experiments will provide a unique 
opportunity to understand the neurophysiological mechanisms of anesthesia modulation of 
human consciousness. Therefore, we will provide a unique opportunity to expand our 
knowledge of anesthesia-modulated human consciousness.  
 
Procedures for minimizing risks. All research subjects will go through a screening process for 
inclusion and exclusion criteria performed by licensed physician. A licensed physician will be 
present at all MRI scanning sessions to monitor the subjects. When subjects express or exhibit 
anxiety regarding the scanner setting, they will be allowed to discuss these feelings. Attempts 
will be made to minimize the discomfort and anxiety. When in the scanner, subjects will be 
provided with a squeeze-ball alarm that will alert the scanner technician and the researcher that 
the subject desires to come out of the scanner. In such instances, the subject will immediately 
be removed from the scanner and appropriate measures will be taken to ensure his or her 
psychological health. Earplugs, demonstrated to reduce scanner noise to a non-damaging level, 
will be used to minimize hearing risks.  
In addition, any other health problem that would be aggravated by an MRI scan will also be a 
cause for terminating the subject’s participation. In the event of serious cardiac-respiratory 
problems or other medical emergencies, the hospital code team will be activated. Other medical 


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problems will be treated by the monitoring physician. Any medical problems that arise after 
release, although unlikely, will be treated by a physician from the research team. All subjects will 
have to arrange transportation after the study, and agree to not drive, work, operate machinery, 
or make legal decisions for 24 hours after the study. Subjects will be informed of their right to 
withdraw from the study at any time. 
A protocol has been established to handle unexpected medical emergencies arising in the 
scanner suite. This protocol deals with medical issues and the duties of each team member. 
This includes stopping the scanner, removing the patient and calling for outside medical 
assistance. All members of the research team participate in periodic emergency protocol drills in 
the scanner suite and a copy of the written protocol and protocol termination guidelines are 
present at all times. Subjects requiring intervention for any neurological or cardiovascular 
adverse event will be transferred to the Emergency Department for further evaluation and 
treatment as seen fit by the attending physician. More serious cardiac events such as 
ventricular tachycardia, ventricular fibrillation or any unstable rhythm will be immediately treated 
according to current Advanced Cardiovascular Life Support (ACLS) protocols. Research team 
physicians have immediate access to valium, diphenhydramine, epinephrine, lidocaine, and 
NTG for emergency use, in addition to a fully supplied and operational “crash cart” with EKG, 
defibrillator, suction, oxygen, and airway management equipment. 
 
Confidentiality. Strict subject confidentiality will be maintained. Subjects will be assigned a 
code number following their first contact in the protocol. This number will be used throughout the 
experiment and will be the only identifier on behavioral and physiological archival data, and 
magnetic resonance (MR) scans. The identity of subjects will not be revealed at scientific 
meetings, in publications or other vehicles of public communication. Data will be pooled across 
subjects where appropriate. Only the PIs, Co-investigators, and the study coordinator will have 
access to the ID code, which will be stored in a locked file separate from the data. 
Any behavioral data collected on the subjects will be coded by study ID numbers and entered 
directly into notebook computers used in the field. These computers are password protected 
and stored behind a locked door when not in use. Clinical and biographic data are entered into 
the database using the ID number only. Only select staff members have access to the actual 
paper copies. Medical information will be released by name only to health care providers, and 
then only with written permission from the subject.  
 
References 
 
1. 
Liu X, Lauer KK, Ward BD, Rao SM, Li SJ, Hudetz AG. Propofol disrupts functional 
interactions between sensory and high-order processing of auditory verbal memory. Hum Brain 
Mapp. 2012 Oct; 33(10(:2487-98. 
2. 
Ward BD. Deconvolution analysis of fMRI time series data: Medical College of 
Wisconsin; 2006. 
3. 
Desmond JE, Glover GH. Estimating sample size in functional MRI (fMRI) neuroimaging 
studies: statistical power analyses. J Neurosci Methods. 2002 Aug 30;118(2):115-28. 
4. 
Hudetz AG, Liu X, Ward BD, Li S. Thalamocortical networks participate in propofol-
induced unconsciousness: a functional imaging study. The 15th WFSA World Congress of 
Anaesthesiologists (WCA); 25-30 March; La Rural, Buenos Aires, Argentina2012. 
5. 
Liu X, Lauer KK, Ward BD, Li S, Hudetz AG. Differential Effects of Propofol Anesthesia 
on Specific and Nonspecific Thalamocortical Systems. Anesthesiology. 2012 Jan;118(1): 59-69. 
6. 
Cohen J. Statistical power analysis for the behavioral sciences. 2nd ed. Hillsdale, N.J.: 
L. Erlbaum Associates; 1988. 


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7. 
Thirion B, Pinel P, Meriaux S, Roche A, Dehaene S, Poline JB. Analysis of a large fMRI 
cohort: Statistical and methodological issues for group analyses. Neuroimage. 2007 
Mar;35(1):105-20. 
8. 
Liu X, Li SJ, Hudetz AG. Increased precuneus connectivity during propofol sedation. 
Neurosci Lett. 2014 Feb 21; 561: 18-23. 
9. 
Liu X, Ward BD, Binder JR, Li SJ, Hudetz AG: Scale-free functional connectivity of the 
brain is maintained in anethesthetized healthy participants but not in patients with unresponsive 
wakefullness syndrome. PLoS One. 2014 Mar 19;9(3): e92182.