Clinical trial NCT03283150
Conditions: Brain Sedation
Keywords: Deep Brain Stimulation(DBS) Sedation DBS Implantation Microelectrode recording(MER)
Sponsor: University of Wisconsin, Madison
Start date: 2017-12-01; Completion date: 2022-01-20
Enrollment: 20 participants; Allocation: NON_RANDOMIZED; Intervention model: SEQUENTIAL

Brief summary:
Deep brain stimulation (DBS) of different brain nuclei is a treatment for multiple brain disorders. The subthalamic nucleus (STN) and globus pallidus have been used to treat advanced Parkinson's disease for a long time. The ventral intermediate nucleus of the thalamus is an effective target for treating essential tremor patients. STN and the internal segment of the globus pallidus are useful targets for treating dystonia.

To achieve this optimal electrode localization, many centers perform electrophysiological mapping of the target nuclei using microelectrode recording (MER). This way they can achieve precise localization of the electrode. During the mapping procedure, microelectrodes are passed through the target nuclei, and the electrical neuronal activity is observed and recorded. The surgical team can identify the precise location of the target nuclei and its borders according to the typical activity of its neurons.

This study will compare the activity of neurons in several DBS targets before, during and after sedation with propofol, remifentanil and dexmedetomidine. The goal is to understand the effects of anesthetics on the neuronal activity in these targets, allowing us to choose the most appropriate sedation protocol to use during implantation of DBS electrodes in deep brain structures (bearing in mind that each structure may have a different optimal protocol).

Detailed description:
Deep brain stimulation (DBS) of different brain nuclei is evolving as an essential component of the treatment for multiple brain disorders. The subthalamic nucleus (STN) and globus pallidus have been used to treat advanced Parkinson's disease for a long time. The ventral intermediate nucleus of the thalamus is an effective target for treating essential tremor patients. STN and the internal segment of the globus pallidus are useful targets for treating dystonia. Aside from movement disorders DBS has demonstrated efficacy in the treatment of other conditions such as chronic pain, obsessive compulsive disorder, depression and epilepsy. For these illnesses the specific brain region targeted depends upon the illness and the patient's characteristics. As the indications for DBS increase in number, so grows the number of patients that may be helped by this treatment. Increasing numbers of patients are undergoing these procedures for various maladies at our center and at other locations throughout the nation.

To achieve optimal clinical results and avoid side effects, the DBS electrode has to be implanted precisely within the targeted region. This was demonstrated elegantly for parkinsonian patients and the dorsolateral STN, but is likely to be the case for most DBS indications. To achieve this optimal electrode localization, many centers perform electrophysiological mapping of the target nuclei using microelectrode recording (MER). This way they can achieve precise localization of the electrode. During the mapping procedure, microelectrodes are passed through the target nuclei, and the electrical neuronal activity is observed and recorded. The surgical team can identify the precise location of the target nuclei and its borders according to the typical activity of its neurons.

Dexmedetomidine, propofol and remifentanyl are often used in awake neurosurgical procedures. Dexmedetomidine provides sedation and amnesia with minimal respiratory depression, and improves perioperative hemodynamic stability in neurosurgical patients. Propofol and remifentanil have a much shorter duration of action, and thus allow rapid titration. Both these agents allow reliable and safe sedation for awake craniotomies. However, the effects of any of these three agents on the electrical activity, and whether they will allow safe sedation during DBS electrode implantation at different targets and in different clinical conditions is unclear.

This study will compare the activity of neurons in several DBS targets before, during and after sedation with propofol, remifentanil and dexmedetomidine. The goal is to understand the effects of anesthetics on the neuronal activity in these targets, allowing the study team to choose the most appropriate sedation protocol to use during implantation of DBS electrodes in deep brain structures (bearing in mind that each structure may have a different optimal protocol).

The primary aim is to document the effects of commonly used anesthetic drugs on the neuronal activity during MER in different brain structures that are used as targets for DBS implantation.

The secondary aims is to Identifying effective sedation regimens for the different DBS targets; (2) Documenting the time course of the different drug's effect on the neuronal activity. Having this information will allow planning and performing sedation during the procedure prior to the MER without affecting the quality of the MER. This may prove useful in cases where no sedation regimen is completely devoid of effect on the MER; (3) Creating a database that includes the neuronal activity changes at multiple brain regions under the effect of different sedation drugs to enable further study of the effects of anesthetics on brain regions and the mechanisms underlying loss of consciousness.

Arms: arm 1: Remifentanil will be administered to subjects during microelectrode recordings (MER). arm 2: Propofol will be administered to subjects during MER. arm 3: Dexmedetomidine will be administered to subjects during MER.
Interventions: intervention 1: Remifentanil intervention 2: Propofol intervention 3: Dexmedetomidine
Intervention descriptions: intervention 1: Remifentanyl will be administered for 10 -15 minutes before initiating the MER phase and the patient will be allow to wake up and the bispectral index (BIS) values to normalize to awake level for the MER. intervention 2: Propofol will be administered for 10 -15 minutes before initiating the MER phase and the patient will be allow to wake up and the BIS values to normalize to awake level for the MER. intervention 3: Dexmedetomidine will be administered for 10 -15 minutes before initiating the MER phase and the patient will be allow to wake up and the BIS values to normalize to awake level for the MER.

Protocol documents:
Prot_SAP_000.pdf: 
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Effects of anesthesia drugs on neuronal activity in the basal ganglia and 
thalamus during deep brain stimulation electrode implantation surgery
NCT03283150
Principal Investigator 
Corey Amlong, MD - Department of Anesthesiology 
Co-Investigators 
Robert D. Sanders, MD - Department of Anesthesiology 
Wendell B. Lake, MD - Department of Neurological Surgery 
Aaron Suminski, MD – Department of Anesthesiology 
Summary 
Deep brain stimulation (DBS) is a common procedure performed for multiple neurological and 
psychiatric disorders. During these procedures, microelectrode recording (MER) is often used 
to precisely identify the optimal location for electrode implantation. The effect of sedation and 
anesthesia on the neuronal activity in the target structures is not fully understood, and we do 
not have yet an optimal sedation protocol for this procedure. Hence, many of these procedures 
are performed with the patient fully awake, despite a substantial discomfort this may cause. In 
this study, we will measure the change in neuronal activity in target areas during MER while 
administrating three commonly used sedative drugs: propofol, remifentanil and 
dexmedetomidine. This will be performed following positive target identification with MER in an 
awake patient, and thus allow precise documentation of the effects of anesthetic drugs on the 
neuronal activity without affecting the clinical outcome of the procedure. 


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Contents 
Summary ....................................................................................................................................................... 1 
Abbreviations ................................................................................................................................................ 3 
Background and Significance ........................................................................................................................ 4 
Study Objectives and Endpoints ................................................................................................................... 6 
Study Subjects – Enrollment and Withdrawal: ............................................................................................. 7 
Exclusion criteria: ...................................................................................................................................... 7 
Protected populations: ............................................................................................................................. 7 
Screening and Recruitment: ..................................................................................................................... 8 
Surgical and experimental procedures: ........................................................................................................ 8 
Intraoperative management: .................................................................................................................... 9 
Experimental phase: ............................................................................................................................... 11 
Assessment of Safety: ................................................................................................................................. 12 
Study halting rules .................................................................................................................................. 12 
Minimizing risk to the patient: ................................................................................................................ 13 
Benefit to patient .................................................................................................................................... 13 
Data collection analysis and management: ................................................................................................ 14 
Demographic and clinical data collection and management:................................................................. 14 
Data analysis: .......................................................................................................................................... 15 
Sample size:............................................................................................................................................. 16 
Interim Analysis ....................................................................................................................................... 16 
Data and Safety Monitoring Plan ............................................................................................................ 16 
Study Monitoring, Auditing and Inspecting ............................................................................................ 17 
References: ................................................................................................................................................. 18 


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Abbreviations  
DBS 
 
Deep brain stimulation  
MER  
Microelectrode recording 
STN 
 
Subthalamic nucleus 
UW 
 
University of Wisconsin Hospital and Clinics 
CT 
 
Computed Tomography 
MRI 
 
Magnetic Resonance Imaging 
BIS 
 
Bi-spectral index 
OAA/S  
Observer’s assessment of alertness/sedation scale 
RMS  
Root mean square 
 
 


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Background and Significance 
Deep brain stimulation (DBS) of different brain nuclei is evolving as an essential component of 
the treatment for multiple brain disorders1,2. The subthalamic nucleus (STN) and globus pallidus 
have been used to treat advanced Parkinson's disease for a long time3-5. The ventral 
intermediate nucleus of the thalamus is an effective target for treating essential tremor 
patients6,7. STN and the internal segment of the globus pallidus are useful targets for treating 
dystonia8,9. Aside from movement disorders DBS has demonstrated efficacy in the treatment of 
other conditions such as chronic pain10, obsessive compulsive disorder11, depression12 and 
epilepsy13-15. For these illnesses the specific brain region targeted depends upon the illness and 
the patient’s characteristics. As the indications for DBS increase in number, so grows the 
number of patients that may be helped by this treatment. Increasing numbers of patients are 
undergoing these procedures for various maladies at our center and at other locations 
throughout the nation. 
To achieve optimal clinical results and avoid side effects, the DBS electrode has to be implanted 
precisely within the targeted region. This was demonstrated elegantly for parkinsonian patients 
and the dorsolateral STN16,17, but is likely to be the case for most DBS indications. To achieve 
this optimal electrode localization, many centers perform electrophysiological mapping of the 
target nuclei using microelectrode recording (MER). This way they can achieve precise 
localization of the electrode18,19. During the mapping procedure, microelectrodes are passed 
through the target nuclei, and the electrical neuronal activity is observed and recorded. The 
surgical team can identify the precise location of the target nuclei and its borders according to 
the typical activity of its neurons16,18. 
The MER mapping procedure may take several hours. In some centers the patient’s head is 
motionless and fixed inside a stereotaxic frame throughout the procedure, at others (e.g. our 
institution – University of Wisconsin Hospital and clinics; UW) a frameless navigation system is 
used, but even in this method the patient has to remain in a relatively static position throughout 
the procedure. Some centers use sedation or light general anesthesia during this surgery20-22. 
However, most centers do not routinely use any kind of sedation out of concern that it might 
change the activity of neurons in the target area, and interfere with the precise MER localization 
of the electrode23-25. Other centers (UW included) use sedation during the initial phase, and stop 
it 20-30 minutes before the MER so that the MER (that may take 1-4 hours) is performed with 
patients awake. It is therefore not uncommon for patients to complain of anxiety or discomfort 
during the operation20. 


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Dexmedetomidine, propofol and remifentanyl are often used in awake neurosurgical 
procedures26. Dexmedetomidine provides sedation and amnesia with minimal respiratory 
depression, and improves perioperative hemodynamic stability in neurosurgical patients26,27. 
Propofol and remifentanil have a much shorter duration of action, and thus allow rapid titration. 
Both these agents allow reliable and safe sedation for awake craniotomies28. However, the 
effects of any of these three agents on the electrical activity, and whether they will allow safe 
sedation during DBS electrode implantation at different targets and in different clinical conditions 
is unclear. 
The STN is a well-known and well-studied target for electrode placement that has been in wide-
spread use for many years.  As such there are reports of different drugs that have been used for 
sedation during electrophysiological mapping of the STN, including propofol20,22,29, 
dexmedetomidine21,29, remifentanil20,30, midazolam22,30 and even volatile anesthetics31. Reports 
comparing the clinical results of DBS electrode implantation in fully awake patients versus 
anesthetized patients have demonstrated conflicting results: some have shown inferior long 
term outcome in the anesthetized patients32 while others have not shown a significant 
difference20. However, there is very limited data regarding the actual effects of the different 
anesthetic drugs on STN activity and its effect on the accuracy of MER guided electrode 
placement.  
We demonstrated that propofol transiently decreases STN activity and the signal to noise ratio 
available for STN localization. Activity returned to normal 9±4 minutes after propofol 
administration stopped33. A more recent study from our group suggests similar results but with a 
much slower return to baseline with dexmedetomidine (manuscript in preparation). Others have 
also demonstrated that dexmedetomidine may interfere with MER accuracy34. By contrast, 
MacIver et al. demonstrated that lower doses of propofol and remifentanil exhibit only a minimal 
change on the firing rate of STN neurons35. It is clear than that even for the most studied target 
– the STN; we do not yet have an optimal anesthesia regimen. The information regarding the 
effects of anesthetic on other, newer or less frequently targeted nuclei is sparse, and thus 
recommendations regarding the optimal sedation protocols and their effect on the neuronal 
activity, the accuracy of MER and the clinical outcome are lacking. 
In addition to identifying an effective sedation regiment for these procedures, recording the 
neuronal activity under sedation will enable us to study the effect of anesthetic drugs on the 
target brain structures. As the mechanisms underlying sedation, anesthesia, and loss of 
consciousness remain unclear, study of neuronal activity via MER may enhance our 


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fundamental understanding of the mechanisms underlying anesthetic induced loss of 
consciousness – a great question in our specialty and in our understanding of the brain and 
behavior in general. 
Study Objectives and Endpoints 
In this study, we will compare the activity of neurons in several DBS targets before, during and 
after sedation with propofol, remifentanil and dexmedetomidine. Our goal is to understand the 
effects of anesthetics on the neuronal activity in these targets, allowing us to choose the most 
appropriate sedation protocol to use during implantation of DBS electrodes in deep brain 
structures (bearing in mind that each structure may have a different optimal protocol). We will do 
so using each patient as his/her own control, thus eliminating the subjective report bias of MER 
quality that limits conclusions drawn using surgeons and physiologist reports of MER quality 
under different conditions. We will start with the areas that are commonly targeted during DBS 
procedures at UW: the ventral intermediate nucleus of the thalamus, the STN and the globus 
pallidus. However, as new targets are gaining popularity and are added to the clinical 
procedures offered to the public at UW, we will seek to study the effects of anesthesia on those 
new targets, and find the effects of anesthesia on each new target. 
Our hypothesis is that propofol, remifentanil and dexmedetomidine change the firing rate and 
pattern of deep brain structures to different extent.  
Primary aim: To document the effects of commonly used anesthetic drugs on the neuronal 
activity during MER in different brain structures that are used as targets for DBS implantation.  
Secondary aims: 1) Identifying effective sedation regimens for the different DBS targets; 2) 
Documenting the time course of the different drug’s effect on the neuronal activity. Having this 
information will allow planning and performing sedation during the procedure prior to the MER 
without affecting the quality of the MER. This may prove useful in cases where no sedation 
regimen is completely devoid of effect on the MER; 3) Creating a database that includes the 
neuronal activity changes at multiple brain regions under the effect of different sedation drugs to 
enable further study of the effects of anesthetics on brain regions and the mechanisms 
underlying loss of consciousness. 
Each subject’s participation is for the duration of the surgery. We typically see 30-40 patients for 
DBS electrode implantation surgery per year at UW, of which 70% are expected to consent to 
the study. Thus, assuming we’ll need on average 10-15 patients per drug per target (i.e. a total 


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of 70-105 patients as we already have the data of the effects of propofol and dexmedetomidine 
on the STN) the project will require between two and five years to recruit patients.  
New targets for DBS are continuously discovered and become a standard of care. Once a new 
target is added to the clinical procedures routinely performed at UW, we will add the new target 
to the protocol, and if necessary request a time extension and increase the recruitment goals to 
study these new targets.  The change of protocol to add the new target will be reviewed and 
approved by the IRB first prior to implementing any new targets. 
Study Subjects – Enrollment and Withdrawal: 
All patients scheduled to undergo DBS electrode implantation surgery with MER that agree to 
participate in the experiment and sign an informed consent (supplement 1) are candidates to 
participate in the study, unless one of the exclusion criteria is met. 
Exclusion criteria: 
1. 
Known or suspected obstructive sleep apnea. 
2. 
Suspected difficult intubation. 
3. 
Pregnancy (pregnancy test is standard care for women of childbearing age) 
4. 
Under 18 years of age or over 85 years of age 
5. 
Cognitive disability impairing understanding the experiment or signing the informed 
consent form. 
Protected populations:  
Prisoners – Due to the complexity of state and federal requirements governing the participation 
of prisoners in research, patients who are prisoners will not be considered for participation in 
this trial.  
Pregnancy – Pregnancy is an exclusion criteria 
Cognitive disability – The ability of the patient to sign an informed consent will be evaluated by 
the consenting investigator (MD). A patient deemed impaired in his ability to consent will not 
participate in the study (this is also an exclusion criteria). It should be noted that many of the 
patients undergo routine psycho-cognitive evaluation as part of their evaluation prior to 
undergoing a DBS procedure. 


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Screening and Recruitment:  
Candidates for participation in the study will be identified by Dr. Lake as patients are referred to 
him for the preoperative evaluation (Dr. Lake is a co-investigator, and is also the only physician 
performing these operations clinically at UW, so all patients are referred to him for evaluation). 
Dr. Lake will alert one of the investigators from the department of anesthesiology regarding the 
patient and the dates the patient is scheduled to arrive at UW (for preoperative evaluation, bone 
marker fiducial insertion and the day of their surgery). 
Patients found suitable to participate in the study will receive an explanation and get the 
informed consent form from one of the physicians participating in this study (either 
neurosurgeon or anesthesiologist). Subjects will be given as much time as possible to consider 
participation. There will be a follow-up conversation with the subject to review information about 
the study and discuss the subject’s questions after the subject has had time to read and 
consider the consent form.  Study personnel will be available to answer any questions the 
subject may have about the study.  Potential subjects will be approached to introduce the study 
and will be given the consent form to review during the preoperative evaluation, or when 
hospitalized for bone marker fiducial insertion, allowing them time to go over the consent form 
and make a decision before the day of surgery. The signed informed consent form may be 
collected either before the day of surgery, or on the morning of the surgery, before the patient is 
taken to the operating room.  
Surgical and experimental procedures: 
Patients will undergo the standard DBS implantation surgery practiced at UW.  The procedure 
will differ only during the experimental phase, as specified below in the section, “Experimental 
Phase”. 
The standard surgical procedure is as follows.  The patients will have had a recent bone marker 
fiducial placement and a CT / MRI prior to the DBS placement. They will come to the operating 
room, lines and monitors will be placed for the procedure at the discretion of the 
anesthesiologist (in accordance with UW accepted standards). The head will be prepped and 
draped. Surgery will be performed under local anesthesia with or without sedation as is usually 
performed at UW. 
DBS electrode placement is often done on both sides (two electrodes are implanted). This is 
often done in one day (the patient gets two electrodes on both sides), but sometimes this is 
done in two separate sessions on two different dates (usually if the procedure took a long time, 
or there may be a shift in the brain due to CSF leak). For the purpose of the study, it doesn't 


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matter if this is the first or the second side.  We will perform the experimental phase on the last 
mapping session of the day. 
 
Intraoperative management:   
When the patient initially enters the operating room, standard American Society of 
Anesthesiologists monitors and oxygen by nasal cannula are applied. Bi-spectral index (BIS) 
monitor is placed, and the awake level numerical value is noted.  
Adequate peripheral venous access is secured and the first dose of prophylactic antibiotic is 
administered as indicated (e.g. cefuroxime 1.5 g IV). Lactated ringer solution is the preferred IV 
solution (except for patients in renal failure; normal saline is then used). Fluids are administered 
throughout the case at the anesthesiologist’s discretion.  
 
The surgeon then uses local anesthetic (Bupivacaine 0.25%) for the scalp incision, burr holes 
and craniotomy, and add local anesthesia as required to maintain the patient comfortable and 
pain free.  Once electrodes are positioned, we’ll perform the MER to identify the optimal location 
for the DBS electrode. The number of mapping electrodes will be at the discretion of the 
neurosurgeon as required for the procedure.  The system we use at UW allows as many as 9 
mapping electrodes that may be advanced and recorded simultaneously. The trade-off is that 
more electrodes will allow better mapping and lower the likelihood of need for extra trajectories, 
but will cause more damage to the brain as the electrodes are passed. Three electrodes are 
routinely used at UW, but this can change according to the surgeons decision and the clinical 
scenario.  
Remifentanyl or propofol sedation may be used for the initial part of the procedure (skin incision, 
burr holes and craniotomy and initial insertion of the electrodes). The sedative dose will be at 
the anesthesiologist’s discretion in consultation with the neurosurgeon to achieve optimal 
sedation. Sedation will be held 10-15 minutes before initiating the MER phase, and we will allow 
the patient to wake up and the BIS values to normalize to awake level for the MER. 
We will use the Guideline 4000 system (FHC Inc., Bowdoin, ME) for data acquisition and 
recording. This system is currently being used at UW for MER during this type of surgery. MER 
will commence 15 to 30 mm above the expected target depth (or at the relevant depth for the 
specific target). During MER the electrode will be advanced in progressively smaller steps as 
the target is approached (usually 50-100μm). After each step we will measure the neuronal 


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activity at that depth for a few seconds. Once inside the target nuclei, responses of neuronal 
activity to stimuli may be assessed as required (assessment will be performed as recommended 
to identify the relevant nuclei). The experimental phase (see below) will take place during this 
stage after the target location has been confirmed. In case we do not find the target during the 
electrode pass, identifying other structures along the trajectory may help with planning the next 
trajectory. Once the target is confirmed, MER is continued to identify the ventral border of the 
target nucleus. This is usually detected by a decrease in the neuronal activity of the target 
nucleus, and in some cases identifying typical activity of neighboring nuclei. e.g. the substansia 
nigra below the ventral border of the STN. Identifying the ventral border allows targeting the 
stimulating electrode to the center of the target area. Macrostimulation is performed to estimate 
the clinical response and possible side effects (i.e. are the patient’s symptoms addressed at the 
current electrode position).  Following that, a single permanent stimulating electrode will be 
placed at the same location and fixed to the skull (the routine treatment is a single stimulating 
electrode per affected side \ target). The whole procedure may take from 30 minutes up to three 
hours per side, depending on the number of trajectories required for a successful implantation.  
Once the mapping is done, one stimulating electrode is left in the optimal target. For most 
patients this will be two electrodes in total (one in each side), but in certain cases the surgeon 
may choose to put only one electrode (some patients present with a unilateral disease, and get 
one electrode, and sometimes they may present for a second electrode placement on the other 
side years later after the disease has progressed). For the sake of the study, we will be 
performing the experimental phase on the last electrode trajectory of the day. If the patient is 
getting two electrodes on the same day, this will only be done during the mapping for the 
second electrode, whereas if he gets only one electrode (with a second electrode placement 
planned for a future date, or not even planned yet) we will perform the experimental phase on 
whatever side is done. 
During the procedure, the anesthesiologist will maintain systolic blood pressure below 150 mm 
Hg throughout and below 140 mm Hg when actively passing electrodes. The drugs used to 
control blood pressure will be discussed with the surgeon, and agreed upon according to the 
disease and target nuclei (e.g. we’ll avoid ß blockers in essential tremor patients). In cases of 
extreme hypotension (Systolic blood pressure below 90mmHg) or bradycardia (Heart rate below 
50) at the initiation of the experimental phase, the patient will not receive dexmedetomidine or 
propofol and may be withdrawn from the study. In such a case, all data collected from the 
patient will be purged and not used for further analysis. 


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Experimental phase: 
During the operation, following target identification by the MER and while the recording 
electrode is inside the target area, electrode advancement will be stopped. Following three 
minutes of recording the baseline neuronal activity at the selected location, an anesthetic drug 
will be administered as detailed below until stable sedation is achieved. The administration rate 
can be titrated at the anesthesiologist’s discretion to achieve the optimal clinical sedation goal. 
Our goal is to achieve a drowsy but arousable (by calling his name or a light tap on the 
shoulder) patient – 3 on the observer’s assessment of alertness/sedation (OAA/S) scale36,37 BIS 
value of 60-80 may be used as an adjunct to assess sedation level.  
Following 2-3 minutes of recordings at a stable sedation level, we will stop the sedation and 
allow the patient to recover. Once the patient is awake and cooperative (OAA/S = 4-5) we will 
record another 2-3 minutes of activity. After recording 2-3 minutes of activity in the recovered 
patient, we will resume electrode advancement and MER in order to identify the ventral border 
of the target area, and localize the stimulating electrode. We expect the experimental phase to 
add 30-40 minutes to the procedure. High frequency sampling of the voltage at the tip of the 
electrode will be recorded continuously throughout the experimental phase and saved into 
coded files for the research record. 
We will use 3 sedation protocols for each target:  
1. Propofol infusion will be started at 100 µg/Kg/min and titrated by the anesthesiologist to 
the appropriate sedation depth. 
2. Remifentanyl infusion will be started at 0.05 µg/kg/min and titrated by the 
anesthesiologist to the appropriate sedation depth. 
3. Dexmedetomidine infusion will be started with a loading dose of 0.8 µg/Kg over 10-15 
minutes followed by a maintenance infusion starting at 0.7 µg/Kg/hr and titrated by the 
anesthesiologist to the appropriate sedation depth. 
Each patient will receive only one of these protocols (i.e. each patient will receive only one 
anesthetic drug). For each DBS target we will go through the drugs in a consecutive order, i.e. 
we will recruit patients and treat them with one sedation drug until we have enough data 
regarding the effect of this drug on the target, and then switch to the next drug. This approach 
will enable us to sum the results and draw conclusions rapidly and efficiently. 
Appropriate sedation level should be achieved within 10-20 minutes in all these protocols. 


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Standard practice at UWHC – All the sedation protocols detailed above are routinely used for 
procedural sedation at our department. Propofol sedation is sometimes given as part of the 
treatment for this procedure. It is stopped before MER as described. We monitor the sedation 
depth of our patients but we do not formally use OAA/S as part of standard care. In standard 
care, the doses as well as drugs used (dexmedetomidine, propofol and remifentanil, alone or in 
combination) vary at the anesthesiologist’s discretion. 
Assessment of Safety: 
Study halting rules: 
The study includes short periods of sedation with commonly used anesthesia drugs, under the 
accepted monitoring and supervision for such sedation, thus we consider it a low risk study and 
do not expect any serious side effects. However – any serious complication related to the 
sedation (significant aspiration or other pulmonary complication requiring intubation and 
mechanical ventilation, stroke, myocardial infarction or death) will be reported to the IRB during 
the next work day. The study will be halted until the case is reviewed by all the investigators and 
the data safety monitoring board. If the complication is indeed related to the study according to 
the review held, protocol changes to prevent the recurrence of such an event will be 
recommended, and the study will resume only after the necessary protocol amendments will be 
made. 
Risks 
During the trial the volunteers will receive sedative drugs as a part of the study. These drugs 
may cause bradycardia, hypotension, transient Hypertension, respiratory depression, apnea, 
airway obstruction, oxygen desaturation, muscle rigidity (remifentanil). Propofol emulsion may 
get contaminated with bacteria and cause severe infection if improperly treated or stored 
improperly. Theoretically, long term subclinical effects of the anesthetic drugs may interfere with 
the identification of the ventral border of the target structure, or even with clinical evaluation of 
macrostimulation effect performed at the end of the procedure. A significant miss is very 
unlikely, and the target will be identified prior to the sedation trial to prevent such a case, but 
minor changes in the final depth are theoretically possible. Such changes may drain the pulse 
generator battery slightly faster, as stronger current is required. This shouldn’t be a problem with 
the newer pulse generators, as they have a transcutaneous charging option.  


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Minimizing risk to the patient: 
Administration of anesthetics will be performed in an OR setting, with all the equipment 
necessary to monitor the patients and treat any untoward effect of these drugs. The sedation 
will be performed directly under the supervision of a board certified anesthesiologist 
experienced with administrating these drugs and while the patient is connected to standard ASA 
monitoring (which is routinely used in these cases). The attending anesthesiologist will be in 
charge of treating any untoward event (in case any such event occurs). It should be emphasized 
that the patient will receive sedation (most likely with the same group of drugs, or a combination 
of drugs) as part of their routine clinical treatment. Combining different sedative drugs is a well-
accepted practice that should not present a problem to the treating anesthesiologists,  
Furthermore, our exclusion criteria (obstructive sleep apnea and suspected difficult intubation) 
and protocol (avoiding drug administration in cases of bradycardia or hypotension) are designed 
to avoid the risk of these complications.  
Performing the experiment will increase the surgery duration by the time required to complete 
the experimental phase (estimated 30-40 minutes, depending on the sedation drug). However, 
the patients will be sedated during most of this time, so this should not increase their 
inconvenience and stress level. The added time is relatively short compared to the length of the 
whole procedure (usually 3-5 hours), so it should not have a significant effect on OR time or 
complications. Administrating sedation intermittently, i.e. sedation followed by wake up and then 
re-administration of the sedation is a routine practice in neuro-anesthesia that has been well 
described, and is not considered to be a significant added risk. 
One possible risk of the research protocol is that sedation will affect the MER and thus the final 
position of the electrode. In order to minimize possible interference with target identification, the 
experimental phase will take place during MER of the last location that will be targeted for 
electrode placement on that day, and only after identifying the target area. Thus we will sedate 
the patient only after all the electrode targets for that day were identified, so that the risk for 
adversely affecting the electrode localization is minimal. 
Benefit to patient: 


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No direct benefit to subjects are anticipated.  This research study may benefit other 
people in the future by helping us learn more about how to perform sedation without 
affecting the electrical mapping of the brain.  If we can identify a sedative drug that does 
not affect cell activity in the target region, we will be able to routinely use sedation 
during mapping and increase patient comfort during deep brain surgery. 
Data collection analysis and management: 
Demographic and clinical data collection and management: 
Subject name, age, gender, right/left handedness, date of surgery, anesthesia details (drugs, 
doses, depth of sedation), surgery details (target area, electrode coordinates, structures 
encountered during MER), disease type and duration, primary symptoms, medications, and 
electrophysiological (electrical potential at the tip of the electrode at any point in time during 
MER) data will be collected from the patient chart during the surgical procedure. Data will be 
collected using a pre-defined table (supplement 2) by one of the investigators. 
Collected data will be coded to prevent identification of subjects. The identifiable data (signed 
consent forms and a table of subject codes, names,) will be secured in a locked filing cabinet at 
the Department of Neurosurgery or Department of Anesthesiology for 12 years.  
The rest, de-identifiable data (Anesthesia details, Surgery details, Disease type and duration, 
Primary symptoms, Medications and Electrophysiological data) will be extracted from the 
electronic medical record and entered into an Excel spreadsheet.  The data that is entered into 
the spreadsheet will contain no personal health information and will be coded with a unique 
study ID number and transferred using an encrypted flash drive to analysis computers at the 
department of anesthesiology. This data will not contain any subject identifiers other than the 
subject code, and will the key to the code will be stored in a separate location from the coded 
data. 
Only co-investigators involved in the treatment of the subject and data collection will have 
access to the identifiable patient data. Coded data will be managed by the co-investigators as 
well as students at the Department of Anesthesiology under the supervision of one of the 
investigators. 
The investigators will use their laptops and the department of anesthesiology computers for data 
analysis. Only coded data will be placed on the password-protected laptops set up in 
consultation with data security personnel to ensure that they employ sufficient data security 


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protections.  No subject identifiers other than study code will be placed on the laptop, and no 
links between subject codes and subject identifiers will be on the laptop.  Anyone engaged in 
research activities (for example, participating in data analysis) using either identifiable or coded 
data will be listed as key personnel on the ARROW application. 
Data analysis: 
We will record the neuronal activity at every point along the electrode trajectory according to the 
routine MER protocol at UW. We will evaluate the effect of sedative drugs on the firing rate and 
temporal firing pattern of neurons in the target area at a single location, as well as compare the 
activity along the trajectories.   
We will calculate the root mean square (RMS) of the electrical activity as a measure of the 
spiking rate of neurons in the vicinity of the electrode tip. The RMS has been shown to be a 
useful clinical guide for STN identification and electrode placement16,38. We will normalize the 
RMS to the baseline value recorded at the first 2-5 minutes of MER (before entering the target 
area) to compensate for differences between patients and recording electrodes. In order to 
calculate the change in the normalized RMS following sedation we will compare the mean RMS 
during 2 minutes of the stable recording of the pre-sedation baseline to the mean RMS during 
stable sedation and following recovery. We will use a paired t-test to determine the significance 
of this change.  Alpha of 0.05 will be considered significant. If we do find a significant change we 
will use the continuously recorded data to calculate the average RMS as a function of time to 
examine time course of the change and recovery of the RMS. The time to change and the time 
to return to baseline will be considered as the time that the average RMS crosses the 95% 
confidence interval of the baseline value. We will measure the correlation between the RMS and 
the sedation depth measured by the BIS monitor. 
The oscillatory firing pattern of neuronal activity is also an important indicator of optimal 
electrode placement in certain areas (e.g. STN)17. We will use frequency-domain analysis to 
measure these oscillatory firing patterns in the target area and determine changes following 
administration of sedation and their time course.  
Time to sedation and recovery will be calculated from the clinical data tables recorded during 
the procedure. Mean and standard deviation of these values will be calculated.  
Analysis will be performed using custom software written in Matlab (MathWorks, Natick, MA). 


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Sample size: 
As we have learned during our last study on the effects of dexmedetomidine on the activity in 
the STN, the sample size calculation based on estimation from one drug effect to another, or 
from a certain brain area to another is prone to inaccuracy, leading to either too large or too 
small sample sizes. To avoid that, we will perform a pilot study using the first five patients of 
each target location and anesthesia protocol as a preliminary data collection and use the data 
obtained to calculate the magnitude of sedation effect. If no effect is seen for the first five 
patients, or if the effect is smaller than 10%, we’ll use 10% change as a benchmark to rule out a 
clinically significant effect. We will than calculate the sample size required with alpha of 0.05 
and power of 0.75. 
From our previous experience and from other manuscripts published in the field, we assume 
we’ll need on average 10-15 patients per drug per target, i.e. a total of 70-105 patients (as we 
already have the data of the effects of propofol and dexmedetomidine on the STN). We plan to 
recruit 180 patients to allow for modification of the sample size estimation in case we find out 
that we need more patients than estimated.   
Table 1: Estimate of the number of patients required for the currently 
used clinical targets and drugs 
 
Propofol 
Remifentanil Dexmedetomidine 
Thalamus (vi) 
10-15 
10-15 
10-15 
STN 
Completed 
10-15 
Completed 
Globus pallidus 
10-15 
10-15 
10-15 
 
Interim Analysis:  
Interim analysis of the data will be conducted following the pilot phase (first five patients) of 
each target and drug combination, and then following the recruitment of either 50% of the 
required patients or every 10 patients per target and drug combination. 
Data and Safety Monitoring Plan 
The Data Safety Monitoring Board will consist of 3 members with expertise in anesthesia, 
neurosurgery and electrophysiology. DSMB members are not investigators on the study. The PI 
will report to the board via e-mail (since 1 member is a distance from Madison) following 


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recruitment of every 10 patients, and with every preliminary and interim analysis results. No 
protected health information (PHI) will be included in reports sent via email. The report will 
include the number and type of cases recruited and actually performed, any adverse effects, 
and any obvious effects on the MER reported by the surgeon during surgery. For the interim 
analysis the report will also include the analysis results. The DSMB will communicate via email 
its decisions on whether to continue the study at each of these time points.  
Study Monitoring, Auditing and Inspecting: 
The PI will be responsible to make sure that the data are complete and accurate and AE 
reporting is done per this protocol. 
 
 


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Version 1.4 
February 17, 2020 
 
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1. 
Sharifi MS. Treatment of neurological and psychiatric disorders with deep brain stimulation; 
raising hopes and future challenges. Basic and clinical neuroscience. Summer 2013;4(3):266-270. 
2. 
Chen XL, Xiong YY, Xu GL, Liu XF. Deep brain stimulation. Interventional neurology. Sep 2013;1(3-
4):200-212. 
3. 
Limousin P, Krack P, Pollak P, et al. Electrical stimulation of the subthalamic nucleus in advanced 
Parkinson's disease. The New England journal of medicine. Oct 15 1998;339(16):1105-1111. 
4. 
Walter BL, Vitek JL. Surgical treatment for Parkinson's disease. Lancet Neurol. Dec 
2004;3(12):719-728. 
5. 
Moro E, Lozano AM, Pollak P, et al. Long-term results of a multicenter study on subthalamic and 
pallidal stimulation in Parkinson's disease. Mov Disord. Mar 8 2010. 
6. 
Baizabal-Carvallo JF, Kagnoff MN, Jimenez-Shahed J, Fekete R, Jankovic J. The safety and efficacy 
of thalamic deep brain stimulation in essential tremor: 10 years and beyond. J Neurol Neurosurg 
Psychiatry. May 2014;85(5):567-572. 
7. 
Zhang K, Bhatia S, Oh MY, Cohen D, Angle C, Whiting D. Long-term results of thalamic deep brain 
stimulation for essential tremor. J Neurosurg. Jun 2010;112(6):1271-1276. 
8. 
Volkmann J, Wolters A, Kupsch A, et al. Pallidal deep brain stimulation in patients with primary 
generalised or segmental dystonia: 5-year follow-up of a randomised trial. Lancet Neurol. Dec 
2012;11(12):1029-1038. 
9. 
Kleiner-Fisman G, Liang GS, Moberg PJ, et al. Subthalamic nucleus deep brain stimulation for 
severe idiopathic dystonia: impact on severity, neuropsychological status, and quality of life. J 
Neurosurg. Jul 2007;107(1):29-36. 
10. 
Pereira EA, Boccard SG, Linhares P, et al. Thalamic deep brain stimulation for neuropathic pain 
after amputation or brachial plexus avulsion. Neurosurgical focus. Sep 2013;35(3):E7. 
11. 
Mian MK, Campos M, Sheth SA, Eskandar EN. Deep brain stimulation for obsessive-compulsive 
disorder: past, present, and future. Neurosurgical focus. Aug 2010;29(2):E10. 
12. 
Kocabicak E, Temel Y, Hollig A, Falkenburger B, Tan S. Current perspectives on deep brain 
stimulation for severe neurological and psychiatric disorders. Neuropsychiatric disease and 
treatment. 2015;11:1051-1066. 
13. 
Lega BC, Halpern CH, Jaggi JL, Baltuch GH. Deep brain stimulation in the treatment of refractory 
epilepsy: update on current data and future directions. Neurobiology of disease. Jun 
2010;38(3):354-360. 
14. 
Fisher R, Salanova V, Witt T, et al. Electrical stimulation of the anterior nucleus of thalamus for 
treatment of refractory epilepsy. Epilepsia. May 2010;51(5):899-908. 
15. 
Theodore WH, Fisher RS. Brain stimulation for epilepsy. Lancet Neurol. Feb 2004;3(2):111-118. 
16. 
Zaidel A, Spivak A, Shpigelman L, Bergman H, Israel Z. Delimiting subterritories of the human 
subthalamic nucleus by means of microelectrode recordings and a Hidden Markov Model. Mov 
Disord. Jun 16 2009. 
17. 
Zaidel A, Spivak A, Grieb B, Bergman H, Israel Z. Subthalamic span of beta oscillations predicts 
deep brain stimulation efficacy for patients with Parkinson's disease. Brain. Jul 2010;133(Pt 
7):2007-2021. 
18. 
Hutchison WD, Allan RJ, Opitz H, et al. Neurophysiological identification of the subthalamic 
nucleus in surgery for Parkinson's disease. Ann Neurol. Oct 1998;44(4):622-628. 
19. 
Hamid NA, Mitchell RD, Mocroft P, Westby GW, Milner J, Pall H. Targeting the subthalamic 
nucleus for deep brain stimulation: technical approach and fusion of pre- and postoperative MR 
images to define accuracy of lead placement. J Neurol Neurosurg Psychiatry. Mar 
2005;76(3):409-414. 


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20. 
Hertel F, Zuchner M, Weimar I, et al. Implantation of electrodes for deep brain stimulation of 
the subthalamic nucleus in advanced Parkinson's disease with the aid of intraoperative 
microrecording under general anesthesia. Neurosurgery. Nov 2006;59(5):E1138; discussion 
E1138. 
21. 
Rozet I, Muangman S, Vavilala MS, et al. Clinical experience with dexmedetomidine for 
implantation of deep brain stimulators in Parkinson's disease. Anesth Analg. Nov 
2006;103(5):1224-1228. 
22. 
Venkatraghavan L, Manninen P, Mak P, Lukitto K, Hodaie M, Lozano A. Anesthesia for functional 
neurosurgery: review of complications. J Neurosurg Anesthesiol. Jan 2006;18(1):64-67. 
23. 
Israel Z, Hassin-Baer S. Subthalamic stimulation for Parkinson's disease. Isr Med Assoc J. Jul 
2005;7(7):458-463. 
24. 
Rezai AR, Kopell BH, Gross RE, et al. Deep brain stimulation for Parkinson's disease: surgical 
issues. Mov Disord. Jun 2006;21 Suppl 14:S197-218. 
25. 
Kalenka A, Schwarz A. Anaesthesia and Parkinson's disease: how to manage with new therapies? 
Curr Opin Anaesthesiol. Jun 2009;22(3):419-424. 
26. 
Rozet I. Anesthesia for functional neurosurgery: the role of dexmedetomidine. Curr Opin 
Anaesthesiol. Oct 2008;21(5):537-543. 
27. 
Tanskanen PE, Kytta JV, Randell TT, Aantaa RE. Dexmedetomidine as an anaesthetic adjuvant in 
patients undergoing intracranial tumour surgery: a double-blind, randomized and placebo-
controlled study. Br J Anaesth. Nov 2006;97(5):658-665. 
28. 
Berkenstadt H, Perel A, Hadani M, Unofrievich I, Ram Z. Monitored anesthesia care using 
remifentanil and propofol for awake craniotomy. J Neurosurg Anesthesiol. Jul 2001;13(3):246-
249. 
29. 
Khatib R, Ebrahim Z, Rezai A, et al. Perioperative events during deep brain stimulation: the 
experience at cleveland clinic. J Neurosurg Anesthesiol. Jan 2008;20(1):36-40. 
30. 
Gray H, Wilson S, Sidebottom P. Parkinson's disease and anaesthesia. Br J Anaesth. Apr 
2003;90(4):524; author reply 524-525. 
31. 
Lin SH, Chen TY, Lin SZ, et al. Subthalamic deep brain stimulation after anesthetic inhalation in 
Parkinson disease: a preliminary study. J Neurosurg. Aug 2008;109(2):238-244. 
32. 
Maltete D, Navarro S, Welter ML, et al. Subthalamic stimulation in Parkinson disease: with or 
without anesthesia? Arch Neurol. Mar 2004;61(3):390-392. 
33. 
Raz A, Eimerl D, Zaidel A, Bergman H, Israel Z. Propofol decreases neuronal population spiking 
activity in the subthalamic nucleus of Parkinsonian patients. Anesth Analg. Nov 
2010;111(5):1285-1289. 
34. 
Krishna V, Elias G, Sammartino F, et al. The effect of dexmedetomidine on the firing properties 
of STN neurons in Parkinson's disease. Eur J Neurosci. Aug 2015;42(4):2070-2077. 
35. 
Maciver MB, Bronte-Stewart HM, Henderson JM, Jaffe RA, Brock-Utne JG. Human subthalamic 
neuron spiking exhibits subtle responses to sedatives. Anesthesiology. Aug 2011;115(2):254-264. 
36. 
Chernik DA, Gillings D, Laine H, et al. Validity and reliability of the Observer's Assessment of 
Alertness/Sedation Scale: study with intravenous midazolam. J Clin Psychopharmacol. Aug 
1990;10(4):244-251. 
37. 
Mahon P, Greene BR, Greene C, Boylan GB, Shorten GD. Behaviour of spectral entropy, spectral 
edge frequency 90%, and alpha and beta power parameters during low-dose propofol infusion. 
Br J Anaesth. Aug 2008;101(2):213-221. 
38. 
Moran A, Bar-Gad I, Bergman H, Israel Z. Real-time refinement of subthalamic nucleus targeting 
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2006;21(9):1425-1431. 

ICF_001.pdf: 
Study #: 2016-1420 
Version: 2/5/2020  
 
Page 1 of 8 
University of Wisconsin-Madison 
Consent to Participate in Research 
and 
Authorization to Use Protected Health Information for Research 
 
Study Title for Participants: DBS Sedation Study 
 
Formal Study Title: Effects of anesthesia drugs on neuronal activity in the basal 
ganglia and thalamus during deep brain stimulation electrode implantation surgery 
Lead Researcher: Corey A. Amlong, MD (608) 263-8100 
 
Where Lead Researcher works: University of Wisconsin-Madison, School of Medicine 
and Public Health, Department of Anesthesiology 
 
 
 
____________________________________ __________________________ 
Subject name 
 
 
 
 
MR# 
 
Invitation 
We invite you to take part in a research study about the effects of commonly used 
sedative drugs (propofol, remifentanil and dexmedetomidine) on the activity of cells in 
an area of the brain that is used as a target for deep brain stimulation (DBS) surgery. 
We are inviting you because you are already scheduled to have surgery to implant a 
DBS electrode as treatment for your condition. As part of the DBS surgery, a process 
called ‘electrical mapping’ of the brain is typically done to make sure that the electrode 
is placed in the best location. We hope to see if the sedative changes activity in the 
targeted brain areas.  
The purpose of this consent and authorization form is to give you the information you 
need to decide whether to be in the study. It also explains how health information will be 
used for this study and requests your authorization (permission) to use your health 
information.  Ask questions about anything in this form that is not clear. If you want to 
talk to your family and friends before making your decision, you can. Once we have 
answered all your questions, you can decide if you want to be in the study.  This 
process is called “informed consent.”   
 
 
 
 


Study #: 2016-1420 
Version: 2/5/2020  
 
Page 2 of 8 
 
Why are we doing this study? 
The purpose of this research study is to find out whether sedative drugs change brain 
cell activity in the target brain area during deep brain stimulation. This may help us learn 
how to use sedative drugs without affecting electrical mapping of the brain that takes 
place during DBS surgery.  If we can identify a sedative drug that does not affect cell 
activity in the target region, we will be able to routinely use sedation during mapping and 
increase patient comfort during deep brain surgery. 
Surgery for deep brain stimulation (DBS) is a procedure in which a pacemaker is placed 
in the brain to treat neurologic and psychiatric diseases. This surgery involves placing a 
stimulating electrode in specific brain areas (for each disease there is a specific brain 
target that is used to obtain optimal treatment results). In order to give the best 
treatment with the fewest side effects, the electrode needs to be placed in precisely the 
right location. In many medical centers, including at the University of Wisconsin Hospital 
and Clinics (UWHC), a process called ‘electrophysiological mapping’ is used during the 
surgery to find that precise location in the brain. This mapping is done by passing small 
electrodes through the target brain area to record activity of the cells in this region. The 
surgical team can tell where to place the electrode based on the type of cell activity they 
record.  
Sedative drugs (sleeping medications) such as propofol, remifentanil and 
dexmedetomidine are often used in brain surgery where the patient needs to be awake 
during certain parts of the surgery, and in cases where light sedation may be used to 
keep the patients partially awake. But it is unclear if they change the activity in the target 
brain area during mapping for DBS electrode placement. 
Some medical centers do not give patients any sedative drugs during DBS surgery 
because they are concerned that this medication might change the activity in the target 
area, which might make it harder to pinpoint the exact best location to place the 
electrode. Other medical centers use sedation, but stop it 10-15 minutes before the 
mapping procedure begins. This allows the patient to be awake, which makes the cell 
activity easier to identify, so it might be easier for the surgical team to tell what the best 
location is for implanting the electrode. Having no sedation during mapping can cause 
anxiety or discomfort in patients. At UWHC, we decide on the use of sedation before the 
mapping procedure based on the patient’s condition and surgeon’s preference.  Some 
patients get sedation before the mapping procedure, and some patients do not get 
sedation. If sedation is used, it is stopped 10-15 minutes before the mapping procedure 
begins. After the mapping procedure is over, sedation may be started again for the 
remainder of the procedure. 


Study #: 2016-1420 
Version: 2/5/2020  
 
Page 3 of 8 
This study is being done at the University of Wisconsin-Madison (UW-Madison).  It is 
anticipated that 70-180 people will participate in this study at UW-Madison. 
Funding for this study is provided by the UW-Madison Department of Anesthesiology.  
 
 
What will I do in this study? 
If you decide to participate in this research study, you will have your planned DBS 
surgery just like it usually is done at UW-Madison, except that, instead of being awake 
throughout the entire electrical mapping part of the surgery, you will be sedated for 30-
40 minutes during the last mapping session.  During the last mapping session of the 
surgery, we will sedate you using one of the three study sedatives (propofol, 
remifentanil or dexmedetomidine) and measure the effect of the study drug on the 
activity of the cells of the target area. This research-related sedation will add 30-40 
minutes to the deep brain stimulation procedure.  When we are done measuring the cell 
activity, we will return to the usual way that we do this surgery, which means you will be 
awake for the rest of the mapping, and you will receive standard of care sedation for the 
closure if your physician decides that sedation during closure is right for you.  
How we will use your protected health information (PHI)  
 
Protected health information, also called PHI, is information about your physical or 
mental health that includes your name or other information that can identify you, like 
your date of birth or medical record number. To do this study, we will use the following 
kinds of PHI: 
• Results of tests or procedures done as part of the study 
• Things you tell the researchers about your health 
• Information currently in your medical records as well as information added to 
your medical records during the course of this study. This information could 
include your medical history including your disease type and how long you’ve 
had it, your main symptoms, and medications that you take. We will get this 
information from your health care providers, such as University of Wisconsin 
Hospital and Clinics and UW Health. 
 
 
How long will I be in this study? 
 
You will be part of the study for about 30-40 minutes during your routine DBS surgery.   
 
 


Study #: 2016-1420 
Version: 2/5/2020  
 
Page 4 of 8 
 
How is being in this study different from my regular health care? 
 
People with your condition usually are brought out of sedation and are awake during the 
electrical mapping portion of the surgery.  If you take part in this study, the main 
difference between your regular care and the study is that you will be sedated for 30-40 
minutes during the last mapping session of the DBS surgery using one of the three 
study sedatives (propofol, remifentanil or dexmedetomidine) to measure the effect of the 
study drug on the activity of the cells of the target area. 
 
This study is not part of your health care.   
 
Do I have to be in the study?  What if I say “yes” now and change my 
mind later? 
 
No, you do not have to be in this study. Taking part in research is voluntary.  This 
means that you decide if you want to be in the study.  If you decide now to take part, 
you can choose to leave the study at any time.   
 
If you decide not to take part in the study, or if you choose to leave the study, your 
choice will not affect any treatment relationship you have with healthcare providers at 
UW-Madison, UW Health or any affiliated organizations, or any services you receive 
from them.  No matter what decision you make, and even if your decision changes, 
there will be no penalty to you. You will not lose medical care or any legal rights. 
 
Your authorization for researchers to use your protected health information (PHI) will 
last until the research study is done.  However: 
● You can choose to take back your authorization for researchers to use your 
health information.  You can do this at any time before or during your 
participation in the research.  
● If you take back your authorization, information that was already collected may 
still be used and shared with others, but the researchers will no longer be able 
to collect NEW information about you.   
● If you take back your authorization, you will not be able to take part in the 
research study. 
● To take back your authorization, you will need to tell the researchers by 
writing to the Lead Researcher, Dr. Corey Amlong, at Department of 
Anesthesiology, UW School of Medicine and Public Health, 600 Highland 
Avenue, B6/319 3272 CSC, Madison, WI 53792-3272. 
 
 


Study #: 2016-1420 
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Page 5 of 8 
What are the risks? 
There is a risk that your information could become known to someone not involved in 
this study. 
Participating in the study will lengthen the 3-5- hour surgery by 30-40 minutes.  You will 
be sedated during the research procedures.  The additional time that you will be 
sedated for the study may slightly increase the risks of the DBS implantation procedure. 
The sedative drugs used for the study may cause slow heartbeat, low blood pressure, 
temporary high blood pressure, slow breathing, your breathing may stop temporarily, 
you may have airway obstruction, or a drop in your blood oxygen level.  The drug 
remifentanil can cause muscle rigidity. There is a rare risk that propofol emulsion may 
get contaminated with bacteria and cause severe infection if improperly treated or 
stored. 
Researchers may decide not to give the study sedative and to take you off the study if 
you have very low blood pressure or other issues that would put you at higher risk of 
side effects. 
All the sedative drugs used in this study (propofol, remifentanil or dexmedetomidine) 
have been used successfully for this operation in regular clinical settings (outside of a 
research study). However, these drugs may change brain cell activity in different brain 
areas, which could make it harder for us to find the best spot to place the electrode. In 
order to reduce the chances that this interference will happen, we will give the drug only 
during the last mapping session, after the surgeon has found the target area for the 
electrode location. We will not move the electrode while you receive the drug. Then we 
will begin mapping again only after the drug effects are over. 
 
Will being in this study help me in any way? 
 
Being in this study will not help you directly.  But your participation in the study may 
benefit other people in the future by helping us learn more about how to perform 
sedation without affecting the electrical mapping of the brain. 
 
This study is not a substitute for your regular medical care. You should continue to see 
your regular medical providers. 
 
 
 


Study #: 2016-1420 
Version: 2/5/2020  
 
Page 6 of 8 
 
Will being in this study cost me anything? 
 
There will be no cost to you for any of the study activities or procedures. If you need 
treatment for side effects while you are on the study, you or your insurance will need to 
pay for this treatment.  
 
Will I be paid or receive anything for being in this study? 
 
We will not pay you to take part in this study or pay for any out of pocket expenses 
related to your participation, such as travel costs. 
 
What happens if I am injured or get sick because of this study? 
 
If you are injured or get sick because of this study, medical care is available to you 
through UW Health, your local provider, or emergency services, as it is to all sick or 
injured people. If it is an emergency, call 911 right away or go to the emergency room. 
For non-emergency medical problems, contact your regular health care provider. 
Here are some things you need to know if you get sick or are injured because of this 
research:  
• If the sickness or injury requires medical care, the costs for the care will be billed 
to you or your insurance, just like any other medical costs.  
• Your health insurance company may or may not pay for this care. 
• UW-Madison and UW Health do not have a program to pay you if you get sick or 
are injured because of this study. 
• By signing this consent form and taking part in this study, you are not giving up 
any legal rights you may have. You keep your legal rights to seek payment for 
care required because of a sickness or injury resulting from this study.  
 
How will the researchers keep my research information confidential?  
 
We have strict rules to protect your personal information and protected health 
information (PHI).  We will limit who has access to your health information, your name, 
address, phone number, and other information that can identify you.  We will also store 
this information securely.  We may publish and present what we learn from this study, 
but none of this information will identify you directly without your permission.  
 
However, we cannot promise complete confidentiality. Federal or state laws may permit 
or require us to show information to university or government officials responsible for 
monitoring this study.   
 


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Version: 2/5/2020  
 
Page 7 of 8 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as 
required by U.S. Law. This website will not include information that can identify you. At 
most, the website will include a summary of the results. You can search this website at 
any time. 
 
Who at UW-Madison can use my information? 
• Members of the research team  
• Offices and committees responsible for the oversight of research 
• Personnel who schedule or perform medical tests or procedures, handle 
accounting and billing, or do other tasks related to this study 
Who outside the UW-Madison may receive my information? 
 
• The U.S. Food and Drug Administration (FDA) 
 
Will information from this study go in my medical record? 
 
Some of the information that we collect about you for this study will be put in your 
medical record. This includes information about the procedures performed in the 
hospital, such as the anesthesia used during the procedure, and measurements of 
the cell activity in the target area in your brain. Both you and your UW Health 
providers will be able to see these results.   
 
Authorizing the research team to use your PHI means that we can release it only to 
the people or groups listed above, and only for the purposes described in this form.  
However, once your health information is released outside UW-Madison or UW 
Health it may not be protected by privacy laws and might be shared with others.   
 
Also, if ALL information that can identify you is removed from the health information 
collected in this study, then it is no longer PHI and this authorization will no longer 
limit how the remaining information can be used. This means the information could 
be used or shared for reasons other than the ones described in this form, such as a 
research study about another kind of disease. It also means that the information 
could be shared with researchers working at institutions that are not listed above. 
 
 
 


Study #: 2016-1420 
Version: 2/5/2020  
 
Page 8 of 8 
What if I have questions? 
 
If you have questions about this research, please contact the Lead Researcher, Dr. 
Corey Amlong, at (608) 263-8100. If you have any questions about your rights as a 
research subject or have complaints about the research study or study team, contact 
UW Health Patient Relations at 608-263-8009.  The Patient Relations Representatives 
work with research subjects to address concerns about research participation and assist 
in resolving problems. 
 
Agreement to participate in the research study 
 
You do not have to sign this form. If you refuse to sign, however, you cannot take part in 
this research study. 
 
If you sign the line below, it means that: 
● You have read this consent and authorization form. 
● You have had a chance to ask questions about the research study, and the 
researchers have answered your questions.    
● You want to be in this study. 
● You give authorization for your protected health information to be used and 
shared as described in this form. 
 
 
 
 
______________________________________________________________________ 
Printed Name of Subject 
 
 
 
 
Signature of Research Subject 
 
 
 
                                Date                                    
 
 
 
 
 
 
______________________________________________________________________ 
Signature of Person Obtaining Consent and Authorization                           Date  
 
 
 
**You will receive a copy of this form**