Scalar Closed Loop Intraoperative Study

The investigator will measure DBS local evoked potentials (DLEPs) and/or local field
potentials (LFPs) together with motor symptoms (tremor and/or bradykinesia) in response to
deep brain stimulation (DBS). The study will be conducted in the operating room at Duke
University Medical Center. Additional operating room costs will be covered by institutional
resources at Duke. The study will be performed on subjects who are undergoing implantation of
the DBS system during an awake, stereotactic procedure for PD.

The subject group will only include patients undergoing a DBS implant procedure for PD. The
surgical procedure will proceed as needed for treatment of Parkinson's disease (PD),
including implantation of the DBS electrode (one into STN or dual electrodes into STN and
GPi/GPe) into the targeted regions of the brain. For this research, subjects will receive
temporary (~45 min) percutaneous extensions to the DBS electrode(s) and DBS lead cannula
after implantation. These temporary extensions will connect to both our Duke stimulation and
recording system or the Medtronic RC+S test recording system, alternating as needed, to allow
recording and direct comparison of neural DLEP responses and/or LFPs using the two different
stimulation/recording systems. Details of the stimulation and recording system are provided
in the Study Interventions section. After the study is completed, the second DBS electrode
(if placed) and the temporary percutaneous extensions will be removed. Then, the ordinary
clinical conduct of the procedure will continue for treatment of the patient's movement
disorder.

The investigator will measure tremor and/or bradykinesia in persons with PD during DBS.
Subjects will be familiarized with and able to practice the evaluation tasks before
preparation for surgery. Further, they will be asked to discontinue use of dopaminergic
and/or anti-tremor medications overnight prior to the study (as is the clinical routine), to
reduce variability of motor symptoms due to the time course of medications. The investigator
will conduct evaluations using unilateral stimulation, with the limb contralateral to the
side of stimulation used for measurement of motor symptoms. Subjects may also be asked to
rate any side effects that they experience on a 0 - 10 scale.

Contacts on the subject's DBS electrode will be used for stimulation and recording. The four
DBS contacts are designated as 0-1-2-3 in the ventral-dorsal direction. For monopolar
stimulation, a single contact will be used for cathodic stimulation (1- or 2-) and a
conductive pad will be placed on the subject's skin, outside of the sterile field, to serve
as the return electrode. The recording contacts will be two other contacts on the DBS lead.
For bipolar stimulation, DBS pulses will be applied between two electrode contacts, and the
recording contacts will be the two remaining free contacts. The stimulus waveform will be a
charge-balanced biphasic pulse, with charge restricted to values below the limit set by the
manufacturer, 30 µC/cm2. Another conductive pad will be placed on the subject to serve as the
recording reference. For subjects undergoing the DBS implantation surgery, the DBS lead
cannula or a surgical retractor normally placed at the cranial incision site may also be used
as the recording reference or return electrode.

In subjects with tremor-dominant PD, the investigator will record both the tremor and DLEP
and/or LFP responses from the DBS electrode. Several trials will be conducted with different
stimulation amplitudes, frequencies (≤185 Hz), temporal patterns, and contact configurations.
The stimulation amplitude will be less than that identified to be uncomfortable to the
subject or that generates side effects, as determined by a neurologist and/or neurosurgeon
during the initial testing phase following implantation. The different stimulation parameters
will be delivered in randomized order, and the subject will be blinded to the parameters.
Measurements will be made during 2-minute trials, in which stimulation will be off for the
first minute of the trial, and on for the remaining minute. At 30 s into both the off
(baseline) and on phases of the trial, tremor will be measured for 20 s. The neural activity
will also be measured from the electrode during both the off and on phases. The total amount
of time necessary for data collection will be about 45 minutes.

Tremor will be measured using an accelerometer taped to the back of the subject's hand, and
with the wrist extended such that the hand is parallel to the forearm. The elbow may either
be supported or unsupported, depending on which induces greater tremor (determined prior to
any trials in each subject). Tremor as measured by an accelerometer correlates well with
clinical tremor rating scales [Elble et al, 2006].

In subjects with Parkinson's disease who do not have dominant tremor symptoms, the
investigator will record both bradykinesia testing responses and DLEP and/or LFP potentials.
Several trials will be conducted with different stimulation amplitudes, mean frequencies
(≤185 Hz), temporal patterns, and contact configurations. The maximum amplitude delivered
will be determined as described as above. The different stimulation parameters will be
delivered in randomized order, and the subject will be blinded to the parameters.
Measurements will be made in 10-minute trials, in which stimulation will be off for the first
five minutes of the trial, and on for the remaining five minutes. At approximately 90, 210
and 250 s into both the off (baseline) and on phases of the trial, bradykinesia will be
measured for 20 s. The neural activity will also be measured from the electrode during both
the off and on phases of the trial. The total amount of time necessary for data collection
will be about 45 minutes.

For bradykinesia measurements, the subject will be instructed to press alternately the right
and left buttons of a computer mouse with the index and middle finger of their hand as
rapidly and regularly as possible. Bradykinesia will be measured as the timing of alternating
finger presses, a validated test of bradykinesia [Taylor-Tavares et al., 2005].

Before DBS surgery, the subject's baseline pathological motor symptoms may be assessed in the
pre-operative setting, to familiarize the patient with the task ahead of the implant
procedure. Tremor or bradykinesia will be measured using the previously-described
accelerometer measurement or the mouse click task, respectively. This task will take about 5
minutes, and will be performed in the DBS-off condition. No sedation will be administered
until after this has been completed.

Following DBS surgery, the subject's pre-operative MRI and post-operative high-resolution CT
scans may be used to determine the location of DBS electrode contacts within the brain.
Placement of the electrode during DBS implant surgery will not be altered by the research
study.

Inclusion Criteria:

- Parkinson's disease (PD) patients who are scheduled to already undergo the planned
deep brain electrode placement for treatment of their movement disorder at Duke
University Medical Center.

- Able to understand the study and consent form, and interested in proceeding with
research during the invasive brain surgery to receive a DBS system for treatment of
PD.

Exclusion Criteria:

- Inability to execute the motor tasks during the study.