Effects of Stimulation Patterns of Deep Brain Stimulation

This study will be conducted in the operating rooms at Duke University Medical Center, Emory
University Hospital, University of Florida Shands Hospital or the UF Health Florida Surgical
Center. The study will be performed during surgery on subjects who are undergoing
implantation of the deep brain stimulation (DBS) system during an awake procedure, or on
subjects who are receiving surgical replacement of the implanted pulse generator (IPG) due to
depleted batteries.

Subjects will receive temporary sterile extensions to the DBS electrode. These temporary
extensions will connect to a stimulation and recording system and allow recording of neural
activity. Over the course of ~45 minutes different non-regular temporal patterns of
stimulation will be delivered unilaterally and the effects on neural activity and movement
disorder symptoms will be measured. The stimulus waveform will be a charge-balanced biphasic
pulse, with charge restricted to values below the limit set by the DBS IPG manufacturer, 30
μC/cm². After the study is completed, the temporary extensions will be removed, and the
ordinary clinical conduct of the procedure will continue for treatment of the patient's
movement disorder.

Tremor will be measured using an accelerometer in subjects with essential tremor (ET),
multiple sclerosis (MS) and tremor-dominant Parkinson's disease (PD). Bradykinesia will be
measured using a finger-tapping task on a computer mouse in subjects with Parkinson's disease
who do not have dominant tremor symptoms. Subjects will be familiarized with the motor
symptom evaluation tasks before surgery, and baseline measurements of tremor or bradykinesia
may be recorded. Further, they may be asked to discontinue use of anti-parkinsonian and/or
anti-tremor medications overnight prior to the study, to reduce variability of motor symptoms
due to the time course of medications.

No general anesthesia will be given to subjects during surgery, and the procedure will be
performed under local anesthesia to allow subjects to perform the tasks required in this
study. Further, no sedation will be given to subjects receiving a replacement IPG, which can
cause minor discomfort or anxiety in some patients. Subjects undergoing surgery for electrode
implantation will receive monitored anesthesia care (MAC), in which sedation will be
administered as needed, such that subjects are still responsive and pathological motor
symptoms (tremor or bradykinesia) are present.

Following 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.
However, participation in the study will not modify imaging procedures needed for standard
care, and placement of the electrode during DBS implant surgery will not be altered by the
research study.

There will be no additional costs to subjects as a result of being in this study. Additional
operating room costs will be covered by institutional and/or grant resources.

Inclusion Criteria:

- Diagnosis of Parkinson's Disease (PD), Essential Tremor (ET) or Multiple Sclerosis
(MS)

- Scheduled to undergo Deep Brain Stimulation (DBS) electrode implant or implanted pulse
generator (IPG) replacement surgery

- Neurologically stable

- Able to understand the study and consent form

Exclusion Criteria:

- Inability to execute the motor tasks during the study

- Inability to tolerate withholding anti-parkinsonian and/or anti-tremor medications

- Clinically ineffective DBS