Chronic Effects of Deep Brain Stimulation on Cortical Local Field Potentials in Parkinson's Disease and Dystonia
Phase: NA
Conditions: Parkinson's Disease, Isolated Dystonia
Sponsor: University of California, San Francisco

 
 
 
Chronic effects of deep brain stimulation on cortical local field 
potentials in Parkinson’s disease and primary dystonia Study 
 
(Activa PC+S) 
 
 
 
 
NCT Number:  
NCT01934296 
 
 
 
Document Date: 
September 14, 2017 

Protocol Synopsis 
Title 
Chronic effects of deep brain stimulation on cortical local field potentials in 
Parkinson’s disease and primary dystonia 
Study Phase 
Phase I 
Device(s) 
Device Information:  Devices to be used in this study are grouped below 
according to FDA approval. All are Medtronic Devices. 
Investigational 
• 
Activa PC+S implantable pulse generator, Model 37604 
• 
Sensing Programmer Model 8181 for Activa PC+S 
• 
Sensing Programmer Software Model 8180 for Activa PC+S 
• 
Lead extension Model 37087 
• 
Nexus-D System 
• 
Nexus-D Application Programming Interface (API) 
Intercept Patient Programmer, model 37441Approved for other indications 
• 
Medtronic Lead Model 3391 
• 
Medtronic Resume II  paddle electrode  model 3587A 
Approved for the intended indication  
• 
N'Vision Clinical Programmer  Model 8840 
• 
Clinician Programmer Software Model 8870 
• 
Patient Programmer Model 37642  
• 
Lead Model 3389 
• 
External Neurostimulator 37022 
• 
Lead extension model 37086 
• 
Activa SC 37603 single channel pulse generator 
Indication 
Adults with Parkinson's disease (PD) or primary generalized or segmental 
dystonia, who experience inadequate symptom relief in the setting of optimal 
medical therapy by a movement disorders neurologist, and who have been 
offered implantation of a deep brain stimulator system. 
Sponsor Contact 
Philip Starr, Ph.D., MD 
Professor of Neurological Surgery 
University of California, San Francisco 
779 Moffitt, 505 Parnassus Ave 
San Francisco, CA 94143 
Phone: 415.353.2071 
Fax:  415.353.2889 

starrp@neurosurg.ucsf.edu 
Medical Safety 
Monitor 
The medical safety monitor board (MSMB) consists of a neurologist and 
neurosurgeon outside of our home institution, who have no direct involvement 
in this study but who have expertise in implantable devices. The neurologist is 
Dr. Michael Okun at the University of Florida, Gainesville, and the neurosurgeon 
is Dr. Jeff Ojemann at the University of Washington, Seattle.    Treatment 
related adverse events assessed as definitely, probably, or possibly related to 
study procedures and either serious or unexpected, noted by any study 
personnel will be reported within 10 working days of their knowledge of the 
event to the MSMB.  The MSMB will then advise the PI on potential changes in 
procedures to improve safety, or, in the event of multiple serious adverse 
events, may invoke stopping rules.  
Treatment 
Long-term stimulation of the basal ganglia for Parkinson’s disease or primary 
dystonia 
Study Site 
University of California, San Francisco 
779 Moffitt, 505 Parnassus Ave 
San Francisco, CA 94143 
Study Design 
This is a single-center study of the neurophysiology of human movement 
disorders with two goals: 1) Assess the feasibility of chronic brain recording 
using a novel fully implantable pulse generator (Medtronic Activa PC+S), which 
has the capability of sensing and storing local field potentials (LFPs) recorded 
from implanted electrodes, in addition to providing therapeutic deep brain 
stimulation (DBS).  2)  Study acute and chronic effects of therapeutic DBS on 
cortical LFPs. Participants will also have the opportunity to participate in an 
add-on study to test practical applications of this device, such as “closed loop” 
stimulation, in which neural feedback is used to program optimal DBS settings.  
These additional studies will utilize the Nexus-D (Medtronic), which streams 
data noninvasively from Activa PC+S to an external computer in near real time. 
         Study subjects will have implanted, in addition to their standard DBS 
electrode(s), a unilateral flexible 4-contact electrode (Medtronic 3391 lead or 
3587A lead).  This lead will be advanced through the same burr hole used for 
the DBS lead implants.  This electrode array does not penetrate the brain 
surface, but rests on the surface of the motor cortex.  The cortical electrode, as 
well as the standard therapeutic DBS electrode implanted on that side, will be 
attached to a Medtronic Activa PC+S pulse generator placed in the ipsilateral 
pectoral area. On the contralateral side, for patients scheduled for bilateral DBS 
implantation, a standard therapeutic DBS electrode will be connected to a 
standard Medtronic single channel pulse generator (Activa SC).  At multiple 
time points up to 24 months post implantation, subjects will have outpatient 
visits to collect data, download cortical LFPs, and, in the add-on Nexus-D study, 
test applications of closed loop DBS. Some subjects who have signed consent 
for the Nexus-D2 substudy will have the option for data downloading and 

operant conditioning at home. The goal of the operant conditioning is to 
evaluate whether PD patient practice in modulating brain activity may lead to 
clinical improvement of PD symptoms 
Objectives 
In fifteen patients undergoing DBS implantation for PD or primary dystonia (10 
PD; 5 dystonia), we will implant a unilateral subdural cortical electrode in 
addition to the DBS electrode, and connect these to a novel implantable pulse 
generator that can store field potential data (Medtronic Activa PC+S).  At 
multiple time points post-implantation in our clinic, we will record and 
download cortical and basal ganglia LFPs on and off of DBS therapy in the 
following behavioral conditions: 
a.) rest  
b.) during a computer controlled binary choice arm reaching task  
c.) walking up and down a hallway 
Hypotheses:  
1) Long term recording  of cortical LFPS is technically feasible with  stable 
signals over 1 year, without adverse events 
2) Chronic (6 and 12 months) basal ganglia DBS alters the spectral 
characteristics of the M1 LFP (spectral power in beta and gamma bands), 
the magnitude of movement related M1 beta band change, and the 
coupling between beta rhythms and broadband gamma activity. We 
expect that in PD, DBS-induced changes will appear in early recordings 
(immediately after starting DBS), whereas in primary dystonia, cortical 
changes will be seen only after long-term DBS. 
3) DBS-induced changes in abnormal cortical oscillatory activity may predict 
the degree of DBS-induced improvement in motor function 
4)  Markers of abnormal cortical or basal ganglia oscillatory activity can help 
determine clinically effective stimulation settings. 
Patient Population 
Study subjects will be adults with Parkinson's disease (PD) or primary dystonia, 
recruited from a clinic population of patients scheduled to undergo unilateral or 
bilateral DBS implantation for amelioration of their movement disorder symptoms.   
Sample Size 
15 subjects 
Efficacy 
Assessments 
Clinical rating scales of motor function:  
For PD patients: Unified Parkinson’s Disease Rating Scale (UPDRS) parts I-IV and 
dyskinesia rating scales.  UPDRS part III will be scored on and off of 
antiparkinsonian medications. For dystonia patients:  Burke-Fahn Marsden 
Dystonia Rating Scale (BFMDRS) and Toronto Western Spasmodic Torticollis 
rating scale (TWSTRS).  
Other rating scales (all patients): Clinician Global Impression of Change (CGI-C) 
and Patient Global Impression of Change (PGI-C).   
Safety 
Assessments 
1)Physical examination at all study visits 
2) Check of pulse generator stimulation parameters, impedance measurements, 
and battery voltage at all study visits 
3) Surgical or nonsurgical protocol-defined adverse events as recorded on 
adverse events case report forms 
4) Assessment of suicidality using the Columbia Suicide Severity Rating Scale, at 
all protocol-defined outpatient visits 

5) In visits where the Nexus will be used for closed loop stimulation,  all possible 
stimulation settings are preselected by clinicians to avoid the possibility of 
producing major stimulation-induced adverse effects 

Statistical Methods and Data Analysis 
ECoG and LFP data will be analyzed in the frequency domain for mean log power in the beta and gamma 
bands, movement related changes in beta and gamma band power, and coupling between low 
frequency rhythms and broadband gamma power  (12, 20, 21). Using a repeated measures ANOVA 
statistical analysis, summary statistics for power in relevant frequency bands, movement related power 
changes, and indices of phase-amplitude coupling will be compared at different time points, different 
DBS conditions (on and off), and different disease states (PD or primary dystonia).  
 
Although the sample size is small, in each disease group we will assess the correlation between these 
brain physiology measures, and clinical instruments used to measure the motor benefit produced by 
DBS.  In particular we will ask: 1) Did the degree of cortical synchronization, as assessed by a 
quantitative index of phase-amplitude coupling (PAC) prior to starting stimulation therapy, correlate 
with the degree of benefit produced by DBS (difference between clinical ratings at 12 months on 
stimulation and baseline pre-implantation, off medication). 2) Did the magnitude of DBS-induced 
suppression of cortical synchronization (difference between PAC on-stimulation at 12 months, versus 
prior to starting stimulation therapy) correlate with the degree of benefit produced by DBS (difference 
between clinical ratings at 12 months on stimulation and baseline pre-implantation, off medication) 3) 
For the add-on study examining potential therapeutic uses of Activa PC+S: 1) Did the DBS stimulation 
settings which minimized metrics of cortical synchronization or basal ganglia synchronization, produce a 
therapeutic benefit compared with the off stimulation and off medication state; and 2) Did operant 
control of cortical or basal ganglia rhythms produce a therapeutic benefit compared with the off 
stimulation and off medication state prior to learning operant control. 
 
Since this is a pilot study of chronic cortical recording, the sample size is likely to be too small to provide 
definitive answers to all research questions.  Based on this exploratory analysis, it is anticipated that the 
next phase of the study will focus on a subset of the research aims, with 10-15 subjects per group.  
 
Sample size calculation:  This is a pilot study of a novel chronic brain recording technique. The goals are 
to assess technique feasibility, to collect pilot data that will be used to frame more detailed hypothesis 
about DBS mechanisms, and (in the add-on study using Nexus-D) to explore potential strategies for 
therapeutic use of the Activa PC+S neural interface. Thus, there is no formal sample size calculation.