Expert Review of Medical Devices
ISSN: (Print) (Online) Journal homepage: https://www.tandfonline.com/loi/ierd20
Device profile of the percept PC deep brain
stimulation system for the treatment of
Parkinson’s disease and related disorders
Joohi Jimenez-Shahed
To cite this article: Joohi Jimenez-Shahed (2021) Device profile of the percept PC deep brain
stimulation system for the treatment of Parkinson’s disease and related disorders, Expert Review of
Medical Devices, 18:4, 319-332, DOI: 10.1080/17434440.2021.1909471
To link to this article: https://doi.org/10.1080/17434440.2021.1909471
© 2021 The Author(s). Published by Informa
UK Limited, trading as Taylor & Francis
Group.
Published online: 05 Apr 2021.
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EXPERT REVIEW OF MEDICAL DEVICES
2021, VOL. 18, NO. 4, 319–332
https://doi.org/10.1080/17434440.2021.1909471
DEVICE PROFILE
Device profile of the percept PC deep brain stimulation system for the treatment of
Parkinson’s disease and related disorders
Joohi Jimenez-Shahed
Movement Disorders Neuromodulation & Brain Circuit Therapeutics, Neurology and Neurosurgery, Icahn School of Medicine at Mount Sinai,
New York, USA
ABSTRACT
ARTICLE HISTORY
Introduction: Several software and hardware advances in the field of deep brain stimulation (DBS) have
been realized in recent years and devices from three manufacturers are available. The Percept™ PC
platform (Medtronic, Inc.) enables brain sensing, the latest innovation. Clinicians should be familiar with
the differences in devices, and with the latest technologies to deliver optimized patient care.
Areas covered: In this device profile, the sensing capabilities of the Percept™ PC platform are
described, and the system capabilities are differentiated from other available platforms. The develop­
ment of the preceding Activa™ PC+S research platform, an investigational device to simultaneously
sense brain signals and provide therapeutic stimulation, is provided to place Percept™ PC in the
appropriate context.
Expert opinion: Percept™ PC offers unique sensing and diary functions as a means to refine ther­
apeutic stimulation, track symptoms and correlate them to neurophysiologic characteristics. Additional
features enhance the patient experience with DBS, including 3 T magnetic resonance imaging compat­
ibility, wireless telemetry, a smaller and thinner battery profile, and increased battery longevity. Future
work will be needed to illustrate the clinical utility and added value of using sensing to optimize DBS
therapy. Patients implanted with Percept™ PC will have ready access to future technology
developments.
Received 4 January 2021
Accepted 24 March 2021
1. Introduction
Deep brain stimulation (DBS) is the surgical standard of care
for patients with movement disorders such as Parkinson’s
disease (PD), essential tremor and dystonia whose symptoms
are inadequately controlled with usual therapies [1], with the
most common use being in the management of advanced PD.
PD is characterized by motor symptoms such as tremor,
bradykinesia and rigidity [2]. The mainstay of medication man­
agement is with levodopa, which is highly effective in control­
ling motor symptoms, but is associated with development of
motor complications [3]. Such motor complications, including
wearing off effects and levodopa-induced dyskinesias, increase
in frequency and severity with advancing disease [4], and can
become more problematic than the primary motor features
themselves. Additionally, patients frequently experience gait
disturbances as the disease progresses along with increasing
impairment in quality of life. DBS can control bothersome
motor complications and refractory tremor, and has proven
efficacy in improving quality of life [5,6].
Essential tremor (ET) is more common than PD, but is less
often treated with DBS despite multiple robust lines of evi­
dence favoring long-term sustained efficacy [7]. It is typically
considered when patients have tried and failed multiple med­
ication management options for tremor, which otherwise
interferes with activities of daily living and quality of life
[6,8]. ET is estimated to affect over 4% of the population
KEYWORDS
Brain sensing; deep brain
stimulation; local field
potentials; movement
disorders; parkinson’s
disease
over the age of 40 years [9], and up to 30–50% of patients
do not respond to the most common medications used to
treat it [10]. Dystonia is a condition whose main feature is
sustained muscle contractions producing an abnormal pos­
ture, which can be quite heterogeneous in manifestations
and etiology [11]. DBS is typically considered when dystonia
is the main source of disability and affects quality of life, and
has not responded to oral treatments or botulinum toxin
injections [6].
Although DBS has established efficacy for managing motor
symptoms in these disease states when applied to the right
patient at the right time, there remain several limitations to
standard DBS delivery paradigms. First, DBS is applied con­
tinuously, which may contribute to stimulation-induced side
effects [12] or adverse consequences of medication reduction
[13], or to complex phenomena such as habituation of symp­
tom control [14]. Second, the process of DBS programming
can be lengthy as it is largely performed on a trial and error
basis [12,15], though there is increasing recognition of the
role of physiology and imaging to guide programming para­
meter selection, including more efficient identification of the
optimal therapeutic contact [16,17]. Third, the energy
demands of continuous stimulation and the inclusion of new
technical capabilities are increasingly difficult to balance with
the energy supplied in a reasonably sized and efficient pulse
generator without requiring recharging, and have led to
CONTACT Joohi Jimenez-Shahed
Joohi.jimenez-shahed@mountsinai.org
Movement Disorders Neuromodulation & Brain Circuit Therapeutics, Neurology
and Neurosurgery, Icahn School of Medicine at Mount Sinai, Mount Sinai West, 1000 10th Avenue, Suite 10C, New York NY 10019, USA
© 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/),
which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way.
320
J. JIMENEZ-SHAHED
system. Safety, battery longevity, and future considerations
will also be discussed.
Article highlights
●
●
●
●
™
Percept PC is the first commercially available device capable of
sensing brain signals (local field potentials, LFPs) while simulta­
neously delivering stimulation.
BrainSense technology contained within the Percept PC DBS
platform can be configured by clinicians to track LFP frequency
bands of interest up to 100Hz and provides the opportunity to
correlate these brain signals with symptoms reported by patients.
Brain sensing is a tool that is not currently associated with any
therapeutic claims, but evidence suggests the potential for clinical
utility, including future closed loop DBS, in the treatment of patients
with movement disorders such as Parkinson’s disease.
Additional system capabilities included in the Percept PC platform
enhance the patient experience with DBS, including 3T magnetic
resonance imaging compatibility, wireless telemetry, a smaller and
thinner battery profile, and increased battery longevity. Software
upgrades can be used to unlock new or expanded capabilities as
they become available.
™
™
™
increased frequency of battery replacement procedures
[18–20].
There has been a marked increase in the past two decade
in our understanding of the neurophysiologic markers under­
lying symptoms of movement disorders that are treated with
DBS, accompanied by the development of DBS technologies
that can be used to both record and modulate these markers
[21]. Local field potentials (LFPs) represent the aggregate
activity of a population of neuronal elements [22] and can
be recorded using both the implanted micro- and macroelectrodes used during DBS surgery and therapy [23,24]. LFP
analysis has provided important insights into the pathophy­
siology of movement disorders and our understanding of
medication and DBS benefits. In PD, bradykinesia and rigidity
correlate with beta band (8–30 Hz) activity, and the degree of
improvement in these symptoms following levodopa or sti­
mulation in the STN correlates with the magnitude of beta
band suppression [25]. Gamma band (31–200 Hz) and high
frequency oscillation (>300 Hz) power recorded in either brain
target in PD patients increases following dopaminergic treat­
ment [26,27], and an increase in gamma power may be seen
during levodopa-induced dyskinesia [28]. In essential tremor,
beta frequency oscillations (8–27 Hz) in the ViM are correlated
with tremor frequency measured peripherally by surface EMG
[29]. Dystonia is characterized by higher power in the 3–12 Hz
frequency range in the GPi, and correlation between LFP
power and dystonic muscle activity has also been demon­
strated [30]. These disease states are increasingly recognized
as network disorders with abnormal synchronization through­
out the cortical-basal ganglia-thalamocortical circuit. For
example in PD, phase amplitude coupling (PAC) between the
beta band oscillations and broad band gamma activity has
been shown within the motor cortex, within the STN, and
between the STN and motor cortex [31–33]. Such coupling is
diminished by levodopa and DBS.
This device profile will review the specifications and func­
tionality of the Percept™ PC, the first commercially available
DBS platform capable of in vivo sensing. A market overview
will provide context for the enhancements included in this
2. Body of the review
2.1. Overview of the market
DBS devices and platforms from multiple manufacturers are
currently available for commercial use, with specific indica­
tions that may vary by geographic region (Table 1). While
each device has specific attributes and some unique features,
the basic principles of stimulation remain identical. The goal is
to apply a discreet electrical field within specific nodes of the
pathologic network responsible for disease manifestations, in
a manner that regularizes neuronal patterns and prevents
transmission of pathologic bursting or oscillatory signals [34].
In movement disorders, the most common DBS targets are the
subthalamic nucleus, the globus pallidus interna, and the
ventral intermediate nucleus of the thalamus.
The process of DBS programming entails shaping the field
of stimulation within that target nucleus in order to engage
the neuronal elements that will lead to symptom reduction,
while avoiding spread of current to those in surrounding
regions that may cause side effects [35]. The tools available
for field optimization within each manufacturer’s DBS platform
are what differentiates them, representing not only a broad
array of features including electrode design, range of stimula­
tion parameters available, and advanced field shaping tools,
but also innovative capabilities such as LFP sensing and lead
visualization software (Table 2). Additional characteristics such
as magnetic resonance imaging (MRI) compatibility, and the
size and recharge ability of the implantable pulse generators
(IPG) are further distinguishing features, though they do not
directly affect programming.
Potential advantages of lead visualization are the opportu­
nity to use an anatomic approach to complex field shaping
and for the individualization of a patient’s therapeutic stimula­
tion parameters, as well as improved efficiency of program­
ming sessions [42]. On the other hand, LFP recordings have
the potential to inform electrode placement during surgery,
identify the likely therapeutic contact, detect motor fluctua­
tions and other clinical states, and serve as a control variable
for closed loop stimulation [43]. The availability of co-existing
features such as new lead and IPG designs, the widened range
of stimulation parameters, and other advanced field shaping
tools enhance the ability to effectively apply these innovative
features in clinical practice [44].
While these technological advances provide greater pro­
gramming capabilities for clinicians and the possibility of datadriven and individualized approaches to programming opti­
mization, the individual systems or features have not been
compared from an efficacy, efficiency or cost-effectiveness
standpoint. There are no evidence-based recommendations
for use of individual devices in specific patient populations.
Decisions related to device selection are determined by
a combination of factors including access to the devices within
the health system, clinician preference or experience, and
patient preference [45].
™
™
™
™
™
™
™
™
™
Vercise Genusd
PD – bilateral STN or GPi
●
PINS MEDICAL
OUS
ROW
Japan only
China only
Infinity
● Clinical applications include PD,
Vercise PC & Gevia
Vercise Genus
tremor, dystonia
● PD – unilateral or bilateral STN or GPi or ● PD – unilateral or bilateral STN or GPi
● PD – unilateral or bilateral STN or
thalamus
GPi
● Tremor – thalamic stimulation for ET or PD
● Disabling tremor – unilateral or bilateral ● Dystonia – unilateral or bilateral STN or GPi ● Tremor – thalamic stimulation for
ViM
ET or PD
● Dystoniac – unilateral or bilateral STN
● Dystonia – unilateral or bilateral
or GPi
STN or GPi
™
™
Vercise Gevia
PD – bilateral STN
or GPi
●
Vercise PC, Gevia and Genusd
PD – unilateral or bilateral STN or GPi
● Tremor – thalamic stimulation for ET or PD
● Dystonia – unilateral or bilateral STN or GPi
●
™
Vercise PC
PD – bilateral STN
or GPi
●
BOSTON SCIENTIFIC
PD = Parkinson’s disease; ET = essential tremor; STN = subthalamic nucleus; GPi = globus pallidus interna; ViM = ventral intermediate nucleus of the thalamus; US = United States; EU = European Union; OUS = outside United
States; ROW = rest of world
a
approved under a humanitarian device exemption; chronic, intractable (drug refractory) primary dystonia, including generalized and/or segmental dystonia, hemidystonia, and cervical dystonia (torticollis), in patients seven
years of age or above
b
intractable, chronic dystonia, including primary and secondary dystonia for patients who are at least 7 years old
c
includes Neural Navigator software
d
Japan does not specify laterality; Australia – bilateral; Brazil – unilateral or bilateral
e
Japan does not specify laterality; Australia – unilateral; Brazil – unilateral or bilateral
f
Japan does not specify laterality; Australia – unilateral or bilateral; Brazil – bilateral
NOTES
™
Infinity
PD – bilateral STN or GPi
● Tremor: unilateral or bilateral ViM
●
ABBOTT
Activa & Percept
(see below, OUS)
PD – bilateral GPi or STN
● Tremor (ET or PD) – unilateral or
bilateral ViM
● Dystonia – unilateral or bilateral GPi
or STN
●
™
Activa & Percept
PD – bilateral GPI or STN
● Tremor (ET or PD) – unilateral ViM
a
● Dystonia – unilateral or bilateral
GPi or STN
●
MEDTRONIC
OTHER Japan, Australia, Brazil
Activa & Percept
d
● PD – GPi or STN
e
● Tremor (ET or PD) – ViM
f
● Dystonia – GPi or STN
EU
US
Table 1. Commercially available deep brain stimulation platforms and their indications by geographic region.
EXPERT REVIEW OF MEDICAL DEVICES
321
322
J. JIMENEZ-SHAHED
Table 2. Tools and design features for stimulation field shaping and their implications.
Tool/Design
Description and Implications
feature
Lead and/or IPG Segmented contacts
Allows axial current steering away from regions causing side effects, or toward fiber
design
tracts that are relevant to clinical improvement; single segment activation widens the
therapeutic window compared to omnidirectional stimulation
Independent current
Caps the total amount of current and distributes portions of the current independently
control to each
through 2 or more contacts, independent of changes in impedance; allows for axial
contact
and longitudinal current steering
Independent frequency Allows individual frequencies to be programmed on each lead or contact that is
control
connected to the same IPG
Range of
Pulse Width <60µsec
Pulse width affects the intensity of the field of stimulation; lower pulse width widens the
stimulation
therapeutic window
parameters
Programming
software
Decision support tool*
Advanced field
shaping tools
Interleaving, or multistim set
BrainSense
Visualization
SureTune
Hyperpolarizes membranes immediately below the electrode, but elicits action
potentials at a distance from the electrode via the return current, potentially
mitigating stimulation side effects
A specific frequency range of LFP signals can be recorded simultaneously while
delivering stimulation, can be monitored in relation to stimulation adjustment, and
can be correlated with patient reported events, such as medication intake or clinical
symptoms
VTA models represented in relation to the lead and relative to an anatomic atlas, with
the possibility of manual adjustment of anatomic regions
VTA models represented in relation to the lead and relative to an anatomic atlas
VTA models and lead location in relation to patient-specific anatomy
™
™
™
™
GUIDE
GUIDE XT,
STIMVIEW
†
™ XT
™
[36]
Infinity
Vercise
[37]
Vercise
[38]
Visual representations of stimulation responses, occurrences of stimulation-induced
[36]
symptom relief and side effects; facilitates clinician review and selection of optimal
stimulation parameters
A current fractionalization approach that rapidly alternates multiple stimulation sets at [37]
a shared frequency, but can have other different stimulation parameters (PW and
Amp); allows complex field shaping
Anodic stimulation
LFP Sensing
Reference(s) Platforms
[39]
®
™
™
™
™
™
™
™
Activa™
Percept™
Infinity™
PINS
Vercise™
Infinity
Vercise
Percept
Infinity
Vercise
PINS
Infinity
Vercise
™
[46]
Percept
PINS
[36]
Activa
[42]
[40,41]
™
™
Vercise™
Vercise™
IPG = implantable pulse generator; LFP = local field potential; PW = pulse width; Amp = amplitude
*Infinity software = Informity ; Vercise software = Neural Navigator
†
GUIDE XT and STIMVIEW XT are not currently available in the US market
™
™
™
™
™
2.2 Introduction to the Percept™ PC DBS platform
The Medtronic Percept™ PC DBS device [46] is the first commer­
cially available platform for patients with movement disorders
that is capable of in vivo brain sensing. All other DBS devices
deliver electrical stimulation without recording, while Percept™
PC does both. The system, like all other DBS systems, is comprised
of a DBS electrode, extension wire and IPG (Figure 1).
Accompanying non-implanted hardware includes a clinician pro­
gramming tablet, communicator and a patient controller (Figure
2). Electrical current is generated in the neurostimulator (IPG) and
travels via the extension wire to the DBS lead and into the
targeted tissue. One or two DBS electrodes can be connected to
the dual channel IPG. The power source for the IPG is a hybrid
combined silver vanadium oxide primary cell, which has implica­
tions for the ability to reliably predict when battery replacement
will be needed [47]. The Percept™ PC IPG is compatible with
Medtronic lead models 3387 and 3389 (used for movement
disorders and epilepsy), lead model 3391 (used for psychiatric
disorders), and extension model 37,086. The lead models differ in
terms of length and spacing of the contacts.
2.2.1. BrainSense™ technology
Sensing functions in Percept™ PC are accomplished using
BrainSense™ technology, by measuring LFPs using the contacts
adjacent to the stimulating contact (Figure 3). LFPs represent the
aggregate electrical activity of the group of neurons surrounding
the recording contact [22]. A monopolar stimulation configura­
tion is required in order to record these brain signals because it
enables a geometrically symmetric sensing configuration around
the stimulating contact, thereby improving common mode rejec­
tion of the stimulus artifact [44]. The Percept™ PC IPG is
embedded with patented software for real-time LFP signal pro­
cessing and analysis, which are in turn stored on the IPG for later
download by the clinician. The sensing noise floor is <300 nano­
volts per root Hertz (nV/rtHz) and the input sensing range is
0.55–400 microvolts root mean square (µVrms). With implanted
leads in place, a survey of LFP activity can be conducted. This
‘BrainSense survey’ is conducted with stimulation OFF and gen­
erates a graph of the differential in LFP signal between any two
contact pairs (Figure 4). It takes about 90 seconds to generate this
data, which is automatically processed via fast Fourier transform
and presented as LFP magnitude (µVp, microvolts peak) vs. fre­
quency (Hz) from each of the contact combinations (6 per hemi­
sphere). This survey allows the clinician to determine if any signal
is detectable and from which contact pairs. With a low pass filter
of 100 Hz, the Percept™ IPG is able to record signals in the delta,
theta, alpha, beta, and low gamma ranges [44].
A ‘signal test’ is then performed, during which an impedance
check (to exclude recording pairs where a short or open circuit is
present) and artifact check (to exclude electrocardiogram and
motion artifacts) occur using the contact combinations where
simultaneous stimulation and sensing can occur (Figure 3). The
system will display any LFP peaks that are present, and automati­
cally select the largest peak that is in the beta or gamma frequency
range, with power >1.1 (µVp). The clinician can examine the power
and frequency of any other LFP peaks that may be present, and
ultimately identify the frequency signal of interest to be tracked
EXPERT REVIEW OF MEDICAL DEVICES
323
™ PC implantable pulse generator has a volume of 33 cm3 and mass of 61 g. Its dimensions are 68 mm x 55 mm x 11 mm. image provided by
Figure 1. The Percept
Medtronic, Inc.
over time. Signals with lower power (≤1.1 µVp) are more difficult to
track. Absence of a suitable or expected signal can be related to
electrode positioning, medication state, artifacts, or abnormal
impedances. All data is sampled at 250 Hz in the time domain
with two low pass filters at 100 Hz, one high pass filter at 1 Hz and
another high pass filter that can be configured by the clinician to
be at 1 Hz or 10 Hz. The signal is transformed to the frequency
domain and the power is detected for display.
LFP signals can be recorded in two scenarios – out-of-clinic,
and in-clinic. Out-of-clinic recordings are captured between
square wave pulses and displayed as an average power of
10 minute epochs in the ‘Timeline’ view of the programming
tablet (Figure 5). The recorded frequency band of LFP activity
is approximately 5 Hz wide surrounding the band selected by
the physician (for example, with a selected frequency of 20 Hz,
the system may record the LFP signal in the 18–23 Hz range).
Data from out-of-clinic recordings can only be viewed when
the patient returns to clinic and the clinician programming
tablet is connected via telemetry to the patient’s IPG. Up to
60 days of data can be stored, after which the oldest data is
overwritten.
Patients can be asked to participate in annotating this
data using the ‘Events’ function. A 30-second snapshot of
LFP data is taken directly after a patient marks an event
that is predetermined by the clinician. Examples of clinically
relevant events include ‘took medications’, ‘dystonia epi­
sode’, or ‘dyskinesia’, and can be identified and/or selected
at the discretion of the clinician and patient (Figure 2). Up to
four types of events can be identified for annotation, and up
to 400 snapshots can be stored (200 per hemisphere). Events
can also be marked and time stamped without LFP snapshots
(up to 900 events) for later review by the clinician upon
telemetry connection in clinic. The events will be displayed
in a timeline or summary format along with corresponding
LFP recordings.
Another feature of the BrainSense™ technology is the abil­
ity to evaluate the dynamics of the LFP band of interest over
time, referred to as setting ‘LFP thresholds’. Once the patient is
at a stable therapeutic setting, and LFP bands of interest are
identified to fluctuate in response to stimulation levels, LFP
thresholds can be set (Figure 6). This allows the clinician to set
reference points of LFP magnitude to track them over time. In
324
J. JIMENEZ-SHAHED
™
Figure 2. The Percept PC patient controller. the first panel shows the therapy status. the second panel shows the different stimulation groups programmed in to
the device, which the patient can select as needed. The third panel shows the customized events selected for the patient to mark through the day as needed. Image
provided by Medtronic, Inc.
™
Figure 3. Sensing configurations in the Percept PC platform are shown in (3a) stimulation can be provided at contact 1 with sensing at contacts 0–2, at contact 2
with sensing at contacts 1–3, or at contacts 1 and 2 with sensing at contacts 0–3. in this signal test, the system has identified peak beta band activity at 22.46 Hz on
contact 1 (3b), 13.67 Hz on contact (3c), and 15.63 Hz on contacts 1 and 2 (3d). the strongest beta power is in contact 1 (3b) which is selected as active therapy to
be clinically programmed. The 5 Hz band of LFP activity around 22.46 Hz (3b) will be passively sensed and the LFP magnitude of 3.36 indicates a strong signal for
passive sensing. image provided by Medtronic, Inc.
this scenario, stimulation amplitude is used as an actuator to
influence the LFP for measurement purposes [48]. A low
amplitude is identified where the signal of interest is of
greater magnitude, and the corresponding LFP power is cap­
tured as the ‘upper LFP threshold’. A higher stimulation ampli­
tude (that does not elicit side effects) is identified where the
signal of interest has lower magnitude, and the corresponding
LFP power is captured as the ‘lower LFP threshold’. Once these
threshold recordings are enabled, passive sensing out-of-clinic
will yield data that can be visualized in graphical format as
percentage of time spent where the LFP power is above,
below or between these thresholds. In the case of beta band
tracking in PD, these data may indicate the proportion of time
a patient spends in the ‘symptomatic’ (beta power is stronger,
above the upper threshold) or ‘treated’ (beta power is weaker,
below the lower threshold) states.
EXPERT REVIEW OF MEDICAL DEVICES
™
325
™
Figure 4. The BrainSense survey performed on the Percept PC platform in a patient with Parkinson’s disease treated with left STN DBS, captured when OFF
medications. This function shows the LFP frequency range measured at six different contact combinations (listed on the left side). The highlighted sensing channel, 0
to 3 (white line), shows a peak in the beta frequency range at 20.51 Hz and with a magnitude of 1.15. Beta peaks at the same frequency are seen in other sensing
channels but with a lower magnitude.
™
Figure 5. The ‘timeline’ view of the Percept PC platform in an unmedicated patient with Parkinson’s disease treated with left STN DBS. Figure (5a) shows the
results of passive LFP sensing in the band of interest during a 24-hour period on 13 November 2020. The orange line at the bottom indicates that stimulation was
OFF during this period. (5b) shows the LFP magnitude in the band of interest during a 24-hour period on 28 November 2020. the button in the top right corner
indicates that stimulation was ON, and the orange line at the bottom shows that stimulation was titrated by the patient just before 12:00pm without resulting
change in LFP magnitude. (5c) shows that on 19 November 2020, the patient marked an episode of toe curling at 9:13am. the inset shows the LFP snapshot across
a range of frequencies for the 30-second time period after the event was marked.
In-clinic LFP activity can be visualized using the ‘Streaming’
view. Here the clinician can view the tracked LFP power in real
time from both hemispheres (if there are two electrodes in
place and configured for sensing) and can track any changes
in the LFP that may result from stimulation adjustment or
during examination tasks or other activities requested by the
clinician (Figure 7). This data, along with all out-of-clinic LFP
sensing and diary information retrieved during an in-clinic
session can be exported to a JavaScript Object Notation
(JSON) file for offline analysis.
DBS programming using the Percept™ PC DBS device is
accomplished in a similar fashion to programming using
326
J. JIMENEZ-SHAHED
™
Figure 6. Capturing LFP Thresholds and the LFP chart. LFP thresholds are set in the BrainSense setup activity and LFP charts are visualized in the ‘events’ tab of
the clinician programmer. (6a) shows the amplitudes used to set LFP thresholds for chronic passive sensing in the left STN. The upper threshold is set using an
amplitude of 1.2 mA (solid teal line), which produced incomplete clinical benefit for the patient. The LFP magnitude at that amplitude is set as the upper threshold
(dotted teal line). The lower threshold is set using an amplitude of 2.8 mA (solid yellow line), which was just below the level at which side effects were experienced.
The LFP magnitude at that amplitude is set as the lower threshold (dotted yellow line). (6b) shows the LFP chart based on this dual threshold sensing over 4 days of
recordings. The proportion of time in a 24-hour period spent with actual LFP magnitude above the upper threshold, below the lower threshold, or between
thresholds is indicated by the colored blocks.
Figure 7. In this ‘Streaming’ view, the top panel shows the LFP power in the selected band in real time while the bottom panel shows the trends in LFP power since
the beginning of the streaming session. In addition, both panels show that LFP thresholds have been set (as described in Figure 6) – the green dotted line for the
upper threshold and yellow dotted line for the lower threshold. In this snapshot, stimulation at 3.1 mA, 60 µsec and 130 Hz (right side of the screen) is associated
with LFP magnitude that usually falls below the lower threshold, indicating suppression of the band of interest. No stimulation changes were made during this
streaming session, as indicated by the level line adjacent to the label ‘mA’ in both panels. however, stimulation can be adjusted by the clinician to observe for any
effects on LFP magnitude. Image provided by Medtronic, Inc.
Medtronic’s previous Activa™ platform with some exceptions
related to differences in the range of options that are avail­
able. For example, Activa™ devices can be programmed in
either constant current or constant voltage mode, whereas
Percept™ PC devices are restricted to current mode (Table
3). The step size in terms of amplitude titration is more refined
with Percept™ PC devices, where increments of 0.05 mA can
be used for current strength titration from 0 to 12.5 mA, after
which a 0.1 mA step size is available, through 25.5 mA of
current. The range of pulse widths available for programming
is wider with Percept™ PC (20–450µsec that can be titrated in
10µsec steps, vs. 60–450µsec for Activa™ devices) as is the
range of frequencies (2–250 Hz vs. 30–250 Hz for Activa™
devices in constant current mode). Stimulation can be imple­
mented with or without sensing. Telemetry sessions lasting 1
h (including streaming) are estimated to reduce IPG longevity
by one day [48]. Continuous passive sensing in the out-ofclinic setting requires much less energy than telemetry. In an
IPG with a 5-year estimated longevity (based on stimulation
parameters and other factors), for each month that continuous
EXPERT REVIEW OF MEDICAL DEVICES
327
Table 3. IPG specifications and range of programming parameters for different deep brain stimulation platforms.
Pulse width
(µsec)
Frequency
(Hz)
0–25.5 mA
20–450
2–250
No
2 sets of 8
0–25.5 mA (current mode) or 0–10.5 V (voltage
mode)
0–12.75 mA
0.1–20 mA
0–25.0 mA (current mode) or 0–10.0 V (voltage
mode)
0–12.0 mA
60–450
2–250
Yes
20–500
10–450
30–450
2–240
2–255
2–250
No
Yes
Yes
40–1000
1–333
Yes
2 sets of 8 (PC, RC) or
1 set of 8 (SC)
2 sets of 8
1 set of 8 or 2 sets of 8
2 sets of 4 (dual channel) or 1 set of 4 (single
channel)
1 set of 4
Amplitude (mA or V)
™
™
Infinity™
Vercise™
PINS
Percept
PC
Activa
Neuropacea
Rechargeable
IPG?
Contact Connections
IPG = implantable pulse generator; PC = primary cell; RC = rechargeable; SC = single channel
a
stimulation is delivered in bursts of duration 10 msec to 5 seconds
passive sensing is turned on, the corresponding reduction in
longevity is estimated to be 5.4 days [49].
2.2.2. Additional specifications
Additional specifications in the Percept™ PC represent improve­
ments upon the Activa™ platform. The system is conditionally
compatible with 3 T MRI scanners. Clinicians can review system
components within the clinician programmer to determine MRI
eligibility and then configure the ‘MRI mode’ for the patient. In this
mode, the stimulation is switched to a bipolar therapy group that
allows it to remain active during scanning, and once enabled,
patients can switch into this mode using their own controller,
and back to therapeutic stimulation after the scan is complete.
During programming sessions, wireless telemetry allows more
freedom of patient movement to assess symptom changes in
response to adjustments. The IPG itself is 20% smaller and 20%
thinner than the Activa™ PC IPG and has more rounded corners to
enhance patient comfort (Figure 1). The IPG itself, as previously
mentioned, is manufactured to allow real-time prediction of
remaining battery life, and can realize a 15% increase in longevity
over the Activa™ PC IPG without BrainSense™ technology usage.
With median energy use in a typical patient with PD and up to
2 months of BrainSense™ usage, the IPG is predicted to last over
5 years before requiring replacement. Lastly, software upgrades
can be used to release new or expanded capabilities once they
become available, without need for a new system to be implanted.
Future additions to the Percept™ platform are anticipated to
include a directional lead and a rechargeable IPG.
2.2.3. Safety, contraindications and cost-effectiveness
There are no new safety concerns regarding the Percept™ PC
DBS device, which carries the same contraindications, warn­
ings and precautions as other DBS devices manufactured by
Medtronic, Inc., and which are detailed in the ‘Information for
Prescribers’ manual [50]. Data security is ensured by both
application-level and tablet-based encryption [46]. LFP trans­
mission uses the same encrypted Medtronic propriety teleme­
try as all other telemetry with the implanted device [51].
Further protections for the therapy applications on the clin­
ician programmer are provided by anti-tampering and antireverse engineering capabilities [52]. There are no contraindi­
cations to sensing but the use of sensing to inform clinical
decision making remains unestablished. There are no costeffectiveness data for the Percept™ PC DBS device.
2.3. Clinical profile and post-marketing findings
There are no clinical studies on Percept™ PC devices to date.
Medtronic’s research program with the Activa™ PC+S (primary
cell plus sensing) platform was used as the supporting evi­
dence for approval of Percept™ PC devices. The Activa™ PC+S
is a chronically implanted, fully internalized but investigational
LFP sensing system designed for use in humans in the context
of clinical research protocols. The prototype of the Activa™ PC
+S was a bi-directional brain machine interface that was
intended to simultaneously sense meaningful brain signals in
the presence of therapeutic stimulation, and was first devel­
oped utilizing an existing neurostimulator [53]. It was estab­
lished on the premise that a variety of brain diseases will have
a detectable biomarker encoded in LFP activity that can be
used as a control signal for closed loop stimulation. This
prototype was further developed and studied in an in vivo
model to modulate the circuit of Papez [54]. In this study,
a biomarker was identified and mapped into classifier and
control-policy algorithms that were stored on the device, in
order to continuously titrate stimulation amplitude to achieve
the desired network effect. Further effort was then undertaken
to eliminate stimulation artifact from the recorded signals in
order to optimize sensing and algorithm performance, such
that the system could chronically detect seizure activity using
a classification algorithm and adjust stimulation on the basis
of its output [44], thereby providing the initial proof of con­
cept of closed loop DBS.
The Activa™ PC+S was first tested in non-human primates
to detect movement-related changes in cortex over physio­
logically relevant frequency bands with a detectable signal
for 24 months, suggesting utility in the evaluation of neuro­
stimulation effects in the long term [55]. When implanted in
five non-human primates with experimentally-induced par­
kinsonism, the Activa™ PC+S demonstrated the ability to
record dynamic changes in LFPs related to different clinical
states, such as at rest, and during passive joint manipulation
and reaching behavior, and concurrent to deep brain stimu­
lation [56]. This device was developed as an investigational
yet translational research platform to be used in order to
enable the process of biomarker discovery and control algo­
rithm development and protoyping, with the eventual goal
of creating a fully developed closed loop neuromodulation
system [54].
Various LFP characteristics are well-recognized to relate to
symptoms of PD [22] and can be used to differentiate medication
328
J. JIMENEZ-SHAHED
‘ON’, medication ‘OFF’, tremor, dyskinesia, and sleep states.
Although the majority of work has been done in the STN, some
data regarding LFP features in the GPi and ViM of PD patients is
also described [57]. Less information is available about the LFP
features in essential tremor and dystonia. Some investigators have
studied the utility of LFPs in informing the care of patients treated
with DBS for management of movement disorders including
intraoperative targeting [58,59] and selection of stimulation para­
meters such as the optimal therapeutic stimulation contact [16].
Studies reporting on LFP data collected from the Activa™ PC+S
system have yielded important information regarding LFP
dynamics in relation to technical difficulties [60,61], to different
actions or tasks [62,63], to time and improvement of PD motor
symptoms [63–65], to inter-individual variability and disease sever­
ity [63,66], and to varied stimulation parameters and medications
[65,67], all of which will have implications for understanding the
feasibility and long-term utility of sensing, especially as they relate
to the future possibility of closed loop DBS.
3. Alternative devices
There are no commercially available alternative sensing
devices for DBS in movement disorders. Tables 1 and Tables
2 compare the indications and capabilities of Percept™ to
those of competing DBS platforms. A research device with
similar LFP sensing capabilities is available with
a rechargeable IPG (Model G106R, Pins Medical Co., Ltd,
China) [68,69]. Published reports describe its chronic record­
ing capabilities to differentiate sleep from wakefulness [70]
and its ability to suppress STN beta band activity in PD
patients [71]. Commercially available devices from the same
company are available in China (Table 3) without sensing
capabilities. Two other systems that can record LFP signals
from externalized DBS macroelectrodes and deliver adaptive
DBS have also been described in research use [72,73]. Lastly,
the RNS® System (NeuroPace, Mountain View, CA, USA) is
a responsive stimulation system indicated for adjunctive ther­
apy in reducing partial onset seizure frequency in adults that
are refractory to two or more antiepileptic medications [74]. It
is a closed loop system that delivers programmable bursts of
stimulation upon seizure detection, with a published report in
a series of five subjects with medically refractory Tourette
syndrome (TS) in which stimulation was delivered in the
centromedian-parafascicular complex of the thalamus [75].
In this report, changes in tic symptoms were shown to corre­
late with modulation of gamma oscillations. In another report
of a single TS patient treated in the same target with the same
device [76], the control signal used for adaptive stimulation
was a spectral feature in the 5–15 Hz band, which was asso­
ciated with effective tic reduction.
4. Regulatory status
Percept™ PC is approved for use in the United States, has CE
mark approval for the European Union, and is also approved in
Japan, Brazil and Australia with indications for the treatment
of Parkinson’s disease, tremor and dystonia (Table 1). The
United States Food and Drug Administration approved
Percept™ PC as a Class III device on June 25, 2020.
5. Conclusion
As presented in this device profile, Percept™ PC builds on the
existing Activa™ clinical and research platforms to provide
both innovative technologies and general device improve­
ments to DBS. The hallmark feature is its BrainSense™ tech­
nology, which allows clinicians to select and track brain signals
(LFPs) of interest and relate them to clinical symptoms
reported by the patient. Additional device features such as
3 T MRI compatibility, wireless telemetry, IPG design and
increased longevity all have the potential to improve the
patient experience with DBS. The platform itself holds no
new therapeutic or efficacy claims, and as such does not
pose new safety concerns.
6. Expert opinion
The discovery that LFP recordings from the deep brain nuclei
that are targeted for DBS therapy in patients with movement
disorders provide informational content related to the disease
state has opened up an exciting world of research aimed at
understanding the neurophysiologic correlates of disease.
Along with this, the possibility of using these unique brain
signals to further individualize and personalize DBS therapy
through closed loop stimulation of pathologic network activity
has garnered increasing interest and dedicated investigation
over the last decade. Important steps in this process are to
understand the type and nature of the neurophysiologic bio­
markers that are present in diseased networks and how best
to modulate them with stimulation to optimize therapeutic
efficacy.
The unique development pathway for the sensing technol­
ogy contained in the Percept™ PC involved first creating
a translational research platform (the Activa™ PC+S) that was
intended to enable biomarker discovery and control algorithm
development for future closed loop stimulation. As a result of
experience gained through the Activa™ PC+S and its proto­
types, the Percept™ PC now represents the first opportunity
to observe and capture brain signals of interest in the broader
population of patients receiving DBS while also delivering
stimulation, all outside the research environment. Within the
BrainSense™ platform, the immediate benefits of brain sen­
sing and diary functions include implications for programming
and correlating symptoms with neurophysiologic features.
Using the Percept™ PC, clinicians will gain experience with
passive sensing in patients with movement disorders and gain
familiarity with how LFP signals relate to factors such as
electrode placement, medication states, stimulation, disease
characteristics, and clinical symptoms. Well-designed postmarket clinical trials will be needed to illustrate the clinical
utility and added value of using sensing to optimize DBS
therapy, and in which populations. One such study, the
ADAPT-PD trial (NCT04547712) has recently launched with
the goal of investigating an adaptive DBS algorithm for perso­
nalized therapy in PD. In this single-blind study, 100 partici­
pants implanted with the Percept™ PC device will be enrolled
and randomized to a crossover sequence of adaptive DBS
using either a single or dual threshold mode. The primary
outcome measure will be the change in duration of ON time
EXPERT REVIEW OF MEDICAL DEVICES
without troublesome dyskinesia between baseline and 1 and
2 months post-randomization.
In addition, the Percept™ PC harbors added benefits to the
care of DBS patients. Design features may improve patient com­
fort, reduce the frequency of IPG exchanges required, and may
remove obstacles to the non-DBS care of patients with move­
ment disorders (ie, the patient-enabled MRI mode with 3 T con­
ditional safety). A new controller allows patients a more intuitive
option to engage with their therapy and partner with their
treating clinician in recognizing and understanding symptoms.
Patients with existing Medtronic DBS leads can readily transition
to a Percept™ PC at the time of IPG replacement and potentially
capture its benefits, including sensing.
While the many new features in Percept™ PC represent
a major step forward in terms of tools available to clinicians
in order to optimize the care of movement disorders patients
with DBS, it is important to recognize a few of its limitations. In
newly implanted patients, capitalizing on BrainSense™ tech­
nology during post-operative management still depends
greatly on accurate electrode placement. To date, the
Percept™ PC is only able to record LFPs post-implantation,
so alternate methods need to be used to verify that
a potentially useful signal is present intra-operatively.
Second, the device only records from specific stimulation
configurations, the use of which again depends on electrode
placement, but also patient-specific disease features. For
example, when stimulation of the dorsal contact is required
in the STN for management of dyskinesia in PD,
a corresponding sensing configuration may not be possible
to achieve. Third, the Percept™ PC will only record a specified
5 Hz-wide band of LFP activity, or can portray the frequency
band of interest as being above, below or between specified
thresholds of LFP magnitude. Interpretation of the nature of
patient-marked events may therefore depend on accurate
identification of relevant LFP bands, or when peak beta fre­
quency is being tracked, may be limited to understanding
whether they occur during medication ‘ON’ or ‘OFF’ states.
Fourth, although Percept™ PC is available for use in tremor
and dystonia patients, the LFP patterns in these disorders are
not as well described as in PD and further research is required
to understand how sensing can be used to optimize care in
these populations [77–79]. Lastly, there is increasing evidence
regarding the informational content within the high-frequency
oscillations of deep brain nuclei (i.e., LFPs occurring in the
200–450 Hz range) which can be linked to lower frequency
oscillations via phase amplitude coupling [80–82], but these
are outside the range of detection by the Percept™ PC.
As with any new technology, initial high rates of adoption
are likely to be seen as clinicians explore the potential for
value added to their practices and care of their patients.
However, there is an anticipated learning curve that will be
required for physicians to familiarize themselves with
a neurophysiologic approach to understanding disease and
DBS care which may be more time consuming. This com­
bined with the limitations of Percept™ PC in its current form
may therefore temper initial interest for some practitioners.
However, continued research efforts will progressively eluci­
date strategies for the application of brain sensing, to which
patients implanted now will have access when they become
329
fully realized. Alternately, external factors such as patient
and clinician preferences, and institutional factors may influ­
ence decisions to implant Percept™ PC devices. Renewed
interest is likely to be seen as new hardware (such as
a directional lead or rechargeable IPG) or software upgrades
with demonstrated utility become available. When a fully
closed-loop system is developed within the Percept™ plat­
form, it will require that currently implanted patients transi­
tion to a rechargeable IPG. Regardless, the promise of an
evolving menu of features available on the Percept™ PC
platform is likely to provide multiple opportunities to opti­
mize DBS care delivery and the patient experience now and
into the future.
6.1. Five-year view
Percept™ PC and its predecessor, the Activa™ PC+S, were
developed with the goal in mind of identifying disease bio­
markers that can be used in closed loop neuromodulation
systems. Closed loop DBS for movement disorders such as
Parkinson’s disease holds promise to reduce side effects and
improve efficiency while maintaining or even enhancing motor
symptom control. Several pilot studies of closed loop DBS have
already shown evidence of short-term success in small num­
bers of patients at reducing PD or tremor symptoms at lower
therapeutic current [83,84] but longer term studies in larger
patient groups will be needed. Additional work is needed to
identify whether closed loop DBS is better deployed as an ondemand therapy or with continuous modulation based on
a changing control signal, and whether that control signal
should be based on intrinsic signals such as LFPs or peripheral
ones such as wearable sensors [85]. A combination of
approaches will likely need to be available in order to address
the unique needs of individual patients. Continued innovation
across these areas is likely to result in further refinements in
DBS delivery methods and improved outcomes for patients
with movement disorders, can be applied to other disease
states or to non-motor features, and will hopefully be readily
accessible to patients with movement disorders through sim­
ple software upgrades.
Funding
This paper was not funded.
Reviewer disclosures
One peer reviewer is a shareholder of Newronika SPA. Peer reviewers on
this manuscript have no other relevant financial relationships or otherwise
to disclose.
Declaration of interest
J Jimenez-Shahed has received consulting fees from Abbott/St. Jude
Medical for service on a study advisory board. The author has no other
relevant affiliations or financial involvement with any organization or
entity with a financial interest in or financial conflict with the subject
matter or materials discussed in the manuscript apart from those
disclosed.
330
J. JIMENEZ-SHAHED
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