published: 12 April 2021
Frontiers in Neurology | www.frontiersin.org 1April 2021 | Volume 12 | Article 595741
Mount Sinai Hospital, United States
Rukmini Mridula Kandadai,
Nizam’s Institute of Medical
National Taiwan University
This article was submitted to
a section of the journal
Frontiers in Neurology
Received: 17 August 2020
Accepted: 01 March 2021
Published: 12 April 2021
Li J, Mei S, Jia X and Zhang Y (2021)
Evaluation of the Direct Effect of
Bilateral Deep Brain Stimulation of the
Subthalamic Nucleus on
Levodopa-Induced On-Dyskinesia in
Front. Neurol. 12:595741.
Evaluation of the Direct Effect of
Bilateral Deep Brain Stimulation of
the Subthalamic Nucleus on
Levodopa-Induced On-Dyskinesia in
Jiping Li 1, Shanshan Mei 2, Xiaofei Jia 1and Yuqing Zhang1
1Beijing Institute of Functional Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China, 2Department of
Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China
Objective: This study aimed to evaluate the direct anti-dyskinesia effect of deep brain
stimulation (DBS) of subthalamic nucleus (STN) on levodopa-induced on-dyskinesia in
Parkinson’s disease (PD) patients during the early period after surgery without reducing
the levodopa dosage.
Methods: We retrospectively reviewed PD patients who underwent STN-DBS
from January 2017 to October 2019 and enrolled patients with levodopa-induced
on-dyskinesia before surgery and without a history of thalamotomy or pallidotomy. The
Uniﬁed Dyskinesia Rating Scale (UDysRS) parts I+III+IV and the Uniﬁed Parkinson’s
Disease Rating Scale part III (UPDRS-III) were monitored prior to surgery, and at the
3-month follow-up, the location of active contacts was calculated by postoperative
CT–MRI image fusion to identify stimulation sites with good anti-dyskinesia effect.
Results: There were 41 patients enrolled. The postoperative levodopa equivalent daily
dose (LEDD) (823.1 ±201.5 mg/day) was not signiﬁcantly changed from baseline (844.6
±266.1 mg/day, P=0.348), while the UDysRS on-dyskinesia subscores signiﬁcantly
decreased from 24 (10–58) to 0 (0–18) [median (range)] after STN stimulation (P<
0.0001). The levodopa-induced on-dyskinesia recurred in stimulation-off/medication-on
state in all the 41 patients and disappeared in 39 patients when DBS stimulation was
switched on at 3 months of follow-up. The active contacts which correspond to good
effect for dyskinesia were located above the STN, and the mean coordinate was 13.05
±1.24 mm lateral, −0.13 ±1.16 mm posterior, and 0.72 ±0.78 mm superior to the
Conclusions: High-frequency electrical stimulation of the area above the STN can
directly suppress levodopa-induced on-dyskinesia.
Keywords: deep brain stimulation, dyskinesia, Parkinson’s disease, subthalamic nucleus, motor complications
Li et al. Direct Anti-dyskinesia Effect of STN-DBS
Dyskinesia is one of the most troublesome symptoms of
advanced Parkinson’s disease (PD), often induced by long-term
dopaminergic treatment (levodopa-induced dyskinesia, LID).
Following the deﬁnition in the Uniﬁed Dyskinesia Rating Scale
(UDysRS) (1), LID is divided into two types: (1) on-dyskinesia
and (2) oﬀ-dystonia. On-dyskinesia, which refers to the choreic
and dystonic movements that occur when medicine is working
(1), is present in 70–80% of PD patients who experience
Deep brain stimulation (DBS) of subthalamic nucleus (STN)
could reduce the required levodopa dosage for symptom control
(3,4), and the majority of researchers opine that the anti-
dyskinesia eﬀect of STN stimulation is mainly due to the
signiﬁcant postoperative reduction of levodopa medication (5–
8), which is an indirect inhibition. However, Kim et al. found
that LID was reduced following STN-DBS in PD regardless
of whether the levodopa dosage was reduced (9), and by
developing a multiple regression model to predict postoperative
dyskinesia scores, Mossner et al. found that STN-DBS improved
dyskinesia beyond levodopa reduction (10). In addition, some
data suggested that STN-DBS may also have direct anti-
dyskinesia eﬀect (9,11–15). In our center, we switch on the
stimulation within 3 days after DBS implantation without
levodopa dosage reduction till the ﬁrst follow-up at 3 months
postoperatively, which provides an opportunity to evaluate the
direct anti-dyskinesia eﬀect of STN-DBS.
The DBS strategies could be diﬀerent for on-dyskinesia
and oﬀ-dystonia: stimulating the sensorimotor region could
signiﬁcantly improve cardinal parkinsonian symptoms (tremor,
rigidity, and bradykinesia) (16) and also signiﬁcantly improve
oﬀ-dystonia (6,17), while stimulating STN itself could not
suppress on-dyskinesia (11) and even induce dyskinesia (18–
20); therefore, this study only focuses on levodopa-induced
on-dyskinesia. We retrospectively reviewed the changes of on-
dyskinesia without medication reduction during the ﬁrst 3
months postoperatively to evaluate the direct anti-dyskinesia
eﬀect of STN-DBS on levodopa-induced on-dyskinesia and tried
to identify stimulation sites with good anti-dyskinesia eﬀect.
We retrospectively reviewed the clinical records of 146
PD patients who underwent STN-DBS by the same two
neurosurgeons (Zhang and Li) at the Xuanwu Hospital of Capital
Medical University from January 2017 to October 2019. Patients
who suﬀered from preoperative levodopa-induced on-dyskinesia
and with a score of Uniﬁed Parkinson’s Disease Rating Scale
(UPDRS) (part IV, item 32) ≥1 were included, and patients
who had a history of thalamotomy or pallidotomy, which
may suppress LID, were excluded. Eventually, 41 patients were
included in this study. Of the 41 patients, 23 were female and
18 were male. Their mean age was 62.7 ±8.2 years. The mean
duration of disease before the surgery was 10.4 ±3.7 years.
Forty patients presented with peak-dose dyskinesia and 1 patient
(P2) with square-wave dyskinesia. Thirty-three patients had
bilateral on-dyskinesia and 8 patients had unilateral dyskinesia
at baseline (Supplementary Table 1). All these patients met the
MDS diagnostic criteria of PD and had bilateral STN-DBS
implantation. The study was approved by the Ethics Committee
of Xuanwu Hospital of Capital Medical University.
DBS Surgical Procedure and Coordinates
of DBS Electrode
DBS electrode implantation was performed under local
anesthesia. The CRW stereotactic frame (Radionics, Webster,
New York, USA) was applied under local anesthesia, then
CT scanning was performed. The CT images were fused
immediately with the preoperative magnetic resonance imaging
(MRI; Siemens 3.0 Tesla, Sonata, Germany) images through
the StealthStation Surgical Navigation System (Medtronic,
Minneapolis, Minnesota, USA), and the coordinates of the
target and the entrance trajectory were deﬁned on stereotactic
MRI images by directly visualizing the STN. Intraoperative
microelectrode single needle recording (MER) using the
Microdrive system (Alpha Omega Engineering, Nazareth, Israel)
was performed, starting from 10 mm above the target. After the
precise localization of the target point, DBS electrodes (Model
3389, Medtronic, Minneapolis, MN, USA) with four contacts
were placed in such a way that the metal tip of the DBS electrode
was located 2–3 mm above the ventral STN border, and the
contacts were positioned and labeled as follows: contacts 0 and 1,
inside the STN; contact 2, dorsal margin of the STN; and contact
3, above the STN. Then, the DBS electrodes were tunneled
and connected to a rechargeable implantable pulse generator
RC, Medtronic, Minneapolis, MN, USA) implanted in
the subclavian region under general anesthesia. Postoperative CT
images were fused with the preoperative MRI images to conﬁrm
the ﬁnal position of the electrode metal tip and the trajectory
of the DBS electrode and to calculate the coordinates of each
contact, and the distance from the metal tip to the center of each
contact (distal to proximal: contact 0, contact 1, contact 2, and
contact 3) was 0.75, 2.75, 4.75, and 6.75 mm, respectively.
DBS programming was initiated within 3 days after surgery with
an initial setting of 60–90 µs/130–160 Hz/1.0–1.5 V. Patients
underwent adjustment of stimulation settings until optimal
control of the symptoms was established during hospitalization.
The adjustment strategy of DBS programming was as follows:
ﬁrstly, we used unipolar stimulation and chose the contact
which positioned at the dorsal margin of the STN as the active
contact for patients with LID and the contact inside the STN
for patients without LID; if the patient did not achieve good
control of symptoms, then it was changed to dual-contact
monopolar stimulation (a contact within the STN +a contact
above the STN); ﬁnally, interleaving stimulation was utilized,
Patients had the ﬁrst postoperative clinical assessments and
adjustment of stimulation settings and medication in the 3-
month follow-up. On the 1st day of follow-up, the stimulation
parameters were carefully screened following all contacts in
Frontiers in Neurology | www.frontiersin.org 2April 2021 | Volume 12 | Article 595741
Li et al. Direct Anti-dyskinesia Effect of STN-DBS
FIGURE 1 | LEDD changes and outcome of UDysRS and UPDRS-III. (A) LEDD: at baseline 844.6 ±266.1 mg/day, at 3 months of follow-up 823.1 ±201.5 mg/day.
(B) Violin with plots showing UDysRS (I+III+IV) scores: 24 (10–58) at baseline to 0 (0–18) at 3 months of follow-up. (C) UPDRS-III: Med-off 49.95 ±13.30, Med-on
21.03 ±11.87 at baseline; Med-off/Stim-on 20.88 ±7.68, Med-on/Stim-on 15.55 ±7.11 at 3 months of follow-up. The values are presented as mean ±standard
deviation or median (range). ****, P<0.0001; **, P<0.01; ns, non-signiﬁcant; LEDD,levodopa equivalent daily dose; UDysRS, Uniﬁed Dyskinesia Rating Scale;
UPDRS-III, Uniﬁed Parkinson’s Disease Rating Scale part III.
medication-oﬀ (Med-oﬀ ) state after at least 12 h without taking
any anti-parkinsonian medication in the morning; the contacts
and stimulation parameters were optimized to obtain maximum
clinical beneﬁt and minimal side eﬀects. After switching oﬀ DBS
for 30 min, patients took the usual ﬁrst morning dose of levodopa;
if on-dyskinesia occurred, then we switched on the DBS to test the
anti-dyskinesia eﬀect of active contacts.
Clinical Assessment and Statistical
The outcome assessments consisted of the on-dyskinesia
subscores of the UDysRS (parts I+III+IV) and UPDRS-III
before surgery and 3 months after surgery. Baseline assessments
of UPDRS-III were completed in Med-oﬀ state after at least
12 h without taking any anti-parkinsonian medication, and
UPDRS-III of the Med-on state was the maximum improvement
following a dose of levodopa equal to 150% of the patient’s
usual ﬁrst morning dose. At the 3-month follow-up, all scores
were assessed in DBS stimulation-on (Stim-on) condition on
the 2nd day following the same dose of levodopa as baseline.
The clinical improvement was computed as ([(Prescores –
Postscores)/Prescores] ∗100%). Student’s t-test or the Wilcoxon
signed-rank test was used to determine whether there was a
signiﬁcant diﬀerence between the clinical scale scores at baseline
and at 3 months follow-up. Statistical analysis was performed
with SPSS (version 20.0; SPSS Inc, Chicago, IL). P<0.05 were
considered statistically signiﬁcant.
The postoperative levodopa equivalent daily dose (LEDD) (823.1
±201.5 mg/day) was not signiﬁcantly changed from the baseline
(844.6 ±266.1 mg/day, P=0.348) (Figure 1A). There were 39
patients without levodopa dosage reductions, and 2 patients (P38,
P40) with the addition of amantadine and a reduction of LEDD
for persistent dyskinesia after surgery.
However, the UDysRS on-dyskinesia subscores signiﬁcantly
reduced after STN-DBS stimulation [from baseline 24 (10–58)
to 0 (0–18), median (range), P<0.0001; Figure 1B); 36/41
(87.8%) patients scored 0 on UPDRS-IV item 32, and only
5 patients (P27, P28, P30, P38, P40) continued to experience
persistent dyskinesia, and their dyskinesia was observed in
four experimental conditions with stimulation and medication
on and oﬀ subdivided into the following (Table 1): 1 patient
(P27) presented with stimulation-induced dyskinesia (SID),
2 patients (P28, P30) presented with unilateral levodopa-
induced on-dyskinesia, and the remaining 2 patients (P38,
P40) experienced abnormal involuntary movements after DBS
surgery despite medication withdrawal and cessation of DBS
stimulation, which may be induced by a microlesion in the STN
due to surgery (surgery-related dyskinesia, SRD) (21). In other
words, levodopa-induced on-dyskinesia was completely relieved
in 39/41 (95%) patients.
There were a 57.5 ±14.5% improvement in UPDRS-III scores
in Med-oﬀ/Stim-on state relative to the Med-oﬀ state at baseline
(from 49.95 ±13.30 to 20.88 ±7.68, P<0.0001) and a 69.0 ±
12.4% improvement in Med-on/Stim-on relative to the Med-oﬀ
at baseline (from 49.95 ±13.30 to 15.55 ±7.11, P<0.0001)
Coordinates of Electrode and
Four electrodes were implanted deeper than planning: the left
electrode of P28, the right electrode of P30, and the bilateral
electrodes of P41 (Figures 2A–C), and the vertical coordinates
(Z-axis) of the electrode metal tip were −7.50, −7.71, −8.31, and
−7.65 mm, respectively, inferior to the midcommissural point.
P41 underwent dorsal relocation of bilateral DBS electrodes
on the 6th day postoperatively by withdrawing the left DBS
electrode 4 mm and the right electrode 2 mm (Figure 2D). The
ﬁnal coordinates of the electrode metal tip relative to the
midcommissural point are described in Table 2.
DBS programing settings are summarized in Table 2 and
Supplementary Table 1. A total of 74 STN-DBS electrodes were
programmed for levodopa-induced on-dyskinesia management,
and a complete relief of such dyskinesia was found in 72
electrodes (Figure 3A): dual-contact monopolar stimulation or
Frontiers in Neurology | www.frontiersin.org 3April 2021 | Volume 12 | Article 595741
Li et al. Direct Anti-dyskinesia Effect of STN-DBS
TABLE 1 | Body parts involved by dyskinesia.
Patients On-dyskinesia at baseline Dyskinesia at 3-month follow-up Type of
dyskinesia in Stim-on
Med-off/Stim-off Med-on/Stim-off Med-off/Stim-on Med-on/Stim-on
P27 Left upper limb – Left upper limb Left foot Left foot SID
P28 Left limbs and right upper limb – Left limbs and right
– Right upper limb LID
P30 Upper limbs – Upper limbs – Left upper limb LID
P38 Four limbs and trunk Right foot Four limbs Right foot Right foot SRD
P40 Neck, four limbs, and trunk Right foot Four limbs and trunk Right foot Right foot SRD
SID, stimulation-induced dyskinesia; LID, levodopa-induced dyskinesia; SRD, surgery-related dyskinesia.
FIGURE 2 | 3D illustration for the localization of electrode contacts (Model
3389, Medtronic) by lead-DBS software: (A) patient 28, (B) patient 30, and (C)
patient 41 (initial implantation): the left electrode of P28, the right electrode of
P30, and the bilateral electrodes of P41 were implanted deeper than planning,
and the most dorsal contact (contact 3) was located inside the STN; on the
other hand, the right electrode of P28 and the left electrode of P31 were
implanted as planning: contacts 0 and 1 were located inside the STN, contact
2 was located at the dorsal margin of the STN, and contact 3 was located
above the STN. (D) patient 41 (after relocation).
interleaving stimulation (two active contacts: C+1–3– or C+0–
3– or C+0–2–) was utilized in 66 electrodes and unipolar
stimulation (C+2–) was utilized in 6 electrodes.
At 3 months follow-up, all the patients still presented
with choreatic on-dyskinesia in Med-on/Stim-oﬀ condition;
by testing the eﬀort of these 138 active contacts, we found
that the direct suppression of levodopa-induced on-dyskinesia
was achieved by the stimulation of dorsal contacts (contact
3 in 65 electrodes and contact 2 in 7 electrodes), which
were located above 1 mm inferior to the anteroposterior
commissure plane (Z= −1); the mean coordinate of these
72 contacts was 13.05 ±1.24 mm lateral, −0.13 ±1.16 mm
posterior, and 0.72 ±0.78 mm superior to the midcommissural
point, and the majority (85%) were above the anteroposterior
commissure plane (Figures 3B,C). The unipolar stimulation
(C+3–) was utilized in two electrodes (left electrode of
P28 and right electrode of P30) but failed to suppress the
TABLE 2 | Position of the electrodes and DBS settings.
Localization and DBS settings Left electrode Right electrode
Coordinates of the
electrode metal tip
relative to the
Lateral (X-axis) −11.55 ±1.22
(−8.38 to −14.05)
(−0.56 to −4.90)
(−0.74 to −4.64)
Vertical (Z-axis) −4.91 ±1.15
(−1.86 to −7.50)
(−3.65 to −7.71)
Frequency (Hz) 145.73 ±15.63
Pulse widths (µs) 85.12 ±13.25
Amplitudes (V) 2.17 ±0.38
The values are presented as mean ±standard deviation (minimum–maximum).
contralateral LID; this two contacts were located within STN
There were 55 contacts of 31 electrodes (19 patients) that
were found to induce dyskinesia (SID) (Supplementary Table 1),
which were located inside the STN. The SID was completely
relieved by changing to dorsal contact stimulation or dual-
contact monopolar stimulation in 18 patients, while 1 patient
experienced persistent SID (P27) at 3 months postoperatively.
There were four patients (P37–40) who experienced SRD:
in two patients, SRD self-resolved before 3 months follow-
up (P37, P39), while it persisted in the remaining two
patients (P38, P40). Infection of the incision occurred in one
Case Description for Special Cases
There was one patient (P41) who continued to experience
persistent bilateral levodopa-induced on-dyskinesia after DBS
stimulation by using the most dorsal contacts, even reducing
the medication from Madopar 125 mg every 4 hours(q4h)
to 62.5 mg q4h, and the coordinates of the electrode metal
tip relative to the midcommissural point were left (X,
Y,Z−12.35, −5.74, −8.31 mm) and right (10.85, −2.59,
Frontiers in Neurology | www.frontiersin.org 4April 2021 | Volume 12 | Article 595741
Li et al. Direct Anti-dyskinesia Effect of STN-DBS
FIGURE 3 | Distribution of electrode and active contacts. (A) Distribution of 72 electrodes which got good LID management, and all DBS electrodes were mapped to
the right side to allow for direct comparison. The X-coordinate is positive toward the lateral. Unipolar stimulation in 6 electrodes (yellow plots are active contacts) and
double monopolar stimulation or interleaving stimulation in 66 electrodes (red and blue plots are active contacts); red plots and yellow plots were the contacts
corresponding to good anti-dyskinesia effect, while blue plots were the contacts corresponding to good effect for PD motor symptoms but without anti-dyskinesia
effect; black plots were inactive contacts. (B) Distribution of the 72 active contacts which showed successful anti-dyskinesia effect, 2D diagram in an anterior view;
(C) Z-coordinate of the 72 active contacts which showed successful anti-dyskinesia effect: 0.72 ±0.78 mm (−1∼2.36 mm). The values were presented as mean ±
standard deviation (minimum–maximum); 61/72 (85%) were above the anteroposterior commissure plane (Z=0).
−7.65 mm). Bilateral DBS electrodes were dorsally repositioned
under a local anesthetic on the 6th day postoperatively by
withdrawing the left DBS electrode 4 mm and the right
electrode 2 mm, and there was sustained relief of dyskinesia
using the most dorsal contacts without levodopa reduction
At 3 months follow-up, there were ﬁve patients (P27, P28,
P30, P38, and P40) who continued to experience persistent
dyskinesia: SRD for two patients (P38, P40) and it ﬁnally self-
resolved between 4 and 6 months postoperatively; SID for
one patient (P27) and it was completely relieved after 1 year
postoperatively when his tremor became less prominent and
a good eﬀect was obtained under the SID threshold; and the
remaining two patients had unilateral levodopa-induced on-
dyskinesia (P28, P30), which was ﬁnally completely relieved after
In our study, from the overall level, we found that
the LEDD after surgery was not signiﬁcantly changed
from baseline, but UDysRS on-dyskinesia subscores
signiﬁcantly decreased; from the individual level, we
found that levodopa-induced on-dyskinesia recurred
in Stim-oﬀ/Med-on state and disappeared when DBS
stimulation was switched on in 39/41 (95%) patients
at the 3-month follow-up. All these ﬁndings conﬁrm
that STN-DBS stimulation can directly suppress
The key point is which speciﬁc region of STN or around
STN is responsible for the direct anti-dyskinesia eﬀect. We found
that stimulating STN itself could not suppress on-dyskinesia,
even induce dyskinesia, which is consistent with previous reports
Frontiers in Neurology | www.frontiersin.org 5April 2021 | Volume 12 | Article 595741
Li et al. Direct Anti-dyskinesia Effect of STN-DBS
(11,18–20). The active contacts which correspond to good anti-
dyskinesia eﬀect in our study were all located above 1 mm inferior
to the anteroposterior commissure plane (Z= −1), where the
dorsal margin of the STN is estimated by microrecording (4,
22). This ﬁnding suggests that stimulation above the STN can
result in direct suppression of on-dyskinesia. Several previous
studies, by superimposing the location of the electrodes onto
the Schaltenbrand–Wahren atlas (13) or using the volume
of tissue-activated models (23), had the same ﬁndings. The
above STN area is a complex area between the dorsal STN
border and the ventral thalamus (23), including the zona
incerta (24) and Forel’s ﬁeld H (25), where pallidothalamic,
pallidosubthalamic, or subthalamopallidal ﬁbers are densely
distributed (13). Stimulation of these ﬁbers may cause similar
eﬀects to pallidal DBS and, therefore, directly suppress dyskinesia
(11–14). In addition, we found the majority (86%) of these
active contacts located above the anteroposterior commissure
plane (Z=0), and the average vertical coordinate (Z-axis) was
0.72 mm superior to the midcommissural point (Z= +0.72),
which is dorsally compared with the dorsal margin of the STN
and consistent with Yoichi’s observations (12). It suggests that
the dorsal portion of above STN area may have a more deﬁnite
The anti-dyskinesia eﬀect of STN-DBS in our study is much
better than that reported in previous literature, which is mainly
due to our strategy to implant Medtronic 3389 DBS electrode
2–3 mm above compared with the conventional procedure as
described previously (26,27). STN-DBS could not achieve a
good anti-dyskinesia eﬀect probably because the DBS electrode
was implanted too deep to provide adequate coverage of the
above STN. That is what happened to the four electrodes
that were implanted deeper than planning, and two of them,
which were able to suppress dyskinesia after dorsal relocation,
conﬁrmed it also. Thus, the depth of electrode insertion for
STN-DBS is the crucial point for dyskinesia suppression. What
is more, the hot spot for optimal improvement of motor
symptoms of PD was dorsal to the center of the STN, but within
STN boundaries (22,28,29). Hence, we implanted the DBS
electrode in such a way that the metal tip of the electrode was
positioned 2–3 mm above the ventral margin of the STN, to
ensure that the contacts cover the dorsal two-thirds portion of
the STN [the motor region of the STN (30)] and above STN
area, and the clinical outcome suggests that this implantation
Also (and this is important!), we carefully observed
the relationship between dyskinesia, medication, and DBS
stimulation to subdivide the type of postoperative dyskinesia.
After STN-DBS, especially during the early postoperative period,
dyskinesia could be complicated. Besides LID, two new types
of dyskinesia came out: (1) SID (18–20), which is deﬁned as
abnormal involuntary movements that occur when stimulation
is on and disappear when stimulation is oﬀ; 46.3% (19/41) of
patients in our study developed SID, while SID was completely
relieved in 95% (18/19) of patients by adjustment of DBS
stimulation settings. (2) SRD, which persisted despite levodopa
withdrawal (Med-oﬀ) and cessation of stimulation (Stim-oﬀ)
after STN-DBS surgery, may be induced by a microlesion in the
STN and self-resolved in several weeks or months (21). Four
patients in our study suﬀered from SRD and it self-resolved
between 2 weeks and 6 months. The two types of dyskinesia
were considered transient adverse eﬀects of STN-DBS surgery,
but they usually predict a good outcome of DBS (18–21). In
our study, postoperative dyskinesia all presented choreatic
abnormal involuntary movements; since the same expression
of dyskinesia may have diﬀerent etiologies and diﬀerent
treatment strategies, it is important to subdivide postoperative
dyskinesia for the evaluation of the eﬀect of STN-DBS on a
certain type of dyskinesia and to determine an appropriate
High-frequency electrical stimulation of the area above the
STN can directly suppress levodopa-induced on-dyskinesia,
and the STN-DBS strategy for PD patients with levodopa-
induced on-dyskinesia is simultaneously stimulating both the
sensorimotor region of the STN and the area above the STN.
The depth of electrode insertion for STN-DBS to provide
adequate coverage of the above STN is the crucial point for
DATA AVAILABILITY STATEMENT
The original contributions presented in the study are included
in the article/Supplementary Material, further inquiries can be
directed to the corresponding author/s.
The studies involving human participants were reviewed and
approved by the ethics committee of Xuanwu Hospital of Capital
Medical University. The patients/participants provided their
written informed consent to participate in this study.
JL was the major contributor in writing the manuscript and
contributed to the DBS programming. SM contributed to the
diagnosis and clinical assessment of the patients. JL and YZ
contributed to DBS surgery. XJ contributed to data acquisition.
SM and YZ contributed to the manuscript editing. YZ was the
guarantor of integrity of the entire study. All the authors had
collectively poured in a lot of eﬀorts into this study, read, and
approved the ﬁnal manuscript.
YZ was supported by the Wu Jieping
Medical Foundation (320.6750.19089-78).
Frontiers in Neurology | www.frontiersin.org 6April 2021 | Volume 12 | Article 595741
Li et al. Direct Anti-dyskinesia Effect of STN-DBS
We would like to acknowledge Mr. Yubao Song for graph making
and our DBS nurse specialist Wenjie Zhang for her assistance in
the management of patients.
The Supplementary Material for this article can be found
online at: https://www.frontiersin.org/articles/10.3389/fneur.
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Conﬂict of Interest: The authors declare that the research was conducted in the
absence of any commercial or ﬁnancial relationships that could be construed as a
potential conﬂict of interest.
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Frontiers in Neurology | www.frontiersin.org 7April 2021 | Volume 12 | Article 595741