Research progress in the efficacy of deep brain stimulation with different targets in Parkinson's disease

AI Xiang-bai, HUANG Xiao-gan, WANG Yi-tian, LI Jun-ju, ZHAO Jian-nong?

1.Hainan Medical University, Haikou 571199, China

2.Hainan General Hospital, Haikou 570311, China

Keywords:

ABSTRACT

Parkinson’s disease (PD) is a chronic progressive neurodegenerative disease, the main motor features include resting tremor, bradykinesia, stiffness and postural balance disorder.Non-motor symptoms include neuropsychiatric symptoms, sleep disorders, autonomic dysfunction, etc[1].Deep brain stimulation(DBS) is a stereotactic procedure in which stimulating electrodes are implanted into specific brain regions to achieve long-term highfrequency electrical stimulation for therapeutic effects.DBS can significantly improve the symptoms of PD such as tremor, rigidity,and akinesia[2].The most commonly used targets of DBS are the subthalamic nucleus (STN) and globus pallidus (GPi)[3].There is no significant difference in the improvement of PD motor symptoms between STN-DBS and GPi-DBS, and the former can reduce the amount of postoperative levodopa, while there are few studies on non-motor symptoms.This article analyzes the efficacy of nonmotor symptoms in detail.Both VIM and PSA are effective in the treatment of essential tremor (ET) and tremor dominant PD patients.This article not only makes a comparative analysis of tremor, but also analyzes the efficacy of single and bilateral targets and postoperative side effects.The cerebellopontine crural nucleus(PPN) is used to improve gait disorders and balance disorders in patients with PD.However, PPN has poor efficacy on resting tremor, stiffness or bradykinesia.There are few research targets for gait disorders and postural balance disorders at home and abroad.The PPN, STN, and GPi are innovatively compared in the study of gait disorders and postural balance disorders.Dyskinesia (LID) is the most common complication in PD patients with long-term drug treatment.There are few studies on the efficacy of LID in different targets.The clinical symptoms of PD are many and complex, and no single target can cover all the symptoms, and the effects of different targets on different symptoms are quite different.There is no consensus on the ideal target of DBS in PD patients.Only a few studies have directly compared the efficacy of STN, GPi and VIM DBS, and there are few studies on non-motor symptoms, most of which focus on motor symptoms.The purpose of this article is to provide personalized treatment basis for PD patients to select appropriate targets for DBS according to different symptoms, so as to obtain the best treatment and reduce postoperative side effects.This article reviews the efficacy of DBS at different targets in the treatment of PD.

1.Deep brain stimulation and target sites

1.1 Subthalamic nucleus (STN)and globus pallidus (GPi)

1.1.1 Tremor and rigidity

The STN is a core basal ganglia structure involved in the control of motor, cognitive, motivational, and affective functions.The tripartite subdivision hypothesis divides these functions into distinct sensorimotor, cognitive/associative, and limbic subregions based on the topography of cortical projections[4].Globopallidus pallidus(GPi) is located in the medial part of the lenticular nucleus, which is one of the important nuclei of the basal ganglia.It is named because of the sparse distribution of blood vessels and its pale color on fresh specimens[5].The globus pallidus consists of internal (GPi)and external (GPe) components.Within the GPi, there are three distinct functional areas: the posterior ventrolateral sensorimotor area, the anterior association area, and the anterior ventral limbic area.Sensorimotor regions of the GPi are commonly DBS targets for PD and dystonia[6].STN and GPi are the main targets of DBS in the treatment of PD.There is no significant difference in motor improvement between STN-DBS and GPi-DBS in the Unified Parkinson’s Disease Rating Scale Ⅲ (UPDRSⅢ) score.STN-DBS has obvious advantages in reducing the dose of postoperative anti-PD drugs, and it should be the first choice for patients with behavioral disorders caused by dopaminergic drugs[7].However, while no difference was observed in the on phase, a significant difference was seen in the off phase; STN is more effective in improving motor function during the off phase[8].For bradykinesia, STN-DBS provided 48% and 36% improvement from baseline to 6 and 12 months, respectively, whereas GPi-DBS provided 30% and 32%improvement from baseline to 6 and 12 months, respectively.For stiffness, STN-DBS provided 53% and 43% improvement, whereas GPi-DBS provided 23% and 28% improvement from baseline to 6 and 12 months, respectively.Compared with GPi-DBS, STN-DBS had greater reductions in bradykinesia and stiffness at 6 months after implantation (respectively P＜0.001 and P=0.025).There was no difference between the two groups at 12 months after implantation[9].Because there is no significant difference in motor symptom relief between STN-DBS and GPi-DBS, STN-DBS can effectively reduce the postoperative oral dose of levodopa, so STN-DBS is preferred over GPi-DBS.

1.1.2 Postural balance disorder

Levodopa had less negative effects on posture in STN-DBS patients than in GPi-DBS patients.STN-DBS patients had higher UPDRS scores than GPi-DBS, and in the off state, STN-DBS patients had worse motor signs.Although, the STN group was more affected by PD.This suggests that L-dopa replacement is more effective for posture in STN-DBS group than in GPi group[10].Patients with postural instability difficulty (PIGD) benefit least from GPi-DBS and STN-DBS, while tremor dominant motor subtypes respond better to GPi-DBS in terms of gait.In combination with levodopa, GPi-DBS seems to preserve postural instability and gait disorders better than STN-DBS[11].DBS-STN and DBS-GPi are less beneficial for postural disorders, and the choice of targets should take into account other symptoms.

1.1.3 Freezing of Gait (FOG)

FOG is a common disabling symptom of PD, which is characterized by transient inability to step or extremely short strides,usually occurring at the beginning of gait or when turning around during walking.There are differences in gait indicators between FOG episodes, and stride length is significantly reduced, with frequent leg tremors during episodes[12].Some studies have found that GPi-DBS is more effective than STN-DBS in improving PD gait.The effects of GPi-DBS on gait are different from those of STN-DBS.GPi-DBS mainly affects gait speed, while STN-DBS mainly affects stride length without changing rhythm[13].Deep brain stimulation (DBS) of GPi has consistently shown excellent and sustained motor deficit reduction.GPi stimulation resulted in a 57% reduction in medically treated dyskinesia at 12 months of follow-up, whereas STN stimulation resulted in a 21% reduction according to the Clinical Dyskinesia Rating Scale.Dyskinesia was improved in GPi (89%) compared to STN stimulation (62%)[14].FOG in the dopaminergic drug off state occurs much more often than FOG in the dopaminergic drug on state, although some FOG can even become severe as dopaminergic drugs are added.DBS of the STN with regular high-frequency stimulation can alleviate some FOG in some patients, especially those related to the drug off state,while DBS can also produce FOG in other PD patients.Compared with high-frequency stimulation (most commonly 130Hz), lowfrequency stimulation (most commonly 60 Hz) has been shown to improve FOG and other axial symptoms (for example, speech and swallowing function) in patients with bilateral STN-PD[15].A recent meta-analysis showed that both STN-DBS and GPi-DBS improved postural instability or gait dysfunction in the early stage, but by 2 years after surgery, STN-DBS patients had more severe postural and gait problems than before surgery.After DBS5, postural and gait problems worsened regardless of STN-DBS or GPi-DBS.Another 5-year follow-up of STN-DBS documented some deterioration of STN-DBS mediated effects on axial signs and aprasia[16].Both STNDBS and GPI-DBS can improve the freezing of gait in PD patients,and the latter has a better effect on freezing of gait.For PD patients with freezing of gait as the main symptom, GPi is recommended as the target, and the long-term efficacy of STN-DBS is better than that of GPI-DBS.

1.1.4 Dyskinesia (LID)

Levodopa-induced dyskinesia (LID) is the most common complication in PD patients with long-term drug therapy.LID includes a variety of different hyperactivity phenomena, including chorea, dystonia, stereotyping, and akathisia[17].Both STNDBS and GPi-DBS could control the effect of LID, but GPi-DBS was more effective than STN-DBS in the treatment of LID [the improvement rate of LID at 18 months after surgery was (96.5±5.9)% and (68.2±33.9) %, respectively, P ＜ 0.05], which was consistent with the results of previous studies.In addition, the results showed that STN-DBS and GPi-DBS could be achieved within 6 months after surgery; The LID was significantly improved and maintained stable for a long time[18].Clinical outcomes of 43 patients with preoperative LID treated with DBS targeting STN(20/43) or GPi(23/43) were retrospectively evaluated.According to the Unified Movement Disability Rating Scale, both STN and GPi groups showed significant improvement in LID compared to baseline.60.73 ± 40.29% (mean ± standard deviation) and 93.78±14.15%,respectively.In addition, GPi-DBS provided greater clinical benefit in improving movement disorders compared with STN (P ＜0.05).Compared with the GPi group, the STN group had a greater reduction in levodopa equivalent dose (43.81% vs 13.29%, P ＜ 0.05)[19].Both STN-DBS and GPi-DBS can relieve LID, and the latter is more effective, because the relief of LID in STN-DBS group is mainly mediated by the reduction of dopaminergic drugs, while GPi stimulation may provide a direct anti-dyskinesia effect.For LID caused by levodopa, STN can be selected as the target, and for LID in PD patients, GPi is recommended as the target.

1.1.5 Cognitive impairment and depression

Both cognitive impairment and depression are prone to advanced PD, and dementia affects up to 80% of patients in the late stage of the disease.Detailed evaluation shows that there is frontal lobe dysfunction even in the early stage of the disease[20].PD is associated with a relatively high incidence of emotional and cognitive dysfunction, and DBS of STN and GPi has been shown to modestly ameliorate emotional dysfunction and cognitive decline,particularly in verbal fluency tasks.Several controlled studies have provided evidence that DBS of the STN may lead to cognitive or psychiatric sequelae.However, recent meta-analyses have shown declines in psychomotor speed, memory, attention, executive function, and global cognition in patients with STN DBS.GPi-DBS resulted in less neurocognitive decline than STN-DBS[21].GPi-DBS is associated with better recovery of verbal fluency and better relief of depressive symptoms.A better quality of life was obtained using GPi-DBS.Previous studies have reported negative emotional and neurocognitive effects of DBS, particularly for STN-DBS.However,their results have great heterogeneity and controversial results.One possible explanation is that STN-DBS may easily affect nearby fibrous pathways that regulate limbic function.Therefore, GPi may be the preferred target for PD patients with depressive symptoms[22].There is controversy about the research on cognitive impairment and depression after DBS.Most literatures show that GPi has better effects than STN for patients with cognitive impairment or depression.1.1.6 Sleep

Recent studies have shown that STN-DBS improves both subjective and objective sleep measures in PD patients.After bilateral STNDBS, wakefulness after sleep onset was reduced, continuous sleep time and sleep efficiency were increased, nocturnal mobility was improved, and restless legs syndrome was improved.There was a significant improvement in nocturnal motor symptoms and overall sleep quality, but no effect on sleep fragmentation and excessive daytime sleepiness.This suggests that STN-DBS may act by reducing motor symptoms and has no significant effect on central sleep regulation.On the other hand, STN-DBS can improve nocturia,which may contribute to improved sleep quality.In this report,bilateral STN-DBS did not improve excessive daytime sleepiness or sleep behavior disorder.GPi-DBS can improve sleep quality and reduce subjective daytime sleepiness in individuals without anti-PD drug treatment.It is difficult to say whether dopaminergic drugs or GPi-DBS itself are involved in the positive effects on sleep[23].Both STN and GPi have been shown to affect the interaction between wake-sleep, and the effect may be greater for REM sleep in particular.Despite the availability of more data on STN-DBS,DBS at both sites improved objective and subjective sleep measures in PD patients.Of note, nocturnal motor symptoms appear to be significantly improved after DBS treatment, with an average Parkinsonian sleep rating scale improvement of 16% for STN and 8% for GPi[24].The STN is superior to GPi in sleep time and sleep efficiency.For patients with obvious sleep disorders, STN can be used as a target.

2.Ventrointermediate nucleus of thalamus (VIM)

2.1 Essential tremor (ET)

Deep brain stimulation of the ventral intermediate nucleus (VIMDBS) is a powerful treatment option for ET and tremor-dominant PD patients with severe, drug-refractory tremor[25].ET, also known as essential tremor, is defined as an isolated tremor syndrome consisting of bilateral action tremor of the upper limbs for at least 3 years, with or without tremor elsewhere, and in the absence of other neurological signs.After VIM-DBS stimulation, tremor was consistently improved in PD and essential tremor (ET) patients(mean improvement, 70% and 66% at 1 year, respectively; 63%and 48% after 10 years; P＜0.05).There was no significant loss of stimulation benefits over time (P＞ 0.05)[26].The control of tremor by Vim stimulation appears to worsen over time, with 73% of patients in one series experiencing an attenuated stimulation benefit within 5 years after implantation.In another long-term study, tremor reduction after DBS implantation changed from 50% at 3 years to 15% at 10 years[27].VIM-DBS also has drawbacks and is not sufficient to address other key motor features of PD.There was no improvement in UPDRS III score, stiffness, akinesia, or postural instability, although more than 80% of the benefit in contralateral tremor persisted beyond 5 years in carefully selected patients.VIMDBS can now be considered for PD patients with slow progression and mainly tremor[28].For ET or tremor dominant PD patients, VIM can be used as a target, but the long-term efficacy is decreasing.It should be noted that VIM cannot relieve other motor symptoms.

2.2 Unilateral and bilateral

Several studies have shown that unilateral VIM-DBS reduces global tremor at 12 months.With unilateral VIM-DBS, the reported overall tremor reduction ranged from 53.4% to 62.8%.Unilateral DBS significantly improved action tremor involving the contralateral upper limb, with tremor scores decreasing by 38.2% to 78.9%.In the long-term follow-up of up to 5 years, the data showed that patients with unilateral VIM-DBS had excellent reduction of action tremor in the contralateral upper limb (60.3%-75%); Bilateral VIM-DBS is safe and leads to a greater reduction in global tremor because both sides of the body are treated.Bilateral VIM-DBS can reduce the global tremor by 66%-78%.In addition, bilateral VIM-DBS showed better improvements in axial and head and neck tremor and voice tremor[29].In a recent systematic review of 40 studies, the specific reduction in overall tremor at 12 months after unilateral VIM-DBS in ET ranged from 53.4% to 62.8%; Action tremor was the most sensitive symptom, reduced by 78.9%.Bilateral stimulation has also been shown to be safe and effective for increasing (and bilateral)tremor relief (overall reduction ranging from 66% to 78%) and better control of axial and acoustic tremor[27].Unilateral VIM-DBS is not as effective as bilateral VIM-DBS in improving tremor.Therefore,bilateral VIM-DBS is recommended for the treatment of ET or tremor dominant PD patients.tremor) and voice tremor[31].Bilateral VIM-DBS can improve ET,but it also increases the risk of dysarthria and gait disorders.There is a contradiction between unilateral or bilateral VIM-DBS.

3.Cerebellopontine peduncular nucleus (PPN)

The PPN is a part of the midbrain motor area, located in the brainstem and connected to the basal ganglia and spinal cord.Ppndbs is an experimental treatment to improve gait disturbances and balance disorders in PD patients, although results have varied between surgical centers and a limited number of participants(approximately 100 PD patients had electrodes implanted in the PPN).Meta-analysis of clinical trials could summarize the effects of PPN-DBS on these symptoms and help to assess the potential role of PPN-DBS treatment in gait disorders.PPN-DBS did not significantly improve resting tremor, stiffness, or bradykinesia in any of the non-pharmacological treatments of UPDRS Part Ⅲ[32].The combination of PPN-DBS and levodopa significantly reduced the frequency of freezing episodes and falls.In addition, one study showed that unilateral or bilateral stimulation improved freezing of gait (FOG), and it seems that unilateral or bilateral PPN stimulation is effective for the treatment of FOG.As for the preferred stimulation frequency, it is generally believed that low frequency PPN is more effective, but comparative studies of high and low frequency PPN stimulation are lacking[33].PPN-DBS was effective in improving gait score of UPDRS Ⅲ-29 during drug withdrawal, but it was second only to STN-DBS and GPi-DBS.In addition, PPN-DBS also ranked last in the improvement of motor symptom scores in PD patients[10].The use of PPN is limited, mainly because it has a single effect,and it is not as effective as STN and GPi in relieving gait disorders and balance disorders, and it cannot relieve tremor, stiffness, and bradykinesia, resulting in limited use.

2.3 Side effects

The most common stimulus-induced side effects associated with VIM-DBS were dysarthria and gait disturbance.In the unilateral cohort, DBS-related dysarthria and gait impairment occurred in 8%and 8% of patients, respectively.Bilateral VIM-DBS resulted in an additional 63% improvement in midline tremor at the cost of DBSrelated dysarthria and gait impairment in 10% and 26% of patients,respectively[30].Another study found that 25% of patients with VIMDBS from unilateral to bilateral developed new dysarthria[30].Gait disturbances and dysarthria were significantly higher in patients with bilateral DBS than in those with unilateral DBS.Previous studies have also reported that stimulation-induced side effects are more common after bilateral surgery than after unilateral surgery, and the risk of dysarthria and ataxia associated with bilateral surgery is two to three times higher.However, bilateral stimulation is more effective than unilateral stimulation in the treatment of severe bilateral tremor and tremor combined with midline axial tremor (for example, head

4.Posterior subthalamic area (PSA)

4.1 Tremors

The PSA consists of an amorphous band (Zi) and a quasi-domain front radiation.This region is located anterolateral to the red nucleus,posteromedial to the STN, inferior to the ventral thalamic nucleus,and anteromedial to the posterior limb of the internal capsule[34].PSA is an effective target for DBS in ET, and in this prospective trial, PSA-DBS reduced tremor severity in patients with drugrefractory ET.Compared with VIM-DBS, PSA-DBS proved to be more effective, producing optimal stimulation at lower amplitudes and at least equivalent tremor control[35].It has been suggested that bilateral PSA-DBS is associated with significant improvement in patient motor symptoms, particularly upper limb tremor and quality of life.These clinical benefits were evident at the 1-month follow-up and were maintained at the 6-month and eventual (9 or 12 months)follow-up.At the final follow-up, the patient’s motor symptoms were reduced by nearly 90% compared to their symptom severity before DBS treatment.Interestingly, bilateral PSA-DBS was also associated with a significant improvement in head tremor.This latter finding compares favorably with the 30-57% improvement in head tremor after unilateral VIM-DBS and the 51-86% improvement observed after bilateral VIM-DBS[36].VIM, PSA and the same VIM and PSA stimulation were compared and no difference in the overall results of tremor suppression was observed.Another retrospective,nonrandomized study reported a 70% reduction in hand tremor in the VIM group and an 89% reduction in the PSA group[37].

4.2 Related Side effects

There was no significant difference in tremor reduction between the VIM and PSA groups.The VIM group (50%) had a better reduction in tremor than the PSA group (34%).Regarding the side effects of PSA-DBS, dysarthria was seen in 74% of patients, ataxia and imbalance in 37%, and paresthesia in 11%.VIM-DBS showed a high incidence of stimulus-related side effects, such as dysarthria (9%),imbalance (4%), and paresthesia.PSA-DBS using lower voltages is associated with better tremor control and hand function, resulting in fewer adverse events[38].Gait disturbances and paresthesia are more often associated with PSA stimulation, and paresthesia is usually transient.However, when paesthesia persists, it can be eliminated by adjusting DBS parameters, such as decreasing amplitude or bipolar stimulation.Paresthesia can be overcome by procedural adjustments.Paresthesia can be reduced by decreasing the stimulus amplitude because it is voltage dependent.Slow, gradual increases in amplitude and the use of bipolar stimulation to minimize the spread of current to the nearby medial lemniscidal system are effective in improving stimulus-induced pathesia[39].

5.Amorphous band (ZI)

The ZI is located dorsal and posterior to the STN and consists of caudal and cephalic parts.ZI is a part of the PSA located ventral to the VIM and between the red nucleus and STN.Stimulation of the tail has recently been shown to be more effective in treating tremor[40].The study showed that the mean reduction in tremor reported by ZI-DBS across all etiologies was 79%; VIM (50% reduction in tremor, P＜0.001) or STN (60% reduction in tremor, P=0.006), Zi stimulation provided statistically significant relief of tremor[41].This study compared the efficacy of ZI-DBS and VIM-DBS on tremor relief, and the results showed that both ZI-DBS and VIM-DBS were effective and safe for ET treatment.The 32% (VIM) and 59%(ZI) reductions in tremor are consistent with previous reports of the effectiveness of DBS in these targets.The degree of tremor reduction was higher in the ZI group, confirming the alleged superiority of this goal[42].ZI/PSA constitutes a more and possibly more effective DBS target than VIM for the suppression of limb tremor[43].VIMDBS patients (75%) reported stimulation-induced dysarthrimias more frequently than ZI-DBS patients (39%), and more ZI-DBS patients (46%) reported side effects of visual stimulation than VIMDBS patients (16%).There were no differences in motor, sensory,psychological, seizure, or other categories[44].

6.Discussion and Prospect

Among the DBS targets of PD, STN and GPi are the most commonly used.There is no significant difference in the improvement of PD motor symptoms between STN-DBS and GPi-DBS.STN-DBS is superior to GPi-DBS in terms of drug reduction.However, GPi-DBS is more effective than STN-DBS in improving PD gait.In addition, it has been confirmed that DBS is less effective than standard medical therapy if used alone.Therefore, it is preferable to combine DBS with anti-parkinsonian drug treatment.In terms of postural balance disorders and gait disorders, GPi-DBS combined with levodopa can better control postural balance disorders and gait disorders than STN-DBS.Both STN-DBS and GPI-DBS can improve the freezing of gait in PD patients, and the latter has a better effect on the freezing of gait.For PD patients with freezing of gait as the main symptom, GPi can be selected as the target, and the long-term efficacy of STN-DBS is also better than that of GPI-DBS.In terms of LID, both STN-DBS and GPi-DBS could control LID, but the effect of GPi-DBS on LID was stronger than that of STN-DBS.Because STN-DBS alleviates LID, mediated mainly by reduction of dopaminergic drugs, GPi stimulation may provide a direct antidyskinesia effect.For LID caused by levodopa,STN can be selected as the target, and for LID in PD patients, GPi is a better target.DBS of STN and GPi have been shown to slightly improve mood dysfunction and cognitive impairment, and GPi has better efficacy than STN in patients with cognitive impairment and depression.Both STN and GPi improved objective and subjective sleep quality in PD patients.Stn-db can also improve nocturia, which may help to improve sleep quality.STN is superior to GPi in sleep duration and sleep efficiency.

VIM-DBS is mainly used for ET or PD patients with tremor, and it can provide long-term benefit for tremor relief.“However, there was no improvement in UPDRS III score, stiffness, akinesia, or postural instability.” Although bilateral VIM-DBS reduced global tremor to a greater extent than unilateral VIM-DBS.However, it should be noted that the side effects of bilateral VIM-DBS such as dysarthria, ataxia,and balance disorder also increased.

PPN-DBS improves gait disorder and balance disorder in PD patients, and has no significant improvement in resting tremor,stiffness or bradykinesia.PPN-DBS, which can significantly improve gait and balance disorders, may be the preferred target for PD patients with axial symptoms.There is no significant difference in reducing tremor between PSA-DBS and VIM-DBS, and VIMDBS is prone to dysarthria.While PSA is associated with gait disorders and paresthesia.Paresthesia can be reduced by decreasing the stimulus amplitude because it is voltage dependent.Regarding the side effects of PSA-DBS, dysarthria was seen in 74% of patients,ataxia and imbalance in 37%, and paresthesia in 11%.VIM-DBS showed a high incidence of stimulus-related side effects, such as dysarthria (9%), imbalance (4%), and paresthesia.PSA-DBS using lower voltages was associated with better tremor control and hand function, resulting in fewer adverse events.GPI-DBS, STNDBS and PPN-DBS can all improve gait disorders.GPi-DBS has the best improvement of gait disorders, followed by STN-DBS and PPN-DBS.In addition, PPN-DBS also ranked last in terms of improvement in motor symptom scores in PD patients.

ZI is a part of PSA.Zi-dbs has a significant effect on tremor relief,and the relief effect is better than VIM-DBS.ZI/PSA constitutes a more and possibly more potent DBS target than VIM for the suppression of limb tremor.VIM-DBS patients (75%) reported stimulation-induced dysarthrimias more frequently than ZI-DBS patients (39%), and more ZI-DBS patients (46%) reported side effects of visual stimulation than VIM-DBS patients (16%).There were no differences in motor, sensory, psychological, seizure, or other categories.

The selection of DBS targets is complex.It is necessary to comprehensively consider the patient’s motor symptoms and nonmotor symptoms, so as to provide personalized treatment basis for PD patients to select the appropriate target targets in DBS.The efficacy of existing DBS targets is limited and the long-term efficacy is uncertain.The current DBS targets cannot meet the needs of all PD patients.In fact, no single approach fits all patients.Clinicians should select the appropriate DBS target according to the patient’s symptoms to achieve the best therapeutic effect.We need to continue to explore new targets.As the targets are constantly updated and improved, DBS will bring more benefits to PD patients in the future.

All authors declare that there are no conflicts of interest.

Author’s contribution

Ai Xiangbai: topic selection, writing and revision of the paper;Huang Xiaogan and Wang Yitian: review and revision of paper; Zhao Jiannong: Instructor.