Editing Deep brain stimulation (section)

==Clinical usage ==
The surgery is utilized in Parkinson's to help with motor symptoms and reduce dopaminergic medication, but it does not usually help with axial non motor symptoms such as posture, gait instability, mechanical falls and can have adverse effects such as loss of cognitive function, depression, apathy, and suicide.<ref name="two Spanish"/>

Selection of the correct individual to have the procedure is a complicated process. Multiple clinical characteristics are taken into account, including identifying the most troubling symptoms, current medications and [[comorbidity|comorbidities]]. Surgery and aftercare are typically managed by multidisciplinary teams at specialized institutions. The right side of the brain is stimulated to address symptoms on the left side of the body and vice versa.<ref name ="Lozano 2017"/>

The surgery is usually contraindicated in individuals who have dementia, suffer from depression or other psychiatric disorders, or who have frequent falls despite being in their best on-drug state. Systematic assessment of benign or even beneficial precursor symptoms of a hyperdopaminergic syndrome such as do-it-yourself activities, creativity, and nocturnal hyperactivity also help prevent the devastating behavioral [[addiction]]s or [[impulse-control disorder]]s that can occur after the procedure.<ref name="Lancet Neurol 2014"/>

Stereotactic MRI is used to localize the target nuclei, though it is more susceptible to anatomic field distortion than [[cerebral ventriculography|ventriculography]], the latter is not done anymore as it is considered too invasive for its benefit with anatomic precision and the advent of high Tesla intraoperative MRIs. The awake variant of the surgery allows symptom testing in real time. Several motor symptoms, except gait, can be evaluated, but wrist rigidity is often done because it does not require the patient's active participation and can be scored in the [[operating room]] by use of a semi-quantitative scale. Speech and tremor can also be assessed in real time, though speech may be difficult to evaluate due to fatigue that occurs for the patient during the later hours of the procedure. When the best tract has been identified, the corresponding microelectrode is removed and replaced by a permanent lead.<ref name ="Benabid 2009">{{cite journal |last1=Benabid |first1=AL |last2=Chabardes |first2=S |last3=Mitrofanis |first3=J |last4=Pollak |first4=P |title=Deep brain stimulation of the subthalamic nucleus for the treatment of Parkinson's disease. |journal=The Lancet. Neurology |date=January 2009 |volume=8 |issue=1 |pages=67–81 |doi=10.1016/S1474-4422(08)70291-6 |pmid=19081516}}</ref> Because of its larger size, the GPi does not necessarily require microrecording prior to placement of a chronic lead, leading to a reduced risk of hemorrhage or cognitive deficit.<ref name="J clin neurosci 2009 Mexico City">{{cite journal |last1=Andrade |first1=P |last2=Carrillo-Ruiz |first2=JD |last3=Jiménez |first3=F |title=A systematic review of the efficacy of globus pallidus stimulation in the treatment of Parkinson's disease. |journal=Journal of Clinical Neuroscience |date=July 2009 |volume=16 |issue=7 |pages=877–81 |doi=10.1016/j.jocn.2008.11.006 |pmid=19398341}}</ref>

Post operative programming after DBS is complex and personalized, but poorly standardized across institutions despite decades of research. In practice, it is still an [[iterative design|iterative]] [[trial and error]] based process. Parameters are initially set based on experience and then adjusted according to individual clinical response. Though this works for symptoms that respond quickly to stimulation such as tremor, for other symptoms with a more delayed or nuance response profile, it carries risk of chronic overstimulation leading to adverse events such as impairment of gait and speech. Inappropriate stimulation can also cause non-motor side effects such as impaired cognition or manic disinhibition. Such effects are usually energy-dependent and reversible with adjustment.<ref name = "Handbook Clinical Neurology 2022">{{cite book |last1=Pozzi |first1=NG |last2=Isaias |first2=IU |chapter=Adaptive deep brain stimulation: Retuning Parkinson's disease |title=Neuroplasticity - from Bench to Bedside |series=Handbook of Clinical Neurology |date=2022 |volume=184 |pages=273–284 |doi=10.1016/B978-0-12-819410-2.00015-1 |pmid=35034741|isbn=978-0-12-819410-2 }}</ref>  Though it is recognized that the most important parameter in stimulation is frequency over voltage or pulse-width, there is no global consensus about the initial parameters of DBS, nor is there a protocol for stimulation options in case of poor outcome.<ref name="J clin neurosci 2009 Mexico City"/>

In distinction to DBS, although surgical lesions in the globus pallidus improve dyskinesias and Parkinsonian symptoms, they are irreversible and carry a risk of permanent neurologic deficit. Similarly, lesions of the STN improve parkinsonian symptoms, but can cause hemiballism.<ref name ="Lancet 2012">{{cite journal |last1=Fasano |first1=A |last2=Daniele |first2=A |last3=Albanese |first3=A |title=Treatment of motor and non-motor features of Parkinson's disease with deep brain stimulation. |journal=The Lancet. Neurology |date=May 2012 |volume=11 |issue=5 |pages=429–42 |doi=10.1016/S1474-4422(12)70049-2 |pmid=22516078}}</ref>

=== Parkinson's disease ===
DBS is used to manage Parkinson's disease symptoms that are resistant to medication.<ref name=NINDS/><ref name="USDHHS">U.S. Department of Health and Human Services. [https://web.archive.org/web/20090709234432/http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/DeviceApprovalsandClearances/Recently-ApprovedDevices/ucm083894.htm FDA approves implanted brain stimulator to control tremors.]</ref> The ideal candidate for DBS is one that does not have dementia, is not severely depressed, and who does not have falls while being in their best on-drug state, but who do have disabling motor fluctuations or dyskinesias that necessitate bilateral surgery.<ref name="Lancet Neurol 2014"/> It is treated by applying high-frequency (> 100&nbsp;Hz) stimulation to target structures in the deep [[subcortical]] [[white matter]] of the basal ganglia. Frequently used targets include the [[subthalamic nucleus]] (STN), [[pallidum|globus pallidus internus]] (GPi) and ventrointermediate nucleus of the [[thalamus]] (VIM). Neurostimulation can be considered for people who have Parkinson's with motor fluctuations and tremors inadequately controlled by medication, or to those who are intolerant to medication as long as they do not have severe [[wikt:neuropsychiatric|neuropsychiatric]] problems.<ref name="pmid20937936">{{cite journal | vauthors = Bronstein JM, Tagliati M, Alterman RL, Lozano AM, Volkmann J, Stefani A, Horak FB, Okun MS, Foote KD, Krack P, Pahwa R, Henderson JM, Hariz MI, Bakay RA, Rezai A, Marks WJ, Moro E, Vitek JL, Weaver FM, Gross RE, DeLong MR | display-authors = 6 | title = Deep brain stimulation for Parkinson disease: an expert consensus and review of key issues | journal = Archives of Neurology | volume = 68 | issue = 2 | page = 165 | date = February 2011 | pmid = 20937936 | pmc = 4523130 | doi = 10.1001/archneurol.2010.260 }}</ref> A >30% degree of symptom responsiveness to dopamine is a strong predictor of a good response to DBS surgery, though it is not mandatory. This has led most centers to require evaluation both on and off dopamine prior to the procedure to increase the likelihood of success.<ref name="Zhang 2022">{{cite journal |last1=Lin |first1=Z |last2=Zhang |first2=C |last3=Li |first3=D |last4=Sun |first4=B |title=Preoperative Levodopa Response and Deep Brain Stimulation Effects on Motor Outcomes in Parkinson's Disease: A Systematic Review. |journal=Movement Disorders Clinical Practice |date=February 2022 |volume=9 |issue=2 |pages=140–155 |doi=10.1002/mdc3.13379 |pmid=35146054|pmc=8810442 }}</ref> DBS is not currently considered to be a [[disease-modifying treatment]].<ref>{{cite journal |last1=Torres |first1=N |last2=Molet |first2=J |last3=Moro |first3=C |last4=Mitrofanis |first4=J |last5=Benabid |first5=AL |title=Neuroprotective Surgical Strategies in Parkinson's Disease: Role of Preclinical Data. |journal=International Journal of Molecular Sciences |date=20 October 2017 |volume=18 |issue=10 |page=2190 |doi=10.3390/ijms18102190 |doi-access=free |pmid=29053638|pmc=5666871 }}</ref>  Shorter disease duration pre-operatively tends to lead to better results after surgery.{{citation needed|date=April 2025}} The response from DBS is only as good as the patient's best "on" time, with the exception of tremor, which may show greater improvement than that seen with medication.<ref name="E-medicine 2024">{{cite journal |last1=Slavin |first1=Konstantin |title=Deep Brain Stimulation for Parkinson Disease: Overview, Mechanism of Action, Advantages and Disadvantages |journal=Medscape |date=26 February 2024 |url=https://emedicine.medscape.com/article/1965354}}</ref>

====Target and therapy comparisons====
[[File:Dbs diagram - stn vs gpi.jpg|thumb|STN vs GPi with probe locations and pros and cons of each]]
Initially, the STN was considered superior to the GPi for tremor reduction, rigidity, and bradykinesia as well as enabling greater reductions in dopaminergic medication following surgery and the GPi superior for reducing dyskinesia.<ref name="psycnet"/> Longer term studies have found the two targets to be equivalent in motor symptoms, but both relatively ineffective for cognitive and axial motor symptoms of Parkinson's disease such as gait, posture and speech.<ref name="two Spanish"/>

Comparison of the STN and GPi in DBS is also inconsistent due to different medical centers tending to have better results with specific nuclei and studies focusing on short as opposed to long term results. The three most commonly studied targets to date are the globus pallidus internus (GPi), subthalamic nucleus (STN) and ventrointermediate nucleus (VIM). DBS has also been compared to infusion therapies such as intestinal levodopa and subcutaneous apomorphine. The vast majority of DBS research to date has been on the subthalamic nucleus.<ref name="Lancet Neurol 2014"/><ref name="E-medicine 2024"/>

A large inclusive meta analysis that compared the STN to the GPi between 6–12 months found the STN to be superior for motor symptoms and activities of daily living, but found studies to be too heterogenous or insufficient to compare the targets for dyskinesia, daily off time, quality of life, or levodopa reduction.<ref name="Nature 2021"/>

In longer term studies, however, the impact of the two nuclei on motor symptoms equalizes, but the GPi becomes superior to the STN for improvement of activities of daily living and dyskinesia. Conversely, the STN is superior to the GPi for reduction of dopamine medication. Both short and long term analyses showed the targets to be equivalent as far as adverse events.<ref name="Zhang 2021"/>

A meta-regression showed that combined with levodopa, the GPi preserved postural instability and gait disability better than the STN.<ref>{{cite journal |last1=Xu |first1=F |last2=Ma |first2=W |last3=Huang |first3=Y |last4=Qiu |first4=Z |last5=Sun |first5=L |title=Deep brain stimulation of pallidal versus subthalamic for patients with Parkinson's disease: a meta-analysis of controlled clinical trials. |journal=Neuropsychiatric Disease and Treatment |date=2016 |volume=12 |pages=1435–44 |doi=10.2147/NDT.S105513 |doi-access=free |pmid=27382286|pmc=4922776 }}</ref> Gait or dysarthria are often unaffected or even worsened by DBS, particularly in ON medication state. When comparing 60 vs 130&nbsp;Hz, 60&nbsp;Hz frequency substantially reduced gait freezing, but subsequent studies have not replicated this, often finding worsening motor symptoms and less gait benefit with lower frequencies. A recent retrospective study showed 64% of patients had subjective improvement of axial symptoms when switching from higher to lower frequency stimulation with increased voltage.<ref name="Vanderbilt 2017">{{cite journal |last1=Fang |first1=JY |last2=Tolleson |first2=C |title=The role of deep brain stimulation in Parkinson's disease: an overview and update on new developments. |journal=Neuropsychiatric Disease and Treatment |date=2017 |volume=13 |pages=723–732 |doi=10.2147/NDT.S113998 |doi-access=free |pmid=28331322|pmc=5349504 }}</ref>

=====Short term comparisons=====
An indirect systems analysis compared the DBS to the STN, DBS of the GPi, subthalamotomy, jejunal levodopa, and subcutaneous apomorphine, in the first 6 months. Different results were seen depending on dopamine responsivity and whether motor symptoms (UPDRS II) or activities of daily living (UPDRS III) were assessed:<ref name = "AIIMS meta analysis 2022"/>

{| class="wikitable"
|+
!Symptom
!Dopamine responsivity
!Most effective therapy
!Patient preference (%)
|-
|Motor symptoms (UPDRS III)
|Dopamine unresponsive ''off state''
|Unilateral STN + contralateral subthalamotomy > Bilateral STN DBS > unilateral subthalamotomy > Bilateral GPi DBS
|90% / 70% / 65% / 55%
|-
|Motor symptoms (UPDRS III)
|Dopamine responsive ''on state''
|GPI = unilateral subthalamotomy + STN > jejunal levodopa
|80% / 80% / 80%
|-
|Activities of daily living (UPDRS II)
|Dopamine unresponsive ''off state''
|Unilateral STN + contralateral subthalamotomy > STN DBS > GPi DBS
|90% / 70% / 64%
|-
|Activities of daily living (UPDRS II)
|Dopamine responsive ''on state''
|Jejunal levodopa > STN DBS > unilateral pallidotomy
|90% / 50% / 66%
|}

A Bayesian analysis utilizing the minimal clinically important difference (MCID) compared DBS (predominantly of the STN and to a lesser degree GPi) to infusions of intestinal dopamine, apomorphine, and medical therapy. The analysis was significantly limited because it followed dopamine prospectively only to 3 months but other therapies such as DBS to five years. There was also a 10-fold difference in the quantity of DBS patients as compared to other therapies. They found LCIG to be similar to DBS, though with a wider confidence interval for dopamine due to lower quantity of participants. In the non-prospective cohort groups, LCIG lost its benefit for activities of daily living after 2–3 years. Both therapies were superior to apomorphine and best medical therapy for activities of daily living and "on" time for dopamine responsiveness, while DBS had the highest rate of adverse effects, particularly surgical and neuropsychiatric. LCIG was similar to DBS in effect on quality of life, though the analysis for levodopa was again underpowered.<ref name="Nijhuis MID 2021">{{cite journal |last1=Nijhuis |first1=FAP |last2=Esselink |first2=R |last3=de Bie |first3=RMA |last4=Groenewoud |first4=H |last5=Bloem |first5=BR |last6=Post |first6=B |last7=Meinders |first7=MJ |title=Translating Evidence to Advanced Parkinson's Disease Patients: A Systematic Review and Meta-Analysis. |journal=Movement Disorders |date=June 2021 |volume=36 |issue=6 |pages=1293–1307 |doi=10.1002/mds.28599 |pmid=33797786|pmc=8252410 }}</ref>

A short term meta-analysis that primarily looked at changes within the first year found the STN to be better than the GPi for motor symptoms and activities of daily living, but they included studies that analyzed the targets separately. For activities of daily living (UPDRS II) with DBS during the dopamine unresponsive state, patients improved 50% with STN but only 20% with GPi. For motor symptoms (UPDRS III), there was a 50% with STN but only 30% with GPi-DBS. STN reduced dyskinesia by 64%, OFF time by 69%, improved QOL by 20%, Levodopa dose was reduced 50%. GPi insufficient data to assess for dyskinesia OFF time, and levodopa reduction.<ref name="Nature 2021">{{cite journal |last1=Lachenmayer |first1=ML |last2=Mürset |first2=M |title=Subthalamic and pallidal deep brain stimulation for Parkinson's disease-meta-analysis of outcomes. |journal=npj Parkinson's Disease |date=6 September 2021 |volume=7 |issue=1 |page=77 |doi=10.1038/s41531-021-00223-5 |pmid=34489472|pmc=8421387 }}</ref>

A meta analysis following 1148 patients for a year and with an equal distribution between groups found that both STN and GPi improved motor function, but in different ways. GPi preserved postural instability and gait disability better than STN. GPi did not produce any significant improvement over STN in motor symptoms during the on state, though a point estimate favored the use of GPi. Motor symptoms in the off state showed that STN did not produce any significant improvement over GPi, though again a point estimate favored the use of STN. STN had a larger dopamine reduction than GPi, while GPi improved depression more than STN after surgery. Compared to the GPi, the STN showed more improvement in off state motor symptoms and activities of daily living. Conversely, the GPi was better than the STN for on state motor symptoms and activities of daily living,<ref>{{cite journal |last1=Xu |first1=F |last2=Ma |first2=W |title=Deep brain stimulation of pallidal versus subthalamic for patients with Parkinson's disease: a meta-analysis of controlled clinical trials. |journal=Neuropsychiatric Disease and Treatment |date=2016 |volume=12 |pages=1435–44 |doi=10.2147/NDT.S105513 |doi-access=free |pmid=27382286|pmc=4922776 }}</ref> similar to data from the Netherlands NSTAPS study.<ref>{{cite journal |last1=Odekerken |first1=VJ |last2=de Bie |first2=RM |title=Subthalamic nucleus versus globus pallidus bilateral deep brain stimulation for advanced Parkinson's disease (NSTAPS study): a randomised controlled trial. |journal=The Lancet. Neurology |date=January 2013 |volume=12 |issue=1 |pages=37–44 |doi=10.1016/S1474-4422(12)70264-8 |pmid=23168021}}</ref>

=====Long term comparisons=====
[[File:Rate of adverse events after dbs.jpg|thumb|Persistent adverse effects after DBS can include decline in speech, gait, loss of cognitive function and depression, though problems with cognition mitigate after the first year.<ref name = "Persistent 2018"/>]]
In the longer term and with trials comparing targets head to head, STN and GPi were found to be equal for activities of daily living in the off state and for motor function in both the on and off state. GPi had less dyskinesia and improved activities of daily living in the on state for advanced Parkinson's disease. There was no significant difference between the STN and GPi for motor scores during the on medication phase.<ref name="Zhang 2021">{{cite journal |last1=Zhang |first1=J |last2=Li |first2=J |last3=Chen |first3=F |last4=Liu |first4=X |last5=Jiang |first5=C |last6=Hu |first6=X |last7=Ma |first7=L |last8=Xu |first8=Z |title=STN versus GPi deep brain stimulation for dyskinesia improvement in advanced Parkinson's disease: A meta-analysis of randomized controlled trials. |journal=Clinical Neurology and Neurosurgery |date=February 2021 |volume=201 |page=106450 |doi=10.1016/j.clineuro.2020.106450 |pmid=33421741}}</ref> The GPi reduces dyskinesia through a medication independent mechanism and has less neuropsychiatric effects (ie. depression, apathy, and suicide).<ref name="Lancet Neurol 2014"/> The long term duration of therapeutic benefit has not been clearly established, though reports suggest that individuals may have sustained clinical improvement for at least 10 years.<ref name="DBS review NJEM 2012"/>

There is usually a greater improvement in akinesia targeting the STN as compared to the pallidus, while there may be a wearing off of the initially excellent antiakinetic effect with pallidal stimulation after 5 years.<ref name="Lancet Neurol 2014"/> Conversely, deep brain stimulation of the GPi has consistently shown superior and sustained reduction in dyskinesia.<ref name = "JAMA Neurol 2018">{{cite journal |last1=Ramirez-Zamora |first1=A |last2=Ostrem |first2=JL |title=Globus Pallidus Interna or Subthalamic Nucleus Deep Brain Stimulation for Parkinson Disease: A Review. |journal=JAMA Neurology |date=1 March 2018 |volume=75 |issue=3 |pages=367–372 |doi=10.1001/jamaneurol.2017.4321 |pmid=29356826}}</ref> Although overall gait has been reported to improve consistently after DBS, postural instability, which can affect gait, is less likely to respond. A greater number of falls occur after surgery with DBS of the STN as compared to the GPi.<ref name = "JAMA Neurol 2018"/>

GPi programming requires less-intensive monitoring of medication and stimulation adjustments in most patients. The STN has multiple motor, cognitive, and limbic pathways that are not completely anatomically segregated. In contrast, the larger size of the GPi motor region reduces the likelihood of the current spreading into adjacent functional areas or to the internal capsule, causing less neuropsychological side effects,<ref name = "JAMA Neurol 2018"/> long term comorbidities<ref>{{cite journal |last1=Sako |first1=W |last2=Miyazaki |first2=Y |last3=Izumi |first3=Y |last4=Kaji |first4=R |title=Which target is best for patients with Parkinson's disease? A meta-analysis of pallidal and subthalamic stimulation. |journal=Journal of Neurology, Neurosurgery, and Psychiatry |date=September 2014 |volume=85 |issue=9 |pages=982–6 |doi=10.1136/jnnp-2013-306090 |pmid=24444854}}</ref> and global cognitive decline.<ref>{{cite journal |last1=Rački |first1=V |last2=Hero |first2=M |title=Cognitive Impact of Deep Brain Stimulation in Parkinson's Disease Patients: A Systematic Review. |journal=Frontiers in Human Neuroscience |date=2022 |volume=16 |page=867055 |doi=10.3389/fnhum.2022.867055 |doi-access=free |pmid=35634211|pmc=9135964 }}</ref> This could be due to the GPi being separate from the limbic component of the STN, the greater dopamine reduction allowed with STN stimulation, or that the  vast preponderance of studies in the literature are about the STN, causing an inadvertent [[publication bias]].<ref name="Lancet Neurol 2014"/><ref name="E-medicine 2024"/>

For individuals with unsatisfactory outcomes after DBS in Parkinson's, lead revision resulted in 30% improvement when leads were repositioned from the GPi to the STN, and no improvement when repositioned from the GPi to the STN. The cases in which improvement occurred were when there was clear evidence of lead mispositioning.<ref>{{cite journal |last1=Ten Brinke |first1=TR |last2=Odekerken |first2=VJJ |last3=van Laar |first3=T |last4=van Dijk |first4=JMC |last5=Dijk |first5=JM |last6=van den Munckhof |first6=P |last7=Schuurman |first7=PR |last8=de Bie |first8=RMA |title=Substituting the Target After Unsatisfactory Outcome of Deep Brain Stimulation in Advanced Parkinson's Disease: Cases From the NSTAPS Trial and Systematic Review of the Literature. |journal=Neuromodulation: Journal of the International Neuromodulation Society |date=August 2018 |volume=21 |issue=6 |pages=527–531 |doi=10.1111/ner.12732 |pmid=29164735|url=https://pure.rug.nl/ws/files/64715824/Substituting_the_Target_After_UnsatisfactoryOutcome_of_Deep_Brain_Stimulation_inAdvanced_Parkinson_s_Disease_Cases_From_theNSTAPS_Trial_and_Systematic_Review_of_theLiterature.pdf }}</ref>

A [[Bayesian statistics|Bayesian]] analysis comparing DBS with intestinal levodopa, subcutaneous apomorphine and best medical therapy found DBS and intestinal levodopa to be the superior treatments, though it did not distinguish specific nuclei as DBS targets. In the setting of this limitation, they found intestinal levodopa being the best at improving quality of life more and DBS being the best at reducing off time.<ref>{{cite journal |last1=Antonini |first1=A |title=Comparative Effectiveness of Device-Aided Therapies on Quality of Life and Off-Time in Advanced Parkinson's Disease: A Systematic Review and Bayesian Network Meta-analysis. |journal=CNS Drugs |date=December 2022 |volume=36 |issue=12 |pages=1269–1283 |doi=10.1007/s40263-022-00963-9 |pmid=36414908|pmc=9712309 }}</ref> A more specific Bayesian [[Monte Carlo method|Monte Carlo]] analysis comparing individual nuclei found bilateral STN, GPi and intrajejunal levodopa to be better than either subcutaneous apomorphine or best medical therapy. Amongst the three, STN had the greatest likelihood of improvement, though it was not statistically significant.<ref name = "AIIMS meta analysis 2022">{{cite journal |last1=Rajan |first1=R |last2=Garg |first2=K |last3=Srivastava |first3=AK |last4=Singh |first4=M |title=Device-Assisted and Neuromodulatory Therapies for Parkinson's Disease: A Network Meta-Analysis. |journal=Movement Disorders |date=September 2022 |volume=37 |issue=9 |pages=1785–1797 |doi=10.1002/mds.29160 |pmid=35866929}}</ref>

====Post operative complications====
The overall rate of intracranial hemorrhage at surgery is 5%, with symptomatic hemorrhage in 2% and hemorrhage causing permanent deficit or death in 1%. Stroke occurred in 1%, infection in 8%, lead erosion without infection in 2%, lead fracture in 8%, lead migration in 10%, and death in 2%.<ref name="An update on best practice of deep">{{cite journal |last1=Hartmann |first1=CJ |last2=Fliegen |first2=S |last3=Groiss |first3=SJ |last4=Wojtecki |first4=L |last5=Schnitzler |first5=A |title=An update on best practice of deep brain stimulation in Parkinson's disease. |journal=Therapeutic Advances in Neurological Disorders |date=2019 |volume=12 |page=1756286419838096 |doi=10.1177/1756286419838096 |pmid=30944587|pmc=6440024 }}</ref> Additional adverse events include the need for revision in 5%, lead malposition 3%, surgical site complications 3%, hardware-related complications 2%, and seizure 2%. There was a significant non-linear increase with each additional track, for example in situations when leads needed to be repositioned or in multiple target procedures.<ref>{{cite journal |last1=Rasiah |first1=NP |last2=Maheshwary |first2=R |last3=Kwon |first3=CS |last4=Bloomstein |first4=JD |last5=Girgis |first5=F |title=Complications of Deep Brain Stimulation for Parkinson Disease and Relationship between Micro-electrode tracks and hemorrhage: Systematic Review and Meta-Analysis. |journal=World Neurosurgery |date=March 2023 |volume=171 |pages=e8–e23 |doi=10.1016/j.wneu.2022.10.034 |pmid=36244666}}</ref>

In the short term, studies have reported a risk of cerebral hemorrhage of 1.4%, hardware infection 1.1%, post operative mental status change occurred in 4.6%, and seizure occurred in 1.4%; in the longer term adverse events include confusion at 3.9%, hardware infection at 4.5%, implantable pulse generator malfunction 1.4%.<ref name="Zhang 2022"/>

Image guided lead placement tends to have shorter surgical times and lower rates of intracranial hemorrhage. Combined methods that use both microelectrode recording and image guidance are not as brief in operating room time and have a higher risk of hemorrhage, but result in more accurate lead placement.<ref>{{cite journal |last1=Yin |first1=Z |last2=Luo |first2=Y |title=Is awake physiological confirmation necessary for DBS treatment of Parkinson's disease today? A comparison of intraoperative imaging, physiology, and physiology imaging-guided DBS in the past decade. |journal=Brain Stimulation |date=July 2019 |volume=12 |issue=4 |pages=893–900 |doi=10.1016/j.brs.2019.03.006 |pmid=30876883}}</ref>

====Caregivers====
More than half of caregivers rate DBS to the STN negatively at one year after surgery. Some of the symptoms caregivers were unhappy about included mania, apathy, depression, impulsivity, compulsivity, aggressiveness and disinhibition. Children of individuals with Parkinson's tended to be happier than spouses. Concerns raised by caregivers included dyskinesia impacting the [[physiognomy]] of their loved ones, leading to the inability to control movements and a glassy-eyed appearance. Family relationships changed between partners and children were also stressed because the empathy and self-awareness of patients diminished as they lost their sense of reality over time. The degree of dissatisfaction did not appear to correlate with the success of the surgery as far as motor symptoms, which generally improved.<ref>{{cite journal |last1=Cavallieri |first1=F |last2=Ghirotto |first2=L |title=Caregivers' burden and deep brain stimulation for Parkinson disease: A systematic review of qualitative studies. |journal=European Journal of Neurology |date=March 2024 |volume=31 |issue=3 |pages=e16149 |doi=10.1111/ene.16149 |pmid=37975788|pmc=11235895 }}</ref> Similar dissatisfaction persisted at two years in a separate analysis, with almost 60% of caregivers continuing to report dissatisfaction.<ref>{{cite journal |last1=van Hienen |first1=MM |last2=Contarino |first2=MF |last3=Middelkoop |first3=HAM |last4=van Hilten |first4=JJ |last5=Geraedts |first5=VJ |title=Effect of deep brain stimulation on caregivers of patients with Parkinson's disease: A systematic review. |journal=Parkinsonism & Related Disorders |date=December 2020 |volume=81 |pages=20–27 |doi=10.1016/j.parkreldis.2020.09.038 |pmid=33038702|hdl=1887/3249462 |hdl-access=free }}</ref>

Despite the high dissatisfaction rate of caregivers with surgery, additional measures such as caregiver burden, psychiatric and cognitive functioning and caregiver quality of life remained relatively stable. In addition, both patients and caregivers reported that they would opt for DBS again.<ref>{{cite journal |last1=van Hienen |first1=MM |last2=Contarino |first2=MF |title=Effect of deep brain stimulation on caregivers of patients with Parkinson's disease: A systematic review. |journal=Parkinsonism & Related Disorders |date=December 2020 |volume=81 |pages=20–27 |doi=10.1016/j.parkreldis.2020.09.038 |pmid=33038702|hdl=1887/3249462 |hdl-access=free }}</ref>

====Dyskinesia====
DBS for the GPi has a direct effect on dyskinesia reduction and is more effective than DBS to the STN, with the latter being dependent on dopamine reduction. As such, pallidal surgery is indicated when dyskinesia is a dose-limiting factor preventing higher levels of needed dopaminergic therapy. STN stimulation can also induce persistent contralateral dyskinesia, and in some cases require a repeat surgery to implant GPi rescue leads.<ref>{{cite journal |last1=Munhoz |first1=RP |last2=Cerasa |first2=A |last3=Okun |first3=MS |title=Surgical treatment of dyskinesia in Parkinson's disease. |journal=Frontiers in Neurology |date=2014 |volume=5 |page=65 |doi=10.3389/fneur.2014.00065 |doi-access=free |pmid=24808889|pmc=4010755 }}</ref>

====Gait====
The effect on gait is inconsistent, with multiple studies showing worsening of gait, balance and speech as potential complications of DBS,<ref>{{cite journal |last1=Tanner |first1=CM |last2=Ostrem |first2=JL |title=Parkinson's Disease. |journal=The New England Journal of Medicine |date=1 August 2024 |volume=391 |issue=5 |pages=442–452 |doi=10.1056/NEJMra2401857 |pmid=39083773}}</ref> with DBS to the STN carrying a higher risk of gait dysfunction.<ref>{{cite journal |last1=Tsuboi |first1=T |last2=Au |first2=KLK |last3=Deeb |first3=W |last4=Almeida |first4=L |last5=Foote |first5=KD |last6=Okun |first6=MS |last7=Ramirez-Zamora |first7=A |title=Motor outcomes and adverse effects of deep brain stimulation for dystonic tremor: A systematic review. |journal=Parkinsonism & Related Disorders |date=July 2020 |volume=76 |pages=32–41 |doi=10.1016/j.parkreldis.2020.06.008 |pmid=32559631}}</ref> A study delineating adverse effects by time found that though DBS mitigated gait symptoms after surgery, postoperative postural instability and gait disorders worsened in the long term.<ref name = "Persistent 2018"/>

When axial symptoms are responsive to dopaminergic medications, they are likely to improve with DBS. Several studies reported gait improvement with either STN or GPi DBS, including reduction in freezing of gait, though GPi is generally associated with preserved gait function compared with STN,<ref name="JAMA Neurol 2018"/> and generally more favorable for those with axial symptoms, gait issues, depression, and word fluency problems.<ref name="Vanderbilt 2017"/>

[[Electromyography]] studies of the lower limbs in the study of gait have shown that dopaminergic medication increases distal lower limb muscle activity while STN DBS increases both proximal and distal lower limb muscle activity.<ref>{{cite journal |last1=Islam |first1=A |title=Effect of Parkinson's disease and two therapeutic interventions on muscle activity during walking: a systematic review. |journal=npj Parkinson's Disease |date=2020 |volume=6 |page=22 |doi=10.1038/s41531-020-00119-w |pmid=32964107|pmc=7481232 }}</ref>

In the context of chronic levodopa therapy, the most relevant effect of STN neurostimulation is improvement of motor function during the off state, the period during which symptoms are non responsive to dopamine.<ref name="Lancet 2013">{{cite journal |last1=Deuschl |first1=G |last2=Agid |first2=Y |title=Subthalamic neurostimulation for Parkinson's disease with early fluctuations: balancing the risks and benefits. |journal=The Lancet. Neurology |date=October 2013 |volume=12 |issue=10 |pages=1025–34 |doi=10.1016/S1474-4422(13)70151-0 |pmid=24050735}}</ref>

====Genitourinary and other symptoms====
Benefit after STN DBS has been reported in nonmotor fluctuating symptoms, including urinary dysfunction, [[sialorrhea]], sleep, PD-related pain, and off-period sweating.<ref name = "JAMA Neurol 2018"/>
[[File:Globus pallidus small.gif|thumb|260px|The globus pallidus is targeted in both Parkinson's and dystonia.]]

A meta analysis predominantly looking at DBS to the STN found it led to less urinary urgency, increased bladder capacity and maximum urinary flow rate.<ref>{{cite journal |last1=Gao |first1=L |last2=Wang |first2=M |last3=Zhou |first3=M |last4=Yin |first4=W |last5=Cao |first5=X |title=Impact of deep brain stimulation on urogenital function in Parkinson's disease: a systematic review and meta-analysis. |journal=Frontiers in Neurology |date=2024 |volume=15 |page=1397344 |doi=10.3389/fneur.2024.1397344 |doi-access=free |pmid=39026583|pmc=11254620 }}</ref> Another meta analysis study further distinguished effects by target subgroups, finding that DBS of the GPi and STN have an inhibitory effect on [[detrusor muscle|detrusor]] function at the [[pelvic floor]], leading to an increase in functional urine capacity and retention. DBS of the VIM has the opposite effect, leading to detrusor excitation and improved voiding.<ref>{{cite journal |last1=Jörg |first1=E |last2=Sartori |first2=AM |last3=Hofer |first3=AS |last4=Baumann |first4=CR |last5=Kessler |first5=TM |title=Deep brain stimulation effects on lower urinary tract function: Systematic review and meta-analysis. |journal=Parkinsonism & Related Disorders |date=October 2020 |volume=79 |pages=65–72 |doi=10.1016/j.parkreldis.2020.08.032 |pmid=32889502|doi-access=free }}</ref>

====Mortality====
Long term mortality rates with DBS measure up to 17% with an average age at death of 71 years,<ref>{{cite journal |last1=Rocha |first1=AL |last2=Oliveira |first2=A |last3=Sousa |first3=C |last4=Monteiro |first4=P |last5=Rosas |first5=MJ |last6=Vaz |first6=R |title=Long term mortality of patients with Parkinson's disease treated with deep brain stimulation in a reference center. |journal=Clinical Neurology and Neurosurgery |date=March 2021 |volume=202 |page=106486 |doi=10.1016/j.clineuro.2021.106486 |pmid=33493881}}</ref> with the risk of mortality being more pronounced in cases of advanced disease.<ref>{{cite journal |last1=Ryu |first1=HS |last2=Kim |first2=MS |last3=You |first3=S |last4=Kim |first4=MJ |last5=Kim |first5=YJ |last6=Kim |first6=J |last7=Kim |first7=K |last8=Chung |first8=SJ |title=Mortality of advanced Parkinson's disease patients treated with deep brain stimulation surgery. |journal=Journal of the Neurological Sciences |date=15 October 2016 |volume=369 |pages=230–235 |doi=10.1016/j.jns.2016.08.041 |pmid=27653896}}</ref> DBS of the STN has a three-fold increased mortality compared to the GPi in Parkinson's patients, with most deaths being due to postoperative complications and not directly related to the stimulation itself.<ref name="Mortality">{{cite journal |last1=Negida |first1=A |title=Meta-analysis of mortality following Subthalamic and Pallidal deep brain stimulation for patients with Parkinson's disease |journal=Mov. Disord. |date=2017 |volume=32 (suppl 2). |url=https://www.mdsabstracts.org/abstract/meta-analysis-of-mortality-following-subthalamic-and-pallidal-deep-brain-stimulation-for-patients-with-parkinsons-disease/}}</ref>

[[Image:DBS simulation of subthalamic nucleus.jpg|thumb|260px|The subthalamic nucleus, immediately above the substantia nigra and below the thalamus, is the most common target for treatment in Parkinson's]]

====Neuropsychological effects and suicide====
Neurologic side effects of deep-brain stimulation include cognitive impairment, memory deficits, difficulties with speech, [[Sense of balance|disequilibrium]], [[dysphagia]], and motor and sensory disturbances. Potential psychological side effects include mania, depression, apathy, laughter, crying, panic, fear, anxiety, and suicidal ideation. It is important that individuals be screened before and after the procedure for suicidal ideation, impulsivity (e.g., gambling, impulsive shopping, hypersexuality, etc.), and dopamine dysregulation, an addiction-like syndrome associated with the use of  levodopa.<ref name="DBS review NJEM 2012">{{cite journal |last1=Okun |first1=MS |title=Deep-brain stimulation for Parkinson's disease. |journal=The New England Journal of Medicine |date=18 October 2012 |volume=367 |issue=16 |pages=1529–38 |doi=10.1056/NEJMct1208070 |pmid=23075179}}</ref> The STN, at approximately 160&nbsp;mm<sup>3</sup>, is one-third the size of the GPi (on average 480&nbsp;mm<sup>3</sup>) and has multiple nearby non-motor pathways, the inadvertent activation of which has been suggested to be the cause of emotional dysregulation that can be seen when it is targetted.<ref name = "Persistent 2018">{{cite journal |last1=Yin |first1=Z |last2=Cao |first2=Y |last3=Zheng |first3=S |last4=Duan |first4=J |last5=Zhou |first5=D |last6=Xu |first6=R |last7=Hong |first7=T |last8=Lu |first8=G |title=Persistent adverse effects following different targets and periods after bilateral deep brain stimulation in patients with Parkinson's disease. |journal=Journal of the Neurological Sciences |date=15 October 2018 |volume=393 |pages=116–127 |doi=10.1016/j.jns.2018.08.016 |pmid=30153572}}</ref>

Cognitively, decreased verbal fluency and an increased risk for [[dementia]] can occur due to the wire passing through the prefrontal cortex and [[caudate nucleus]], a path more often seen with subthalamic stimulation than GPi due to its more inferomedial positioning. Long-term follow-up showed a more rapid decline in cognitive function with treatment targeting the subthalamic nucleus than that targeting the GPi.<ref name="DBS review NJEM 2012"/> Without surgery, the risk of developing dementia in Parkinson's is approximately 10% per year with a [[mean]] [[prevalence]] of 40% across the disease<ref>{{cite journal |last1=Aarsland |first1=D |last2=Kurz |first2=MW |title=The epidemiology of dementia associated with Parkinson's disease. |journal=Brain Pathology (Zurich, Switzerland) |date=May 2010 |volume=20 |issue=3 |pages=633–9 |doi=10.1111/j.1750-3639.2009.00369.x |pmid=20522088|pmc=8094858 }}</ref> and a lifetime [[incidence (epidemiology)|incidence]] of 80%.<ref name="Cognition long and short term 2022">{{cite journal |last1=Jahanshahi |first1=M |last2=Leimbach |first2=F |last3=Rawji |first3=V |title=Short and Long-Term Cognitive Effects of Subthalamic Deep Brain Stimulation in Parkinson's Disease and Identification of Relevant Factors. |journal=Journal of Parkinson's Disease |date=2022 |volume=12 |issue=7 |pages=2191–2209 |doi=10.3233/JPD-223446 |pmid=36155529}}</ref> One large meta-analysis suggested the likelihood of dementia increases by 2.5 fold, though the subpopulation in the analysis was limited in quantity.<ref>{{cite journal |last1=Sisodia |first1=V |last2=Malekzadeh |first2=A |last3=Verwijk |first3=E |last4=Schuurman |first4=PR |last5=de Bie |first5=RMA |last6=Swinnen |first6=BEKS |title=Bidirectional Interplay between Deep Brain Stimulation and Cognition in Parkinson's Disease: A Systematic Review. |journal=Movement Disorders |date=May 2024 |volume=39 |issue=5 |pages=910–915 |doi=10.1002/mds.29772 |pmid=38429947|doi-access=free }}</ref> Another meta analysis suggested the incidence as the same.<ref name="Cognition long and short term 2022"/> Additional cognitive changes after STN in Parkinson's were mixed and included an improvement in [[mental chronometry|reaction time]], but also more errors in tasks involving [[inhibitory control|response inhibition]].<ref name="Lancet Neurol 2014"/>

Potential [[neuropsychiatry|neuropsychiatric]] side effects in the short term can occur due to lesional effects, causing disinhibition, mania, [[hallucinations]], [[hypersexuality]], and euphoria. In the long term, this tendency inverts and can evolve into [[apathy]], depression and even suicidal ideation. Some studies report a prevalence of apathy after surgery as high as 70%.<ref>{{cite journal |last1=Zoon |first1=TJC |last2=van Rooijen |first2=G |last3=Balm |first3=GMFC |last4=Bergfeld |first4=IO |last5=Daams |first5=JG |last6=Krack |first6=P |last7=Denys |first7=DAJP |last8=de Bie |first8=RMA |title=Apathy Induced by Subthalamic Nucleus Deep Brain Stimulation in Parkinson's Disease: A Meta-Analysis. |journal=Movement Disorders |date=February 2021 |volume=36 |issue=2 |pages=317–326 |doi=10.1002/mds.28390 |pmid=33331023|pmc=7986158 }}</ref> These effects can be due to misplacement of electrodes, miscalibration, or even well placed electrodes that inadvertently stimulate adjacent [[limbic system|limbic circuits]] adjacent to the target nuclei. Though [[dopamine withdrawal syndrome]] due to the reduced dose of [[levodopa]] required after surgery (typically 70%) could contribute to these findings, it does not completely account for them.<ref name = "Suicide">{{cite journal |last1=Xu |first1=Y |title=Suicide and suicide attempts after subthalamic nucleus stimulation in Parkinson's disease: a systematic review and meta-analysis. |journal=Neurological Sciences |date=January 2021 |volume=42 |issue=1 |pages=267–274 |doi=10.1007/s10072-020-04555-7 |pmid=32643134}}</ref><ref name="Lancet Neurol 2014"/>

The majority of studies indicate an increased risk of suicidal ideation and suicide attempts after treatment with DBS.<ref name = "Suicide"/><ref>{{cite journal |last1=Du |first1=J |last2=Liu |first2=X |title=Parkinson's Disease-Related Risk of Suicide and Effect of Deep Brain Stimulation: Meta-Analysis. |journal=Parkinson's Disease |date=2020 |volume=2020 |page=8091963 |doi=10.1155/2020/8091963 |doi-access=free |pmid=33062248|pmc=7537696 }}</ref> Concerningly, though preoperative screening for depression and suicide are done to mitigate this risk, some studies have shown no evident difference in pre-operative depressive or cognitive status between suicidal and nonsuicidal individuals after surgery.<ref>{{cite journal |last1=Cartmill |first1=T |last2=Skvarc |first2=D |last3=Bittar |first3=R |last4=McGillivray |first4=J |last5=Berk |first5=M |last6=Byrne |first6=LK |title=Deep Brain Stimulation of the Subthalamic Nucleus in Parkinson's Disease: A Meta-Analysis of Mood Effects. |journal=Neuropsychology Review |date=September 2021 |volume=31 |issue=3 |pages=385–401 |doi=10.1007/s11065-020-09467-z |pmid=33606174}}</ref> The risk of suicide is more pronounced with treatment to the STN than the pallidus,<ref name = "Suicide"/><ref>{{cite journal |last1=Mainardi |first1=M |last2=Ciprietti |first2=D |title=Deep brain stimulation of globus pallidus internus and subthalamic nucleus in Parkinson's disease: a multicenter, retrospective study of efficacy and safety. |journal=Neurological Sciences |date=January 2024 |volume=45 |issue=1 |pages=177–185 |doi=10.1007/s10072-023-06999-z |pmid=37555874|pmc=10761504 }}</ref> with studies as soon as 6 months showing increased proxy symptoms of suicide such as depression, isolation, tearfulness, anger, anxiety and hallucinations.<ref>{{cite journal |last1=Weintraub |first1=D |last2=Duda |first2=JE |title=Suicide ideation and behaviours after STN and GPi DBS surgery for Parkinson's disease: results from a randomised, controlled trial. |journal=Journal of Neurology, Neurosurgery, and Psychiatry |date=October 2013 |volume=84 |issue=10 |pages=1113–8 |doi=10.1136/jnnp-2012-304396 |pmid=23667214|pmc=4594869 }}</ref> As with other neuropsychiatric effects that are more common with the STN, it is thought to be due to a combination of the levodopa dose reduction that occurs after surgery, adjacent subthalamic limbic circuit activation and disinhibition.<ref name = "Suicide"/>

Both depression<ref>{{cite journal |last1=Giannini |first1=G |last2=Francois |first2=M |title=Suicide and suicide attempts after subthalamic nucleus stimulation in Parkinson disease. |journal=Neurology |date=2 July 2019 |volume=93 |issue=1 |pages=e97–e105 |doi=10.1212/WNL.0000000000007665 |pmid=31101738}}</ref> and euphoria<ref>{{cite journal |last1=Combs |first1=HL |last2=Folley |first2=BS |last3=Berry |first3=DT |last4=Segerstrom |first4=SC |last5=Han |first5=DY |last6=Anderson-Mooney |first6=AJ |last7=Walls |first7=BD |last8=van Horne |first8=C |title=Cognition and Depression Following Deep Brain Stimulation of the Subthalamic Nucleus and Globus Pallidus Pars Internus in Parkinson's Disease: A Meta-Analysis. |journal=Neuropsychology Review |date=December 2015 |volume=25 |issue=4 |pages=439–54 |doi=10.1007/s11065-015-9302-0 |pmid=26459361}}</ref> have been reported after DBS. Comparative studies between the STN and GPi have suggested higher depression rates for the STN.<ref name = "JAMA Neurol 2018"/> With acute neurostimulation to the STN, depression can occur after left sided stimuation, whereas right sided stimulation can produce mirthful laughter.<ref name = "Lancet 2004">{{cite journal |last1=Walter |first1=BL |last2=Vitek |first2=JL |title=Surgical treatment for Parkinson's disease. |journal=The Lancet. Neurology |date=December 2004 |volume=3 |issue=12 |pages=719–28 |doi=10.1016/S1474-4422(04)00934-2 |pmid=15556804}}</ref>

The improvement in motor symptoms but progressive deterioration of axial symptoms such as gait, vocal control, and neuropsychiatric side effects has led to a new phenotype of Parkinson's patient in the long term with mitigated or well controlled non axial motor symptoms, but with progressive worsening of axial motor symptoms (bradykinesia, dysarthria, postural instability, freezing of gait) and cognitive symptoms such as dementia and hallucinations.<ref name="two Spanish">{{cite journal |last1=Rodriguez-Oroz |first1=MC |last2=Moro |first2=E |last3=Krack |first3=P |title=Long-term outcomes of surgical therapies for Parkinson's disease. |journal=Movement Disorders |date=December 2012 |volume=27 |issue=14 |pages=1718–28 |doi=10.1002/mds.25214 |pmid=23208668|url=https://archive-ouverte.unige.ch/unige:95930 }}</ref>
[[File:Non motor vs motor dbs over time.jpg|thumb|DBS improves non-axial motor symptoms with Parkinson's, leading to a new chronic phenotype dominated by axial motor symptoms (gait dysfunction, dysarthria, [[camptocormia]]) and cognitive decline, features which generally do not improve and can worsen after surgery.]]

At baseline, the total lifetime risk of suicide in Parkinson's at baseline is 22% for ideation and 1% for attempts, with the general population at 13% ideation and 5% attempts.<ref>{{cite journal |last1=Mai |first1=AS |last2=Chao |first2=Y |title=Risk of Suicidal Ideation and Behavior in Individuals With Parkinson Disease: A Systematic Review and Meta-Analysis. |journal=JAMA Neurology |date=1 January 2024 |volume=81 |issue=1 |pages=10–18 |doi=10.1001/jamaneurol.2023.4207 |pmid=37955917|pmc=10644251 }}</ref>

====Posture====
Parkinson's is often characterized by [[camptocormia]], a classic stooped [[kyphosis|kyphotic]] posture that develops as the disease progresses as well as [[Pleurothotonus|Pisa syndrome]], characterized by a persistent tilted posture. The impact of DBS to the STN or GPi on posture in Parkinson's have been heterogenous and inconsistent at best.<ref>{{cite journal |last1=Chan |first1=AK |last2=Chan |first2=AY |last3=Lau |first3=D |last4=Durcanova |first4=B |last5=Miller |first5=CA |last6=Larson |first6=PS |last7=Starr |first7=PA |last8=Mummaneni |first8=PV |title=Surgical management of camptocormia in Parkinson's disease: systematic review and meta-analysis. |journal=Journal of Neurosurgery |date=1 August 2019 |volume=131 |issue=2 |pages=368–375 |doi=10.3171/2018.4.JNS173032 |pmid=30215560}}</ref> Though some studies have shown positive effect, the quality of evidence is quite low.<ref>{{cite journal |last1=Spindler |first1=P |last2=Alzoobi |first2=Y |last3=Kühn |first3=AA |last4=Faust |first4=K |last5=Schneider |first5=GH |last6=Vajkoczy |first6=P |title=Deep brain stimulation for Parkinson's disease-related postural abnormalities: a systematic review and meta-analysis. |journal=Neurosurgical Review |date=October 2022 |volume=45 |issue=5 |pages=3083–3092 |doi=10.1007/s10143-022-01830-3 |pmid=35790655|pmc=9492622 }}</ref>

The pedunculopontine nucleus (PPN) is being studied as a target for postural instability and [[Parkinsonian gait|gait freezing]], but clinical research is still in its early stages.<ref name ="PPN Consensus 2018">{{cite journal |last1=Garcia-Rill |first1=E |last2=Saper |first2=CB |last3=Rye |first3=DB |last4=Kofler |first4=M |last5=Nonnekes |first5=J |last6=Lozano |first6=A |last7=Valls-Solé |first7=J |last8=Hallett |first8=M |title=Focus on the pedunculopontine nucleus. Consensus review from the May 2018 brainstem society meeting in Washington, DC, USA. |journal=Clinical Neurophysiology |date=June 2019 |volume=130 |issue=6 |pages=925–940 |doi=10.1016/j.clinph.2019.03.008 |pmid=30981899|pmc=7365492 }}</ref> It is located in the mesopontine tegmentum next to the crossing of the superior cerebellar peduncle and is theorized to play a role in reflex reactions, sleep-wake cycles, posture and gait.<ref name ="PPN Consensus 2018"/> It is inhibited by the GPi while the STN excites it.<ref name = "Persistent 2018"/> Freezing, as part of the pattern of akinesia, usually responds to levodopa. When freezing of gait persists, and is not improved by drugs, it is usually not improved by STN stimulation.<ref name ="Benabid 2009"/> The loss of verbal fluency after PPN or VIM stimulation is greater than even that seen with the STN.<ref>{{cite journal |last1=Rački |first1=V |last2=Hero |first2=M |last3=Rožmarić |first3=G |last4=Papić |first4=E |last5=Raguž |first5=M |last6=Chudy |first6=D |last7=Vuletić |first7=V |title=Cognitive Impact of Deep Brain Stimulation in Parkinson's Disease Patients: A Systematic Review. |journal=Frontiers in Human Neuroscience |date=2022 |volume=16 |page=867055 |doi=10.3389/fnhum.2022.867055 |doi-access=free |pmid=35634211|pmc=9135964 }}</ref>

====Quality of life====
A study comparing quality of life and adverse affects from patient perspective found that DBS had a more positive effect on quality of life than subcutaneous apomorphine, intestinal dopamine and best medical therapy, but also the highest rate of adverse effects.<ref name="Nijhuis MID 2021"/> DBS has been found to be superior to best medical therapy in impact on quality of life, though no study to date has shown to favor the GPi or STN specifically.<ref name="JAMA Neurol 2018"/><ref>{{cite journal |last1=Rughani |first1=A |last2=Hamani |first2=C |title=Congress of Neurological Surgeons Systematic Review and Evidence-Based Guideline on Subthalamic Nucleus and Globus Pallidus Internus Deep Brain Stimulation for the Treatment of Patients With Parkinson's Disease: Executive Summary. |journal=Neurosurgery |date=1 June 2018 |volume=82 |issue=6 |pages=753–756 |doi=10.1093/neuros/nyy037 |pmid=29538685|pmc=6636249 }}</ref> A Bayesian analysis found intestinal dopamine has been shown to be superior to both DBS and best medical therapy for quality of life.<ref>{{cite journal |last1=Antonini |first1=A |last2=Pahwa |first2=R |last3=Odin |first3=P |last4=Isaacson |first4=SH |last5=Merola |first5=A |last6=Wang |first6=L |last7=Kandukuri |first7=PL |last8=Alobaidi |first8=A |last9=Yan |first9=CH |last10=Bao |first10=Y |last11=Zadikoff |first11=C |last12=Parra |first12=JC |last13=Bergmann |first13=L |last14=Chaudhuri |first14=KR |title=Comparative Effectiveness of Device-Aided Therapies on Quality of Life and Off-Time in Advanced Parkinson's Disease: A Systematic Review and Bayesian Network Meta-analysis. |journal=CNS Drugs |date=December 2022 |volume=36 |issue=12 |pages=1269–1283 |doi=10.1007/s40263-022-00963-9 |pmid=36414908|pmc=9712309 }}</ref> Younger age, early onset of Parkinson's, less dyskinesia, and higher quality of life before surgery predict higher quality of life following the procedure.<ref>{{cite journal |last1=Geraedts |first1=VJ |last2=Feleus |first2=S |last3=Marinus |first3=J |last4=van Hilten |first4=JJ |last5=Contarino |first5=MF |title=What predicts quality of life after subthalamic deep brain stimulation in Parkinson's disease? A systematic review. |journal=European Journal of Neurology |date=March 2020 |volume=27 |issue=3 |pages=419–428 |doi=10.1111/ene.14147 |pmid=31876047|hdl=1887/3206659 |hdl-access=free }}</ref>

====Sleep====
The effects of DBS on sleep are heterogenous but it generally improves in quality over time.<ref>{{cite journal |last1=Liu |first1=Y |last2=Zhang |first2=L |title=Subthalamic nucleus deep brain stimulation improves sleep in Parkinson's disease patients: a retrospective study and a meta-analysis. |journal=Sleep Medicine |date=October 2020 |volume=74 |pages=301–306 |doi=10.1016/j.sleep.2020.07.042 |pmid=32882663}}</ref> There is an increase of complex behavior during REM sleep after surgery independent of DBS target, while REM sleep without atonia increases with STN and decreases with GPi.<ref>{{cite journal |last1=Cavalloni |first1=F |last2=Bargiotas |first2=P |title=A case series and systematic review of rapid eye movement sleep behavior disorder outcome after deep brain stimulation in Parkinson's disease. |journal=Sleep Medicine |date=January 2021 |volume=77 |pages=170–176 |doi=10.1016/j.sleep.2020.11.025 |pmid=33412362|url=https://boris.unibe.ch/149175/ }}</ref>

====Speech and swallowing====
Almost 40% of patients develop speech impairment after DBS to the STN, with only 10% improving after reprogramming.<ref>{{cite journal |last1=Swinnen |first1=BEKS |last2=Lotfalla |first2=V |title=Programming Algorithm for the Management of Speech Impairment in Subthalamic Nucleus Deep Brain Stimulation for Parkinson's Disease. |journal=Neuromodulation |date=April 2024 |volume=27 |issue=3 |pages=528–537 |doi=10.1016/j.neurom.2023.05.002 |pmid=37452799|doi-access=free }}</ref> DBS to the GPi improves speech, in contrast to the STN, thalamus or zona incerta.<ref>{{cite journal |last1=Baudouin |first1=R |last2=Lechien |first2=JR |title=Deep Brain Stimulation Impact on Voice and Speech Quality in Parkinson's Disease: A Systematic Review. |journal=Otolaryngology–Head and Neck Surgery |date=March 2023 |volume=168 |issue=3 |pages=307–318 |doi=10.1177/01945998221120189 |pmid=36040825}}</ref> Up to 33% of patients can develop problems with speech after bilateral DBS to the STN, both by formal metrics<ref name="Swallowing Mvmt Disorders 2017">{{cite journal |last1=Alomar |first1=S |last2=King |first2=NK |last3=Tam |first3=J |last4=Bari |first4=AA |last5=Hamani |first5=C |last6=Lozano |first6=AM |title=Speech and language adverse effects after thalamotomy and deep brain stimulation in patients with movement disorders: A meta-analysis. |journal=Movement Disorders |date=January 2017 |volume=32 |issue=1 |pages=53–63 |doi=10.1002/mds.26924 |pmid=28124434}}</ref> and as subjectively reported by individuals and their families.<ref name="Swallowing ENT review 2023">{{cite journal |last1=Baudouin |first1=R |last2=Lechien |first2=JR |last3=Carpentier |first3=L |last4=Gurruchaga |first4=JM |last5=Lisan |first5=Q |last6=Hans |first6=S |title=Deep Brain Stimulation Impact on Voice and Speech Quality in Parkinson's Disease: A Systematic Review. |journal=Otolaryngology–Head and Neck Surgery |date=March 2023 |volume=168 |issue=3 |pages=307–318 |doi=10.1177/01945998221120189 |pmid=36040825}}</ref> This is less than that seen after thalamotomy (40%). The numbers are significantly lower for unilateral treatment, at 10-15%, but the symptomatic improvement with this is also one-sided, making it more appropriate for individuals with asymmetric disease.<ref name="Swallowing Mvmt Disorders 2017"/>

Speech impairment occurs in up to 20% of patients with DBS to the VIM of the thalamus. Focused ultrasound, by comparison, causes speech impairment in 15% of patients when done unilaterally and 40% when bilateral.<ref>{{cite journal |last1=Alomar |first1=S |last2=King |first2=NK  |title=Speech and language adverse effects after thalamotomy and deep brain stimulation in patients with movement disorders: A meta-analysis. |journal=Movement Disorders  |date=January 2017 |volume=32 |issue=1 |pages=53–63 |doi=10.1002/mds.26924 |pmid=28124434}}</ref>

Swallowing function after DBS can be impacted, analysis showing that it is either stable or improved after DBS to the GPi and has more variable effect after DBS to the STN, possibly worsening in on medication states, but stable or improved in off states.<ref>{{cite journal |last1=Yu |first1=H |last2=Takahashi |first2=K |last3=Bloom |first3=L |last4=Quaynor |first4=SD |last5=Xie |first5=T |title=Effect of Deep Brain Stimulation on Swallowing Function: A Systematic Review. |journal=Frontiers in Neurology |date=2020 |volume=11 |page=547 |doi=10.3389/fneur.2020.00547 |doi-access=free |pmid=32765388|pmc=7380112 }}</ref>

Speech disorders are more common after STN surgery, though dysphagia is more common after DBS to the GPi, an important finding because [[aspiration pneumonia]] is the most common cause of death in Parkinson's. The two nuclei have differing effects on the pedunculopontine nucleus, which in turn affects swallowing through the [[solitary nucleus]]. The GPi inhibits the PPN, while the STN excites it.<ref name ="Persistent 2018"/>

====Parkinsonian Tremor====
For Parkinson's tremor alone, DBS has similar efficacy to MR guided focused ultrasound.<ref name ="Bayesian 2021">{{cite journal |last1=Lin |first1=F |last2=Wu |first2=D |last3=Yu |first3=J |last4=Weng |first4=H |last5=Chen |first5=L |last6=Meng |first6=F |last7=Chen |first7=Y |last8=Ye |first8=Q |last9=Cai |first9=G |title=Comparison of efficacy of deep brain stimulation and focused ultrasound in parkinsonian tremor: a systematic review and network meta-analysis. |journal=Journal of Neurology, Neurosurgery, and Psychiatry |date=18 January 2021 |volume=92 |issue=4 |pages=434–443 |doi=10.1136/jnnp-2020-323656 |pmid=33461975}}</ref> DBS of the VIM is more commonly done with tremor-dominant variants of Parkinson's and [[essential tremor]]. It can cause dysarthria in about 20% of patients.<ref name="Lancet 2004"/> A Bayesian meta-analysis comparing multiple targets found STN DBS to be best for motor symptoms over the GPi and caudal zona incerta, but DBS as similar in efficacy to MR guided focused ultrasound for essential tremor.<ref name ="Bayesian 2021"/> DBS of the subthalamic nucleus has a more sudden effect on tremor, while tremor reduction in GPi can be delayed.{{citation needed|date=April 2025}}

A [[forest plot]] meta analysis found that DBS targeted at GPi and STN in the on-medication phase were similar; however, in the off-medication phase, Vim-targeted DBS was the superior target and could be a choice as a DBS target for tremor-dominant Parkinsonism.<ref>{{cite journal |last1=Mao |first1=Z |last2=Ling |first2=Z |last3=Pan |first3=L |last4=Xu |first4=X |last5=Cui |first5=Z |last6=Liang |first6=S |last7=Yu |first7=X |title=Comparison of Efficacy of Deep Brain Stimulation of Different Targets in Parkinson's Disease: A Network Meta-Analysis. |journal=Frontiers in Aging Neuroscience |date=2019 |volume=11 |page=23 |doi=10.3389/fnagi.2019.00023 |doi-access=free |pmid=30853908|pmc=6395396 }}</ref>

====Methodological limitations ====
In trials on interventions, symptom scales such as the [[Unified Parkinson's Disease Rating Scale]] (UPDRS III) are typically used. These metrics measure motor function with a score from 0 to 108. Alternatively, the 39-item Parkinson's disease questionnaire (PDQ-39) has been utilized to measure disease specific quality of life with a score between 0 and 100. The effectiveness of an intervention is usually based on comparison of these scores in [[treatment and control groups]]. It has been pointed out that a statistically significant numerical difference in a scale or questionnaire does not necessarily translate to a clinically meaningful impact for the individual.<ref>{{cite journal |last1=Petersen |first1=JJ |last2=Juul |first2=S |last3=Jørgensen |first3=CK |last4=Gluud |first4=C |last5=Jakobsen |first5=JC |title=Deep brain stimulation for neurological disorders: a protocol for a systematic review with meta-analysis and Trial Sequential Analysis of randomised clinical trials. |journal=Systematic Reviews |date=13 October 2022 |volume=11 |issue=1 |page=218 |doi=10.1186/s13643-022-02095-z |doi-access=free |pmid=36229825|pmc=9558400 }}</ref> Beyond this, the scales can be subjective and susceptible to [[placebo effect]]s and physician bias.<ref name="Lancet 2004"/> The minimal important difference (MID) or minimal clinically important difference (MCID) has been suggested as a more pragmatic metric to standardize the clinical impact of an intervention, though it has not yet been widely adopted. It is defined as the smallest difference in symptom scores that an individual would consider clinically meaningful.<ref>{{cite journal |last1=Petersen |first1=JJ |last2=Juul |first2=S |last3=Kamp |first3=CB |last4=Løkkegaard |first4=A |last5=Jakobsen |first5=JC |title=We need to rethink outcomes in Parkinson's disease research. |journal=BMJ (Clinical Research Ed.) |date=18 October 2024 |volume=387 |pages=q2280 |doi=10.1136/bmj.q2280 |pmid=39424336}}</ref>

=== Essential tremor ===
[[File:VIM of thalamus diagram.jpg|thumb|Ventrointermediate nucleus of the thalamus, the target nucleus for essential and Parkinson's tremor.]]
Essential tremor, the most common movement disorder, is a chronic condition characterized by involuntary and rhythmic shaking.<ref>{{Cite web |title=Essential Tremor: Essential Facts for Patients |url=https://www.movementdisorders.org/MDS/Resources/Patient-Education/Essential-Tremor.htm |access-date=2024-09-22 |website=www.movementdisorders.org}}</ref> It was the first indication to be approved for DBS (alongside Parkinsonian tremor) and before DBS had a long history of being treated with ablative brain lesioning.<ref>{{Cite journal |last1=Neudorfer |first1=Clemens |last2=Kultas-Ilinsky |first2=Kristy |last3=Ilinsky |first3=Igor |last4=Paschen |first4=Steffen |last5=Helmers |first5=Ann-Kristin |last6=Cosgrove |first6=G. Rees |last7=Richardson |first7=R. Mark |last8=Horn |first8=Andreas |last9=Deuschl |first9=Günther |date=April 2024 |title=The role of the motor thalamus in deep brain stimulation for essential tremor |journal=Neurotherapeutics |language=en |volume=21 |issue=3 |pages=e00313 |doi=10.1016/j.neurot.2023.e00313 |pmc=11103222 |pmid=38195310}}</ref>

Frequencies above 100&nbsp;Hz are most effective for cessation of tremor, while lower frequencies have less effect.<ref>{{Cite journal |last1=Benabid |first1=A.L. |last2=Pollak |first2=P. |date=February 1991 |title=Long-term suppression of tremor by chronic stimulation of the ventral intermediate thalamic nucleus |url=https://linkinghub.elsevier.com/retrieve/pii/014067369191175T |journal=The Lancet |language=en |volume=337 |issue=8738 |pages=403–406 |doi=10.1016/0140-6736(91)91175-T |pmid=1671433|url-access=subscription }}</ref> In clinical practice, frequencies between 80 and 180&nbsp;Hz are typically applied. DBS electrodes commonly target the ventrointermediate nucleus of the thalamus (VIM) or ventrally adjacent areas in the [[zona incerta]] or posterior thalamus. Multiple targets along the circuitry of the cerebellothalamic pathway (also referred to as the dentatorubrothalamic or dentatothalamic tract) have been shown to have similar therapeutic effect.<ref>{{Cite journal |last1=Nowacki |first1=Andreas |date=May 2022 |title=Probabilistic Mapping Reveals Optimal Stimulation Site in Essential Tremor |url=https://onlinelibrary.wiley.com/doi/10.1002/ana.26324 |journal=Annals of Neurology |language=en |volume=91 |issue=5 |pages=602–612 |doi=10.1002/ana.26324 |pmid=35150172 |issn=0364-5134}}</ref><ref>{{Cite journal |last1=Neudorfer |first1=Clemens |date=May 2022 |title=Personalizing Deep Brain Stimulation Using Advanced Imaging Sequences |url=https://onlinelibrary.wiley.com/doi/10.1002/ana.26326 |journal=Annals of Neurology |language=en |volume=91 |issue=5 |pages=613–628 |doi=10.1002/ana.26326 |pmid=35165921 |issn=0364-5134}}</ref><ref>{{Cite journal |last1=Fox |first1=Michael D. |last2=Deuschl |first2=Günther |date=May 2022 |title=Converging on a Neuromodulation Target for Tremor |url=https://onlinelibrary.wiley.com/doi/10.1002/ana.26361 |journal=Annals of Neurology |language=en |volume=91 |issue=5 |pages=581–584 |doi=10.1002/ana.26361 |pmid=35362142 |issn=0364-5134|url-access=subscription }}</ref>

Possible side effects of DBS for essential tremor include speech difficulties and paresthesia. Similar targets have previously been applied to treat essential tremor using surgical lesioning, for instance using [[HIFU|MR-guided Focused Ultrasound]], [[Radiosurgery|Gamma-Knife Radiosurgery]] or conventional [[Radiofrequency ablation|radiofrequency lesioning]]. The annual volume of [[MRgFUS]] [[thalamotomy|thalamotomies]] has overtaken DBS for treatment of tremor.<ref>{{Cite journal |last1=Joutsa |first1=Juho |last2=Lipsman |first2=Nir |last3=Horn |first3=Andreas |last4=Cosgrove |first4=G Rees |last5=Fox |first5=Michael D |date=2023-08-01 |title=The return of the lesion for localization and therapy |url=https://academic.oup.com/brain/article/146/8/3146/7114971 |journal=Brain |language=en |volume=146 |issue=8 |pages=3146–3155 |doi=10.1093/brain/awad123 |issn=0006-8950 |pmc=10393408 |pmid=37040563}}</ref>

=== Dystonia ===
DBS is also used to treat [[dystonia]], a [[movement disorder]] characterized by sustained repetitive muscle contractions causing painful abnormal postures and involuntary movements. DBS is effective in treating primary generalized dystonia, and also used for focal variants such as cervical and task-specific dystonias. In studies targeting the GPi using high frequency DBS there were improvements of ~45% within the first six months of treatment.<ref name="nejm.org"/>

In contrast to some symptoms in Parkinson's disease or essential tremor, improvements in dystonia are appear over weeks to months. The delay is thought to be a consequence of the complexity of dystonic motor circuits and the time required for long-term neuroplastic remodeling. Despite its slower onset, many individuals experience lasting and meaningful improvements.

Recent large-scale mapping efforts have suggested slightly different optimal target sites for different kinds of dystonia.<ref>{{Cite journal |last1=Horn |first1=Andreas |date=2022-04-05 |title=Optimal deep brain stimulation sites and networks for cervical vs. generalized dystonia |journal=Proceedings of the National Academy of Sciences |language=en |volume=119 |issue=14 |pages=e2114985119 |doi=10.1073/pnas.2114985119 |doi-access=free |issn=0027-8424 |pmc=9168456 |pmid=35357970|bibcode=2022PNAS..11914985H }}</ref><ref>{{Citation |last1=Butenko |first1=Konstantin |title=Engaging dystonia networks with subthalamic stimulation |date=2024-05-25 |language=en |doi=10.1101/2024.05.24.24307896 |pmc=11188120 |pmid=38903109 |journal=MedRxiv: The Preprint Server for Health Sciences }}</ref><ref>{{Cite journal |last1=Neumann |first1=Wolf-Julian|date=December 2017 |title=A localized pallidal physiomarker in cervical dystonia |url=https://onlinelibrary.wiley.com/doi/10.1002/ana.25095 |journal=Annals of Neurology |language=en |volume=82 |issue=6 |pages=912–924 |doi=10.1002/ana.25095 |pmid=29130551 |issn=0364-5134|url-access=subscription }}</ref><ref>{{Cite journal |last1=Barow |first1=Ewgenia |date=November 2014 |title=Deep brain stimulation suppresses pallidal low frequency activity in patients with phasic dystonic movements |journal=Brain |language=en |volume=137 |issue=11 |pages=3012–3024 |doi=10.1093/brain/awu258 |issn=1460-2156 |pmc=4813762 |pmid=25212852}}</ref>

=== Obsessive-Compulsive-Disorder ===
DBS for OCD,<ref name=":8">{{Cite journal |last1=Nuttin |first1=Bart |last2=Cosyns |first2=Paul |last3=Demeulemeester |first3=Hilde |last4=Gybels |first4=Jan |last5=Meyerson |first5=Björn |date=October 1999 |title=Electrical stimulation in anterior limbs of internal capsules in patients with obsessive-compulsive disorder |url=https://linkinghub.elsevier.com/retrieve/pii/S0140673699023764 |journal=The Lancet |language=en |volume=354 |issue=9189 |page=1526 |doi=10.1016/S0140-6736(99)02376-4|pmid=10551504 |url-access=subscription }}</ref> Tourette's Syndrome,<ref name="linkinghub.elsevier.com">{{Cite journal |last1=Vandewalle |first1=V |last2=van der Linden |first2=Chr |last3=Groenewegen |first3=Hj |last4=Caemaert |first4=J |date=February 1999 |title=Stereotactic treatment of Gilles de la Tourette syndrome by high frequency stimulation of thalamus |url=https://linkinghub.elsevier.com/retrieve/pii/S0140673698059649 |journal=The Lancet |language=en |volume=353 |issue=9154 |page=724 |doi=10.1016/S0140-6736(98)05964-9|pmid=10073521 |url-access=subscription }}</ref> and dystonia were first completed in 1999.<ref>{{Cite journal |last1=Krauss |first1=Joachim K |last2=Pohle |first2=Thomas |last3=Weber |first3=Sabine |last4=Ozdoba |first4=Christoph |last5=Burgunder |first5=Jean-Marc |date=September 1999 |title=Bilateral stimulation of globus pallidus internus for treatment of cervical dystonia |url=https://linkinghub.elsevier.com/retrieve/pii/S0140673699800221 |journal=The Lancet |language=en |volume=354 |issue=9181 |pages=837–838 |doi=10.1016/S0140-6736(99)80022-1|pmid=10485734 |url-access=subscription }}</ref> The original target studied was the [[anterior limb of the internal capsule]],<ref name=":8" /> though multiple sites have been probed since then. Within the internal capsule, large probabilistic mapping trials have identified two therapeutic sites,<ref>{{Cite journal |last1=Meyer |first1=Garance M. |last2=Hollunder |first2=Barbara |date=July 2024 |title=Deep Brain Stimulation for Obsessive-Compulsive Disorder: Optimal Stimulation Sites |url=https://linkinghub.elsevier.com/retrieve/pii/S0006322323017857 |journal=Biological Psychiatry |language=en |volume=96 |issue=2 |pages=101–113 |doi=10.1016/j.biopsych.2023.12.010 |pmc=11190041 |pmid=38141909|pmc-embargo-date=July 15, 2025 }}</ref> one thought to corresponding to the [[basal ganglia|direct pathway]] in the basal ganglia<ref name="ReferenceA">{{Cite journal |last1=Li |first1=Ningfei |date=2020-07-03 |title=A unified connectomic target for deep brain stimulation in obsessive-compulsive disorder |journal=Nature Communications |language=en |volume=11 |issue=1 |page=3364 |doi=10.1038/s41467-020-16734-3 |issn=2041-1723 |pmc=7335093 |pmid=32620886|bibcode=2020NatCo..11.3364L }}</ref> to the subthalamic nucleus and other midbrain regions, the other [[Indirect pathway|indirect]].

A potential circuit structure that seems to combine most effective targets in both the ALIC and STN region has been identified and termed the OCD response tract, though multiple targets have been probed and found to have effect.<ref name="ReferenceA"/><ref>{{Cite journal |last1=Gadot |first1=Ron |date=July 2024 |title=Tractography-Based Modeling Explains Treatment Outcomes in Patients Undergoing Deep Brain Stimulation for Obsessive-Compulsive Disorder |journal=Biological Psychiatry |language=en |volume=96 |issue=2 |pages=95–100 |doi=10.1016/j.biopsych.2023.01.017 |pmc=10387502 |pmid=36948900}}</ref>

DBS for OCD received a [[humanitarian device exemption]] from the FDA in 2009.<ref>{{Cite web |title=FDA Humanitarian Device Exemption Approval for OCD |url=https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfhde/hde.cfm?id=375533|archive-url=https://web.archive.org/web/20201020021025/https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfhde/hde.cfm?id=375533|url-status=dead|archive-date=October 20, 2020}}</ref> In Europe, the CE Mark for Deep Brain Stimulation (DBS) for Obsessive-Compulsive Disorder (OCD) was active from 2009 to 2022 but not renewed due to a lack of government health coverage.<ref name="nature.com"/><ref>{{Cite journal |last1=Mosley |first1=Philip E |last2=Velakoulis |first2=Dennis |last3=Farrand |first3=Sarah |last4=Marsh |first4=Rodney |last5=Mohan |first5=Adith |last6=Castle |first6=David |last7=Sachdev |first7=Perminder S |date=May 2022 |title=Deep brain stimulation for treatment-refractory obsessive-compulsive disorder should be an accepted therapy in Australia |url=http://journals.sagepub.com/doi/10.1177/00048674211031482 |journal=Australian & New Zealand Journal of Psychiatry |language=en |volume=56 |issue=5 |pages=430–436 |doi=10.1177/00048674211031482 |pmid=34263654 |issn=0004-8674|url-access=subscription }}</ref>

=== Epilepsy ===
[[File:Vagus nerve stimulation.jpg|thumb|260px|Vagus nerve stimulator for epilepsy.]]

DBS has been studied for treatment resistant epilepsy with seizure foci not amenable to surgical resection or [[vagus nerve stimulation]];<ref>{{Cite journal |last1=Benbadis |first1=Selim R. |last2=Geller |first2=Eric |last3=Ryvlin |first3=Philippe |last4=Schachter |first4=Steven |last5=Wheless |first5=James |last6=Doyle |first6=Werner |last7=Vale |first7=Fernando L. |date=November 2018 |title=Putting it all together: Options for intractable epilepsy |url=https://linkinghub.elsevier.com/retrieve/pii/S1525505018303834 |journal=Epilepsy & Behavior |language=en |volume=88 |pages=33–38 |doi=10.1016/j.yebeh.2018.05.030|pmid=30241957 |url-access=subscription }}</ref> almost 40% of individuals with the disease are inadequately treated with medication alone.<ref>{{cite journal |display-authors=6 |vauthors=Sultana B, Panzini MA, Veilleux Carpentier A, Comtois J, Rioux B, Gore G, Bauer PR, Kwon CS, Jetté N, Josephson CB, Keezer MR |date=April 2021 |title=Incidence and Prevalence of Drug-Resistant Epilepsy: A Systematic Review and Meta-analysis |journal=Neurology |volume=96 |issue=17 |pages=805–817 |doi=10.1212/WNL.0000000000011839 |pmid=33722992 |s2cid=233401199 |hdl-access=free |hdl=1866/26896}}</ref>

[[Responsive neurostimulation device|Responsive neurostimulation]] is a form of adaptive brain stimulation that targets the [[Anterior nuclei of thalamus|anterior nucleus of the thalamus]]. The anterior nuclei of the thalamus is the only FDA approved target for epilepsy treatment, with some individuals achieving more than a 50% decrease in seizures. Other brain regions being studied as potential targets include:
* Centromedian nucleus (CM): Located in the thalamus, CM-DBS has been used in some cases of generalized epilepsy, including [[Lennox–Gastaut syndrome|Lennox-Gastaut]] syndrome. It targets the thalamocortical networks involved in seizure propagation and has been reported to help reduce seizure severity and frequency.<ref name=":9">{{Cite journal |last1=Vetkas |first1=Artur |last2=Fomenko |first2=Anton |last3=Germann |first3=Jürgen |last4=Sarica |first4=Can |last5=Iorio-Morin |first5=Christian |last6=Samuel |first6=Nardin |last7=Yamamoto |first7=Kazuaki |last8=Milano |first8=Vanessa |last9=Cheyuo |first9=Cletus |last10=Zemmar |first10=Ajmal |last11=Elias |first11=Gavin |last12=Boutet |first12=Alexandre |last13=Loh |first13=Aaron |last14=Santyr |first14=Brendan |last15=Gwun |first15=Dave |date=March 2022 |title=Deep brain stimulation targets in epilepsy: Systematic review and meta-analysis of anterior and centromedian thalamic nuclei and hippocampus |url=https://onlinelibrary.wiley.com/doi/10.1111/epi.17157 |journal=Epilepsia |language=en |volume=63 |issue=3 |pages=513–524 |doi=10.1111/epi.17157 |pmid=34981509 |issn=0013-9580|url-access=subscription }}</ref>
* Hippocampus: Particularly in patients with temporal lobe epilepsy, hippocampal DBS has been investigated as an option due to its role in seizure propagation and memory function. Studies have generally shown promising results, particularly for temporal lobe seizures.<ref name=":9" />
* Subthalamic nucleus (STN): Commonly used in Parkinson's disease, the STN has also been explored as a target for epilepsy due to its involvement in motor control and seizure modulation. Initial studies have shown seizure reduction, especially in patients with the focal subtype of the disease.<ref>{{Cite journal |last1=Yan |first1=Hao |last2=Ren |first2=Liankun |last3=Yu |first3=Tao |date=December 2022 |title=Deep brain stimulation of the subthalamic nucleus for epilepsy |journal=Acta Neurologica Scandinavica |language=en |volume=146 |issue=6 |pages=798–804 |doi=10.1111/ane.13707 |issn=0001-6314|doi-access=free |pmid=36134756 }}</ref>

=== Tourette syndrome ===
{{further|Management of Tourette syndrome}}
DBS has been used experimentally for individuals with severe [[Tourette syndrome]] that do not respond to conventional treatment. Despite early successes, DBS remains a highly [[Biomedical research|experimental]] procedure for the illness, with more study needed to fully understand its clinical effects.<ref name=Singer2011>{{cite book |doi=10.1016/B978-0-444-52014-2.00046-X |chapter=Tourette syndrome and other tic disorders |title=Hyperkinetic Movement Disorders |series=Handbook of Clinical Neurology |year=2011 | vauthors = Singer HS |volume=100 |pages=641–657 |pmid=21496613 |isbn=978-0-444-52014-2 }} Also see {{cite journal | vauthors = Singer HS | title = Tourette's syndrome: from behaviour to biology | journal = The Lancet. Neurology | volume = 4 | issue = 3 | pages = 149–159 | date = March 2005 | pmid = 15721825 | doi = 10.1016/S1474-4422(05)01012-4 | doi-broken-date = 3 April 2025 | s2cid = 20181150 }}</ref><ref name=Robertson2011>{{cite journal | vauthors = Robertson MM | title = Gilles de la Tourette syndrome: the complexities of phenotype and treatment | journal = British Journal of Hospital Medicine | volume = 72 | issue = 2 | pages = 100–107 | date = February 2011 | pmid = 21378617 | doi = 10.12968/hmed.2011.72.2.100 }}</ref><ref name=Du2010>{{cite journal | vauthors = Du JC, Chiu TF, Lee KM, Wu HL, Yang YC, Hsu SY, Sun CS, Hwang B, Leckman JF | display-authors = 6 | title = Tourette syndrome in children: an updated review | journal = Pediatrics and Neonatology | volume = 51 | issue = 5 | pages = 255–264 | date = October 2010 | pmid = 20951354 | doi = 10.1016/S1875-9572(10)60050-2 | doi-access = free }}</ref><ref>[[Tourette Association of America|Tourette Syndrome Association]]. [https://web.archive.org/web/20051122154536/http://tsa-usa.org/news/DBS-Statement.htm Statement: Deep Brain Stimulation and Tourette Syndrome.] Retrieved November 22, 2005.</ref> The procedure is well tolerated, but complications include "short battery life, abrupt symptom worsening upon cessation of stimulation, hypomanic or manic conversion, and the significant time and effort involved in optimizing stimulation parameters".<ref name=Malone>{{cite book |chapter=Behavioral neurosurgery |pages=241–247 |chapter-url={{Google books|hhE74A1fTQkC|page=241|plainurl=yes}} |pmid=16536372 | vauthors = Walkup JT, Mink JW, Hollenbeck PJ |title=Tourette Syndrome |series=Advances in Neurology |date=2006 |volume=99 |publisher=Lippincott Williams & Wilkins |isbn=978-0-7817-9970-6 }}</ref>
The first clinical use of DBS for Tourette's Syndrome was carried out in 1999<ref name="linkinghub.elsevier.com"/> in follow up to earlier studies on ablative lesions.<ref>{{Cite journal |last=Hassler |first=Rolf |title=raitement stéréotaxique des tics et cris inarticulés ou coprolaliques considérés comme phénomene d'obsession motrice au cours de la maladie de Gilles de la Tourette |journal=Rev Neurol |publication-date=1970}}</ref>

The procedure is invasive and expensive and requires long-term expert care and its benefits for severe Tourette's are inconclusive. Tourette's is more common in children, tending to remit spontaneously in adulthood, limiting the applicability of surgery in these populations. It also may not always be obvious how to utilize DBS for a particular person because the diagnosis of Tourette's is based on a history of symptoms rather than an examination of neurological activity.

The [[Tourette Association of America]] recommends that the procedure be reserved for adults with severe debilitating treatment resistant variants of the disease, and without comorbidities such as substance abuse or personality disorders.<ref name=Malone/>

=== Depression ===
Though depression can be a contraindication for electrostimulation of other chronic neurologic diseases in the basal ganglia, the therapy can also be used for treatment of severe depression. The target for electrostimulation in depression is more [[anterior]] and superficial at the frontal lobes, as opposed to other motor disorders where it is deeper in the basal ganglia. Beginning in the 1950s, treatment has been attempted in the [[Brodmann area 25|subcallosal cingulate region]]<ref>{{Cite journal |last1=Mayberg |first1=Helen S. |date=March 2005 |title=Deep Brain Stimulation for Treatment-Resistant Depression |url=https://linkinghub.elsevier.com/retrieve/pii/S089662730500156X |journal=Neuron |language=en |volume=45 |issue=5 |pages=651–660 |doi=10.1016/j.neuron.2005.02.014|pmid=15748841 }}</ref> and the ventral capsule/ventral striatum <ref>{{Cite journal |last1=Dougherty |first1=Darin D. |date=August 2015 |title=A Randomized Sham-Controlled Trial of Deep Brain Stimulation of the Ventral Capsule/Ventral Striatum for Chronic Treatment-Resistant Depression |url=https://linkinghub.elsevier.com/retrieve/pii/S0006322314009688 |journal=Biological Psychiatry |language=en |volume=78 |issue=4 |pages=240–248 |doi=10.1016/j.biopsych.2014.11.023|pmid=25726497 |url-access=subscription }}</ref> have shown mixed outcomes.

[[Diffusion tensor tractography|Diffusion-weighted imaging based tractography]] has led to the theoretical discovery of the so-called 'depression switch',<ref>{{Cite journal |last1=Choi |first1=Ki Sueng |last2=Riva-Posse |first2=Patricio |last3=Gross |first3=Robert E. |last4=Mayberg |first4=Helen S. |date=2015-11-01 |title=Mapping the "Depression Switch" During Intraoperative Testing of Subcallosal Cingulate Deep Brain Stimulation |journal=JAMA Neurology |language=en |volume=72 |issue=11 |pages=1252–1260 |doi=10.1001/jamaneurol.2015.2564 |issn=2168-6149 |pmc=4834289 |pmid=26408865}}</ref> the intersection of four bundles that allowed more deliberate targeting of DBS in the subcallosal area and improved results in additional open-label studies.<ref>{{Cite journal |last1=Riva-Posse |first1=P |date=April 2018 |title=A connectomic approach for subcallosal cingulate deep brain stimulation surgery: prospective targeting in treatment-resistant depression |journal=Molecular Psychiatry |language=en |volume=23 |issue=4 |pages=843–849 |doi=10.1038/mp.2017.59 |issn=1359-4184 |pmc=5636645 |pmid=28397839}}</ref> While anatomical descriptions as well as supposed mechanisms for this target site have been debated,<ref>{{Cite journal |last1=Haber |first1=Suzanne N. |last2=Yendiki |first2=Anastasia |author-link2=Anastasia Yendiki |last3=Jbabdi |first3=Saad |date=November 2021 |title=Four Deep Brain Stimulation Targets for Obsessive-Compulsive Disorder: Are They Different? |journal=Biological Psychiatry |language=en |volume=90 |issue=10 |pages=667–677 |doi=10.1016/j.biopsych.2020.06.031 |pmc=9569132 |pmid=32951818}}</ref><ref>{{Cite journal |last1=Bouthour |first1=Walid |last2=Mégevand |first2=Pierre |last3=Donoghue |first3=John |last4=Lüscher |first4=Christian |last5=Birbaumer |first5=Niels |last6=Krack |first6=Paul |date=June 2019 |title=Biomarkers for closed-loop deep brain stimulation in Parkinson disease and beyond |url=https://www.nature.com/articles/s41582-019-0166-4 |journal=Nature Reviews Neurology |language=en |volume=15 |issue=6 |pages=343–352 |doi=10.1038/s41582-019-0166-4 |pmid=30936569 |issn=1759-4758|url-access=subscription }}</ref> clinical effects of this DBS target in patients with TRD have been promising.<ref>{{Cite journal |last1=Bewernick |first1=Bettina H. |last2=Kayser |first2=Sarah |last3=Gippert |first3=Sabrina M. |last4=Switala |first4=Christina |last5=Coenen |first5=Volker A. |last6=Schlaepfer |first6=Thomas E. |date=May 2017 |title=Deep brain stimulation to the medial forebrain bundle for depression- long-term outcomes and a novel data analysis strategy |url=https://linkinghub.elsevier.com/retrieve/pii/S1935861X17306034 |journal=Brain Stimulation |language=en |volume=10 |issue=3 |pages=664–671 |doi=10.1016/j.brs.2017.01.581|pmid=28259544 |url-access=subscription }}</ref>

=== Chronic pain ===
Stimulation of the [[periaqueductal gray]] and [[Periventricular nucleus|periventricular gray]] for [[Pain#Nociceptive|nociceptive pain]], and the [[internal capsule]], [[ventral posterolateral nucleus]], and [[ventral posteromedial nucleus]] for [[Pain#Nociceptive|neuropathic pain]] has produced impressive results with some people, but results vary. One study<ref name="Young">{{cite journal |vauthors=Young RF, Brechner T |date=March 1986 |title=Electrical stimulation of the brain for relief of intractable pain due to cancer |journal=Cancer |volume=57 |issue=6 |pages=1266–1272 |doi=10.1002/1097-0142(19860315)57:6<1266::aid-cncr2820570634>3.0.co;2-q |pmid=3484665 |s2cid=41929961 |doi-access=}}</ref> of 17 people with intractable cancer pain found that 13 were virtually pain-free and only four required opioid analgesics on release from hospital after the intervention. Most ultimately did resort to opioids, usually in the last few weeks of life.<ref name="Johnson">{{cite book |title=Clinical pain management: Cancer pain |vauthors=Johnson MI, Oxberry SG, Robb K |publisher=Hodder Arnold |year=2008 |isbn=978-0-340-94007-5 |editor=Sykes N, Bennett MI & Yuan C-S |edition=2nd |location=London |pages=235–250 |chapter=Stimulation-induced analgesia}}</ref> DBS has also been applied for [[phantom limb pain]].<ref>{{cite journal |display-authors=6 |vauthors=Kringelbach ML, Jenkinson N, Green AL, Owen SL, Hansen PC, Cornelissen PL, Holliday IE, Stein J, Aziz TZ |date=February 2007 |title=Deep brain stimulation for chronic pain investigated with magnetoencephalography |journal=NeuroReport |volume=18 |issue=3 |pages=223–228 |citeseerx=10.1.1.511.2667 |doi=10.1097/wnr.0b013e328010dc3d |pmid=17314661 |s2cid=7091307}}</ref>