Editing Deep brain stimulation (section)

====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>