Editing Subthalamic nucleus (section)

==Pathophysiology==
Lesioning the STN leads to alleviation of motor symptoms such as [[Hypokinesia|akinesia]], [[Rigidity (neurology)|rigidity]], and [[tremor]] in [[Parkinson's disease|Parkinson disease]]. This was first shown in the [[MPTP]] primate model in a paper by [[Hagai Bergman|Bergman]] and colleagues.<ref>{{cite journal | vauthors = Bergman H, Wichmann T, DeLong MR | title = Reversal of experimental parkinsonism by lesions of the subthalamic nucleus | journal = Science | volume = 249 | issue = 4975 | pages = 1436–1438 | date = September 1990 | pmid = 2402638 | doi = 10.1126/science.2402638 | bibcode = 1990Sci...249.1436B }}</ref> This inspired Benazzouz and colleagues to probe deep brain stimulation of the nucleus, which was known to exert similar effects as ablative lesions.<ref>{{cite journal | vauthors = Benazzouz A, Gross C, Féger J, Boraud T, Bioulac B | title = Reversal of rigidity and improvement in motor performance by subthalamic high-frequency stimulation in MPTP-treated monkeys | journal = The European Journal of Neuroscience | volume = 5 | issue = 4 | pages = 382–389 | date = April 1993 | pmid = 8261116 | doi = 10.1111/j.1460-9568.1993.tb00505.x }}</ref> Soon after, the team of [[Alim Louis Benabid]] showed that deep brain stimulation of the nucleus leads to symptom relief in human patients with Parkinson disease, as well,<ref>{{cite journal | vauthors = Pollak P, Benabid AL, Gross C, Gao DM, Laurent A, Benazzouz A, Hoffmann D, Gentil M, Perret J | title = [Effects of the stimulation of the subthalamic nucleus in Parkinson disease] | journal = Revue Neurologique | volume = 149 | issue = 3 | pages = 175–176 | date = 1993 | pmid = 8235208 | url = https://pubmed.ncbi.nlm.nih.gov/8235208 }}</ref> which led to the establishment of the currently [[Food and Drug Administration|FDA]] approved and widely applied form of [[deep brain stimulation]]. The first to be stimulated are the terminal arborisations of afferent axons, which modify the activity of subthalamic neurons. However, it has been shown in thalamic slices from mice,<ref>{{cite journal | vauthors = Bekar L, Libionka W, Tian GF, Xu Q, Torres A, Wang X, Lovatt D, Williams E, Takano T, Schnermann J, Bakos R, Nedergaard M | title = Adenosine is crucial for deep brain stimulation-mediated attenuation of tremor | journal = Nature Medicine | volume = 14 | issue = 1 | pages = 75–80 | date = January 2008 | pmid = 18157140 | doi = 10.1038/nm1693 | s2cid = 7107064 }}</ref> that the stimulus also causes nearby astrocytes to release [[adenosine triphosphate]] (ATP), a precursor to [[adenosine]] (through a catabolic process). In turn, adenosine A1 receptor activation depresses excitatory transmission in the thalamus, thus mimicking [[ablation]] of the subthalamic nucleus.

Before the [[Hagai Bergman|Bergman]] paper, the stereotactic field avoided lesioning the nucleus, since it was known that unilateral destruction or disruption of the subthalamic nucleus — which may result from naturally occurring strokes — may lead to [[hemiballismus]]. While this remains generally true, iatrogenic lesioning of the STN has been carried out numerous times and has recently gained new wind with the advent of [[HIFU|MR guided focused ultrasound]], which has also been probed for subthalamic nucleotomies to treat Parkinson disease.<ref>{{cite journal | vauthors = Martínez-Fernández R, Máñez-Miró JU, Rodríguez-Rojas R, Del Álamo M, Shah BB, Hernández-Fernández F, Pineda-Pardo JA, Monje MH, Fernández-Rodríguez B, Sperling SA, Mata-Marín D, Guida P, Alonso-Frech F, Obeso I, Gasca-Salas C, Vela-Desojo L, Elias WJ, Obeso JA | title = Randomized Trial of Focused Ultrasound Subthalamotomy for Parkinson's Disease | journal = The New England Journal of Medicine | volume = 383 | issue = 26 | pages = 2501–2513 | date = December 2020 | pmid = 33369354 | doi = 10.1056/NEJMoa2016311 }}</ref> Curiously, a team around [[Michael D. Fox|Michael Fox]] could recently show that, while some lesions that led to hemiballism were indeed in and around the STN, the majority of reported cases were in other regions of the brain.<ref>{{cite journal | vauthors = Laganiere S, Boes AD, Fox MD | title = Network localization of hemichorea-hemiballismus | journal = Neurology | volume = 86 | issue = 23 | pages = 2187–2195 | date = June 2016 | pmid = 27170566 | pmc = 4898318 | doi = 10.1212/WNL.0000000000002741 }}</ref>

As one of the STN's suspected functions is in impulse control, dysfunction in this region has been implicated in [[obsessive–compulsive disorder]].<ref>{{cite book| vauthors = Carter R |title=The Human Brain Book|pages=58,233}}</ref> Application of high frequency pulses by [[deep brain stimulation]] has shown some promise in correcting severe impulsive behavior and has been [[Food and Drug Administration|FDA]] approved for treatment resistant cases with the disorder.<ref>{{cite journal | vauthors = Mallet L, Polosan M, Jaafari N, Baup N, Welter ML, Fontaine D, du Montcel ST, Yelnik J, Chéreau I, Arbus C, Raoul S, Aouizerate B, Damier P, Chabardès S, Czernecki V, Ardouin C, Krebs MO, Bardinet E, Chaynes P, Burbaud P, Cornu P, Derost P, Bougerol T, Bataille B, Mattei V, Dormont D, Devaux B, Vérin M, Houeto JL, Pollak P, Benabid AL, Agid Y, Krack P, Millet B, Pelissolo A | title = Subthalamic nucleus stimulation in severe obsessive-compulsive disorder | journal = The New England Journal of Medicine | volume = 359 | issue = 20 | pages = 2121–2134 | date = November 2008 | pmid = 19005196 | doi = 10.1056/NEJMoa0708514 | doi-access = free }}</ref>