Editing Striatum (section)

==Clinical significance==

===Parkinson's disease and other movement disorders===
[[Parkinson's disease]] results in loss of dopaminergic innervation to the dorsal striatum (and other basal ganglia) and a cascade of consequences. [[Atrophy]] of the striatum is also involved in [[Huntington's disease]], and [[movement disorder]]s such as [[chorea]], [[choreoathetosis]], and [[dyskinesias]].<ref name="lancetseminar">{{cite journal |author=Walker FO |title=Huntington's disease |journal=[[The Lancet|Lancet]] |volume=369 |issue=9557 |pages=218–28 |date=January 2007 |pmid=17240289 |doi=10.1016/S0140-6736(07)60111-1 |s2cid=46151626 }}</ref> These have also been described as ''circuit disorders'' of the basal ganglia.<ref>{{Cite journal|pmid=17210805|year=2007|last1=Delong|first1=M. R.|title=Circuits and circuit disorders of the basal ganglia|journal=Archives of Neurology|volume=64|issue=1|pages=20–4|last2=Wichmann|first2=T.|doi=10.1001/archneur.64.1.20|doi-access=|s2cid=9606341 }}</ref>

===Addiction===
[[File:Overview of reward structures in the human brain.jpg|thumb|Overview of reward structures and associated pathways]]
[[Addiction]], a disorder of the brain's [[reward system]], arises through the [[gene expression|overexpression]] of [[FOSB#DeltaFosB|DeltaFosB]] (ΔFosB), a [[transcription factor]], in the [[D1-type]] [[medium spiny neuron]]s of the [[ventral striatum]]. ΔFosB is an [[inducible gene]] which is increasingly expressed in the [[nucleus accumbens]] as a result of repeatedly using an addictive drug or overexposure to other addictive stimuli.<ref name="Cellular basis">{{cite journal | author = Nestler EJ | title = Cellular basis of memory for addiction | journal = Dialogues Clin. Neurosci. | volume = 15 | issue = 4 | pages = 431–443 |date=December 2013  | doi = 10.31887/DCNS.2013.15.4/enestler | pmid = 24459410 | pmc = 3898681 }}</ref><ref name="Natural and drug addictions">{{cite journal | vauthors = Olsen CM | title = Natural rewards, neuroplasticity, and non-drug addictions | journal = Neuropharmacology | volume = 61 | issue = 7 | pages = 1109–22 | date = Dec 2011 | pmid = 21459101 | pmc = 3139704 | doi = 10.1016/j.neuropharm.2011.03.010 }}<br />[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3139704/table/T1/?report=objectonly Table 1]</ref>

===Bipolar disorder===
An association has been observed between striatal expression of variants of the [[PDE10A]] gene and some [[bipolar I disorder]] patients. Variants of other genes, [[DISC1]] and [[GNAS complex locus|GNAS]], have been associated with [[bipolar II disorder]].<ref>{{cite journal |last1=McDonald |first1=M-L |last2=MacMullen |first2=C |last3=Liu |first3=D J |last4=Leal |first4=S M |last5=Davis |first5=R L |title=Genetic association of cyclic AMP signaling genes with bipolar disorder |journal=Translational Psychiatry |date=2 October 2012 |volume=2 |issue=10 |pages=e169 |doi=10.1038/tp.2012.92 |pmid=23032945 |pmc=3565822 }}</ref>

===Autism spectrum disorder===

[[Autism spectrum|Autism spectrum disorder]] (ASD)  is characterized by cognitive inflexibility and poor understanding of social systems. This inflexible behavior originates in defects in the pre-frontal cortex as well as the striatal circuits.<ref>{{cite journal |last1=Fineberg |first1=Naomi A |last2=Potenza |first2=Marc N |last3=Chamberlain |first3=Samuel R |last4=Berlin |first4=Heather A |last5=Menzies |first5=Lara |last6=Bechara |first6=Antoine |last7=Sahakian |first7=Barbara J |last8=Robbins |first8=Trevor W |last9=Bullmore |first9=Edward T |last10=Hollander |first10=Eric |title=Probing Compulsive and Impulsive Behaviors, from Animal Models to Endophenotypes: A Narrative Review |journal=Neuropsychopharmacology |date=25 November 2009 |volume=35 |issue=3 |pages=591–604 |doi=10.1038/npp.2009.185 |pmc=3055606 |pmid=19940844 }}</ref> The defects in the striatum seem to specifically contribute to the motor, social and communication impairments seen in ASD patients. In mice which have an ASD-like phenotype induced via the overexpression of the [[EIF4E|eukaryotic initiation of translation factor 4E]], it has been shown that these defects seem to stem from the reduced ability to store and process information in the striatum, which leads to the difficulty seen in forming new motor patterns, as well as disengaging from existing ones.<ref>{{cite journal |last1=Santini |first1=Emanuela |last2=Huynh |first2=Thu N. |last3=MacAskill |first3=Andrew F. |last4=Carter |first4=Adam G. |last5=Pierre |first5=Philippe |last6=Ruggero |first6=Davide |last7=Kaphzan |first7=Hanoch |last8=Klann |first8=Eric |title=Exaggerated translation causes synaptic and behavioural aberrations associated with autism |journal=Nature |date=23 December 2012 |volume=493 |issue=7432 |pages=411–415 |doi=10.1038/nature11782 |pmid=23263185 |pmc=3548017 |bibcode=2013Natur.493..411S }}</ref>

===Dysfunction===

Dysfunction in the ventral striatum can lead to a variety of disorders, most notably [[Major depressive disorder|depression]] and [[Obsessive–compulsive disorder|obsessive-compulsive disorder]]. Because of its involvement in reward pathways, the ventral striatum has also been implicated in playing a critical role in addiction. It has been well established that the ventral striatum is strongly involved in mediating the reinforcing effects of drugs, especially stimulants, through dopaminergic stimulation.<ref>{{cite journal |last1=Everitt |first1=Barry J. |last2=Robbins |first2=Trevor W. |title=From the ventral to the dorsal striatum: Devolving views of their roles in drug addiction |journal=Neuroscience & Biobehavioral Reviews |date=November 2013 |volume=37 |issue=9 |pages=1946–1954 |doi=10.1016/j.neubiorev.2013.02.010 |pmid=23438892 |doi-access=free }}</ref>

=== Language disorders ===
Lesions to the striatum have been associated with deficits in speech production and comprehension. While striatal damage can impact all levels of language, damage can broadly be characterized as affecting the ability to manipulate linguistic units and rules, resulting in the promotion of default linguistic forms in conflicting situations in which selection, inhibition, and monitoring load is increased.<ref>{{Cite journal |last=Fedorenko |first=Evelina |date=2014 |title=The role of domain-general cognitive control in language comprehension |journal=Frontiers in Psychology |volume=5 |page=335 |doi=10.3389/fpsyg.2014.00335  |doi-access=free|pmid=24803909 |pmc=4009428 |issn=1664-1078}}</ref> Two subregions of the striatum have been shown to be particularly important in language: the [[caudate nucleus]] and left [[putamen]]. Lesions localized to the caudate nucleus, as well as direct electrical stimulation, can result in [[Paraphasia|lexical paraphasias]] and perservations (continuations of an utterance after the stimulus has ceased), which is associated with inhibited executive control, in the sense that executive control allows for the selection of the best choice among competing alternatives).<ref>{{Cite journal |last1=Kreisler |first1=A. |last2=Godefroy |first2=O. |last3=Delmaire |first3=C. |last4=Debachy |first4=B. |last5=Leclercq |first5=M. |last6=Pruvo |first6=J.-P. |last7=Leys |first7=D. |date=2000-03-14 |title=The anatomy of aphasia revisited |url=https://n.neurology.org/content/54/5/1117 |journal=Neurology |language=en |volume=54 |issue=5 |pages=1117–1123 |doi=10.1212/WNL.54.5.1117 |issn=0028-3878 |pmid=10720284|s2cid=21847976 }}</ref> Stimulation of the putamen results in the inhibition of articulatory sequences and the inability to initiate motor speech commands.<ref>{{Cite journal |last1=Robles |first1=S. Gil |last2=Gatignol |first2=P. |last3=Capelle |first3=L. |last4=Mitchell |first4=M.-C. |last5=Duffau |first5=H. |date=2005-07-01 |title=The role of dominant striatum in language: a study using intraoperative electrical stimulations |journal=Journal of Neurology, Neurosurgery & Psychiatry |language=en |volume=76 |issue=7 |pages=940–946 |doi=10.1136/jnnp.2004.045948 |issn=0022-3050 |pmid=15965199|doi-access=free |pmc=1739710 }}</ref><ref>{{Cite journal |last1=Guenther |first1=Frank H. |last2=Ghosh |first2=Satrajit S. |last3=Tourville |first3=Jason A. |date=2006-03-01 |title=Neural modeling and imaging of the cortical interactions underlying syllable production |journal=Brain and Language |volume=96 |issue=3 |pages=280–301 |doi=10.1016/j.bandl.2005.06.001 |pmid=16040108 |issn=0093-934X|pmc=1473986 }}</ref>