Editing Tourette syndrome (section)

== Mechanism ==
[[File:Basal ganglia and related structures (2).svg|thumb|upright=1.6|alt=The basal ganglia at the brain's center with the thalamus next to it. Nearby related brain structures are also shown.|The [[basal ganglia]] and [[thalamus]] are implicated in Tourette syndrome.]]
The exact [[pathophysiology|mechanism]] affecting the inherited vulnerability to Tourette's is not well established.<ref name= Fernandez /> Tics are believed to result from dysfunction in [[Cerebral cortex|cortical]] and subcortical brain regions: the [[Human thalamus|thalamus]], [[basal ganglia]] and [[frontal lobe|frontal cortex]].{{sfnp|Walkup|Mink|Hollenback|2006|p=xv}} [[Neuroanatomic]] models suggest failures in circuits connecting the brain's cortex and subcortex;<ref name=Zinner /> [[Neuroimaging|imaging techniques]] implicate the frontal cortex and basal ganglia.<ref name=Bloch2011 /> In the 2010s, neuroimaging and [[Postmortem studies|postmortem brain studies]], as well as [[animal studies|animal]] and [[Genetic analysis|genetic studies]],<ref name= Morand />{{sfnp|Sukhodolsky|Gladstone|Kaushal|Piasecka|2017|p= 246}} made progress towards better understanding the neurobiological mechanisms leading to Tourette's.<ref name= Morand /> These studies support the basal ganglia model, in which [[neuron]]s in the [[striatum]] are activated and inhibit outputs from the basal ganglia.{{sfnp|Sukhodolsky|Gladstone|Kaushal|Piasecka|2017|p= 245}}

[[Cortico-basal ganglia-thalamo-cortical loop|Cortico-striato-thalamo-cortical]] (CSTC) [[Neural circuit#Circuitry|circuits]], or neural pathways, provide inputs to the basal ganglia from the cortex. These circuits connect the basal ganglia with other areas of the brain to transfer information that regulates planning and control of movements, behavior, decision-making, and learning.<ref name= Morand /> Behavior is regulated by cross-connections that "allow the integration of information" from these circuits.<ref name= Morand /> Involuntary movements may result from impairments in these CSTC circuits,<ref name= Morand /> including the [[sensorimotor cortex|sensorimotor]], [[limbic system|limbic]], [[Cerebral cortex#Association areas|language]] and [[Orbitofrontal cortex|decision making]] pathways.<!-- Cox JH 2018 --> Abnormalities in these circuits may be responsible for tics and premonitory urges.<ref>{{cite journal |vauthors=Cox JH, Seri S, Cavanna AE |title=Sensory aspects of Tourette syndrome |journal=Neurosci Biobehav Rev |volume=88 |pages=170–176 |date=May 2018 |pmid=29559228 |doi=10.1016/j.neubiorev.2018.03.016 |s2cid=4640655 |url=https://publications.aston.ac.uk/id/eprint/33055/1/Sensory_aspects_of_Tourette_syndrome.pdf |type=Review |access-date=March 18, 2020 |archive-date=December 1, 2020 |archive-url=https://web.archive.org/web/20201201152445/https://publications.aston.ac.uk/id/eprint/33055/1/Sensory_aspects_of_Tourette_syndrome.pdf |url-status=live }}</ref>

The [[caudate nuclei]] may be smaller in subjects with tics compared to those without tics, supporting the hypothesis of pathology in CSTC circuits in Tourette's.<ref name= Morand /> The ability to suppress tics depends on brain circuits that "regulate response inhibition and cognitive control of motor behavior".{{sfnp|Sukhodolsky|Gladstone|Kaushal|Piasecka|2017|p= 246}} Children with TS are found to have a larger [[prefrontal cortex]], which may be the result of an adaptation to help regulate tics.{{sfnp|Sukhodolsky|Gladstone|Kaushal|Piasecka|2017|p= 246}} It is likely that tics decrease with age as the capacity of the frontal cortex increases.{{sfnp|Sukhodolsky|Gladstone|Kaushal|Piasecka|2017|p= 246}} Cortico-basal ganglia (CBG) circuits may also be impaired, contributing to "sensory, [[limbic]] and executive" features.<ref name= Dale2017 /> The release of [[dopamine]] in the basal ganglia is higher in people with Tourette's, implicating biochemical changes from "overactive and dysregulated dopaminergic transmissions".<ref name= Baldermann />

[[Histamine]] and the [[H3 receptor]] may play a role in the alterations of neural circuitry.<ref name= Dale2017 /><ref>{{cite journal |vauthors=Rapanelli M, Pittenger C |title=Histamine and histamine receptors in Tourette syndrome and other neuropsychiatric conditions |journal=Neuropharmacology |volume=106 |pages=85–90 |date=July 2016 |pmid=26282120 |doi=10.1016/j.neuropharm.2015.08.019|s2cid=20574808 | type= Review}}</ref><ref>{{cite journal |vauthors=Rapanelli M |title=The magnificent two: histamine and the H3 receptor as key modulators of striatal circuitry |journal=Prog. Neuropsychopharmacol. Biol. Psychiatry |volume=73 |pages=36–40 |date=February 2017 |pmid=27773554 |doi=10.1016/j.pnpbp.2016.10.002 |s2cid=23588346 |type= Review}}</ref><ref>{{cite journal |vauthors=Bolam JP, Ellender TJ |title=Histamine and the striatum |journal=Neuropharmacology |volume=106 |pages=74–84 |date=July 2016 |pmid=26275849 |pmc=4917894 |doi=10.1016/j.neuropharm.2015.08.013 |type= Review}}</ref> A reduced level of histamine in the H3 receptor may result in an increase in other neurotransmitters, causing tics.<ref>{{cite journal |vauthors=Sadek B, Saad A, Sadeq A, Jalal F, Stark H |title=Histamine H3 receptor as a potential target for cognitive symptoms in neuropsychiatric diseases |journal=Behav. Brain Res. |volume=312 |pages=415–430 |date=October 2016 |pmid=27363923 |doi=10.1016/j.bbr.2016.06.051 |s2cid=40024812 |type= Review}}</ref> Postmortem studies have also implicated "dysregulation of neuroinflammatory processes".<ref name= Fernandez />