Editing Huntington's disease (section)

===Macroscopic changes===
{{See also|Basal ganglia disease}}
[[File:Basal_ganglia_and_related_structures_(2).svg|thumb|upright=1.4|alt=Diagram of a side view of the brain and part of the spinal cord, the front of the brain is to the left, in the centre are red and blue masses, the red mass largely overlaps the blue and has an arm that starts at its leftmost region and forms a spiral a little way out tapering off and ending in a nodule directly below the main mass |The area of the brain most damaged in early Huntington's disease is the [[dorsal striatum]] made up of the [[caudate nucleus]] and the [[putamen]].]]

Initially, damage to the brain is regionally specific with the [[dorsal striatum]] in the subcortical [[basal ganglia]] being primarily affected, followed later by [[cerebral cortex|cortical]] involvement in all areas.<ref name="Nopoulos">{{cite journal | vauthors = Nopoulos PC | title = Huntington disease: a single-gene degenerative disorder of the striatum | journal = Dialogues in Clinical Neuroscience | volume = 18 | issue = 1 | pages = 91–98 | date = March 2016 | pmid = 27069383 | pmc = 4826775 | doi = 10.31887/DCNS.2016.18.1/pnopoulos }}</ref><ref name="McColgan">{{cite journal | vauthors = McColgan P, Tabrizi SJ | title = Huntington's disease: a clinical review | journal = European Journal of Neurology | volume = 25 | issue = 1 | pages = 24–34 | date = January 2018 | pmid = 28817209 | doi = 10.1111/ene.13413 | doi-access = free }}</ref> Other areas of the [[basal ganglia]] affected include the [[substantia nigra]]; cortical involvement includes [[Cortical layers|cortical layers 3, 5, and 6]]; also evident is involvement of the [[hippocampus]], [[Purkinje cell]]s in the [[Cerebellum#Purkinje layer|cerebellum]], lateral tuberal nuclei of the [[hypothalamus]] and parts of the [[thalamus]].<ref name="lancet07" /> These areas are affected according to their structure and the types of neurons they contain, reducing in size as they lose cells.<ref name="lancet07" /> Striatal [[medium spiny neuron]]s are the most vulnerable, particularly ones with [[Neural pathway|projections]] towards the [[external globus pallidus]], with [[interneuron]]s and spiny cells projecting to the [[internal globus pallidus]] being less affected.<ref name="lancet07" /><ref>{{cite book | vauthors = Purves D, Augustine GA, Fitzpatrick D, Hall W, LaMantia AS, McNamara JO, Williams SM | veditors = Purves D | title = Neuroscience | url = https://www.ncbi.nlm.nih.gov/books/bv.fcgi?call=bv.View..ShowTOC&rid=neurosci.TOC&depth=2 | edition = 2nd | publisher = Sinauer Associates | location = Sunderland, MA | isbn = 978-0-87893-742-4 | chapter = Modulation of Movement by the Basal Ganglia – Circuits within the Basal Ganglia System | chapter-url = https://www.ncbi.nlm.nih.gov/books/bv.fcgi?highlight=Huntington's%20disease&rid=neurosci.section.1251 | access-date = 1 April 2009 | year = 2001 | url-status=live | archive-url = https://web.archive.org/web/20090218192801/http://www.ncbi.nlm.nih.gov/books/bv.fcgi?call=bv.View..ShowTOC&rid=neurosci.TOC&depth=2 | archive-date = 18 February 2009}}</ref> HD also causes an [[astrogliosis|abnormal increase]] in [[astrocyte]]s and activation of the brain's immune cells, [[microglia]].<ref name="pmid17965655">{{cite journal | vauthors = Lobsiger CS, Cleveland DW | title = Glial cells as intrinsic components of non-cell-autonomous neurodegenerative disease | journal = Nature Neuroscience | volume = 10 | issue = 11 | pages = 1355–1360 | date = November 2007 | pmid = 17965655 | pmc = 3110080 | doi = 10.1038/nn1988 }}</ref>

The basal ganglia play a key role in movement and behavior control. Their functions are not fully understood, but theories propose that they are part of the cognitive [[executive function|executive system]]<ref name="pmid16496032"/> and the motor circuit.<ref name="pmid10923984"/> The basal ganglia ordinarily inhibit a large number of circuits that generate specific movements. To initiate a particular movement, the cerebral cortex sends a signal to the basal ganglia that causes the inhibition to be released. Damage to the basal ganglia can cause the release or reinstatement of the inhibitions to be erratic and uncontrolled, which results in an awkward start to the motion or motions to be unintentionally initiated or in a motion to be halted before or beyond its intended completion. The accumulating damage to this area causes the characteristic erratic movements associated with HD known as chorea, a [[dyskinesia]].<ref name="pmid10923984">{{cite journal | vauthors = Crossman AR | title = Functional anatomy of movement disorders | journal = Journal of Anatomy | volume = 196 | issue = Pt 4 | pages = 519–525 | date = May 2000 | pmid = 10923984 | pmc = 1468094 | doi = 10.1046/j.1469-7580.2000.19640519.x }}</ref> Because of the basal ganglia's inability to inhibit movements, individuals affected by it inevitably experience a reduced ability to produce speech and swallow foods and liquids (dysphagia).<ref>{{Cite book|title = Motor Speech Disorders: Substrates, Differential Diagnosis, and Management | edition = 3rd | vauthors = Duffy J |publisher = Elsevier|year = 2013|location = St. Louis, Missouri|pages = 196–7}}</ref>